Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.

α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.

Incidence and predictors of neck and widespread pain after motor vehicle collision among US litigants and nonlitigants.

Debate continues regarding the influence of litigation on pain outcomes after motor vehicle collision (MVC). In this study we enrolled European Americans presenting to the emergency department (ED) in the hours after MVC (n=948). Six weeks later, participants were interviewed regarding pain symptoms and asked about their participation in MVC-related litigation. The incidence and predictors of neck pain and widespread pain 6weeks after MVC were compared among those engaged in litigation (litigants) and those not engaged in litigation (nonlitigants). Among the 859 of 948 (91%) participants completing 6-week follow-up, 711 of 849 (83%) were nonlitigants. Compared to nonlitigants, litigants were less educated and had more severe neck pain and overall pain, and a greater extent of pain at the time of ED evaluation. Among individuals not engaged in litigation, persistent pain 6weeks after MVC was common: 199 of 711 (28%) had moderate or severe neck pain, 92 of 711 (13%) had widespread pain, and 29 of 711 (4%) had fibromyalgia-like symptoms. Incidence of all 3 outcomes was significantly higher among litigants. Initial pain severity in the ED predicted pain outcomes among both litigants and nonlitigants. Markers of socioeconomic disadvantage predicted worse pain outcomes in litigants but not nonlitigants, and individual pain and psychological symptoms were less predictive of pain outcomes among those engaged in litigation. These data demonstrate that persistent pain after MVC is common among those not engaged in litigation, and provide evidence for bidirectional influences between pain outcomes and litigation after MVC.

Patients with traumatic subarachnoid hemorrhage are at low risk for deterioration or neurosurgical intervention.

BACKGROUND: Current standard of care for patients with traumatic intracranial hemorrhage (TIH) includes neurosurgical consultation and/or transfer to a trauma center with neurosurgical backup. We hypothesize that a set of low-risk criteria can be applied to such patients to identify those who may not require neurosurgical evaluation. METHODS: This is a cross-sectional study of consecutive emergency department patients in 2009 and 2010 with TIH on computerized tomographic scan owing to blunt head trauma. Patients presented to an urban academic Level I trauma center (volume, 92,000) were older than 15 years and had a Glasgow Coma Scale (GCS) score of 13 or greater. Charts were abstracted using a standardized data form by two emergency physicians. Our principal outcome was deterioration represented by a composite of neurosurgical intervention, clinical deterioration, or worsening computerized tomographic scan result. RESULTS: During the study period, 404 patients were seen with TIH and met our inclusion criteria, and 48 of those patients (11.8%) deteriorated. Patients with isolated subarachnoid hemorrhage, were less likely to deteriorate (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.011-0.58). Characteristics associated with deterioration were subdural hematomas (OR, 2.63; 95% CI, 1.198-5.81) or presenting GCS of less than 15 (OR, 2.12; 95% CI, 1.01-4.43).The use of anticoagulant medications or antiplatelet agents were not associated with deterioration for warfarin, aspirin, or clopidogrel; however bleeding diatheses were corrected with vitamin K, fresh frozen plasma, and platelets as necessary. CONCLUSION: Patients with isolated traumatic subarachnoid hemorrhage are at low risk for deterioration. These individuals may not need neurosurgical consultation or transfer to a trauma center where neurosurgical backup is available. Those patients with subdural hematoma or a GCS of less than 15 have a higher risk of deterioration and require neurosurgical evaluation. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Alternative perspective on the control of transpiration by radiation.

Stomatal responses to light are important determinants for plant water use efficiency and for general circulation models, but a mechanistic understanding of these responses remains elusive. A recent study [Pieruschka R, Huber G, Berry JA (2010) Proc Natl Acad Sci USA 107:13372-13377] concluded that stomata respond to total absorbed radiation rather than red and blue light as previously thought. We tested this idea by reexamining stomatal responses to red and blue light and to IR radiation. We show that responses to red and blue light are not consistent with a response to total absorbed radiation and that apparent stomatal responses to IR radiation are explainable as experimental artifacts. In addition, our data and analysis provide a method for accurately determining the internal temperature of a leaf.

A comparison of 2 protocols to detect intimate partner violence.

PURPOSE: Intimate partner violence (IPV) frequently results in maxillofacial injuries. The purpose of this study is to compare 2 protocols to identify women who self-report IPV-related injuries. MATERIALS AND METHODS: Using a cross-sectional study design, we enrolled a sample of injured women who presented to the emergency department (ED) for evaluation and treatment. The predictor variable was the protocol used to identify injury etiology, that is, an innovative diagnostic protocol (DP) or the ED's standard operating procedure (SOP). The outcome variable was self-reported injury etiology categorized as IPV or other. Descriptive and bivariate statistics were computed. Sensitivity, specificity, positive predictive value, negative predictive value, and odds ratios were computed (with P < or = .05 being considered statistically significant). RESULTS: The sample was composed of 286 women with a mean age of 45.8 years. The self-reported prevalence of IPV-related injuries was 11.5% and 5% for the DP and SOP, respectively (P = .03). The diagnostic statistics for the DP and SOP, respectively, were as follows: sensitivities, 94% and 50%; specificities, 76% and 95%; positive predictive values, 34% and 50%; and negative predictive values, 98% and 95%. In the adjusted model the women evaluated with the DP had a 38-fold increased likelihood of reporting IPV (P < .01) when compared with the SOP. CONCLUSIONS: These results suggest that the proposed DP is associated with an increased frequency of self-reported IPV-related injuries when compared with the ED's SOP.