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INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p

INTRODUCTION: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. OBJECTIVE: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. METHODS: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. RESULTS: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. CONCLUSION: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.

Abstract Current navigational aids for blind people do not provide spatial information that meets the requirements of blind and visually impaired people (BVIP) for travel, and traditional map-based navigation services cannot be used directly for navigation. The purpose of this paper is to establish a spatial data model that aligns with their outdoor travel requirements to assist them in accessing spatial information. In alignment with the analysis of spatial information requirements for blind people during outdoor travel, the proposed data model divides the outdoor space into the path layer, the functional layer, the obstacle layer, and the transport and weather layer. Areas such as schools and sports fields, which fulfill certain requirements for them, are categorized as functional features. Essential public transportation stations for outdoor travel are included in transport station features, while obstacles that pose threats to their safety constitute obstacle features. Various features in space are spatially connected through different paths. The proposed semantic information properties enhance the information content representation of the features. The geometry of the features and the topological relationships between them are recorded and used for path planning and navigation in combination with the path layer. Finally, the eastern campus of Jiangxi University of Science and Technology served as an experimental area for the development of a prototype system based on the data model, and a case analysis was provided.

Ryan S D’Souza,1 Yeng F Her,1 Nasir Hussain,2 Jay Karri,3 Michael E Schatman,4 Aaron K Calodney,5 Christopher Lam,6 Thomas Buchheit,7 Brennan J Boettcher,8 George C Chang Chien,9 Scott G Pritzlaff,10 Christopher Centeno,11 Shane A Shapiro,12 Johana Klasova,1 Jay S Grider,13 Ryan Hubbard,14 Eliana Ege,15 Shelby Johnson,8 Max H Epstein,16 Eva Kubrova,8 Mohamed Ehab Ramadan,17 Alexandra Michelle Moreira,18 Swarnima Vardhan,19 Yashar Eshraghi,20 Saba Javed,21 Newaj M Abdullah,22 Paul J Christo,17 Sudhir Diwan,23 Leslie C Hassett,24 Dawood Sayed,6 Timothy R Deer25 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Anesthesiology, The Ohio State Wexner Medical Center, Columbus, OH, USA; 3Departments of Orthopedic Surgery and Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 4Department of Anesthesiology, Perioperative Care, & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 5Precision Spine Care, Tyler, TX, USA; 6Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 7Department of Anesthesiology, Duke University, Durham, NC, USA; 8Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; 9Department of Regenerative Medicine, GCC Institute, Torrance, CA, USA; 10Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 11Centeno-Schultz Clinic, Broomfield, CO, USA; 12Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL, USA; 13Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, KY, USA; 14Department of Sports Medicine, Anderson Orthopedic Clinic, Arlington, VA, USA; 15Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, TX, USA; 16Department of Physical Medicine & Rehabilitation, Harvard Medical School, Boston, MA, USA; 17Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA; 18Department of Physical Medicine & Rehabilitation, University of Miami/Jackson Memorial Hospital, Miami, FL, USA; 19Department of Internal Medicine, Yale New Haven Health – Bridgeport Hospital, Bridgeport, CT, USA; 20Department of Anesthesiology & Critical Care Medicine, Ochsner Health System, New Orleans, LA, USA; 21Department of Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 22Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; 23Department of Pain Medicine, Advanced Spine on Park Avenue, New York City, NY, USA; 24Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA; 25Department of Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USACorrespondence: Ryan S D’Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1-(507)-284-9696, Fax +1-(507)-266-7732, Email dsouza.ryan@mayo.eduPurpose: Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial.Methods: The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of “disagree” or “abstain”, they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved.Results: Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies.Conclusion: In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose–response associations, and comparative analysis between different injectable biologics.Keywords: regenerative medicine, injectable biologics, platelet-rich plasma, mesenchymal stem cell, bone marrow aspirate concentrate, pain medicine

Social and economic inequality are chronic stressors that continually erode the mental and physical health of marginalized groups, undermining overall societal resilience. In this comprehensive review, we synthesize evidence of greater increases in mental health symptoms during the COVID-19 pandemic among socially or economically marginalized groups in the United States, including (a) people who are low income or experiencing homelessness, (b) racial and ethnic minorities, (c) women and lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) communities, (d) immigrants and migrants, (e) children and people with a history of childhood adversity, and (f) the socially isolated and lonely. Based on this evidence, we propose that reducing social and economic inequality would promote population mental health and societal resilience to future crises. Specifically, we propose concrete, actionable recommendations for policy, intervention, and practice that would bolster five "pillars" of societal resilience: (1) economic safety and equity, (2) accessible healthcare, including mental health services, (3) combating racial injustice and promoting respect for diversity, equity, and inclusion, (4) child and family protection services, and (5) social cohesion. Although the recent pandemic exposed and accentuated steep inequalities within our society, efforts to rebuild offer the opportunity to re-envision societal resilience and policy to reduce multiple forms of inequality for our collective benefit.

BACKGROUND: Effortful control, or the regulation of thoughts and behaviour, is a potential target for preventing childhood obesity. OBJECTIVES: To assess effortful control in infancy through late childhood as a predictor of repeated measures of body mass index (BMI) from infancy through adolescence, and to examine whether sex moderates the associations. METHODS: Maternal report of offspring effortful control and measurements of child BMI were obtained at 7 and 8 time points respectively from 191 gestational parent/child dyads from infancy through adolescence. General linear mixed models were used. RESULTS: Effortful control at 6 months predicted BMI trajectories from infancy through adolescence, F(5,338) = 2.75, p = 0.03. Further, when effortful control at other timepoints were included in the model, they added no additional explanatory value. Sex moderated the association between 6-month effortful control and BMI, F(4, 338) = 2.59, p = 0.03, with poorer infant effortful control predicting higher BMI in early childhood for girls, and more rapid increases in BMI in early adolescence for boys. CONCLUSIONS: Effortful control in infancy was associated with BMI over time. Specifically, poor effortful control during infancy was associated with higher BMI in childhood and adolescence. These findings support the argument that infancy may be a sensitive window for the development of later obesity.

