The behavioral effects of gestational and lactational benzo[a]pyrene exposure vary by sex and genotype in mice with differences at the Ahr and Cyp1a2 loci.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) and known carcinogen in the Top 10 on the United States' list of priority pollutants. Humans are exposed through a variety of sources including tobacco smoke, grilled foods and fossil fuel combustion. Recent studies of children exposed to higher levels of PAHs during pregnancy and early life have identified numerous adverse effects on the brain and behavior that persist into school age and adolescence. Our studies were designed to look for genotype and sex differences in susceptibility to gestational and lactational exposure to BaP using a mouse model with allelic differences in the aryl hydrocarbon receptor and the xenobiotic metabolizing enzyme CYP1A2. Pregnant dams were exposed to 10 mg/kg/day of BaP in corn oil-soaked cereal or the corn oil vehicle alone from gestational day 10 until weaning at postnatal day 25. Neurobehavioral testing began at P60 using one male and one female per litter. We found main effects of sex, genotype and treatment as well as significant gene x treatment and sex x treatment interactions. BaP-treated female mice had shorter latencies to fall in the Rotarod test. BaP-treated high-affinity AhrbCyp1a2(-/-) mice had greater impairments in Morris water maze. Interestingly, poor-affinity AhrdCyp1a2(-/-) mice also had deficits in spatial learning and memory regardless of treatment. We believe our findings provide future directions in identifying human populations at highest risk of early life BaP exposure, because our model mimics known human variation in our genes of interest. Our studies also highlight the value of testing both males and females in all neurobehavioral studies.

Increased Health Care Costs and Opioid Use in Patients with Anxiety and Depression Undergoing Rotator Cuff Repair.

PURPOSE: To (1) quantify the prevalence of mood disorders in patients undergoing arthroscopic rotator cuff repair (RCR) by use of a large claims database and (2) compare opioid use and medical costs in the year before and the year after RCR between patients with and without comorbid mood disorders. METHODS: A large claims database was queried to identify patients who underwent arthroscopic RCR (Current Procedural Terminology code 29827) between October 2010 and December 2015. All patients were then screened for insurance claims relating to either anxiety or depression. We compared net costs and opioid use both 1 year preoperatively and 1 year postoperatively between patients with and without mood disorders by use of an analysis of covariance. RESULTS: A total of 170,329 patients (97,427 male patients [57.2%] and 72,902 female patients [42.8%]) undergoing arthroscopic RCR were identified. Of the 170,329 patients, 46,737 (27.4%) had comorbid anxiety or depression, and after adjustment for preoperative cost, sex, age, and both preoperative and postoperative opioid use, the 1-year postoperative cost was 7.05% higher for those with a preoperative mood disorder than for those without a mood disorder. In addition, opioid use both in the 180 days prior to surgery (36.7% vs 26.9%) and more than 90 days after surgery (33.0% vs 27.2%) was substantially greater in the group with comorbid depression or anxiety. CONCLUSIONS: In patients with comorbid mood disorders, opioid use and health care costs were increased both preoperatively and postoperatively. The increased cost in this patient population is estimated at $62.3 million annually. In an effort to provide high-quality, value-based care, treatment strategies should be developed to identify these patients preoperatively and provide the appropriate resources needed to improve the probability of a successful surgical outcome. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic study.

Depression and Anxiety Are Associated With Increased Health Care Costs and Opioid Use for Patients With Femoroacetabular Impingement Undergoing Hip Arthroscopy: Analysis of a Claims Database.

PURPOSE: To determine if opioid use and health care costs in the year before and following hip arthroscopy for femoroacetabular impingement (FAI) differ between those with or without depression or anxiety. METHODS: Using the Truven Health Marketscan database, FAI patients who underwent hip arthroscopy between October 2010 and December 2015 were identified (Current Procedural Terminology codes 29914 [femoroplasty], 29915 [acetabuloplasty], and/or 29916 [labral repair]). Patients were excluded if they had incomplete coverage for 1 year either before or following surgery. The number of patients with 1 or more claims related to depression or anxiety during the year before surgery was quantified (International Statistical Classification Diseases and Related Health-9 codes 296, 298, 300, 309, 311). Health care costs in the year before and following hip arthroscopy were compared between those with or without depression or anxiety. We also compared the number of patients in each group who filled a narcotic pain prescription within 180 days before surgery as well as >60 or >90 days after hip arthroscopy. RESULTS: Depression or anxiety claims were seen in 5,208/14,830 patients (35.1%) before surgery. A significantly greater proportion of those with preoperative depression or anxiety filled opioid-related prescriptions in the 6 months before surgery (36.2% vs 25.6%, P < .0001) and both >60 days (31.3% vs 24.7%, P < .0001) and >90 days after surgery (29.5% vs 23.4%, P < .0001). The group with preoperative depression or anxiety had significantly greater health care costs both before ($8,775 vs $5,674, P < .0001) and following surgery ($5,287 vs $3,908, P < .0001). CONCLUSIONS: Both before and following hip arthroscopy, opioid use and health care costs were significantly greater for FAI patients with comorbid depression or anxiety. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic study.