Dynamics of diurnal cortisol and alpha-amylase secretion and their associations with PTSD onset in recent interpersonal trauma survivors.

BACKGROUND: Dysfunction in major stress response systems during the acute aftermath of trauma may contribute to risk for developing posttraumatic stress disorder (PTSD). The current study investigated how PTSD diagnosis and symptom severity, depressive symptoms, and childhood trauma uniquely relate to diurnal neuroendocrine secretion (cortisol and alpha-amylase rhythms) in women who recently experienced interpersonal trauma compared to non-traumatized controls (NTCs). METHOD: Using a longitudinal design, we examined diurnal cortisol and alpha-amylase rhythms in 98 young women (n = 57 exposed to recent interpersonal trauma, n = 41 NTCs). Participants provided saliva samples and completed symptom measures at baseline and 1-, 3-, and 6-month follow-up. RESULTS: Multilevel models (MLMs) revealed lower waking cortisol predicted the development of PTSD in trauma survivors and distinguished at-risk women from NTCs. Women with greater childhood trauma exposure exhibited flatter diurnal cortisol slopes. Among trauma-exposed individuals, lower waking cortisol levels were associated with higher concurrent PTSD symptom severity. Regarding alpha-amylase, MLMs revealed women with greater childhood trauma exposure exhibited higher waking alpha-amylase and slower diurnal alpha-amylase increase. CONCLUSIONS: Results suggest lower waking cortisol in the acute aftermath of trauma may be implicated in PTSD onset and maintenance. Findings also suggest childhood trauma may predict a different pattern of dysfunction in stress response systems following subsequent trauma exposure than the stress system dynamics associated with PTSD risk; childhood trauma appears to be associated with flattened diurnal cortisol and alpha-amylase slopes, as well as higher waking alpha-amylase.

Longitudinal Predictors of Pain in Pediatric Sickle Cell Disease.

OBJECTIVE: Despite the identified pathophysiology of vaso-occlusive pain in sickle cell disease (SCD), predictors of pain in youth with SCD remain elusive. In this study, we measured changes in pain frequency, intensity, and interference over 1 year and examined biopsychosocial risk factors (SCD disease severity, age, female, depression, and sleep quality) as possible longitudinal predictors. METHODS: Medical history was obtained from retrospective chart review for 79 children with SCD (ages 2-18 years; 48.1% female; 100% Black/African American; 83.5% SCD, SS genotype). As part of a clinical screening protocol, caregivers (n = 79) and youth 8-18 years (n = 43) completed psychosocial questionnaires approximately 1 year apart (M = 15.52 months, SD = 5.69). Zero-order correlations, paired t-tests, and hierarchical linear models examined longitudinal predictors of pain. The longitudinal bidirectional relationship between pain and sleep was also examined. RESULTS: The rate of severe SCD disease increased from 41.8% to 55.7% across the year, while most hematologic medical parameters remained stable. Increased depression and pain interference at survey 1 significantly predicted increased pain interference at survey 2. Poor sleep quality and increased pain frequency at survey 1 predicted increased pain frequency at survey 2. Finally, increased pain interference at survey 1 predicted poor sleep quality at survey 2. DISCUSSION: History of pain, depression, and sleep quality were longitudinal predictors of pain over 1 year in youth with SCD. Identifying longitudinal predictors of pain may lead to earlier identification of patients with a high-risk SCD pain phenotype and earlier medical, psychological, and behavioral interventions.

Adversity type and timing predict temporal summation of pain in African-American adults.

African Americans are disproportionately exposed to adversity across the lifespan, which includes both stressful and traumatic events. Adversity, in turn, is associated with alterations in pain responsiveness. Racial differences in pain responsiveness among healthy adults are well established. However, the extent to which adversity type and timing are associated with alterations in pain responsiveness among healthy African-American adults is not well understood. The present study included 160 healthy African-American adults (98 women), ages 18 to 45. Outcome measures included pain tolerance and temporal summation of pain to evoked thermal pain. Composite scores were created for early-life adversity (childhood trauma, family adversity) and recent adversity (perceived stress, chronic stress burden). A measure of lifetime racial discrimination was also included. Higher levels of recent adversity were associated with higher temporal summation of pain, controlling for gender, age, and education. Neither early-life adversity nor lifetime racial discrimination were associated with temporal summation of pain. The present findings suggest that heightened temporal summation of pain among healthy African-American adults is associated with exposure to recent adversity events. Improved understanding of how recent adversity contributes to heightened temporal summation of pain in African Americans could help to mitigate racial disparities in pain experiences by identifying at-risk individuals who could benefit from early interventions.