Timothy Deer,1,* Robert Heros,2,* Edward Tavel,3 Sayed Wahezi,4 Robert Funk,5 Patrick Buchanan,6 Anne Christopher,7 Jacqueline Weisbein,8 Christopher Gilligan,9 Denis Patterson,10 Ajay Antony,11 Mohab Ibrahim,12 Nathan Miller,13 Keith Scarfo,14 Gayle Johnson,15 Thadchaigeni Panchalingam,15 Udoka Okaro,15 James Yue16 1Pain Management, The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 2Pain Management, Spinal Diagnostics, Tualatin, OR, USA; 3Pain Management, Clinical Trials of South Carolina, Charleston, SC, USA; 4Pain Management, Montefiore Medical Center, Bronx, NY, USA; 5Pain Management, Indiana Spine Group, Indianapolis, IN, USA; 6Pain Management, Spanish Hills Interventional Pain Specialists, Camarillo, CA, USA; 7Pain Management, Saint Louis Pain Consultants, Chesterfield, MO, USA; 8Pain Management, Napa Valley Orthopedic Medical Group, Napa, CA, USA; 9Pain Management, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA; 10Pain Management, Nevada Advanced Pain Specialists, Reno, NV, USA; 11Pain Management, the Orthopedic Institute, Gainesville, FL, USA; 12Pain Management, Coastal Pain & Spinal Diagnostics Medical Group, Carlsbad, CA, USA; 13Pain Management, Banner University Medical Center, Tucson, AZ, USA; 14Pain Management, Rhode Island Hospital, Providence, RI, USA; 15Neuromodulation, Abbott Labs, Austin, TX, USA; 16Orthopaedic spine Surgery, Connecticut Orthopedics, Hamden, CT, USA*These authors contributed equally to this workCorrespondence: Timothy Deer, Pain Management, The Spine and Nerve Center of the Virginias, 400 Court Street, Suite 100, Charleston, WV, 25301, USA, Tel +1 304 347 – 6120, Fax +1 304 347 – 6126, Email doctdeer@aol.comAim: Low Back Pain (LBP) is a prevalent condition. Spinal cord stimulation (SCS) has emerged as a more effective, long-term treatment compared to conventional medical management (CMM). The DISTINCT study enrolled and randomized chronic LBP patients with no indication of traditional spine surgery. This analysis focuses comparing study outcomes on patients initially randomized to receive CMM treatment and subsequently crossed over to SCS after 6 months.Purpose: To compare the therapeutic effectiveness and cost-efficiency of passive recharge burst SCS to CMM.Patients and Methods: A total of 269 patients were enrolled with 162 randomly assigned to SCS and 107 to CMM. The DISTINCT study design allowed a crossover to the alternative treatment arm after 6 months. Patients underwent a trial and received a permanent implant if they reported ≥ 50% pain reduction. Outcome analysis included pain (NRS), disability (ODI), catastrophizing (PCS), quality of life (PROMIS-29) and health care utilization.Results: Seventy out of eighty-one patients opted to cross over to trial SCS at 6M with 94% (66/70) undergoing a trial. Among those, 88% (58/66) reported a ≥ 50% or more pain relief and 55 received a permanent implant. At 12M visit, 71.4% reported a ≥ 50% pain improvement sustained at the 18M visit, with 24.5% (12/49) indicating a ≥ 80% improvement. Disability reductions (79% meeting the minimally important difference of a 13-point decrease), decreased catastrophizing, and significant improvements in all PROMIS-29 domains were noted. Furthermore, 42% of the patients reported decreased or discontinued opioid usage. Clinical benefits at the 12M visit were sustained through the 18M visit accompanied by a significant reduction in healthcare utilization and a $1214 cost savings.Conclusion: SCS demonstrates superior, long-term performance and safety outcomes compared to CMM therapy in LBP patients who received both CMM and SCS therapy. Additionally, SCS patients experienced reduced healthcare resource utilization and lower costs compared to those receiving CMM.Keywords: DISTINCT, low back pain, BurstDR, spinal cord stimulation, healthcare utilization, persistent spinal pain syndrome, neuromodulation

Abstract Introduction Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. Methods Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. Results A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria (“Day 0 successes”) and those who did not (“needed longer to evaluate the therapy”). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. Conclusions The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. Trial Registration The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).

Abstract Whilst. pharmacological therapies remain the cornerstone of pain management in chronic pain, factors including the current opioid epidemic have led to non-pharmacological techniques becoming a more attractive proposition. We explored the prevalence of medical device use and their treatment efficacy in non-cancer pain management. A systematic methodology was developed, peer reviewed and published in PROSPERO (CRD42021235384). Key words of medical device, pain management devices, chronic pain, lower back pain, back pain, leg pain and chronic pelvic pain using Science direct, PubMed, Web of Science, PROSPERO, MEDLINE, EMBASE, PorQuest and ClinicalTrials.gov. All clinical trials, epidemiology and mixed methods studies that reported the use of medical devices for non-cancer chronic pain management published between the 1st of January 1990 and the 30th of April 2022 were included. 13 studies were included in systematic review, of these 6 were used in the meta-analysis. Our meta-analysis for pain reduction showed that transcutaneous electrical nerve stimulation combined with instrument-assisted soft tissue mobilization treatment and pulsed electromagnetic therapy produced significant treatment on chronic lower back pain patients. Pooled evidence revealed the use of medical device related interventions resulted in 0.7 degree of pain reduction under a 0–10 scale. Significant improvement in disability scores, with a 7.44 degree reduction in disability level compared to a placebo using a 50 score range was also seen. Our analysis has shown that the optimal use of medical devices in a sustainable manner requires further research, needing larger cohort studies, greater gender parity, in a more diverse range of geographical locations.

