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 a substantial burden at the individual, community, and health care 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 (DER), depression, and completed brief physical function tasks. In data analytic models, sociodemographic variables were included as covariates. Analyses revealed that emotion regulation mediated the relationship between ACEs and cLBP severity at rest (indirect effect = .15 [95% CI {.06-.25}]) and with movement (indirect effect = 1.50 [95% CI {.69-2.57}]). Findings suggest ACEs are linked to cLBP severity in adulthood through DER. This aligns with research demonstrating that childhood maltreatment can lead to DER, which perpetuate over the lifespan to impact adult health outcomes. PERSPECTIVE: This study presents emotion dysregulation as a psychological pathway through which childhood adversity may contribute to cLBP in adulthood. This work may bolster our understanding of social experiences as risk factors for chronic pain, while identifying targets for clinical intervention. 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" (ClinicalTrials.gov ID: NCT03338192).

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.

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.

A regulatory pathway model of neuropsychological disruption in Havana syndrome.

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.

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.

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.

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.

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.

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.

Proteomic Network Analysis of Bronchoalveolar Lavage Fluid in Ex-Smokers to Discover Implicated Protein Targets and Novel Drug Treatments for Chronic Obstructive Pulmonary Disease.

Bronchoalveolar lavage of the epithelial lining fluid (BALF) can sample the profound changes in the airway lumen milieu prevalent in chronic obstructive pulmonary disease (COPD). We compared the BALF proteome of ex-smokers with moderate COPD who are not in exacerbation status to non-smoking healthy control subjects and applied proteome-scale translational bioinformatics approaches to identify potential therapeutic protein targets and drugs that modulate these proteins for the treatment of COPD. Proteomic profiles of BALF were obtained from (1) never-smoker control subjects with normal lung function (n = 10) or (2) individuals with stable moderate (GOLD stage 2, FEV1 50−80% predicted, FEV1/FVC < 0.70) COPD who were ex-smokers for at least 1 year (n = 10). After identifying potential crucial hub proteins, drug−proteome interaction signatures were ranked by the computational analysis of novel drug opportunities (CANDO) platform for multiscale therapeutic discovery to identify potentially repurposable drugs. Subsequently, a literature-based knowledge graph was utilized to rank combinations of drugs that most likely ameliorate inflammatory processes. Proteomic network analysis demonstrated that 233 of the >1800 proteins identified in the BALF were significantly differentially expressed in COPD versus control. Functional annotation of the differentially expressed proteins was used to detail canonical pathways containing the differential expressed proteins. Topological network analysis demonstrated that four putative proteins act as central node proteins in COPD. The drugs with the most similar interaction signatures to approved COPD drugs were extracted with the CANDO platform. The drugs identified using CANDO were subsequently analyzed using a knowledge-based technique to determine an optimal two-drug combination that had the most appropriate effect on the central node proteins. Network analysis of the BALF proteome identified critical targets that have critical roles in modulating COPD pathogenesis, for which we identified several drugs that could be repurposed to treat COPD using a multiscale shotgun drug discovery approach.

Computational prediction of intracellular targets of wild-type or mutant vesicular stomatitis matrix protein.

The matrix (M) protein of vesicular stomatitis virus (VSV) has a complex role in infection and immune evasion, particularly with respect to suppression of Type I interferon (IFN). Viral strains bearing the wild-type (wt) M protein are able to suppress Type I IFN responses. We recently reported that the 22-25 strain of VSV encodes a wt M protein, however its sister plaque isolate, strain 22-20, carries a M[MD52G] mutation that perturbs the ability of the M protein to block NFκB, but not M-mediated inhibition of host transcription. Therefore, although NFκB is activated in 22-20 infected murine L929 cells infected, no IFN mRNA or protein is produced. To investigate the impact of the M[D52G] mutation on immune evasion by VSV, we used transcriptomic data from L929 cells infected with wt, 22-25, or 22-20 to define parameters in a family of executable logical models with the aim of discovering direct targets of viruses encoding a wt or mutant M protein. After several generations of pruning or fixing hypothetical regulatory interactions, we identified specific predicted targets of each strain. We predict that wt and 22-25 VSV both have direct inhibitory actions on key elements of the NFκB signaling pathway, while 22-20 fails to inhibit this pathway.

Stress-induced analgesia: an evaluation of effects on temporal summation of pain and the role of endogenous opioid mechanisms.