Place and Pain: Association Between Neighborhood SES and Quantitative Sensory Testing Responses in Youth With Functional Abdominal Pain.

OBJECTIVE: Neighborhood socioeconomic status (SES) is linked to self-reported pain severity and disability but its association with evoked pain responsiveness in individuals with chronic pain remains unclear. The present study examined relations between neighborhood SES, assessed through the area deprivation index (ADI), and static and dynamic pain response indices. It was hypothesized that youth with functional abdominal pain (FAP) living in lower SES neighborhoods would exhibit lower pain threshold, lower pain tolerance, and reduced conditioned pain modulation (CPM) compared to youth living in higher SES neighborhoods. METHODS: Participants were 183 youth with FAP and their parents. Youth completed a quantitative sensory testing protocol. Family addresses were used to compute ADI scores. Thermal stimuli for pain threshold and tolerance were delivered to participants' forearms using thermodes. CPM, an index of descending pain inhibition, was determined using a thermode as test stimulus and a hot water bath as conditioning stimulus. RESULTS: As hypothesized, youth with FAP living in lower SES neighborhoods exhibited weaker CPM. Contrary to hypotheses, lower neighborhood SES was associated with neither pain thresholds nor with pain tolerance. CONCLUSIONS: These findings demonstrated the independent contribution of place of residence-an often neglected component of the biopsychosocial model-to efficiency of descending pain inhibition. Understanding the mechanisms that account for such associations between place and pain could guide the development of public health and policy initiatives designed to mitigate chronic pain risk in underserved and economically marginalized communities.

Perceived Injustice Helps Explain the Association Between Chronic Pain Stigma and Movement-Evoked Pain in Adults with Nonspecific Chronic Low Back Pain.

OBJECTIVE: For most patients with chronic low back pain (cLBP), the cause is "nonspecific," meaning there is no clear association between pain and identifiable pathology of the spine or associated tissues. Laypersons and providers alike are less inclined to help, feel less sympathy, dislike patients more, suspect deception, and attribute lower pain severity to patients whose pain does not have an objective basis in tissue pathology. Because of these stigmatizing responses from others, patients with cLBP may feel that their pain is particularly unjust and unfair. These pain-related injustice perceptions may subsequently contribute to greater cLBP severity. The purpose of this study was to examine whether perceived injustice helps explain the relationship between chronic pain stigma and movement-evoked pain severity among individuals with cLBP. METHODS: Participants included 105 patients with cLBP who completed questionnaires assessing chronic pain stigma and pain-related injustice perception, as well as a short physical performance battery for the assessment of movement-evoked pain and physical function. RESULTS: Findings revealed that perceived injustice significantly mediated the association between chronic pain stigma and cLBP severity (indirect effect = 6.64, 95% confidence interval [CI] = 2.041 to 14.913) and physical function (indirect effect = -0.401, 95% CI = -1.029 to -0.052). Greater chronic pain stigma was associated with greater perceived injustice (P = 0.001), which in turn was associated with greater movement-evoked pain severity (P = 0.003). CONCLUSIONS: These results suggest that perceived injustice may be a means through which chronic pain stigma impacts nonspecific cLBP severity and physical function.

Psychobiology of cumulative trauma: hair cortisol as a risk marker for stress exposure in women.