Ganesan Baranidharan,1,2 Beatrice Bretherton,1,3 Richard G Feltbower,4 Jake Timothy,5 Almas Latif Khan,6,7 Ashok Subramanian,8 Mushtaq Ahmed,9 Tracey A Crowther,1,10 Helen Radford,10,11 Harun Gupta,12 Muthusamy Chandramohan,13 Douglas P Beall,14 Timothy R Deer,15 Thomas Hedman16 1Pain Management Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 2School of Medicine, University of Leeds, Leeds, UK; 3School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK; 4Leeds Institute for Data Analytics, School of Medicine, University of Leeds, Leeds, UK; 5Department of Neuroscience, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 6Department of Spine Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 7Institute of Medical and Biological Engineering, University of Leeds, Leeds, UK; 8Somerset Spinal Surgery Service, Musgrove Park Hospital, Taunton, UK; 9Department of Trauma and Orthopaedic Surgery, Dudley Group NHS Foundation Trust, Dudley, UK; 10Research & Innovation, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 11Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK; 12Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 13Radiology Department, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK; 14Comprehensive Specialty Care, Edmond, OK, USA; 15The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 16Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USACorrespondence: Ganesan Baranidharan, Pain Management Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK, Email g.baranidharan@nhs.netPurpose: An early-stage, multi-centre, prospective, randomised control trial with five-year follow-up was approved by Health Research Authority to compare the efficacy of a minimally invasive, laterally implanted interspinous fixation device (IFD) to open direct surgical decompression in treating lumbar spinal stenosis (LSS). Two-year results are presented.Patients and Methods: Forty-eight participants were randomly assigned to IFD or decompression. Primary study endpoints included changes from baseline at 8-weeks, 6, 12 and 24-months follow-ups for leg pain (visual analogue scale, VAS), back pain (VAS), disability (Oswestry Disability Index, ODI), LSS physical function (Zurich Claudication Questionnaire), distance walked in five minutes and number of repetitions of sitting-to-standing in one minute. Secondary study endpoints included patient and clinician global impression of change, adverse events, reoperations, operating parameters, and fusion rate.Results: Both treatment groups demonstrated statistically significant improvements in mean leg pain, back pain, ODI disability, LSS physical function, walking distance and sitting-to-standing repetitions compared to baseline over 24 months. Mean reduction of ODI from baseline levels was between 35% and 56% for IFD (p< 0.002), and 49% to 55% for decompression (p< 0.001) for all follow-up time points. Mean reduction of IFD group leg pain was between 57% and 78% for all time points (p< 0.001), with 72% to 94% of participants having at least 30% reduction of leg pain from 8-weeks through 24-months. Walking distance for the IFD group increased from 66% to 94% and sitting-to-standing repetitions increased from 44% to 64% for all follow-up time points. Blood loss was 88% less in the IFD group (p=0.024) and operating time parameters strongly favoured IFD compared to decompression (p< 0.001). An 89% fusion rate was assessed in a subset of IFD participants. There were no intraoperative device issues or re-operations in the IFD group, and only one healed and non-symptomatic spinous process fracture observed within 24 months.Conclusion: Despite a low number of participants in the IFD group, the study demonstrated successful two-year safety and clinical outcomes for the IFD with significant operation-related advantages compared to surgical decompression.Keywords: lumbar spinal stenosis, surgical decompression, posterior lateral arthrodesis, patient reported outcomes, minimally invasive spine, interspinous fixation device

Prenatal and postpartum depression are highly prevalent worldwide, and emerging evidence suggests they contribute to impairments in children's executive functions. Studies of maternal depression, however, have focused on the postpartum and postnatal periods with relatively less consideration of prenatal influences on child development. This study of the large population-based Avon Longitudinal Study of Parents and Children U.K. cohort estimates latent classes of maternal depression across the prenatal, postpartum, and postnatal periods to capture heterogeneity in the developmental timing and length of maternal depression, as well as to test whether latent classes differ in children's executive function impairments in middle childhood. Repeated measures latent class analysis yielded five groups demonstrating unique patterns of change in maternal depression from pregnancy through early childhood (n = 13,624). Latent classes differed in executive functions at age 8 among a subsample of children (n = 6,870). Children exposed to chronic maternal depression beginning in utero showed the most impairments in inhibitory control while accounting for child sex, verbal IQ, parents' highest education level, and average family income in childhood. The critical roles of the timing and length of children's exposure to maternal depression are discussed in relation to executive function development, prevention, and intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Summary: Background: Poor prenatal maternal sleep is a pervasive, yet modifiable, health concern affecting maternal and foetal wellbeing. Experimental rodent studies demonstrate that prenatal maternal sleep deprivation affects offspring brain development and leads to adverse outcomes, including increased anxiety-like behaviour. We examined the relation between prenatal maternal sleep quality and neonatal white matter development and subsequent infant negative emotionality. Methods: Participants included 116 mother-infant (53% female) dyads. Prenatal sleep quality was prospectively assessed three times during gestation (16, 29, and 35 gestational weeks) using the Pittsburgh Sleep Quality Index. Neonatal white matter, as indexed by fractional anisotropy (FA), was assessed via diffusion weighted magnetic resonance imaging. Negative emotionality was measured via behavioural observation and maternal report when the infant was 6-months of age. Findings: More prenatal sleep problems across pregnancy were associated with higher neonatal FA in the uncinate fasciculus (left: b = 0.20, p = .004; right: b = 0.15, p = .027). Higher neonatal uncinate FA was linked to infant negative emotionality, and uncinate FA partially mediated the association between prenatal maternal sleep and behavioural observation of infant negative emotionality. Interpretation: Findings highlight prenatal sleep as an environmental signal that affects the developing neonatal brain and later infant negative emotionality. Funding: National Institutes of Health (R01MH109662, R01HL155744, P50HD103573, K12AR084226, F32 Training fellowships MH125572, HL165844, MH106440, and diversity supplement R01HL155744-01S1).

ABSTRACT: Background: Low back pain (LBP) is a highly prevalent, disabling condition affecting millions of people. Patients with an identifiable anatomic pain generator and resulting neuropathic lower extremity symptoms often undergo spine surgery, but many patients lack identifiable and/or surgically corrective pathology. Nonoperative treatment options often fail to provide sustained relief. Spinal cord stimulation (SCS) is sometimes used to treat these patients, but the lack of level 1 evidence limits its widespread use and insurance coverage. The DISTINCT RCT study evaluates the efficacy of passive recharge burst SCS compared to conventional medical treatment (CMM) in alleviating chronic, refractory axial low back pain. Methods: This prospective, multicenter, randomized, study with an optional 6-month crossover involved patients who were not candidates for lumbar spine surgery. The primary and secondary endpoints evaluated improvements in low back pain intensity (NRS), back pain-related disability (ODI), pain catastrophizing (PCS), and healthcare utilization. Patients were randomized to SCS therapy or CMM at 30 US study sites. Results: The SCS arm reported an 85.3% NRS responder rate (≥ 50% reduction) compared to 6.2% (5/81) in the CMM arm. After the 6M primary endpoint, SCS patients elected to remain on assigned therapy and 66.2% (49/74) of CMM patients chose to trial SCS (crossover). At the 12M follow-up, SCS and crossover patients reported 78.6% and 71.4% NRS responder rates. Secondary outcomes indicated significant improvements in ODI, PCS, and reduced healthcare utilization. Six serious adverse events were reported and resolved without sequelae. Conclusion: DISTINCT chronic low back pain patients with no indication for corrective surgery experienced a significant and sustained response to burst SCS therapy for up to 12 months. CMM patients who crossed over to the SCS arm reported profound improvements after 6 months. This data advocates for a timely consideration of SCS therapy in patients unresponsive to conservative therapy.

