Incidence of persistent opioid use following traumatic injury.

INTRODUCTION: Major traumatic injuries are a known risk factor for persistent opioid use, but data describing the relationship between specific traumatic injuries and opioid use is lacking. METHODS: We used insurance claims data from January 1, 2001 to December 31, 2020 to estimate the incidence of new persistent opioid use in three hospitalized trauma populations: individuals hospitalized after burn injury (3809, 1504 of whom required tissue grafting), individuals hospitalized after motor vehicle collision (MVC; 9041), and individuals hospitalized after orthopedic injury (47, 637). New persistent opioid use was defined as receipt of ≥1 opioid prescriptions 90-180 days following injury in an individual with no opioid prescriptions during the year prior to injury. RESULTS: New persistent opioid use was observed in 12% (267/2305) of individuals hospitalized after burn injury with no grafting, and 12% (176/1504) of burn injury patients requiring tissue grafting. In addition, new persistent opioid use was observed in 16% (1454/9041) of individuals hospitalized after MVC, and 20% (9455/47, 637) of individuals hospitalized after orthopedic trauma. In comparison, rates of persistent opioid use in all trauma cohorts (19%, 11, 352/60, 487) were greater than the rates of persistent opioid use in both non-traumatic major surgery (13%) and non-traumatic minor surgery (9%). CONCLUSIONS: These data demonstrate that new persistent opioid use frequently occurs in these common hospitalized trauma populations. Improved interventions to reduce persistent pain and opioid use in patients hospitalized after these and other traumas are needed.

Monitoring Knee Contact Force with Force-Sensing Insoles.

Numerous applications exist for monitoring knee contact force (KCF) throughout activities of daily living. However, the ability to estimate these forces is restricted to a laboratory setting. The purposes of this study are to develop KCF metric estimation models and explore the feasibility of monitoring KCF metrics via surrogate measures derived from force-sensing insole data. Nine healthy subjects (3F, age 27 ± 5 years, mass 74.8 ± 11.8 kg, height 1.7 ± 0.08 m) walked at multiple speeds (0.8-1.6 m/s) on an instrumented treadmill. Thirteen insole force features were calculated as potential predictors of peak KCF and KCF impulse per step, estimated with musculoskeletal modeling. The error was calculated with median symmetric accuracy. Pearson product-moment correlation coefficients defined the relationship between variables. Models develop per-limb demonstrated lower prediction error than those developed per-subject (KCF impulse: 2.2% vs 3.4%; peak KCF: 3.50% vs. 6.5%, respectively). Many insole features are moderately to strongly associated with peak KCF, but not KCF impulse across the group. We present methods to directly estimate and monitor changes in KCF using instrumented insoles. Our results carry promising implications for internal tissue loads monitoring outside of a laboratory with wearable sensors.

CpG Methylation Levels in HPA Axis Genes Predict Chronic Pain Outcomes Following Trauma Exposure.

Chronic post-traumatic musculoskeletal pain (CPTP) is a common outcome of traumatic stress exposure. Biological factors that influence the development of CPTP are poorly understood, though current evidence indicates that the hypothalamic-pituitary-adrenal (HPA) axis plays a critical role in its development. Little is known about molecular mechanisms underlying this association, including epigenetic mechanisms. Here, we assessed whether peritraumatic DNA methylation levels at 248 5'-C-phosphate-G-3' (CpG) sites in HPA axis genes (FKBP5, NR3C1, CRH, CRHR1, CRHR2, CRHBP, POMC) predict CPTP and whether identified CPTP-associated methylation levels influence expression of those genes. Using participant samples and data collected from trauma survivors enrolled into longitudinal cohort studies (n = 290), we used linear mixed modeling to assess the relationship between peritraumatic blood-based CpG methylation levels and CPTP. A total of 66 (27%) of the 248 CpG sites assessed in these models statistically significantly predicted CPTP, with the three most significantly associated CpG sites originating from the POMC gene region (ie, cg22900229 [ß = .124, P < .001], cg16302441 [ß = .443, P < .001], cg01926269 [ß = .130, P < .001]). Among the genes analyzed, both POMC (z = 2.36, P = .018) and CRHBP (z = 4.89, P < .001) were enriched in CpG sites significantly associated with CPTP. Further, POMC expression was inversely correlated with methylation levels in a CPTP-dependent manner (6-months NRS<4: r = -.59, P < .001; 6-months NRS ≥ 4: r = -.18, P = .2312). Our results suggest that methylation of HPA axis genes including POMC and CRHBP predict risk for and may contribute to vulnerability to CPTP. PERSPECTIVE: Peritraumatic blood levels of CpG methylation sites in HPA axis genes, particularly CpG sites in the POMC gene, predict CPTP development. This data substantially advances our understanding of epigenetic predictors and potential mediators of CPTP, a highly common, morbid, and hard-to-treat form of chronic pain.

Early Pain Catastrophizing Exacerbates Impaired Limb Loading and 6-Minute Walk Test Distance 12 Months After Lower Extremity Fracture.