Childhood trauma (CT) is associated with long-lasting alterations of the hypothalamic-pituitary-adrenal (HPA) axis and elevated risk for stress exposure in adulthood. Although HPA alterations are present in the early aftermath of trauma, it remains unclear how initial HPA activity is associated with subsequent stress exposure and whether CT exposure influences the strength and direction of this association. The present study examined prospective associations between hair cortisol content (HCC) and stress exposure from baseline to 3-month follow-up in young adult women with recent (i.e. past 3 months) exposure to interpersonal violence (IPV; i.e. physical or sexual assault) and non-traumatized controls. History of significant CT abuse or neglect was determined based on clinical cutoffs for a self-report CT measure: 12 women had abuse or neglect and recent IPV exposure (CT + IPV); 7 women had abuse or neglect but no IPV exposure (CT); 15 women had no history of trauma (NTC). HCC was computed for 3 cm sections reflecting cortisol secretion during the 3 months preceding the baseline assessment. The interaction of cumulative trauma and HCC predicted stress exposure over 3-month follow-up, controlling for baseline stress exposure and depressive symptoms. Simple slopes analyses revealed that lower baseline HCC predicted greater stress exposure in the CT + IPV group compared to the CT group; HCC was not associated with stress exposure in the NTC group. The present findings highlight the potential utility of HCC as a predictor of stress exposure for women with a history of childhood abuse or neglect, particularly in the context of recent IPV. Lay summary Adults with a history of CT show long-lasting alterations in major stress response systems, including the HPA axis. They are also more likely to experience stressful life events in adulthood. However, it is not clear how altered HPA activity influences risk for stress exposure and whether CT affects their relationship. The results from this study show that lower HPA activity (measured with hair cortisol) predicted greater stress exposure in women with CT - particularly for women who also experienced recent incidents involving physical or sexual assault.

Salivary stress biomarkers of recent nicotine use and dependence.

BACKGROUND: Although stress plays a critical role in vulnerability to nicotine use and dependence, the stress response factors that contribute to smoking behaviors remain poorly elucidated. To minimize the confounding effects of chronic nicotine use, assessing individuals with relatively short smoking histories is critical for characterizing the neurobiological substrates associated with nicotine dependence early in the course of illness. OBJECTIVES: This pilot study examined sympathetic nervous system (alpha-amylase) and hypothalamic-pituitary-adrenal axis (cortisol, dehydroepiandrosterone) responses to the Trier Social Stress Test (TSST) in young adult smokers. Associations among objective indices of recent smoking (salivary cotinine, carbon monoxide in the breath [CO]), behavioral measures of nicotine dependence and withdrawal, and salivary biomarkers in response to the TSST were investigated. METHODS: Smokers (N = 64; 28 males, 36 females) provided saliva samples at 30 min intervals for 2 h prior to the TSST and every 10 min for 1 h following the TSST. RESULTS: Alpha-amylase responses to the TSST were positively associated with salivary cotinine levels but negatively associated with CO levels. Individuals with a lower level of nicotine dependence had increased cortisol responses to the stressor, whereas those with a higher level of nicotine dependence did not show any cortisol changes in response to the stressor. CONCLUSIONS: These findings indicate that different mechanisms may be involved at different levels of nicotine dependence severity. Recent nicotine use and lower dependence severity may be associated with increased activation of the stress response systems. In contrast, more severe levels of dependence may downregulate stress response systems.

Dynamic modulation of innate immune response by varying dosages of lipopolysaccharide (LPS) in human monocytic cells.

Innate monocytes and macrophages can be dynamically programmed into distinct states depending upon the strength of external stimuli. Innate programming may bear significant relevance to the pathogenesis and resolution of human inflammatory diseases. However, systems analyses with regard to the dynamic programming of innate leukocytes are lacking. In this study, we focused on the dynamic responses of human promonocytic THP-1 cells to lipopolysaccharide (LPS). We observed that varying dosages of LPS differentially modulate the expression of selected pro- and anti- inflammatory mediators such as IL-6 and IL-33. Super-low dosages of LPS preferentially induced the pro-inflammatory mediator IL-6, while higher dosages of LPS induced both IL-6 and IL-33. Mechanistically, we demonstrated that super-low and high doses of LPS cause differential activation of GSK3 and Akt, as well as the transcription factors FoxO1 and CREB. Inhibition of GSK3 enabled THP-1 cells to express IL-33 when challenged with super-low dose LPS. On the other hand, activation of CREB with adenosine suppressed IL-6 expression. Taken together, our study reveals a dynamic modulation of monocytic cells in response to varying dosages of endotoxin, and may shed light on our understanding of the dynamic balance that controls pathogenesis and resolution of inflammatory diseases.