Dawood Sayed,1 Timothy R Deer,2,3 Vinicius Tieppo Francio,1 Christopher M Lam,1 Kamil Sochacki,4 Nasir Hussain,5 Tristan E Weaver,5 Jay Karri,6,7 Vwaire Orhurhu,8,9 Natalie Holmes Strand,10 Jacqueline Soicher Weisbein,11 Jonathan M Hagedorn,12 Ryan S D’Souza,12 Ryan R Budwany,2 Ahish Chitneni,13 Kasra Amirdelfan,14 Michael J Dorsi,15 Dan TD Nguyen,16 Christopher Bovinet,17 Alaa Abd-Elsayed18 1Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 2Pain Services, Spine and Nerve Center of the Virginias, Charleston, WV, USA; 3Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USA; 4Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson, New Brunswick, NJ, USA; 5Anesthesiology, the Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Orthopedic Surgery, University of Maryland School of Medicine, Baltimore, MD, USA; 7Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 8Department of Anesthesiology, University of Pittsburgh Medical Center, Williamsport, PA, USA; 9Pain Medicine, MVM Health, East Stroudsburg, PA, USA; 10Anesthesiology and Pain Medicine, Mayo Clinic, Phoenix, AZ, USA; 11Interventional Pain Management, Napa Valley Orthopaedic Medical Group, Napa, CA, USA; 12Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 13Department of Rehabilitation & Regenerative Medicine, New York Presbyterian – Columbia & Cornell, New York, NY, USA; 14Director of Clinical Research, Boomerang Healthcare, Walnut Creek, CA, USA; 15Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA; 16Neuroradiology & Pain Solutions of Oklahoma, Edmond, OK, USA; 17The Spine Center of SE Georgia, Brunswick, GA, USA; 18Anesthesiology, University of Wisconsin, Madison, WI, USACorrespondence: Dawood Sayed, Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA, Tel +1 785-550-5800, Email dsayed@kumc.eduAbstract: Clinical management of sacroiliac disease has proven challenging from both diagnostic and therapeutic perspectives. Although it is widely regarded as a common source of low back pain, little consensus exists on the appropriate clinical management of sacroiliac joint pain and dysfunction. Understanding the biomechanics, innervation, and function of this complex load bearing joint is critical to formulating appropriate treatment algorithms for SI joint disorders. ASPN has developed this comprehensive practice guideline to serve as a foundational reference on the appropriate management of SI joint disorders utilizing the best available evidence and serve as a foundational guide for the treatment of adult patients in the United States and globally.Keywords: sacroiliac joint, sacroiliitis, chronic pain, best practices, radiofrequency ablation, sacroiliac joint fusion

Dawood Sayed,1 Timothy Ray Deer,2 Jonathan M Hagedorn,3 Asim Sayed,4 Ryan S D’Souza,3 Christopher M Lam,1 Nasir Khatri,5 Zohra Hussaini,1 Scott G Pritzlaff,6 Newaj Mohammad Abdullah,7 Vinicius Tieppo Francio,1 Steven Michael Falowski,8 Yussr M Ibrahim,9 Mark N Malinowski,10 Ryan R Budwany,2 Natalie Holmes Strand,11 Kamil M Sochacki,12 Anuj Shah,13 Tyler M Dunn,11 Morad Nasseri,14 David W Lee,15 Leonardo Kapural,16 Marshall David Bedder,17,18 Erika A Petersen,19 Kasra Amirdelfan,20 Michael E Schatman,21,22 Jay Samuel Grider23 1Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 2Pain Services, Spine and Nerve Center of the Virginias, Charleston, WV, USA; 3Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 4Podiatry/Surgery, Susan B. Allen Memorial Hospital, El Dorado, KS, USA; 5Interventional Pain Medicine, Novant Spine Specialists, Charlotte, NC, USA; 6Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 7Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; 8Neurosurgery, Neurosurgical Associates of Lancaster, Lancaster, PA, USA; 9Pain Medicine, Northern Light Eastern Maine Medical Center, Bangor, ME, USA; 10OhioHealth Neurological Physicians, OhioHealth, Columbus, OH, USA; 11Anesthesiology and Pain Medicine, Mayo Clinic, Phoenix, AZ, USA; 12Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson, New Brunswick, NJ, USA; 13Department of Physical Medicine and Rehabilitation, Detroit Medical Center, Detroit, MI, USA; 14Interventional Pain Medicine / Neurology, Boomerang Healthcare, Walnut Creek, CA, USA; 15Pain Management Specialist, Fullerton Orthopedic, Fullerton, CA, USA; 16Carolinas Pain Institute, Winston Salem, NC, USA; 17Chief of Pain Medicine Service, Augusta VAMC, Augusta, GA, USA; 18Associate Professor and Director, Addiction Medicine Fellowship Program, Department Psychiatry and Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA, USA; 19Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 20Director of Clinical Research, Boomerang Healthcare, Walnut Creek, CA, USA; 21Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 22Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 23Anesthesiology, Division of Pain Medicine, University of Kentucky College of Medicine, Lexington, KY, USACorrespondence: Dawood Sayed, Anesthesiology and Pain Medicine, the University of Kansas Medical Center, Kansas City, KS, USA, Tel +1 785-550-5800, Email dsayed@kumc.eduIntroduction: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN.Objective: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN.Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process.Results: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria.Conclusion: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.Keywords: diabetes, painful diabetic neuropathy, neuropathy, spinal cord stimulation, chronic pain, diabetic neuropathy

