Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain: intersectional considerations.

Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6-37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4-13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function.

Background: The concordance between radiograph-derived Kellgren-Lawrence (KL) scores for knee osteoarthritis (KOA) and experimental and clinical pain and KOA-related physical function is conflicting. Objectives: We investigate whether the inclusion of dispositional traits reduces variability between KOA radiographic findings, experimental pain, clinical pain, and function in individuals with knee pain. Design: This study is a cross-sectional, secondary analysis of data collected from the UPLOAD-II study. Methods: Adults aged 45-85 years with and without knee pain were enrolled. Data collected included sociodemographics, knee radiographs, experimental pain, clinical pain and function, and trait affect. Vulnerable and protective dispositional traits were classified from combined positive and negative trait affect measures. KL scores were determined from the knee radiographs. Unadjusted and adjusted (age, sex, comorbidities, and body mass index) regression analyses were completed with SAS version 9.4 (Cary, NC, USA). Results: The study included 218 individuals with a mean age of 58 years, 63.6% women, and 48.2% non-Hispanic black adults. Dispositional traits were associated with the experimental pain measures. No association between radiographic KOA and experimental pain was observed. In a combined and adjusted analysis, dispositional traits were predictive of knee punctate pain temporal summation (p = 0.0382). Both dispositional traits and radiographic KOA scores independently and combined were predictive of Graded Chronic Pain Scale pain and function, and Western Ontario and McMaster University pain and function (ps ⩽ 0.01). Improvements in R2 were noted across all models with the inclusion of dispositional traits. Conclusion: Consideration of dispositional traits reduces the variability between radiographic KOA and pain and function. Non-pathological and associated pain-related psychological factors and dispositional traits might serve as parsimonious proxy tools to improve clinical assessments. Registration: N/A.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function Significance • The concordance between radiographic knee osteoarthritis and experimental and clinical pain is conflicting. • Dispositional traits comprise the infrastructure from which an individual interprets and interacts with the environment and are predictive of sensory sensitivity, response to stress, psychopathology, and behavior. • Consideration of dispositional traits improves the congruence between knee osteoarthritis Kellgren-Lawrence scores, experimental pain, and clinical pain.

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes.

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. METHODS: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. RESULTS: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). IMPLICATIONS: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes.

Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain.

Chronic musculoskeletal pain is a leading cause of disability worldwide. Previous research indicates ethnic/race groups are disproportionately affected by chronic pain conditions. However, when considering socioenvironmental factors these disparities are no longer observed. Ethnic/race group differences have also been reported in pain-related brain structure. Given that environmental and sociocultural factors influence biology and health outcomes, this study aimed to investigate possible environmental and sociocultural contributions to structural differences in pain-related brain regions. A total of 147 non-Hispanic black and non-Hispanic white, middle and older aged adults with knee pain in the past month and a brain MRI are included in the analyses. Individuals also provided information specific to health and pain history and environmental and sociocultural resources. In hierarchical multiple regression models, sociocultural and environmental factors explained 6%-37% of the variance in thickness of pain-related brain regions, with seven of the eight brain regions being statistically significant. In the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus, ethnicity/race provided an additional 4%-13% of explanatory value. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, ethnicity/race was not a predictor after accounting for environmental, sociocultural, and other demographic measures. Findings inform health disparities research by elucidating the complexity of factors contributing to previously reported ethnicity/race group differences.

Elucidating individual differences in chronic pain and whole person health with allostatic load biomarkers.

Chronic pain is a stressor that affects whole person functioning. Persistent and prolonged activation of the body's stress systems without adequate recovery can result in measurable physiological and neurobiological dysregulation recognized as allostatic load. We and others have shown chronic pain is associated with measures of allostatic load including clinical biomarker composites, telomere length, and brain structures. Less is known regarding how different measures of allostatic load align. The purpose of the study was to evaluate relationships among two measures of allostatic load: a clinical composite and pain-related brain structures, pain, function, and socioenvironmental measures. Participants were non-Hispanic black and non-Hispanic white community-dwelling adults between 45 and 85 years old with knee pain. Data were from a brain MRI, questionnaires specific to pain, physical and psychosocial function, and a blood draw. Individuals with all measures for the clinical composite were included in the analysis (n = 175). Indicating higher allostatic load, higher levels of the clinical composite were associated with thinner insula cortices with trends for thinner inferior temporal lobes and dorsolateral prefrontal cortices (DLPFC). Higher allostatic load as measured by the clinical composite was associated with greater knee osteoarthritis pathology, pain disability, and lower physical function. Lower allostatic load as indicated by thicker insula cortices was associated with higher income and education, and greater physical functioning. Thicker insula and DLPFC were associated with a lower chronic pain stage. Multiple linear regression models with pain and socioenvironmental measures as the predictors were significant for the clinical composite, insular, and inferior temporal lobes. We replicate our previously reported bilateral temporal lobe group difference pattern and show that individuals with high chronic pain stage and greater socioenvironmental risk have a higher allostatic load as measured by the clinical composite compared to those individuals with high chronic pain stage and greater socioenvironmental buffers. Although brain structure differences are shown in individuals with chronic pain, brain MRIs are not yet clinically applicable. Our findings suggest that a clinical composite measure of allostatic load may help identify individuals with chronic pain who have biological vulnerabilities which increase the risk for poor health outcomes.