Heightened Temporal Summation of Pain in Patients with Functional Gastrointestinal Disorders and History of Trauma.

BACKGROUND: Individuals with functional gastrointestinal disorders (FGIDs) report experiencing trauma more often than healthy controls, but little is known regarding psychophysical correlates. PURPOSE: The purpose of this study was to test the hypothesis that adolescents and young adults with FGIDs since childhood and a trauma history (n = 38) would exhibit heightened temporal summation to thermal pain stimuli, an index of central sensitization, and greater clinical symptoms compared to patients with FGIDs and no trauma history (n = 95) and healthy controls (n = 135). METHODS: Participants completed self-report measures, an experimental pain protocol, and psychiatric diagnostic interview as part of a larger longitudinal study. RESULTS: FGID + Trauma patients exhibited greater temporal summation than FGID + No Trauma patients and healthy controls. Additionally, FGID + Trauma patients exhibited greater gastrointestinal and non-gastrointestinal symptom severity, number of chronic pain sites, and disability. CONCLUSIONS: Assessing for trauma history in patients with FGIDs could identify a subset at risk for greater central sensitization and pain-related symptoms.

Cortisol response to psychosocial stress during a depressive episode and remission.

This study compared cortisol responses to a standardized psychosocial stressor during a major depressive episode (MDE) and again during remission in adolescents and young adults. Twenty-six individuals with no personal or family history of a major psychiatric disorder (NC) and 24 individuals with a diagnosis of major depressive disorder (MDD) at Time 1 participated in the study. The MDD group showed robust cortisol responses during their index episode and after recovery. In contrast, the NC group showed habituation to the repeated psychosocial stressor, as evident in a flatter cortisol response profile at Time 2. Within the MDD group, net peak cortisol during the first stress test was positively associated with the duration of the index MDE and negatively associated with the total duration of all MDEs. Whereas summary indices of cortisol responses were relatively stable across repeated stress tasks within the MDD group, this was not the case for NC. Results demonstrate that cortisol responses fail to habituate to repeated psychosocial stress during recovery from an MDE and could reflect a trait-like marker of risk for recurrence.

Cortisol reactivity to experimentally manipulated psychosocial stress in young adults at varied risk for depression.

This study examined cortisol and affective reactivity to a psychosocial stress task in 102 young adults who varied in risk for depression (56 remitted depressed, 46 never depressed). Participants were randomly assigned to either a stress (i.e., social-evaluative threat) or control (i.e., no social-evaluative threat) condition. For never-depressed individuals, cortisol responses were significantly greater in the stress compared to the control condition. Moreover, cortisol responses were significantly greater for never-depressed than remitted-depressed individuals in the stress condition. For individuals with a history of depression, cortisol responses did not differ significantly between the stress and control conditions. Negative affective reactivity also was higher for never depressed, but not remitted depressed, individuals in the stress compared to the control condition. Moreover, cortisol responses were inversely related to negative affect during the recovery phase in both stress and control conditions. Findings indicate the lack of a robust cortisol response to social evaluation stress among remitted-depressed individuals as compared to that of never-depressed controls. Future studies should investigate unique and interactive links between these hypothalamic-pituitary-adrenal and affective reactivity alterations and risk for subsequent depressive episodes.

Two prospective studies of changes in stress generation across depressive episodes in adolescents and emerging adults.

The stress generation hypothesis was tested in two different longitudinal studies examining relations between weekly depression symptom ratings and stress levels in adolescents and emerging adults at varied risk for depression. The participants in Study 1 included 240 adolescents who differed with regard to their mothers' history of depressive disorders. Youth were assessed annually across 6 years (Grades 6-12). Consistent with the depression autonomy model, higher numbers of prior major depressive episodes (MDEs) were associated with weaker stress generation effects, such that higher levels of depressive symptoms predicted increases in levels of dependent stressors for adolescents with two or more prior MDEs, but depressive symptoms were not significantly related to dependent stress levels for youth with three or more prior MDEs. In Study 2, the participants were 32 remitted-depressed and 36 never-depressed young adults who completed a psychosocial stress task to determine cortisol reactivity and were reassessed for depression and stress approximately 8 months later. Stress generation effects were moderated by cortisol responses to a laboratory psychosocial stressor, such that individuals with higher cortisol responses exhibited a pattern consistent with the depression autonomy model, whereas individuals with lower cortisol responses showed a pattern more consistent with the depression sensitization model. Finally, comparing across the two samples, stress generation effects were weaker for older participants and for those with more prior MDEs. The complex, multifactorial relation between stress and depression is discussed.

