Association Between Naloxone Coprescription Mandates and Postoperative Outcomes.

INTRODUCTION: The opioid epidemic is a public health issue in the United States. The objective of this study was to evaluate the association between naloxone coprescription mandates and postoperative outcomes. BACKGROUND: Data on naloxone coprescription mandates show mixed evidence for fatal overdoses in the broader population. How these mandates have impacted surgical patients has not been fully explored. METHODS: Healthcare claims data were used to identify all patients undergoing 1 of 50 common procedures between January 1, 2004, and June 30, 2019, and categorized as high risk for opioid overdose. The primary outcomes were an emergency department visit or hospital admission within 30 postoperative days. To reduce confounding, the association between this outcome and the implementation of naloxone coprescription mandates was estimated using a difference-in-differences approach. RESULTS: The study included 429,878 surgical patients with an average age of 54.8 years (SD=15.9 years) and with 257,728 females (60.0%). There was no significant association between naloxone prescribing mandates and the primary outcomes. After adjustment for potential confounders, the incidence of hospital admission was 3.26% after implementation of a naloxone coprescription mandate compared with 3.33% before (difference change: -0.08%, 95% CI: -0.44% to 0.29%, P =0.68). The incidence of an emergency department visit was 7.06% after implementation of a naloxone coprescription mandate compared with 7.73% before (difference: -0.67%, 95% CI: -1.39% to 0.05%, P =0.07). These results were robust to a variety of sensitivity and subgroup analyses. CONCLUSIONS: Naloxone coprescription mandates were not associated with a statistically or clinically significant change in emergency department visits or hospital admissions within 30 postoperative days.

Association Between State Limits on Opioid Prescribing and the Incidence of Persistent Postoperative Opioid Use Among Surgical Patients.

OBJECTIVE: To examine whether laws limiting opioid prescribing have been associated with reductions in the incidence of persistent postoperative opioid use. SUMMARY OF BACKGROUND DATA: In an effort to address the opioid epidemic, 26 states (as of 2018) have passed laws limiting opioid prescribing for acute pain. However, it is unknown whether these laws have achieved their reduced the risk of persistent postoperative opioid use. METHODS: We identified 957,639 privately insured patients undergoing one of 10 procedures between January 1, 2004 and September 30, 2018. We then estimated the association between persistent postoperative opioid use, defined as having filled ≥10 prescriptions or ≥120 days supply of opioids during postoperative days 91-365, and whether opioid prescribing limits were in effect on the day of surgery. States were classified as having: no limits, a limit of ≤7 days supply, or a limit of >7 days supply. The regression models adjusted for observable confounders such as patient comorbidities and also utilized a difference-in-differences approach, which relied on variation in state laws over time, to further minimize confounding. RESULTS: The adjusted incidence of persistent postoperative opioid use was 3.5% (95%CI 3.3%-3.7%) for patients facing a limit of ≤7 days supply, compared with 3.3% (95%CI 3.3%-3.3%) for patients facing no prescribing limits ( P = 0.13 for difference compared to no prescribing limits) and 3.4%, (95%CI 3.2%-3.6%) for patients facing a limit of >7 days supply ( P = 0.43 for difference compared to no prescribing limits). CONCLUSIONS: Laws limiting opioid prescriptions were not associated with subsequent reductions in persistent postoperative opioid use.

Association Between Changes in Postoperative Opioid Utilization and Long-Term Health Care Spending Among Surgical Patients With Chronic Opioid Utilization.