Elucidating factors contributing to disparities in pain-related experiences among adults with or at risk for knee osteoarthritis.

Background and purpose: We and others have reported ethnic/race group differences in clinical pain, physical function, and experimental pain sensitivity. However, recent research indicates that with consideration for socioenvironmental factors, ethnicity/race differences become less or non-significant. Understanding of factors contributing to pain inequities are needed. Guided by the NIA and NIMHD Health Disparities Research Frameworks, we evaluate the contributions of environmental and behavioral factors on previously reported ethnic/race group differences in: (1) clinical pain, (2) physical function, and (3) experimental pain in individuals with knee pain. Methods: Baseline data from Understanding of Pain and Limitations in Osteoarthritis Disease (UPLOAD) and UPLOAD-2 studies were analyzed. Participants were adults 45 to 85 years old who self-reported as non-Hispanic white (NHW) or black (NHB) with knee pain. A health assessment and quantitative sensory testing were completed. Sociodemographics, environmental, health, clinical and experimental pain, and physical functioning measures were included in nested regressions. Results: Pooled data from 468 individuals, 57 ± 8 years of age, 63% women, and 53% NHB adults. As NHB adults were younger and reported greater socioenvironmental risk than the NHW adults, the term sociodemographic groups is used. With inclusion of recognized environmental and behavioral variables, sociodemographic groups remained a significant predictor accounting for <5% of the variance in clinical pain and physical function and <10% of variance in experimental pain. Conclusion: The incorporation of environmental and behavioral factors reduced relationships between sociodemographic groups and pain-related outcomes. Pain sites, BMI, and income were significant predictors across multiple models. The current study adds to a body of research on the complex array of factors contributing to disparities in pain-related outcomes.

King-Devick Test in Wheelchair Sports: Identifying Normative Values and Effects of Exertion on Outcomes.

OBJECTIVE: To establish normative baseline values on the King-Devick (KD) Test for contact wheelchair sport participants. The secondary purpose was to examine the effect of physical exertion on test score. DESIGN: Quasiexperimental. SETTING: Competitive disability sport venues before practices or games. PARTICIPANTS: One-hundred 43 wheelchair rugby or wheelchair basketball (WBB) players completed the study. Participants were predominantly men (87.5%) and played WBB (84%). INTERVENTION: 30-m wheelchair sprint test to fatigue. MAIN OUTCOME MEASURE: King-Devick Baseline Score. RESULTS: Mean KD baseline score was 59.16 ± 15.56 seconds with significant differences ( P < 0.05) identified by sport and impairment type, but not sex. Athletes with spina bifida and cerebral palsy had significantly higher mean baseline KD times than athletes with spinal cord injury. KD scores improved by 3.5% in athletes who reported "light" to "somewhat hard" exertion (RPE = 13). In a subset of athletes who performed sprints until an RPE of 18 was reached, 8 of 12 players (66.7%) demonstrated an improvement in KD score; however, large increases by a few participants caused the noticeable change. CONCLUSIONS: Normative values for wheelchair contact sport athletes are meaningfully slower than able-bodied sports participants. KD score improved with exertion with the greater improvement after moderate-intensity compared with vigorous-intensity exercise. These findings can be applied clinically to monitor athlete safety.

Intermittent Fasting: Potential Utility in the Treatment of Chronic Pain across the Clinical Spectrum.