INTRODUCTION: Acute stress reduces responses to static evoked pain stimuli (stress-induced analgesia [SIA]). Whether SIA inhibits temporal summation of pain, a dynamic evoked pain measure indexing central sensitization, has been little studied and mechanisms were not evaluated. OBJECTIVES: We tested whether acute laboratory stressors reduce temporal summation and whether endogenous opioid (EO) mechanisms contributed. METHODS: Participants were 72 healthy individuals who attended 2 laboratory sessions, receiving either oral naltrexone (50 mg; opioid antagonist) or placebo (randomized, counterbalanced order). In each session, participants underwent a temporal summation protocol with evoked heat pain stimuli, once after extended rest and once after experiencing 2 acute stressors (public speaking and mental arithmetic challenge). Reduced temporal summation in the stress/pain relative to rest/pain condition indexed SIA. RESULTS: Analyses in the placebo condition indicated significant SIA on initial pain ratings but not temporal summation slope (index of central sensitization). This SIA effect was moderated by stress reactivity, with SIA only observed in high stress responders. Analyses comparing SIA across the drug conditions did not reveal any evidence of stress-related EO inhibition of temporal summation outcomes. Moderation analyses revealed that high, but not low, stress responders exhibited paradoxical analgesic effects of naltrexone on initial pain ratings but not temporal summation slopes. Independent of stress effects, significant EO inhibition of temporal summation slopes was observed, but only in females. CONCLUSIONS: Results suggest that acute stress may reduce initial ratings in temporal summation protocols via nonopioid mechanisms but does not alter the temporal summation slope commonly used to index central sensitization.

Social determinants of trauma care: Associations of race, insurance status, and place on opioid prescriptions, postdischarge referrals, and mortality.

BACKGROUND: Racial disparities in trauma care have been reported for a range of outcomes, but the extent to which these remain after accounting for socioeconomic and environmental factors remains unclear. The objective of this study was to evaluate the unique contributions of race, health insurance, community distress, and rurality/urbanicity on trauma outcomes after carefully controlling for specific injury-related risk factors. METHODS: All adult (age, ≥18 years) trauma patients admitted to a single Level I trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed. Primary outcomes were mortality, rehabilitation referral, and receipt of opioids in the emergency department. Demographic, socioeconomic, and injury characteristics as well as indicators of community distress and rurality based on home address were abstracted from a trauma registry database. RESULTS: Analyses revealed that Black patients (n = 13,073) were younger, more likely to be male, more likely to suffer penetrating injuries, and more likely to suffer assault-based injuries compared with White patients (n = 10,946; all p < 0.001). In adjusted analysis, insured patients had a 28% lower risk of mortality (odds ratio, 0.72; p = 0.005) and were 92% more likely to be referred for postdischarge rehabilitation than uninsured patients (odds ratio, 1.92; p = 0.005). Neither race- nor place-based factors were associated with mortality. However, post hoc analyses revealed a significant race by age interaction, with Black patients exhibiting more pronounced increases in mortality risk with increasing age. CONCLUSION: The present findings help disentangle the social determinants of trauma disparities by adjusting for place and person characteristics. Uninsured patients were more likely to die and those who survived were less likely to receive referrals for rehabilitation services. The expected racial disparity in mortality risk favoring White patients emerged in middle age and was more pronounced for older patients. LEVEL OF EVIDENCE: Prognostic and epidemiological, Level III.

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.

Predicting Posttraumatic Stress Disorder Among Survivors of Recent Interpersonal Violence.

A substantial minority of women who experience interpersonal violence will develop posttraumatic stress disorder (PTSD). One critical challenge for preventing PTSD is predicting whose acute posttraumatic stress symptoms will worsen to a clinically significant degree. This 6-month longitudinal study adopted multilevel modeling and exploratory machine learning (ML) methods to predict PTSD onset in 58 young women, ages 18 to 30, who experienced an incident of physical and/or sexual assault in the three months prior to baseline assessment. Women completed baseline assessments of theory-driven cognitive and neurobiological predictors and interview-based measures of PTSD diagnostic status and symptom severity at 1-, 3-, and 6-month follow-ups. Higher levels of self-blame, generalized anxiety disorder severity, childhood trauma exposure, and impairment across multiple domains were associated with a pattern of high and stable posttraumatic stress symptom severity over time. Predictive performance for PTSD onset was similarly strong for a gradient boosting machine learning model including all predictors and a logistic regression model including only baseline posttraumatic stress symptom severity. The present findings provide directions for future work on PTSD prediction among interpersonal violence survivors that could enhance early risk detection and potentially inform targeted prevention programs.

Pre-Exposure Prophylaxis Training among Medical Schools in the United States.

