Andrey V. Bortsov

μ-Opioid receptor gene A118G polymorphism predicts survival in patients with breast cancer.

Background: Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the &mgr;-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival. Methods: A total of 2,039 women ages 23–74 yr (38% African-American, 62% European-American, 55% postmenopausal) diagnosed with breast cancer between 1993–2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival. Results: After Bonferroni correction for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (P < 0.001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared with A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; P = 0.006). Conclusions: These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted.

Association of DASH Diet With Cardiovascular Risk Factors in Youth With Diabetes Mellitus The SEARCH for Diabetes in Youth Study

Background— We have shown that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is related to blood pressure in youth with type 1 and type 2 diabetes mellitus. We explored the impact of the DASH diet on other cardiovascular disease risk factors. Methods and Results— Between 2001 and 2005, data on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein particle density, apolipoprotein B, body mass index, waist circumference, and adipocytokines were ascertained in 2130 youth aged 10 to 22 years with physician-diagnosed diabetes mellitus. Dietary intake was assessed by food frequency questionnaire, categorized into the DASH food groups, and assigned an adherence score. Among youth with type 1 diabetes mellitus, higher adherence to the DASH diet was significantly and inversely associated with low-density lipoprotein/high-density lipoprotein ratio and A1c in multivariable-adjusted models. Youth in the highest adherence tertile had an estimated 0.07 lower low-density lipoprotein/high-density lipoprotein ratio and 0.2 lower A1c levels than those in the lowest tertile adjusted for confounders. No significant associations were observed with triglycerides, low-density lipoprotein particle density, adipocytokines, apolipoprotein B, body mass index Z score, or waist circumference. Among youth with type 2 diabetes mellitus, associations were observed with low-density lipoprotein particle density and body mass index Z score. Conclusions— The DASH dietary pattern may be beneficial in the prevention and management of cardiovascular disease risk in youth with diabetes mellitus.

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

Summary Most individuals with pain sequelae 6 weeks after motor vehicle collision are not engaged in litigation. Evidence supports bidirectional effects between litigation and post–motor vehicle collision musculoskeletal pain outcomes. ABSTRACT 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 6 weeks 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 6 weeks 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.

Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure.

&NA; An association is demonstrated between genetic polymorphisms in the gene coding for a key regulatory molecule in the hypothalamic‐pituitary‐adrenal axis and persistent pain after trauma. &NA; Individual vulnerability factors influencing the function of the hypothalamic‐pituitary‐adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co‐chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department‐based cohorts: a discovery cohort (n = 949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n = 53). DNA was collected from trauma survivors at the time of initial assessment. Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0–10 numeric rating scale. After adjustment for multiple comparisons, 6 FKBP5 polymorphisms showed significant association (minimum P < 0.0001) with both overall and neck pain in the discovery cohort. The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma.

Simulator training enhances resident performance in transesophageal echocardiography.

Background:Standardized training via simulation as an educational adjunct may lead to a more rapid and complete skill achievement. The authors hypothesized that simulation training will also enhance performance in transesophageal echocardiography image acquisition among anesthesia residents. Methods:A total of 42 clinical anesthesia residents were randomized to one of two groups: a control group, which received traditional didactic training, and a simulator group, whose training used a transesophageal echocardiography–mannequin simulator. Each participating resident was directed to obtain 10 commonly used standard views on an anesthetized patient under attending supervision. Each of the 10 selected echocardiographic views were evaluated on a grading scale of 0 to 10, according to predetermined criteria. The effect of the intervention was assessed by using a linear mixed model implemented in SAS 9.3 (SAS Institute Inc., Cary, NC). Results:Residents in the simulation group obtained significantly higher-quality images with a mean total image quality score of 83 (95% CI, 74 to 92) versus the control group score of 67 (95% CI, 58 to 76); P = 0.016. On average, 71% (95% CI, 58 to 85) of images acquired by each resident in the simulator group were acceptable for clinical use compared with 48% (95% CI, 35 to 62) in the control; P = 0.021. Additionally, the mean difference in score between training groups was the greatest for the clinical anesthesia-1 residents (difference 24; P = 0.031; n = 7 per group) and for those with no previous transesophageal echocardiography experience (difference 26; P = 0.005; simulator n = 13; control n = 11). Conclusion:Simulation-based transesophageal echocardiography education enhances image acquisition skills in anesthesiology residents.