Aaron Calodney,1 Nomen Azeem,2 Patrick Buchanan,3 Ioannis Skaribas,4 Ajay Antony,5 Christopher Kim,6 George Girardi,7 Chau Vu,8 Christopher Bovinet,9 Rainer Vogel,10 Sean Li,11 Navdeep Jassal,12 Youssef Josephson,13 Timothy Lubenow,14 Christopher M Lam,15 Timothy R Deer6 1Precision Spine Care, Tyler, TX, USA; 2Florida Spine and Pain Specialists, Tampa, FL, USA; 3Spanish Hills Interventional Pain Specialists, Camarillo, CA, USA; 4Expert Pain P.A, Houston, TX, USA; 5The Orthopaedic Institute, Gainesville, FL, USA; 6The Spine and Nerve Center, Charleston, WV, USA; 7Front Range Pain Medicine, Fort Collins, CO, USA; 8Evolve Restoration Center, Santa Rosa, CA, USA; 9The Spine Center of Southeast Georgia, Brunswick, GA, USA; 10Comprehensive and Interventional Pain Management, Henderson, NV, USA; 11Premier Pain Centers, Shrewsbury, NJ, USA; 12Excel Pain and Spine, Lakeland, FL, USA; 13The Pain Management Center, Voorhees Township, NJ, USA; 14Rush University Medical Center, Chicago, IL, USA; 15University of Kansas Medical Center, Kansas City, KS, USACorrespondence: Aaron Calodney, Precision Spine Care, Tyler, TX, USA, Email aaroncalodney@me.comIntroduction: Research suggests that sacroiliac joint (SIJ) dysfunction is responsible for 15% to 30% of reported low back pain cases. Recently, there has been an increasing interest in SIJ fusion using minimally invasive surgery (MIS) due to safety. Initially, devices designed for MIS were intended for lateral approaches. A minimally invasive sacroiliac fusion implant for use with a posterior approach has been developed and is regulated for clinical use under the regulatory framework required for human cells, tissues, or cellular or tissue-based products (HCT/Ps).Methods: A multi-center, prospective, single-arm study was launched after initial studies provided preliminary data to support safety, efficacy, and durability of this minimally invasive sacroiliac posterior fusion LinQ allograft implant (NCT04423120). Preliminary results were reported previously. Final results for the full participant cohort are presented here.Results: One-hundred and fifty-nine (159) participants were enrolled across 16 investigational sites in the US between January 2020 and March 2022. One-hundred and twenty-two (122) participants were implanted. At the 1-month follow-up, 82 participants satisfied all criteria for the composite responder endpoint, representing 73.2% of the study cohort. These results stayed consistent across the remaining study timepoints with 66.0%, 74.4%, and 73.5% of participants classified as responders at the 3-, 6- and 12-month follow-up visits, respectively. VAS scores were significantly reduced (p < 0.0001) and ODI scores were significantly improved (p < 0.0001). All domains of the PROMIS-29 were also significantly improved (all p’s < 0.0001). Only one procedure-related serious AE was reported in the study.Conclusion: These results suggest that the posterior approach LinQ Implant System is a safe and effective treatment for sacroiliac joint dysfunction at 12 months, with results that are favorable compared to outcomes reported for an FDA-cleared lateral approach.Keywords: sacroiliac joint disease, sacroiliac fusion, single point posterior fusion, back pain, minimally invasive spine surgery, sacroiliitis

Christopher M Lam,1 Sarah A Keim,2 Dawood Sayed,1 Alaa Abd-Elsayed,3 Amitabh Gulati,4 Michael E Schatman,5,6 Timothy Deer,7 Usman Latif1 1Department of Anesthesiology, Pain and Perioperative Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA; 3Department of Anesthesiology and Perioperative Medicine, University of Wisconsin, Madison, WI, USA; 4Department of Anesthesiology and Critical Care, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 5Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 6Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 7The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Christopher M Lam, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 1034, Kansas City, KS, 66160, USA, Tel +1-(704)-488-5665, Fax +1-913-588-3365, Email clam2@kumc.eduBackground: Chronic abdominal pain (CAP) is a common and challenging to treat condition with a global prevalence of up to 25%. Despite extensive evaluation, approximately 40% of patients with CAP have an unknown diagnosis. Medications may be ineffective, and surgery is rarely indicated. Interventional treatment including sympathetic blocks, sympathetic neurolysis, and transversus abdominal plane (TAP) blocks may be an option, but their efficacy can wane over time. Neuromodulation has emerged as an option for these patients, as there is evidence of success with dorsal column spinal cord and dorsal root ganglion (DRG) stimulation. Peripheral nerve stimulation (PNS) may be an alternative option, particularly in higher risk patients or in patients for whom neuraxial access may be unsafe or too technically challenging. Thoracoabdominal nerve peripheral nerve stimulation via a TAP approach may be more specifically targeted in comparison to dorsal column or DRG stimulation. In this short report, we detail a technique that the authors have successfully used for thoracoabdominal nerve PNS via a TAP approach for management of CAP.Methods: This article describes a novel medial to lateral ultrasound guided thoracoabdominal nerve PNS via a TAP approach technique for lead placement and implantation.Results: A medial to lateral ultrasound guided TAP approach as described to successfully implant percutaneous thoracoabdominal nerve PNS leads for management of CAP.Conclusion: The thoracoabdominal nerve PNS via a TAP approach lead placement technique noted in this report has been used as a means for management of CAP utilizing peripheral neuromodulation. Here, we present a short report detailing a potential technique for PNS utilization for management of CAP. Further studies are needed to validate the safety and efficacy of this therapy modality, although the authors have found it to be a viable management option for patients with medically refractory neuropathic CAP.Keywords: peripheral nerve stimulator, neuromodulation, neuropathic pain, ultrasound, thoracic nerves

Mayank Gupta,1,&ast; Anand S Patil,2,&ast; Ahish Chitneni,3 Michael E Schatman,4 Hemant Kalia,5 Timothy R Deer,6 Dawood Sayed,7 Amol Soin,8 Ganesan Baranidharan,9 Peter Staats,10 Leonardo Kapural,11 Phani Ashok Attaluri,12 Paul Verrills,13 Sudhir Diwan,14 Danielle Levin,4 Nimisha Halder,15 Alaa A Abd-Elsayed16 1Kansas Pain Management & Neuroscience Research Center, LLC, Overland Park, KS, USA; 2St. Luke’s Rehabilitation Medical Center, Spokane, WA, USA; 3Newyork-Presbyterian, New York, NY, USA; 4Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 5Rochester Regional Health System, Rochester, NY, USA; 6The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 7The University of Kansas Health System, Kansas City, KS, USA; 8The Ohio Pain Clinic, Dayton, OH, USA; 9Leeds Teaching Hospitals NHS Trust, Leeds, UK; 10National Spine & Pain Centers, Frederick, MD, USA; 11Carolinas Pain Institute, Winston-Salem, NC, USA; 12Olathe Health, Olathe, KS, USA; 13Metro Pain Group, Clayton, VIC, Australia; 14Manhattan Spine & Pain, New York, NY, USA; 15Kansas City University, Kansas City, MO, USA; 16UW Health Pain Services, University of Wisconsin-Madison, Madison, WI, USA&ast;These authors contributed equally to this workCorrespondence: Mayank Gupta, Kansas Pain Management & Neuroscience Research Center, LLC, Overland Park, KS, USA, Email mayank.g@kansaspainmanagement.comAbstract: In this article, we propose a new diagnostic paradigm known as Chronic Abdominal Discomfort Syndrome (CADS). Patient’s presentation centers around chronic abdominal pain not explained by acute pathology with or without accompanying dyspepsia, bloating, nausea and vomiting among other symptoms. The pathophysiology is noted to be neurogenic, possibly stemming from visceral sympathetic nerves or abdominal wall afferent nerves. Diagnosis is supported by signs or symptoms traversing clinical, diagnostic and functional criteria. Included is a tool which can assist clinicians in diagnosing patients with CADS per those domains. We hope to facilitate primary care physicians’ and gastroenterologists’ utilization of our criteria to provide guidance for selecting which patients may benefit from further interventions or evaluation by a pain physician. The pain physician may then offer interventions to provide the patient with relief.Keywords: CADS, chronic abdominal pain, neurogenic abdominal pain, chronic abdominal discomfort

ABSTRACTLassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the in vitro antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.