BACKGROUND: There is growing interest in identifying and developing interventions aimed at reducing the risk of increased, long-term opioid use among surgical patients. While understanding how these interventions impact health care spending has important policy implications and may facilitate the widespread adoption of these interventions, the extent to which they may impact health care spending among surgical patients who utilize opioids chronically is unknown. METHODS: This study was a retrospective analysis of administrative health care claims data for privately insured patients. We identified 53,847 patients undergoing 1 of 10 procedures between January 1, 2004, and September 30, 2018 (total knee arthroplasty, total hip arthroplasty, laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, cesarean delivery, functional endoscopic sinus surgery, transurethral resection of the prostate, or simple mastectomy) who had chronic opioid utilization (≥10 prescriptions or ≥120-day supply in the year before surgery). Patients were classified into 3 groups based on differences in opioid utilization, measured in average daily oral morphine milligram equivalents (MMEs), between the first postoperative year and the year before surgery: "stable" (<20% change), "increasing" (≥20% increase), or "decreasing" (≥20% decrease). We then examined the association between these 3 groups and health care spending during the first postoperative year, using a multivariable regression to adjust for observable confounders, such as patient demographics, medical comorbidities, and preoperative health care utilization. RESULTS: The average age of the sample was 62.0 (standard deviation [SD] 13.1) years, and there were 35,715 (66.3%) women. Based on the change in average daily MME between the first postoperative year and the year before surgery, 16,961 (31.5%) patients were classified as "stable," 15,463 (28.7%) were classified as "increasing," and 21,423 (39.8%) patients were classified as "decreasing." After adjusting for potential confounders, "increasing" patients had higher health care spending ($37,437) than "stable" patients ($31,061), a difference that was statistically significant ($6377; 95% confidence interval [CI], $5669-$7084; P < .001), while "decreasing" patients had lower health care spending ($29,990), a difference (-$1070) that was also statistically significant (95% CI, -$1679 to -$462; P = .001). These results were generally consistent across an array of subgroup and sensitivity analyses. CONCLUSIONS: Among patients with chronic opioid utilization before surgery, subsequent increases in opioid utilization during the first postoperative year were associated with increased health care spending during that timeframe, while subsequent decreases in opioid utilization were associated with decreased health care spending.

Preoperative Opioid Utilization Patterns and Postoperative Opioid Utilization: A Retrospective Cohort Study.

BACKGROUND: Among chronic opioid users, the association between decreasing or increasing preoperative opioid utilization and postoperative outcomes is unknown. The authors hypothesized that decreasing utilization would be associated with improved outcomes and increasing utilization with worsened outcomes. METHODS: Using commercial insurance claims, the authors identified 57,019 chronic opioid users (10 or more prescriptions or 120 or more days supplied during the preoperative year), age 18 to 89 yr, undergoing one of 10 surgeries between 2004 and 2018. Patients with a 20% or greater decrease or increase in opioid utilization between preoperative days 7 to 90 and 91 to 365 were compared to patients with less than 20% change (stable utilization). The primary outcome was opioid utilization during postoperative days 91 to 365. Secondary outcomes included alternative measures of postoperative opioid utilization (filling a minimum number of prescriptions during this period), postoperative adverse events, and healthcare utilization. RESULTS: The average age was 63 ± 13 yr, with 38,045 (66.7%) female patients. Preoperative opioid utilization was decreasing for 12,347 (21.7%) patients, increasing for 21,330 (37.4%) patients, and stable for 23,342 (40.9%) patients. Patients with decreasing utilization were slightly less likely to fill an opioid prescription during postoperative days 91 to 365 compared to stable patients (89.2% vs. 96.4%; odds ratio, 0.323; 95% CI, 0.296 to 0.352; P < 0.001), though the average daily doses were similar among patients who continued to utilize opioids during this timeframe (46.7 vs. 46.5 morphine milligram equivalents; difference, 0.2; 95% CI, -0.8 to 1.2; P = 0.684). Of patients with increasing utilization, 93.6% filled opioid prescriptions during this period (odds ratio, 0.57; 95% CI, 0.52 to 0.62; P < 0.001), with slightly lower average daily doses (44.3 morphine milligram equivalents; difference, -2.2; 95% CI, -3.1 to -1.3; P < 0.001). Except for alternative measures of persistent postoperative opioid utilization, there were no clinically significant differences for the secondary outcomes. CONCLUSIONS: Changes in preoperative opioid utilization were not associated with clinically significant differences for several postoperative outcomes including postoperative opioid utilization.

Association Between Preoperative Benzodiazepine Use and Postoperative Opioid Use and Health Care Costs.