Dietary behavior can have a consequential and wide-ranging influence on human health. Intermittent fasting, which involves intermittent restriction in energy intake, has been shown to have beneficial cellular, physiological, and system-wide effects in animal and human studies. Despite the potential utility in preventing, slowing, and reversing disease processes, the clinical application of intermittent fasting remains limited. The health benefits associated with the simple implementation of a 12 to 16 h fast suggest a promising role in the treatment of chronic pain. A literature review was completed to characterize the physiologic benefits of intermittent fasting and to relate the evidence to the mechanisms underlying chronic pain. Research on different fasting regimens is outlined and an overview of research demonstrating the benefits of intermittent fasting across diverse health conditions is provided. Data on the physiologic effects of intermittent fasting are summarized. The physiology of different pain states is reviewed and the possible implications for intermittent fasting in the treatment of chronic pain through non-invasive management, prehabilitation, and rehabilitation following injury and invasive procedures are presented. Evidence indicates the potential utility of intermittent fasting in the comprehensive management of chronic pain and warrants further investigation.

Relationships Between Cognitive Screening Composite Scores and Pain Intensity and Pain Disability in Adults With/At Risk for Knee Osteoarthritis.

OBJECTIVES: Chronic pain, cognitive deficits, and pain-related disability are interrelated. The prevalence of chronic pain and undiagnosed cognitive difficulties in middle age and older adults is increasing. Of the cognitive systems, executive function and episodic memory are most relevant to chronic pain. We examined the hypothesis that cognitive screening composite scores for executive function and memory would negatively associate with pain intensity and pain disability in a group of middle-aged and older adults with knee pain with or at risk for osteoarthritis. METHODS: A total of 120 adults (44 men/76 women), an average age of 59 years, participated in the study. Demographic, health history, clinical pain, and cognitive measures were completed. Relationships between pain intensity, pain disability, and the Montreal Cognitive Assessment (MoCA) total and composite scores were examined with relevant covariates in the model. RESULTS: MoCA raw scores ranged from 13 to 30 with a mean score of 23.9. Pain intensity was negatively associated with overall MoCA total and executive function and memory composite scores. Pain disability over the previous 6 months was negatively associated with executive function, while pain disability over the past 48 hours was not associated with executive function. CONCLUSION: The results of the current study demonstrates associations between pain metrics and cognitive domain scores within a common cognitive screening tool.

Associations between Vitamin D, Omega 6:Omega 3 Ratio, and Biomarkers of Aging in Individuals Living with and without Chronic Pain.

Elevated inflammatory cytokines and chronic pain are associated with shorter leukocyte telomere length (LTL), a measure of cellular aging. Micronutrients, such as 25-hydroxyvitamin D (vitamin D) and omega 3, have anti-inflammatory properties. Little is known regarding the relationships between vitamin D, omega 6:3 ratio, LTL, inflammation, and chronic pain. We investigate associations between vitamin D, omega 6:3 ratio, LTL, and C-reactive protein (CRP) in people living with/without chronic pain overall and stratified by chronic pain status. A cross-sectional analysis of 402 individuals (63% women, 79.5% with chronic pain) was completed. Demographic and health information was collected. Chronic pain was assessed as pain experienced for at least three months. LTL was measured in genomic DNA isolated from blood leukocytes, and micronutrients and CRP were measured in serum samples. Data were analyzed with general linear regression. Although an association between the continuous micronutrients and LTL was not observed, a positive association between omega 6:3 ratio and CRP was detected. In individuals with chronic pain, based on clinical categories, significant associations between vitamin D, omega 6:3 ratio, and CRP were observed. Findings highlight the complex relationships between anti-inflammatory micronutrients, inflammation, cellular aging, and chronic pain.

Applying the NIA Health Disparities Research Framework to Identify Needs and Opportunities in Chronic Musculoskeletal Pain Research.

Disparities in the experience of chronic musculoskeletal pain in the United States stem from a confluence of a broad array of factors. Organized within the National Institute on Aging Health Disparity Research Framework, a literature review was completed to evaluate what is known and what is needed to move chronic musculoskeletal pain research forward specific to disproportionately affected populations. Peer-reviewed studies published in English, on human adults, from 2000 to 2019, and conducted in the United States were extracted from PubMed and Web of Science. Articles were reviewed for key words that focused on underrepresented ethnic/race groups with chronic musculoskeletal pain applying health factor terms identified in the NIAHealth Disparity Research Framework four levels of analysis: 1) environmental, 2) sociocultural, 3) behavioral, and 4) biological. A total of 52 articles met inclusion criteria. There were limited publications specific to underrepresented ethnic/race groups with chronic musculoskeletal pain across all levels with particular research gaps under sociocultural and biological categories. Current limitations in evidence may be supplemented by a foundation of findings specific to the broader topic of "chronic pain" which provides guidance for future investigations. Study designs including a focus on protective factors and multiple levels of analyses would be particularly meritorious. PERSPECTIVE: Chronic musculoskeletal pain unequally burdens underrepresented ethnic/race groups. In order to move research forward and to systematically investigate the complex array of factors contributing toward health disparities, an organized approach is necessary. Applying the NIA Health Disparities Research Framework, an overview of the current state of evidence specific to chronic musculoskeletal pain and underrepresented ethnic/race groups is provided with future directions identified.