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.

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use.MethodsA 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis.ResultsLogistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: 0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations.ConclusionsStudy interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database.

Many public institutions, including universities and colleges, have committed to Indigenous engagement – the institutional effort to engage with experiences, histories, and perspectives of First Nations, Inuit, and Métis peoples in meaningful ways. In many areas of institutional endeavour, these commitments have frequently included a focus upon spiritual orientations of Indigenous peoples as a central aspect of their knowledge and worldviews. In this study, we sought to acquire knowledge on moral understandings that were resident in the consciousness of Indigenous Elders and Knowledge Keepers situated at universities across Canada. Findings revealed that personal and communal experiences informed a developed sense of responsibility that may be situated in the unique manifestations of their respective knowledge systems, heritages, and consciousnesses. Although non-Indigenous orientations such as those of Christianity informed the narratives of some, a prevailing sense of traditional identity emerged from participants.

Anuj Shah,1 Jonathan M Hagedorn,2 Usman Latif,3 Ashley Bailey-Classen,4 Nomen Azeem,5 Douglas P Beall,6 Pankaj Mehta,7 Chad Stephens,8 Larry Khoo,9 Timothy Ray Deer10 1Department of Physical Medicine and Rehabilitation, Detroit Medical Center, Detroit, MI, USA; 2Department of Anesthesiology and Perioperative Medicine, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 3Department of Anesthesiology and Pain Medicine, University of Kansas Health System, Kansas City, KS, USA; 4Trinity Pain Medicine Associates, Fort Worth, TX, USA; 5Florida Spine & Pain Specialists, Riverview, FL, USA; 6Comprehensive Specialty Care, Edmond, OK, USA; 7Pain Specialists of Austin and Central Texas Pain Center, Austin, TX, USA; 8Noble Pain Management and Sports Medicine, Southlake, TX, USA; 9The Spine Clinic of Los Angeles, Los Angeles, CA, USA; 10The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Anuj Shah, Department of Physical Medicine and Rehabilitation, Detroit Medical Center, 261 Mack Ave, Detroit, MI, 48220, USA, Tel +1 734646-0321, Email Anujshah74@gmail.comIntroduction: Lumbar spinal stenosis (LSS) is a common condition caused by degenerative changes in the lumbar spine with age. LSS is caused by a variety of factors, including degenerative spondylosis and spondylolisthesis. People suffering with LSS experience neurogenic claudication, which causes severe physical limitations, discomfort, and a decrease in quality of life. Less invasive procedures are now being researched to improve the prognosis, success rate, and safety of LSS treatments. Posterior lateral spinal arthrodesis (PLSA) is a new surgical treatment for LSS. This study looks at the procedural and patient safety of PLSA.Materials and methods: This study is a multicenter retrospective analysis of the safety of PLSA who met the clinical indications for PLSA and underwent the procedure at eight interventional spine practices. Data was collected on demographical information, pre-procedural numeric rating scale score (NRS), post-procedural NRS, and complication reporting. Patients who were included had LSS with or without spondylolisthesis and had failed conservative treatments. A descriptive statistical analysis was performed to report the outcomes. Results were reported as mean and standard deviations for continuous outcomes, and frequency (%) for categorical outcomes.Results: This retrospective analysis involved 191 patients and 202 PLSA implants. The majority of patients were male Caucasians with a mean age of 69.2 years and a BMI of 31.1. A large majority of implants were placed at the L4-5 level, and the average pre-procedural NRS was 6.3 while the average post-procedural NRS was 3.1, indicating a 50.8% reduction in pain (p < 0.0001). Two patients reported complications, but they were unrelated to the device or surgical procedure; no infections, device malfunctions, or migrations were reported in the patient cohort.Conclusion: Preliminary results with PLSA implants indicate that it is a safe treatment option for patients with moderate LSS who do not respond to conservative management.Keywords: lumbar spinal stenosis, spondylolisthesis, interspinous fusion, Minuteman, spinal simplicity, posterior lateral spinal arthrodesis

A critical function of flow cytometry is to count the concentration of blood cells, which helps in the diagnosis of certain diseases. However, the bulky nature of commercial flow cytometers makes such tests only available in hospitals or laboratories, hindering the spread of point-of-care testing (POCT), especially in underdeveloped areas. Here, we propose a smart Palm-size Optofluidic Hematology Analyzer based on a miniature fluorescence microscope and a microfluidic platform to lighten the device to improve its portability. This gadget has a dimension of 35 × 30 × 80 mm and a mass of 39 g, less than 5% of the weight of commercially available flow cytometers. Additionally, automatic leukocyte concentration detection has been realized through the integration of image processing and leukocyte counting algorithms. We compared the leukocyte concentration measurement between our approach and a hemocytometer using the Passing-Bablok analysis and achieved a correlation coefficient of 0.979. Through Bland-Altman analysis, we obtained the relationship between their differences and mean measurement values and established 95% limits of agreement, ranging from −0.93×103 to 0.94×103 cells/μL. We anticipate that this device can be used widely for monitoring and treating diseases such as HIV and tumors beyond hospitals.

Abstract In fluorescence microscopy, computational algorithms have been developed to suppress noise, enhance contrast, and even enable super-resolution (SR). However, the local quality of the images may vary on multiple scales, and these differences can lead to misconceptions. Current mapping methods fail to finely estimate the local quality, challenging to associate the SR scale content. Here, we develop a rolling Fourier ring correlation (rFRC) method to evaluate the reconstruction uncertainties down to SR scale. To visually pinpoint regions with low reliability, a filtered rFRC is combined with a modified resolution-scaled error map (RSM), offering a comprehensive and concise map for further examination. We demonstrate their performances on various SR imaging modalities, and the resulting quantitative maps enable better SR images integrated from different reconstructions. Overall, we expect that our framework can become a routinely used tool for biologists in assessing their image datasets in general and inspire further advances in the rapidly developing field of computational imaging.