Interactive models of depression vulnerability: the role of childhood trauma, dysfunctional attitudes, and coping.

OBJECTIVES: This prospective study investigated whether within-individual relations between depression vulnerability factors (childhood trauma, dysfunctional attitudes, maladaptive coping) and depressive symptom trajectories varied as a function of the number of prior major depressive episodes (MDEs) experienced in their lifetime. DESIGN: Participants were 68 young adults who varied with regard to their history of depression; 32 were remitted depressed and 36 were never depressed. METHODS: Depressive symptoms and disorders were assessed using semi-structured psychiatric interviews conducted twice over a 6-month period; interviews yielded weekly ratings of depressive symptoms during the follow-up interval. Childhood trauma, dysfunctional attitudes and coping were assessed with self-report measures. Data analyses were conducted using time-lagged multilevel models. RESULTS: Individuals with more previous MDEs who reported greater childhood trauma exposure, more dysfunctional attitudes, or greater use of maladaptive coping strategies experienced more rapid increases in depressive symptoms during the follow-up period. A significant interaction of coping, number of previous MDEs, and time was found indicating that among individuals with less adaptive coping (i.e., lower primary or lower secondary control coping scores), depressive symptoms rating (DSR) increased significantly in relation to number of prior depressive episodes; no change in DSR was observed for never-depressed individuals. Among individuals with higher primary control coping scores, significant increases in DSR scores were observed for individuals with ≥3 prior MDEs only. CONCLUSIONS: Findings highlight the need for treatment and prevention programmes that target stress reactivity and coping strategies early in the course of depression.

Adverse Childhood Experiences and Chronic Low Back Pain In Adulthood: The Role of Emotion Regulation.

Chronic low back pain (cLBP) is characterized by biopsychosocial determinants that collectively result in substantial burden at the individual, community, and healthcare system levels. A growing body of literature suggests that childhood adversity is longitudinally associated with the development and maintenance of various chronic pain conditions in adulthood. Little research has investigated the psychological processes that might underlie the association between adverse childhood experiences (ACEs) and cLBP. Emotion regulation comprises a substantive part of the subjective experience of pain and may be a potential mechanism through which ACEs contribute to cLBP etiology and maintenance. Thus, the current study examined the extent to which emotion dysregulation mediated the relationship between ACEs and pain severity (pain at rest and movement-evoked pain) in adults with cLBP. Participants included 183 adults (53.0% female, 62.5% non-Hispanic Black) between the ages of 18 and 85 with cLBP. Participants self-reported on ACEs, pain, difficulties in emotion regulation, depression, and completed brief physical function tasks. In data analytic models, sociodemographic variables were included as covariates. Mediation analyses revealed that emotion regulation mediated the relationship between ACEs and cLBP severity at rest (indirect effect = 0.15 (95% CI [0.06 to 0.25]) and with movement (indirect effect = 1.50 (95% CI [0.69 to 2.57]). Findings suggest ACEs are linked to cLBP severity in adulthood though difficulties in emotion regulation. This aligns with research demonstrating that childhood maltreatment can lead to difficulties in emotion regulation which perpetuate over the lifespan to impact adult health outcomes. TRIAL REGISTRATION: This study utilized baseline data collected as part of a parent trial titled "Examining Racial and SocioEconomic Disparities in Chronic Low Back Pain" (ERASED - ClinicalTrials.gov ID: NCT03338192). PERSPECTIVE: This study presents emotion dysregulation as a psychological pathway through which childhood adversity may contribute to chronic low back pain in adulthood. This work may bolster our understanding of social experiences as risk factors for chronic pain, while identifying targets for clinical intervention.