Vulnerable Dispositional Traits and Chronic Pain: Predisposing but not Predetermining.

Dispositional traits can be protective or contribute to increased vulnerability in individuals with chronic pain. This study aims to evaluate the association between two dispositional trait measures, affect balance style and multi-domain trait groups, with psychosocial measures, clinical pain, functional pain, and experimental pain at two years in individuals with chronic knee pain. The study is a prospective analysis of 168 community dwelling individuals aged 45 to 85 years old with knee pain with or at risk for knee osteoarthritis. At baseline, affect balance style and multi-domain trait groups were associated with psychosocial measures, clinical pain, and functional status. At the two-year time point, the multi-domain trait groups were associated with the clinical pain measures. Interestingly, individuals with previously demonstrated vulnerable traits showed more variability in dispositional trait status at the two-year time point compared to those with dispositional traits previously demonstrated as more protective. Findings reiterate that dispositional traits are predisposing but are not predetermining regarding pain-related experiences. PERSPECTIVE: Vulnerable and protective dispositional traits are positively and negatively associated with clinical pain and functional limitations respectively. Although considered relatively stable, a 30-50% shift in dispositional traits was indicated over a two-year period. Findings highlight that dispositional trait are modifiable and thus, predisposing but not predetermining for persisting chronic pain.

Evaluation of the 3-Minute Diagnostic Confusion Assessment Method for Identification of Postoperative Delirium in Older Patients.

Importance: Delirium is a common postoperative complication in older patients that often goes undetected and might lead to worse outcomes. The 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) might be a practical tool for routine clinical diagnosis of delirium. Objective: To assess the 3D-CAM for detecting postoperative delirium compared with the long-form CAM used for research purposes. Design, Setting, and Participants: This cohort study of older patients enrolled in ongoing clinical trials between 2015 and 2018 was conducted at a single tertiary US hospital. Included participants were aged 60 years or older undergoing major elective surgical procedures that required at least a 2-day hospital stay. Data were analyzed between February and April 2019. Exposures: Surgical procedures of at least 2 hours in length requiring general anesthesia with planned extubation. Main Outcomes and Measures: Patients were concurrently assessed for delirium using the 3D-CAM assessment and the long-form CAM, scored based on a standardized cognitive assessment. Agreement between these 2 methods was tested using Cohen κ with repeated measures, a generalized linear mixed-effects model, and Bland-Altman analysis. Results: Sixteen raters conducted 471 concurrent CAM and 3D-CAM interviews including 299 patients (mean [SD] age, 69 [6.5] years), the majority of whom were men (152 [50.8%]), were White (263 [88.0%]), and had noncardiac operations (211 [70.6%]). Both instruments had good intraclass correlation (0.84 for the CAM and 0.98 for the 3D-CAM). Cohen κ demonstrated good overall agreement between the CAM and 3D-CAM (κ = 0.71; 95% CI, 0.58 to 0.83). According to the mixed-effects model, there was statistically significant disagreement between the 3D-CAM and CAM (estimated difference in fixed effect, -0.68; 95% CI, -1.32 to -0.05; P = .04). Bland-Altman analysis showed the probability of a delirium diagnosis with the 3D-CAM was more than twice the probability of a delirium diagnosis with the CAM (probability ratio, 2.78; 95% CI, 2.44 to 3.23). Conclusions and Relevance: The 3D-CAM instrument demonstrated agreement with the long-form CAM and might provide a pragmatic and sensitive clinical tool for detecting postoperative delirium, with the caveat that the 3D-CAM might overdiagnose delirium.

Effect of electroencephalogram-guided anaesthesia administration on 1-yr mortality: follow-up of a randomised clinical trial.