Natalie Strand,1 Ryan S D’Souza,2 Jay Karri,3 Hemant Kalia,4 Jackie Weisbein,5 Brian J Kassa,6 Nasir Hussain,7 Ahish Chitneni,8 Ryan R Budwany,9 Jonathan Hagedorn,2 Jason E Pope,10 Timothy R Deer,11 Dawood Sayed,12 Alaa Abd-Elsayed13 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA; 2Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 3Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA; 4Department of Physical Medicine and Rehabilitation, Rochester Regional Health, Rochester, NY, USA; 5Napa Valley Orthopaedic, Napa, CA, USA; 6Resident in the Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine at the Rehabilitation Institute of Michigan, Detroit, MI, USA; 7Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 8Department of Physical Medicine & Rehabilitation, New York-Presbyterian, New York, NY, USA; 9Resident in the Department of Anesthesiology, West Virginia University, Charleston, WV, USA; 10Interventional Pain Management, Evolve Restorative Center, Santa Rosa, CA, USA; 11Department of Anesthesiology, West Virginia University School of Medicine, Morgantown, WV, USA; 12Department of Anesthesiology, The University of Kansas Medical Center, Kansas City, KS, USA; 13Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USACorrespondence: Natalie Strand, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA, Email Strand.Natalie@mayo.eduAbstract: Cannabinoids have recently gained a renewed interest due to their potential applicability to various medical conditions, specifically the management of chronic pain conditions. Unlike many other medications, medical cannabis is not associated with serious adverse events, and no overdose deaths have been reported. However, both safety and efficacy data for medical cannabis treatment of chronic, nonmalignant pain conditions are lacking. Therefore, representatives from the American Society of Pain and Neuroscience summarize the evidence, according to level and grade, for medical cannabis treatment of several different pain conditions. Treatment of cancer-related pain has prospective evidentiary support for the use of medical cannabis. Although 3 large and well-designed randomized controlled trials investigated cannabis treatment of cancer-related pain, the evidence yielded only a grade D recommendation. Neuropathic pain has been investigated in prospective studies, but a lack of high-quality evidence renders cannabis treatment for this indication a grade C recommendation. Both safety and efficacy data are lacking for use of medical cannabis to treat chronic nonmalignant pain conditions.Keywords: analgesia, chronic pain, marijuana treatment, neuralgia, postoperative pain

Many schools, school districts, and provincial education authorities in Canada are collaborating with Indigenous communities to indigenize content and provide progamming to improve Indigenous student success. With a focus on high school achievement in the area of Indigenous education at the cultural interface of Indigenous communities and Euro-Western educational systems, this article examines the efforts of a school division to impact student achievement and experience. Data from interviews conducted with teachers, educational assistants, and administrators are presented and discussed, evidencing participants' perspectives on these initiatives. This study revealed that, despite numerous institutional and non-institutional challenges, the school division's efforts in Indigenous education programming in many of its high schools have been thriving and have also been well supported compared to other public school divisions in Canada.

Timothy Sowder,1 Dawood Sayed,1 Tyler Concannon,1 Scott H Pew,2 Natalie H Strand,2 Alaa Abd-Elsayed,3 Christopher S Wie,2 Daniel E Gomez Ramos,4 Ahmed M Raslan,5 Timothy R Deer6 1Department of Anesthesiology, University of Kansas Medical Center, Kansas City, KS, USA; 2Department of Anesthesiology, Mayo Clinic, Phoenix, AZ, USA; 3Department of Anesthesiology, University of Wisconsin, Madison, WI, USA; 4Department of Neurology, Mayo Clinic, Phoenix, AZ, USA; 5Department of Neurological Surgery, Oregon Health and Science University, Portland, OR, USA; 6The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Timothy Sowder, Department of Anesthesiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 1034, Kansas City, KS, 66160, USA, Tel +1-913-588-6670, Fax +1-913-588-3365, Email tsowder@kumc.eduAbstract: Radiofrequency ablation (RFA) is a treatment modality used in interventional pain management to treat several conditions including chronic neck or back pain, sacroiliac joint pain, major joint pain, and pain from sites that can be isolated to a sensory nerve amenable to RFA. The goals of such procedures are to reduce pain, improve function, delay need for surgical intervention, and reduce pain medication consumption. As applications for RFA expand through novel techniques and nerve targets, there is concern with how RFA may impact patients with implanted medical devices. Specifically, the electrical currents used in RFA produce electromagnetic interference, which can result in unintentional energy transfer to implanted devices. This may also interfere with device function or cause damage to the device itself. As the number of patients with implanted devices increases, it is imperative to establish guidelines for the management of implanted devices during RFA procedures. This review aims to establish guidelines to assist physicians in the preoperative, intraoperative, and postoperative management of implanted devices in patients undergoing procedures using radiofrequency energy. Here, we provide physicians with background knowledge and a summary of current evidence to allow safe utilization of RFA treatment in patients with implanted devices such as cardiac implantable electronic devices, spinal cord stimulators, intrathecal pumps, and deep brain stimulators. While these guidelines are intended to be comprehensive, each patient should be assessed on an individual basis to optimize outcomes.Keywords: radiofrequency ablation, implanted medical devices, cardiac implantable electronic device, spinal cord stimulator, intrathecal pump, deep brain stimulator