Importance: The association between preoperative benzodiazepine use and long-term postoperative outcomes is not well understood. Objective: To characterize the association between preoperative benzodiazepine use and postoperative opioid use and health care costs. Design, Setting, and Participants: In this cohort study, retrospective analysis of private health insurance claims data on 946 561 opioid-naive patients (no opioid prescriptions filled in the year before surgery) throughout the US was conducted. Patients underwent 1 of 11 common surgical procedures between January 1, 2004, and December 31, 2016; data analysis was performed January 9, 2020. Exposures: Benzodiazepine use, defined as long term (≥10 prescriptions filled or ≥120 days supplied in the year before surgery) or intermittent (any use not meeting the criteria for long term). Main Outcomes and Measures: The primary outcome was opioid use 91 to 365 days after surgery. Secondary outcomes included opioid use 0 to 90 days after surgery and health care costs 0 to 30 days after surgery. Results: In this sample of 946 561 patients, the mean age was 59.8 years (range, 18-89 years); 615 065 were women (65.0%). Of these, 23 484 patients (2.5%) met the criteria for long-term preoperative benzodiazepine use and 47 669 patients (5.0%) met the criteria for intermittent use. After adjusting for confounders, long-term (odds ratio [OR], 1.59; 95% CI, 1.54-1.65; P < .001) and intermittent (OR, 1.47; 95% CI, 1.44-1.51; P < .001) benzodiazepine use were associated with an increased probability of any opioid use during postoperative days 91 to 365. For patients who used opioids in postoperative days 91 to 365, long-term benzodiazepine use was associated with a 44% increase in opioid dose (additional 0.6 mean daily morphine milligram equivalents [MMEs]; 95% CI, 0.3-0.8 MMEs; P < .001), although intermittent benzodiazepine use was not significantly different (0.0 average daily MMEs; 95% CI, -0.2 to 0.2 MMEs; P = .65). Preoperative benzodiazepine use was also associated with increased opioid use in postoperative days 0 to 90 for both long-term (32% increase, additional 1.9 average daily MMEs; 95% CI, 1.6-2.1 MMEs; P < .001) and intermittent (9% increase, additional 0.5 average daily MMEs; 95% CI, 0.4-0.6 MMEs; P < .001) users. Intermittent benzodiazepine use was associated with an increase in 30-day health care costs ($1155; 95% CI, $938-$1372; P < .001), while no significant difference was observed for long-term benzodiazepine use. Conclusions and Relevance: The findings of this study suggest that, among opioid-naive patients, preoperative benzodiazepine use may be associated with an increased risk of developing long-term opioid use and increased opioid dosages postoperatively, and also may be associated with increased health care costs.

Association of Overlapping Surgery With Perioperative Outcomes.

Importance: Overlapping surgery, in which more than 1 procedure performed by the same primary surgeon is scheduled so the start time of one procedure overlaps with the end time of another, is of concern because of potential adverse outcomes. Objective: To determine the association between overlapping surgery and mortality, complications, and length of surgery. Design, Setting, and Participants: Retrospective cohort study of 66 430 operations in patients aged 18 to 90 years undergoing total knee or hip arthroplasty; spine surgery; coronary artery bypass graft (CABG) surgery; and craniotomy at 8 centers between January 1, 2010, and May 31, 2018. Patients were followed up until discharge. Exposures: Overlapping surgery (≥2 operations performed by the same surgeon in which ≥1 hour of 1 case, or the entire case for those <1 hour, occurs when another procedure is being performed). Main Outcomes and Measures: Primary outcomes were in-hospital mortality or complications (major: thromboembolic event, pneumonia, sepsis, stroke, or myocardial infarction; minor: urinary tract or surgical site infection) and surgery duration. Results: The final sample consisted of 66 430 operations (mean patient age, 59 [SD, 15] years; 31 915 women [48%]), of which 8224 (12%) were overlapping. After adjusting for confounders, overlapping surgery was not associated with a significant difference in in-hospital mortality (1.9% overlapping vs 1.6% nonoverlapping; difference, 0.3% [95% CI, -0.2% to 0.7%]; P = .21) or risk of complications (12.8% overlapping vs 11.8% nonoverlapping; difference, 0.9% [95% CI, -0.1% to 1.9%]; P = .08). Overlapping surgery was associated with increased surgery length (204 vs 173 minutes; difference, 30 minutes [95% CI, 24 to 37 minutes]; P < .001). Overlapping surgery was significantly associated with increased mortality and increased complications among patients having a high preoperative predicted risk for mortality and complications, compared with low-risk patients (mortality: 5.8% vs 4.7%; difference, 1.2% [95% CI, 0.1% to 2.2%]; P = .03; complications: 29.2% vs 27.0%; difference, 2.3% [95% CI, 0.3% to 4.3%]; P = .03). Conclusions and Relevance: Among adults undergoing common operations, overlapping surgery was not significantly associated with differences in in-hospital mortality or postoperative complication rates but was significantly associated with increased surgery length. Further research is needed to understand the association of overlapping surgery with these outcomes among specific patient subgroups.