Biobehavioral Predictors of Pain Intensity, Pain Interference, and Chronic Pain Episodes: A Prospective Cohort Study of African-American Adults.

Racial disparities in pain experiences are well-established, with African-American (AA) adults reporting higher rates of daily pain, increased pain severity, and greater pain-related interference compared to non-Hispanic Whites. However, the biobehavioral factors that predict the transition to chronic pain among AA adults are not well understood. This prospective cohort study provided a unique opportunity to evaluate predictors of chronic pain onset among 130 AA adults (81 women), ages 18 to 44, who did not report chronic pain at their baseline assessment and subsequently completed follow-up assessments at 6- and 12-months. Outcome measures included pain intensity, pain-related interference, and chronic pain status. Comprehensive assessments of sociodemographic and biobehavioral factors were used to evaluate demographics, socioeconomic status, stress exposure, psychosocial factors, prolonged hypothalamic-pituitary-adrenal secretion, and quantitative sensory testing responses. At baseline, 30 adults (23.1%) reported a history of prior chronic pain. Over the 12-month follow-up period, 13 adults (10.0%) developed a new chronic pain episode, and 18 adults (13.8%) developed a recurrent chronic pain episode. Whereas socioeconomic status measures (ie, annual income, education) predicted changes in pain intensity over the follow-up period, quantitative sensory testing measures (ie, pain threshold, temporal summation of pain) predicted changes in pain interference. A history of chronic pain and higher depressive symptoms at baseline independently predicted the onset of a new chronic pain episode. The present findings highlight distinct subsets of biobehavioral factors that are differentially associated with trajectories of pain intensity, pain-related interference, and onset of chronic pain episodes in AA adults. PERSPECTIVE: This prospective study sought to advance understanding of biobehavioral factors that predicted pain outcomes over a 12-month follow-up period among AA adults without chronic pain at their initial assessment. Findings revealed distinct subsets of factors that were differentially associated with pain intensity, pain-related interference, and onset of chronic pain episodes.

Predicting incident cardiovascular disease among African-American adults: A deep learning approach to evaluate social determinants of health in the Jackson heart study.

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) as predictors of 10-year CVD risk. Contrary to hypothesis, overall predictive accuracy did not improve when adding social determinants of health. However, social determinants of health comprised eight of the top 15 predictors of first CVD events. The social determinates of health indicators included four socioeconomic factors (insurance status and types), one psychosocial factor (discrimination burden), and three environmental factors (density of outdoor physical activity resources, including instructional and water activities; modified retail food environment index excluding alcohol; and favorable food stores). Findings suggest that whereas understanding biological determinants may identify who is currently at risk for developing CVD and in need of secondary prevention, understanding upstream social determinants of CVD risk could guide primary prevention efforts by identifying where and how policy and community-level interventions could be targeted to facilitate changes in individual health behaviors.

Predicting benzodiazepine prescriptions: A proof-of-concept machine learning approach.

Introduction: Benzodiazepines are the most commonly prescribed psychotropic medications, but they may place users at risk of serious adverse effects. Developing a method to predict benzodiazepine prescriptions could assist in prevention efforts. Methods: The present study applies machine learning methods to de-identified electronic health record data, in order to develop algorithms for predicting benzodiazepine prescription receipt (yes/no) and number of benzodiazepine prescriptions (0, 1, 2+) at a given encounter. Support-vector machine (SVM) and random forest (RF) approaches were applied to outpatient psychiatry, family medicine, and geriatric medicine data from a large academic medical center. The training sample comprised encounters taking place between January 2020 and December 2021 (N = 204,723 encounters); the testing sample comprised data from encounters taking place between January and March 2022 (N = 28,631 encounters). The following empirically-supported features were evaluated: anxiety and sleep disorders (primary anxiety diagnosis, any anxiety diagnosis, primary sleep diagnosis, any sleep diagnosis), demographic characteristics (age, gender, race), medications (opioid prescription, number of opioid prescriptions, antidepressant prescription, antipsychotic prescription), other clinical variables (mood disorder, psychotic disorder, neurocognitive disorder, prescriber specialty), and insurance status (any insurance, type of insurance). We took a step-wise approach to developing a prediction model, wherein Model 1 included only anxiety and sleep diagnoses, and each subsequent model included an additional group of features. Results: For predicting benzodiazepine prescription receipt (yes/no), all models showed good to excellent overall accuracy and area under the receiver operating characteristic curve (AUC) for both SVM (Accuracy = 0.868-0.883; AUC = 0.864-0.924) and RF (Accuracy = 0.860-0.887; AUC = 0.877-0.953). Overall accuracy was also high for predicting number of benzodiazepine prescriptions (0, 1, 2+) for both SVM (Accuracy = 0.861-0.877) and RF (Accuracy = 0.846-0.878). Discussion: Results suggest SVM and RF algorithms can accurately classify individuals who receive a benzodiazepine prescription and can separate patients by the number of benzodiazepine prescriptions received at a given encounter. If replicated, these predictive models could inform system-level interventions to reduce the public health burden of benzodiazepines.