Pre-Exposure Prophylaxis (PrEP) has been shown to be an effective method of HIV prevention for men who have sex with-men (MSM) and -transgender women (MSTGWs), serodiscordant couples, and injection drug users; however fewer than 50 000 individuals currently take this regimen. Knowledge of PrEP is low among healthcare providers and much of this lack of knowledge stems from the lack or exposure to PrEP in medical school. We conducted a cross sectional survey of medical schools in the United States to assess the degree to which PrEP for HIV prevention is taught. The survey consisted Likert scale questions assessing how well the students were prepared to perform each skill associated with PrEP delivery, as well as how PrEP education was delivered to students. We contacted 141 medical schools and 71 responded to the survey (50.4%). PrEP education was only reported to be offered at 38% of schools, and only 15.4% reported specific training for Lesbian, Gay, Bisexual, and Transgender (LGBT) patients. The most common delivery methods of PrEP content were didactic sessions with 11 schools reporting this method followed by problem-based learning, direct patient contact, workshops, and small group discussions. Students were more prepared to provide PrEP to MSM compared to other high-risk patients. Few medical schools are preparing their students to prescribe PrEP upon graduation. Further, there is a need to increase the number of direct patient contacts or simulations for students to be better prepared.

Predicting pain among female survivors of recent interpersonal violence: A proof-of-concept machine-learning approach.

Interpersonal violence (IPV) is highly prevalent in the United States and is a major public health problem. The emergence and/or worsening of chronic pain are known sequelae of IPV; however, not all those who experience IPV develop chronic pain. To mitigate its development, it is critical to identify the factors that are associated with increased risk of pain after IPV. This proof-of-concept study used machine-learning strategies to predict pain severity and interference in 47 young women, ages 18 to 30, who experienced an incident of IPV (i.e., physical and/or sexual assault) within three months of their baseline assessment. Young women are more likely than men to experience IPV and to subsequently develop posttraumatic stress disorder (PTSD) and chronic pain. Women completed a comprehensive assessment of theory-driven cognitive and neurobiological predictors of pain severity and pain-related interference (e.g., pain, coping, disability, psychiatric diagnosis/symptoms, PTSD/trauma, executive function, neuroendocrine, and physiological stress response). Gradient boosting machine models were used to predict symptoms of pain severity and pain-related interference across time (Baseline, 1-,3-,6- follow-up assessments). Models showed excellent predictive performance for pain severity and adequate predictive performance for pain-related interference. This proof-of-concept study suggests that machine-learning approaches are a useful tool for identifying predictors of pain development in survivors of recent IPV. Baseline measures of pain, family life impairment, neuropsychological function, and trauma history were of greatest importance in predicting pain and pain-related interference across a 6-month follow-up period. Present findings support the use of machine-learning techniques in larger studies of post-IPV pain development and highlight theory-driven predictors that could inform the development of targeted early intervention programs. However, these results should be replicated in a larger dataset with lower levels of missing data.

Does Quantitative Sensory Testing Improve Prediction of Chronic Pain Trajectories? A Longitudinal Study of Youth With Functional Abdominal Pain Participating in a Randomized Controlled Trial of Cognitive Behavioral Treatment.

OBJECTIVES: Youth with functional abdominal pain (FAP) experience significant pain-related distress and functional impairment. Although quantitative sensory testing protocols have identified alterations in pain modulatory systems that distinguish youth with FAP from healthy controls, the extent to which evoked pain responses predict subsequent trajectories of pain symptoms and disability over and above established psychosocial risk factors is unclear. METHODS: The present study included 183 adolescents with FAP who were enrolled in a randomized controlled trial comparing an 8-week, internet-delivered program of cognitive behavior therapy (n=90) or pain education (n=93). Participants completed a quantitative sensory testing protocol before the intervention and were followed for 12-month posttreatment. RESULTS: Whereas adolescents with FAP who exhibited stronger baseline conditioned pain modulation (CPM) reported decreases in pain-related interference over follow-up (b=-0.858, SE=0.396, P=0.032), those with weaker CPM exhibited high, relatively stable levels of pain-related interference over time (b=-0.642, SE=0.400, P=0.110). CPM status predicted changes in pain-related interference after controlling for the effects of treatment condition and psychosocial risk factors. Static measures of pain sensitivity (ie, pain threshold, pain tolerance) and temporal summation of second pain were not associated with changes in measures of abdominal pain, gastrointestinal symptom severity, or pain-related interference over follow-up. DISCUSSION: The present findings contribute to a growing literature on the predictive utility of quantitative sensory testing indices and suggest that CPM may complement existing psychosocial risk measures in determining individualized pain-related risk profiles.