OBJECTIVE: Disability is common after lower extremity fracture (LEF). Although psychosocial factors have been associated with patient-reported outcomes after LEF, they have not been associated with objective measures of function. Aberrant gait patterns are important markers of function, but are poorly defined after LEF. The primary purpose of this study was to explore whether pain catastrophizing and fear of movement 6 weeks after surgery were associated with injured limb loading outcomes and 6-minute walk test (6MWT) distance 12 months after femur or tibia fracture. The secondary purpose was to determine if limb loading characteristics differed between injured and uninjured limbs. METHODS: At 6 weeks after LEF, patients completed validated measures of pain catastrophizing, fear of movement, and depression. At 12 months, patients completed a 6MWT while wearing instrumented insoles that recorded the limb loading outcomes of stance time, impulse, and loading rate. Bivariate correlations assessed how patient and psychosocial characteristics at 6 weeks were associated with injured limb loading outcomes and 6MWT distance. Multivariable regression analyses were performed to determine if psychosocial variables were associated with each outcome after controlling for depression and patient demographic and clinical characteristics. Finally, paired t tests compared limb loading outcomes between limbs. RESULTS: Forty-seven participants completed the 6MWT at 12 months (65%), and 38 completed the 6MWT with the instrumented insoles. Fear of movement carried a poor relationship (r = 0.11-0.32) and pain catastrophizing a moderate relationship (r = 0.46-0.54) with 12-month outcomes. The regression results indicated that pain catastrophizing continued to be associated with all outcomes. Finally, the injured limb had significantly lower limb loading outcomes than the uninjured limb at 12 months (Cohen d = 0.54-0.69). CONCLUSION: Pain catastrophizing early after LEF was associated with impaired limb loading and 6MWT distance at 12 months. IMPACT: Impaired limb loading persists 12 months after LEF. Further research is needed to determine whether rehabilitative efforts focused on pain catastrophizing can restore limb loading after LEF.

Decreased quadriceps force steadiness following anterior cruciate ligament reconstruction is associated with altered running kinematics.

BACKGROUND: Anterior cruciate ligament reconstruction is associated with quadriceps dysfunction and altered knee mechanics, but the relationship between these outcomes is not clear. Inclusion of metrics such as the stability of torque output could provide additional insights into the relationship between quadriceps dysfunction and knee mechanics. The purposes of this study were to: (1) measure the difference in quadriceps force steadiness between anterior cruciate ligament reconstructed and contralateral limbs; and (2) assess the relationship of quadriceps force steadiness and peak torque with knee flexion excursion during running. METHODS: Twenty-eight participants (14 female, age 20 (5) years) underwent quadriceps strength testing and gait analysis. Force steadiness was measured with the standard deviation and coefficient of variation of the participants' detrended torque. Knee flexion excursion was calculated during the stance phase of running trials. Differences between limbs for force steadiness and peak torque were assessed with paired sample t-tests, and a Pearson's product-moment correlation coefficient determined the relationship between pairs of variables. FINDINGS: Anterior cruciate ligament reconstructed limbs presented with a significant deficit in relative force steadiness compared to the contralateral limb (4.03 (1.04) % and 3.58 (1.41) % (P < .05), respectively). In addition, the relationship of quadriceps strength and force steadiness with knee flexion excursion was altered in anterior cruciate ligament reconstructed limbs due to the inability of the quadriceps to sustain a controlled force output. INTERPRETATION: These results suggest that considering both the magnitude and quality of force production can provide important insight into comprehensive quadriceps function.

Trauma in Pregnancy: The Relationship of Trauma Activation Level and Obstetric Outcomes.

Trauma in pregnancy is a leading cause of poor fetal and obstetric outcomes. Trauma team activation (TTA) criteria include injury with ≥ 20 weeks gestational age (GA). A retrospective analysis was performed on pregnant patients evaluated at a Level 1 trauma center. Patients were characterized by TTA: full, partial, or non-TTA, and TTA criteria independent of pregnancy. Index trauma and delayed delivery hospitalization outcomes were examined. Bivariate analysis, t test, and logistic regression were used when appropriate. From 2010 to 2015, 216 full, 50 partial, and 50 non-TTAs presented. Independent of pregnancy, 79 per cent of patients did not meet the TTA criteria. Fourteen (4%) had a pregnancy-related complication during index hospitalization (eight fetal and two maternal deaths). Nine of ten deaths occurred in patients meeting TTA independent of pregnancy. Delivery complications were greater in the index (52%, 13/25) versus subsequent (5%, 17/155) hospitalizations and were predicted by the respiratory rate (P = 0.016) and injury severity score (P < 0.001). Poor delayed delivery outcomes were associated with earlier GA (P < 0.002) and longer index hospitalization (P < 0.024). Odds of complication are higher in patients meeting the physiologic and anatomic criteria criteria for TTA versus GA criteria alone, signifying overtriage. Trauma activation protocols should be adapted based on the physiologic and anatomic criteria criteria in pregnant patients.

Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets.

BACKGROUND: Blood platelets undergo a carefully regulated change in shape to serve as the primary mediators of hemostasis and thrombosis. These processes manifest through platelet spreading and aggregation and are dependent on platelet actin cytoskeletal changes orchestrated by the Rho GTPase family member Rac1. To elucidate how Rac1 is regulated in platelets, we captured Rac1-interacting proteins from platelets and identified Rac1-associated proteins by mass spectrometry. FINDINGS: Here, we demonstrate that Rac1 captures the Rac guanine nucleotide exchange factor P-Rex1 from platelet lysates. Western blotting experiments confirmed that P-Rex1 is expressed in platelets and associated with Rac1. To investigate the functional role of platelet P-Rex1, platelets from P-Rex1-/--deficient mice were treated with platelet agonists or exposed to platelet activating surfaces of fibrinogen, collagen and thrombin. Platelets from P-Rex1-/- mice responded to platelet agonists and activating surfaces similarly to wild type platelets. CONCLUSIONS: These findings suggest that P-Rex1 is not required for Rac1-mediated platelet activation and that the GEF activities of P-Rex1 may be more specific to GPCR chemokine receptor mediated processes in immune cells and tumor cells.