Physical activity, sitting time, and thermal quantitative sensory testing responses in African Americans.

Introduction: Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. Objective: This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Methods: Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Results: Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. Conclusions: These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.

Racial, Gender, and Neighborhood-Level Disparities in Pediatric Trauma Care.

BACKGROUND: Disparities in trauma outcomes and care are well established for adults, but the extent to which similar disparities are observed in pediatric trauma patients requires further investigation. The objective of this study was to evaluate the unique contributions of social determinants (race, gender, insurance status, community distress, rurality/urbanicity) on trauma outcomes after controlling for specific injury-related risk factors. STUDY DESIGN: All pediatric (age < 18) trauma patients admitted to a single level 1 trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed (n = 14,398). Primary outcomes were receipt of opioids in the emergency department, post-discharge rehabilitation referrals, and mortality. Multivariate logistic regressions evaluated demographic, socioeconomic, and injury characteristics. Multilevel logistic regressions evaluated area-level indicators, which were derived from abstracted home addresses. RESULTS: Analyses adjusting for demographic and injury characteristics revealed that Black children (n = 6255) had significantly lower odds (OR = 0.87) of being prescribed opioid medications in the emergency department compared to White children (n = 5883). Children living in more distressed and rural communities had greater odds of receiving opioid medications. Girls had significantly lower odds (OR = 0.61) of being referred for rehabilitation services than boys. Post hoc analyses revealed that Black girls had the lowest odds of receiving rehabilitation referrals compared to Black boys and White children. CONCLUSION: Results highlight the need to examine both main and interactive effects of social determinants on trauma care and outcomes. Findings reinforce and expand into the pediatric population the growing notion that traumatic injury care is not immune to disparities.

Cognitive-Affective-Behavioral Pathways Linking Adversity and Discrimination to Daily Pain in African-American Adults.

The tendency to ruminate, magnify, and experience helplessness in the face of pain - known as pain catastrophizing - is a strong predictor of pain outcomes and is associated with adversity. The ability to maintain functioning despite adversity - referred to as resilience - also influences pain outcomes. Understanding the extent to which pain catastrophizing and resilience influence relations between adversity and daily pain in healthy African-American adults could improve pain risk assessment and mitigate racial disparities in the transition from acute to chronic pain. This study included 160 African-American adults (98 women). Outcome measures included daily pain intensity (sensory, affective) and pain impact on daily function (pain interference). Adversity measures included childhood trauma exposure, family adversity, chronic burden from recent stressors, and ongoing perceived stress. A measure of lifetime racial discrimination was also included. Composite scores were created to capture early-life adversity (childhood trauma, family adversity) versus recent-life adversity (perceived stress, chronic burden). Increased pain catastrophizing was correlated with increased adversity (early and recent), racial discrimination, pain intensity, and pain interference. Decreased pain resilience was correlated with increased recent-life adversity (not early-life adversity or racial discrimination) and correlated with increased pain intensity (not pain-related interference). Bootstrapped multiple mediation models revealed that relationships between all adversity/discrimination and pain outcomes were mediated by pain catastrophizing. Pain resilience, however, was not a significant mediator in these models. These findings highlight opportunities for early interventions to reduce cognitive-affective-behavioral risk factors for persisting daily pain among African-American adults with greater adversity exposure by targeting pain catastrophizing.