BACKGROUND: Intraoperative EEG suppression duration has been associated with postoperative delirium and mortality. In a clinical trial testing anaesthesia titration to avoid EEG suppression, the intervention did not decrease the incidence of postoperative delirium, but was associated with reduced 30-day mortality. The present study evaluated whether the EEG-guided anaesthesia intervention was also associated with reduced 1-yr mortality. METHODS: This manuscript reports 1 yr follow-up of subjects from a single-centre RCT, including a post hoc secondary outcome (1-yr mortality) in addition to pre-specified secondary outcomes. The trial included subjects aged 60 yr or older undergoing surgery with general anaesthesia between January 2015 and May 2018. Patients were randomised to receive EEG-guided anaesthesia or usual care. The previously reported primary outcome was postoperative delirium. The outcome of the current study was all-cause 1-yr mortality. RESULTS: Of the 1232 subjects enrolled, 614 subjects were randomised to EEG-guided anaesthesia and 618 subjects to usual care. One-year mortality was 57/591 (9.6%) in the guided group and 62/601 (10.3%) in the usual-care group. No significant difference in mortality was observed (adjusted absolute risk difference, -0.7%; 99.5% confidence interval, -5.8% to 4.3%; P=0.68). CONCLUSIONS: An EEG-guided anaesthesia intervention aiming to decrease duration of EEG suppression during surgery did not significantly decrease 1-yr mortality. These findings, in the context of other studies, do not provide supportive evidence for EEG-guided anaesthesia to prevent intermediate term postoperative death. CLINICAL TRIAL REGISTRATION: NCT02241655.

Optimizing Chronic Pain Treatment with Enhanced Neuroplastic Responsiveness: A Pilot Randomized Controlled Trial.

Chronic pain affects mental and physical health and alters brain structure and function. Interventions that reduce chronic pain are also associated with changes in the brain. A number of non-invasive strategies can promote improved learning and memory and increase neuroplasticity in older adults. Intermittent fasting and glucose administration represent two such strategies with the potential to optimize the neurobiological environment to increase responsiveness to recognized pain treatments. The purpose of the pilot study was to test the feasibility and acceptability of intermittent fasting and glucose administration paired with a recognized pain treatment activity, relaxation and guided imagery. A total of 32 adults (44% W, 56% M), 50 to 85 years of age, with chronic knee pain for three months or greater participated in the study. Four sessions were completed over an approximate two-week period. Findings indicate the ability to recruit, randomize, and retain participants in the protocol. The procedures and measures were reasonable and completed without incident. Participant adherence was high and exit interview feedback positive. In summary, the pilot study was feasible and acceptable, providing the evidence necessary to move forward with a larger clinical trial.

Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis.

BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

Relationships Between Pain, Life Stress, Sociodemographics, and Cortisol: Contributions of Pain Intensity and Financial Satisfaction.

OBJECTIVE: The relationship between psychosocial stress and chronic pain is bidirectional. An improved understanding regarding the relationships among chronic pain, life stress, and ethnicity/race will inform identification of factors contributing to health disparities in chronic pain and improve health outcomes. This study aims to assess relationships between measures of clinical pain, life stress, sociodemographics, and salivary cortisol levels. METHODS: A cross-sectional analysis involving data from 105 non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants aged 45-85 years old with or at risk for knee osteoarthritis. Data included sociodemographics, clinical pain, psychosocial stress, and salivary cortisol across five time points over an approximate 12-hour period. Non-parametric correlation analysis, sociodemographic group comparisons, and regression analyses were performed. RESULTS: Clinical pain and psychosocial stress were associated with salivary cortisol levels, particularly morning waking and the evening to morning awakening slope. With the inclusion of recognized explanatory variables, the Graded Chronic Pain Scale characteristic pain intensity and financial satisfaction were identified as the primary pain and psychosocial measures associated with cortisol levels. Sociodemographic group differences were indicated such that NHB participants reported higher pain-related disability, higher levels of discrimination, lower financial and material satisfaction, and showed higher evening salivary cortisol levels compared to NHW participants. In combined pain and psychosocial stress analyses, greater financial satisfaction, lower pain intensity, and lower depression were associated with higher morning waking saliva cortisol levels while greater financial satisfaction was the only variable associated with greater evening to morning awakening slope. CONCLUSION: Our findings show relationships among clinical pain, psychosocial stress, sociodemographic factors, and salivary cortisol levels. Importantly, with inclusion of recognized explanatory variables, financial satisfaction remained the primary factor accounting for differences in morning waking cortisol and evening to morning awakening cortisol slope in an ethnic/racially diverse group of middle aged and older adults with or at risk for knee osteoarthritis.

Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions: Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures: The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results: Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance: Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02241655.