We tested the hypothesis that a 6-week regimen of simvastatin would attenuate skeletal muscle adaptation to low-intensity exercise. Male C57BL/6J wildtype mice were subjected to 6-weeks of voluntary wheel running or normal cage activities with or without simvastatin treatment (20 mg/kg/d, n = 7–8 per group). Adaptations in in vivo fatigue resistance were determined by a treadmill running test, and by ankle plantarflexor contractile assessment. The tibialis anterior, gastrocnemius, and plantaris muscles were evaluated for exercised-induced mitochondrial adaptations (i.e., biogenesis, function, autophagy). There was no difference in weekly wheel running distance between control and simvastatin-treated mice (P = 0.51). Trained mice had greater treadmill running distance (296%, P<0.001), and ankle plantarflexor contractile fatigue resistance (9%, P<0.05) compared to sedentary mice, independent of simvastatin treatment. At the cellular level, trained mice had greater mitochondrial biogenesis (e.g., ~2-fold greater PGC1α expression, P<0.05) and mitochondrial content (e.g., 25% greater citrate synthase activity, P<0.05), independent of simvastatin treatment. Mitochondrial autophagy-related protein contents were greater in trained mice (e.g., 40% greater Bnip3, P<0.05), independent of simvastatin treatment. However, Drp1, a marker of mitochondrial fission, was less in simvastatin treated mice, independent of exercise training, and there was a significant interaction between training and statin treatment (P<0.022) for LC3-II protein content, a marker of autophagy flux. These data indicate that whole body and skeletal muscle adaptations to endurance exercise training are attainable with simvastatin treatment, but simvastatin may have side effects on muscle mitochondrial maintenance via autophagy, which could have long-term implications on muscle health.
Background: Studies have shown preoperative opioid use to influence outcomes after various surgical procedures. Researchers have not assessed this relationship after rotator cuff repair (RCR). Hypothesis/Purpose: The purpose of this study was to assess the relationship between preoperative opioid use and outcomes after arthroscopic RCR. We hypothesized that patients prescribed higher daily averages of preoperative oral morphine equivalents (OMEs) would show increased rates of 90-day complications and 3-year revision surgery. Study Design: Cohort study; Level of evidence, 3. Methods: The MarketScan claims database was utilized to identify patients who underwent arthroscopic RCR between 2009 and 2018. We used preoperative opioid use status to divide patients into groups based on the average daily OMEs consumed in the 6 months before surgery: opioid-naïve, <1, 1-<5, 5-<10, and ≥10 OMEs per day. We retrieved 90-day complication and 3-year revision surgery rates. Opioid use groups were then compared with binomial logistic regression and generalized linear models. Results: We identified 214,283 patients. Of those patients, 50.7% did not receive any preoperative opioids, while 7.7%, 26.8%, 6.3%, and 8.6% received <1, 1-<5, 5-<10, and ≥10 OMEs per day over a 6-month time period, respectively. Complications increased with increasing preoperative OMEs. Multivariate analysis revealed that any patient using ≥1 OME per day had increased rates of 3-year revision surgery, reoperations, and infections. Specifically, patients averaging ≥10 OMEs per day showed a 103% (odds ratio, 2.03 [95% CI, 1.62-2.54]; P < .001) increase in the odds of revision surgery compared with opioid-naïve patients. Rates of hospital admissions and postoperative emergency department encounters were higher in all opioid use groups. Adjusted differences in 6-month preoperative and 3-month postoperative health care costs were seen in the opioid use groups compared with opioid-naïve patients, ranging from US$1307 to US$5820 ( P < .001). Conclusion: Preoperative opioid use was a risk factor for complications and revision surgery after arthroscopic RCR. We also observed a dose-dependent response between opioid use and postoperative complications.
Introduction Pain control following a total shoulder arthroplasty (TSA) is multifactorial. The current standard of care includes the utilization of a multimodal analgesic approach including breakthrough prescription opioid medication in an effort to provide postoperative analgesia. While this original opioid prescription is sufficient for the majority of patients, some go on to require prolonged opioid use. Our study investigated patient risk factors associated with opioid refill postsurgery. Methods The Truven Marketscan® database was queried for all patients who underwent either a primary anatomic TSA or primary reverse TSA from 2010 to 2017. Opioid data were collected using National Drug Codes (NDC) from outpatient pharmacy claims. Only opioid-naïve patients were included. Patients were then grouped into 1 of 3 cohorts based on postoperative opioid use: 1) Patients with no additional refills, 2) patients with a minimum of one additional refill up through 6 months postoperatively, and 3) patients with additional refills and continued opioid use past 6 months. Results Of the total of 17,706 opioid-naïve patients that underwent a TSA, 10,882 (61.5%) did not have any additional refills, 4473 (25.3%) required an additional prescription within 6 months after surgery, and 2351 (13.3%) had prolonged opioid use beyond 6 months postoperatively. A dose-dependent relationship was identified between initial opioid prescription quantity and risk for refill and prolonged use. The prolonged use group was prescribed an equivalent of 20.0 more 5 mg oxycodone pills than the no refill group and 12.7 more than the refill group ( P < .001). On multivariate analysis, younger age, female gender, and tobacco use, along with the comorbidities of coronary artery disease, clinical depression, diabetes, and rheumatic disease were all found to be predictive factors of prolonged opioid use. Discussion The dose-dependent relationship observed between original opioid prescription data and number of additional refills needed, suggests that initially overprescribing opioids may lead to prolonged dependency. This study also identified several independent risk factors for prolonged opioid use, including younger age, depression, and tobacco use. This study will hopefully help recognize high-risk patient populations and serve as the foundation for future studies into opioid prescription standardization and preoperative opioid education.
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