Association of Early Physical Therapy With Long-term Opioid Use Among Opioid-Naive Patients With Musculoskeletal Pain.

Importance: Nonpharmacologic methods of reducing the risk of new chronic opioid use among patients with musculoskeletal pain are important given the burden of the opioid epidemic in the United States. Objective: To determine the association between early physical therapy and subsequent opioid use in patients with new musculoskeletal pain diagnosis. Design, Setting, and Participants: This cross-sectional analysis of health care insurance claims data between January 1, 2007, and December 31, 2015, included privately insured patients who presented with musculoskeletal pain to an outpatient physician office or an emergency department at various US facilities from January 1, 2008, to December 31, 2014. The sample comprised 88 985 opioid-naive patients aged 18 to 64 years with a new diagnosis of musculoskeletal shoulder, neck, knee, or low back pain. The data set (obtained from the IBM MarketScan Commercial database) included person-level International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis codes, Current Procedural Terminology codes, and date of service as well as pharmaceutical information (National Drug Code, generic name, dose, and number of days supplied). Early physical therapy was defined as at least 1 session received within 90 days of the index date, the earliest date a relevant diagnosis was provided. Data analysis was conducted from March 1, 2018, to May 18, 2018. Main Outcomes and Measures: Opioid use between 91 and 365 days after the index date. Results: Of the 88 985 patients included, 51 351 (57.7%) were male and 37 634 (42.3%) were female with a mean (SD) age of 46 (11.0) years. Among these patients, 26 096 (29.3%) received early physical therapy. After adjusting for potential confounders, early physical therapy was associated with a statistically significant reduction in the incidence of any opioid use between 91 and 365 days after the index date for patients with shoulder pain (odds ratio [OR], 0.85; 95% CI, 0.77-0.95; P = .003), neck pain (OR, 0.92; 95% CI, 0.85-0.99; P = .03), knee pain (OR, 0.84; 95% CI, 0.77-0.91; P < .001), and low back pain (OR, 0.93; 95% CI, 0.88-0.98; P = .004). For patients who did use opioids, early physical therapy was associated with an approximately 10% statistically significant reduction in the amount of opioid use, measured in oral morphine milligram equivalents, for shoulder pain (-9.7%; 95% CI, -18.5% to -0.8%; P = .03), knee pain (-10.3%; 95% CI, -17.8% to -2.7%; P = .007), and low back pain (-5.1%; 95% CI, -10.2% to 0.0%; P = .046), but not for neck pain (-3.8%; 95% CI, -10.8% to 3.3%; P = .30). Conclusions and Relevance: Early physical therapy appears to be associated with subsequent reductions in longer-term opioid use and lower-intensity opioid use for all of the musculoskeletal pain regions examined.

Independent category and spatial encoding in parietal cortex.

The posterior parietal cortex plays a central role in spatial functions, such as spatial attention and saccadic eye movements. However, recent work has increasingly focused on the role of parietal cortex in encoding nonspatial cognitive factors such as visual categories, learned stimulus associations, and task rules. The relationship between spatial encoding and nonspatial cognitive signals in parietal cortex, and whether cognitive signals are robustly encoded in the presence of strong spatial neuronal responses, is unknown. We directly compared nonspatial cognitive and spatial encoding in the lateral intraparietal (LIP) area by training monkeys to perform a visual categorization task during which they made saccades toward or away from LIP response fields (RFs). Here we show that strong saccade-related responses minimally influence robustly encoded category signals in LIP. This suggests that cognitive and spatial signals are encoded independently in LIP and underscores the role of parietal cortex in nonspatial cognitive functions.