Using emergency department-based inception cohorts to determine genetic characteristics associated with long term patient outcomes after motor vehicle collision: Methodology of the CRASH study

BackgroundPersistent musculoskeletal pain and psychological sequelae following minor motor vehicle collision (MVC) are common problems with a large economic cost. Prospective studies of pain following MVC have demonstrated that demographic characteristics, including female gender and low education level, and psychological characteristics, including high pre-collision anxiety, are independent predictors of persistent pain. These results have contributed to the psychological and social components of a biopsychosocial model of post-MVC pain pathogenesis, but the biological contributors to the model remain poorly defined. Recent experimental studies indicate that genetic variations in adrenergic system function influence the vulnerability to post-traumatic pain, but no studies have examined the contribution of genetic factors to existing predictive models of vulnerability to persistent pain.Methods/DesignThe Project CRASH study is a federally supported, multicenter, prospective study designed to determine whether variations in genes affecting synaptic catecholamine levels and alpha and beta adrenergic receptor function augment social and psychological factors in a predictive model of persistent musculoskeletal pain and posttraumatic stress disorder (PTSD) following minor MVC. The Project CRASH study will assess pain, pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in approximately 1,000 patients enrolled from 8 Emergency Departments in four states with no-fault accident laws.DiscussionThe results from this study will provide insights into the pathophysiology of persistent pain and PTSD following MVC and may serve to improve the ability of clinicians and researchers to identify individuals at high risk for adverse outcomes following minor MVC.

Substantial postoperative pain is common among children undergoing laparoscopic appendectomy

Background:  Laparoscopic appendectomy is one of the most common surgical procedures performed in children. However, to our knowledge, the postoperative pain experience of children undergoing laparoscopic appendectomy has never been described. In this study, we assessed the postoperative pain experience of children undergoing laparoscopic appendectomy.

More Educated Emergency Department Patients are Less Likely to Receive Opioids for Acute Pain

Summary Of patients presenting to an emergency department for evaluation after a motor vehicle collision, those with higher educational attainment are less likely to receive opioids. ABSTRACT Inadequate treatment of pain in United States emergency departments (EDs) is common, in part because of the limited and idiosyncratic use of opioids by emergency providers. This study sought to determine the relationship between patient socioeconomic characteristics and the likelihood that they would receive opioids during a pain‐related ED visit. We conducted a cross‐sectional analysis of ED data obtained as part of a multicenter study of outcomes after minor motor vehicle collision (MVC). Study patients were non‐Hispanic white patients between the ages of 18 and 65 years who were evaluated and discharged home from 1 of 8 EDs in 4 states. Socioeconomic characteristics include educational attainment and income. Of 690 enrolled patients, the majority had moderate or severe pain (80%). Patients with higher education attainment had lower levels of pain, pain catastrophizing, perceived life threat, and distress. More educated patients were also less likely to receive opioids during their ED visit. Opioids were given to 54% of patients who did not complete high school vs 10% of patients with post‐college education (χ2 test P < .001). Differences in the frequency of opioid administration between patients with the lowest educational attainment (39%, 95% confidence interval 22% to 60%) and highest educational attainment (13%, 95% confidence interval 7% to 23%) remained after adjustment for age, sex, income, and pain severity (P = .01). In this sample of post‐MVC ED patients, more educated patients were less likely to receive opioids. Further study is needed to assess the generalizability of these findings and to determine the reason for the difference.

Pain distribution and predictors of widespread pain in the immediate aftermath of motor vehicle collision.

Musculoskeletal pain is common after motor vehicle collision (MVC). The study objective was to evaluate distribution of pain and predictors of widespread musculoskeletal pain in the early aftermath (within 48 h) of collision.

Gender differences in acute and chronic pain in the emergency department: Results of the 2014 academic emergency medicine consensus conference pain section

Pain is a leading public health problem in the United States, with an annual economic burden of more than