Timothy Deer,1 Ankur A Patel,2 Dawood Sayed,3 Ashley Bailey-Classen,4 Ashley Comer,1 Benjamin Gill,5 Kiran Patel,6 Alaa Abd-Elsayed,7 Natalie Strand,8 Jonathan M Hagedorn,9 Zohra Hussaini,3 Nasir Khatri,10 Ryan Budwany,1 Melissa Murphy,11 Dan Nguyen,12 Vwaire Orhurhu,13 Morteza Rabii,14 Douglas Beall,15 Stephen Hochschuler,16 Michael E Schatman,17,18 Timothy Lubenow,19 Richard Guyer,16,20 Ahmed M Raslan21 1The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 2Weill Cornell Tri-Institutional Pain Medicine Program, Department of Anesthesiology, Weill Medical College of Cornell University, New York, NY, USA; 3Department of Anesthesiology and Pain Medicine, the University of Kansas Medical Center, Kansas City, KS, USA; 4Trinity Pain Medicine Associates, Fort Worth, TX, USA; 5Department of Physical Medicine and Rehabilitation, University of Missouri, Columbia, MO, USA; 6Lenox Hill Hospital, Northwell Health, New York, NY, USA; 7Department of Anesthesiology, University of Wisconsin, Madison, WI, USA; 8Interventional Pain Management, Mayo Clinic, Scottsdale, AZ, USA; 9Department of Anesthesiology and Perioperative Medicine, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 10Novant Health Spine Specialists, Charlotte, NC, USA; 11North Texas Orthopedics and Spine Center, Grapevine, TX, USA; 12Neuroradiology and Pain Solutions of Oklahoma, Oklahoma City, OK, USA; 13Department of Anesthesia, University of Pittsburgh Medical Center, Susquehanna, PA, USA; 14Crimson Pain Management, Overland Park, Kansas, KS, USA; 15Comprehensive Specialty Care, Edmond, OK, USA; 16Texas Back Institute, Plano, TX, USA; 17Department of Anesthesiology, Perioperative Care and Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 18Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 19Department of Anesthesiology, Rush University Medical Center, Chicago, IL, USA; 20Department of Orthopedic Surgery, University of Texas Southwestern Medical School, Dallas, TX, USA; 21Department of Neurological Surgery, Oregon Health and Science University, Portland, OR, USACorrespondence: Dawood Sayed, The University of Kansas Health System, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA, Tel +1 913-588-5521, Email dsayed@kumc.eduIntroduction: The evolution of treatment options for painful spinal disorders in diverse settings has produced a variety of approaches to patient care among clinicians from multiple professional backgrounds. The American Society of Pain and Neuroscience (ASPN) Best Practice group identified a need for a multidisciplinary guideline regarding appropriate and effective informed consent processes for spine procedures.Objective: The ASPN Informed Consent Guideline was developed to provide clinicians with a comprehensive evaluation of patient consent practices during the treatment of spine pathology.Methods: After a needs assessment, ASPN determined that best practice regarding proper informed consent for spinal procedures was needed and a process of selecting faculty was developed based on expertise, diversity, and knowledge of the subject matter. A comprehensive literature search was conducted and when appropriate, evidence grading was performed. Recommendations were based on evidence when available, and when limited, based on consensus opinion.Results: Following a comprehensive review and analysis of the available evidence, the ASPN Informed Consent Guideline group rated the literature to assist with specification of best practice regarding patient consent during the management of spine disorders.Conclusion: Careful attention to informed consent is critical in achieving an optimal outcome and properly educating patients. This process involves a discussion of risks, advantages, and alternatives to treatment. As the field of interventional pain and spine continues to grow, it is imperative that clinicians effectively educate patients and obtain comprehensive informed consent for invasive procedures. This consent should be tailored to the patient’s specific needs to ensure an essential recognition of patient autonomy and reasonable expectations of treatment.Keywords: informed consent, best practice, clinical guideline, pain medicine, spine intervention, spine surgery

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

The objective of this peripheral nerve stimulation consensus guideline is to add to the current family of consensus practice guidelines and incorporate a systematic review process. The published literature was searched from relevant electronic databases, including PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from database inception to March 29, 2021. Inclusion criteria encompassed studies that described peripheral nerve stimulation in patients in terms of clinical outcomes for various pain conditions, physiological mechanism of action, surgical technique, technique of placement, and adverse events. Twenty randomized controlled trials and 33 prospective observational studies were included in the systematic review process. There is Level I evidence supporting the efficacy of PNS for treatment of chronic migraine headaches via occipital nerve stimulation; chronic hemiplegic shoulder pain via stimulation of nerves innervating the trapezius, supraspinatus, and deltoid muscles; failed back surgery syndrome via subcutaneous peripheral field stimulation; and lower extremity neuropathic and lower extremity post-amputation pain. Evidence from current Level I studies combined with newer technologies facilitating less invasive and easier electrode placement make peripheral nerve stimulation an attractive alternative for managing patients with complex pain disorders. Peripheral nerve stimulation should be used judiciously as an adjunct for chronic and acute postoperative pain following adequate patient screening and positive diagnostic nerve block or stimulation trial.

"Sacrificing Indian Childrens' Rights""Paleface Paternalism""Justice Massacred""Ethnic Errancy""Rose Parade Indian-givers""Slaves to the tribe""Tribal bigotry""Kids pay the price for tribes"The phrases listed above are published titles of newspaper editorials and op-ed essays challenging the legitimacy of the federal Indian Child Welfare Act ("ICWA") in the last 40 years. ICWA is a federal law originally passed in 1978 to address the high rate of removal (and subsequent adoption) of Indian children by state authorities. In passing the law, Congress found "there is no resource that is more vital to the continued existence and integrity of Indian tribes than their children." While there was no significant controversy about the law when it was drafted and passed with unanimous consent in 1978, the application of the law over the past 40 years, the law has come under sustained attack from scholars, attorneys, legislators, think tanks, adoption agencies, and judges. Moreover, while most child custody cases impacted by ICWA are so conventional that they don't warrant any particular attention, almost all national news coverage of ICWA emanates from a few specific high-profile cases in which mainstream news outlets usually characterize ICWA as cultivating unfair battles between Tribal Nations and prospective adoptive parents. Editorials, though, often go further than that, using words like "sacrificing", "massacre", and "slaves" to describe both tribal citizens and tribal nations. This article focuses on how these high-profile cases are characterized in newspaper editorials and op-eds; namely how these authors explicate their colonial views about ICWA, Indian identity, tribal sovereignity, and the virtues of adoption.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. METHODS: A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of COVID-19 inpatients was constructed by matching cases (treated with NSAIDs) and controls (not treated) from 857,061 patients with COVID-19. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. RESULTS: Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: 0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. CONCLUSIONS: Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our findings are the largest EHR-based analysis of the effect of NSAIDs on outcome in COVID-19 patients to date. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database.

Altruistic behavior after stress exposure may have important health and psychological benefits, in addition to broader societal consequences. However, so far experimental research on altruism following acute stress has been limited to adult populations. The current study utilized an experimental design to investigate how altruistic donation behavior among children may be influenced by (a) exposure to an acute social stressor, the Trier Social Stress Test modified for use with children (TSST-M), (b) individual differences in stress physiology, and (c) social support from a parent. The sample consisted of 180 children (54.9% male, 45.1% female; mean age = 9.92 years, SD = 0.56 years) randomly assigned to one of three conditions involving the TSST-M: (a) prepare for the TSST-M alone, (b) prepare for the TSST-M with a parent, and (c) no-stress control group. Results revealed that children made larger donations post-stressor if they were alone before the acute stressor, if they had moderate cardiac autonomic balance, reflecting both parasympathetic and sympathetic influence, and if they were older. Children who prepared for the TSST-M with social support from a parent made comparable donations as children in the no-stress control group, in accord with stress buffering models. Increased altruism following acute stress among children suggests that a comprehensive understanding of the human stress response needs to incorporate "tend-and-befriend" behavior-the tendency for humans to show increased altruistic behavior during times of distress.