Access to care for patients with chronic pain receiving prescription opioids, cannabis, or other treatments.

Changes in chronic noncancer pain treatment have led to decreases in prescribing of opioids and increases in the availability of medical cannabis, despite its federal prohibition. Patients may face barriers to establishing new care with a physician based on use of these treatments. We compared physician willingness to accept patients based on prescription opioid, cannabis, or other pain treatment use. This study of 36 states and Washington, DC, with active medical cannabis programs surveyed physicians who treat patients with chronic noncancer pain between July 13 and August 4, 2023. Of 1000 physician respondents (34.5% female, 63.2% White, 78.1% primary care), 852 reported accepting new patients with chronic pain. Among those accepting new patients with chronic pain, more physicians reported that they would not accept new patients taking prescription opioids (20.0%) or cannabis (12.7%) than those taking nonopioid prescription analgesics (0.1%). In contrast, 68.1% reported willingness to accept new patients using prescribed opioids on a daily basis. For cannabis, physicians were more likely to accept new patients accessing cannabis through medical programs (81.6%) than from other sources (60.2%). Access to care for persons with chronic noncancer pain appears to be the most restricted among those taking prescription opioids, although patients taking cannabis may also encounter reduced access.

Epidemiology of Opioid Prescribing After Discharge From Surgical Procedures Among Adults.

Importance: Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing, data are needed to define the procedures and populations for which most opioid prescribing occurs. Objective: To identify the surgical procedures accounting for the highest proportion of opioids dispensed to adults after surgery in the United States. Design, Setting, and Participants: This cross-sectional analysis of the 2020-2021 Merative MarketScan Commercial and Multi-State Databases, which capture medical and pharmacy claims for 23 million and 14 million annual privately insured patients and Medicaid beneficiaries, respectively, included surgical procedures for individuals aged 18 to 64 years with a discharge date between December 1, 2020, and November 30, 2021. Procedures were identified using a novel crosswalk between 3664 Current Procedural Terminology codes and 1082 procedure types. Data analysis was conducted from November to December 2023. Main Outcomes and Measures: The total amount of opioids dispensed within 3 days of discharge from surgery across all procedures in the sample, as measured in morphine milligram equivalents (MMEs), was calculated. The primary outcome was the proportion of total MMEs attributable to each procedure type, calculated separately among procedures for individuals aged 18 to 44 years and those aged 45 to 64 years. Results: Among 1 040 934 surgical procedures performed (mean [SD] age of patients, 45.5 [13.3] years; 663 609 [63.7%] female patients), 457 016 (43.9%) occurred among individuals aged 18 to 44 years and 583 918 (56.1%) among individuals aged 45 to 64 years. Opioid prescriptions were dispensed for 503 058 procedures (48.3%). Among individuals aged 18 to 44 years, cesarean delivery accounted for the highest proportion of total MMEs dispensed after surgery (19.4% [11 418 658 of 58 825 364 MMEs]). Among individuals aged 45 to 64 years, 4 of the top 5 procedures were common orthopedic procedures (eg, arthroplasty of knee, 9.7% of total MMEs [5 885 305 of 60 591 564 MMEs]; arthroscopy of knee, 6.5% [3 912 616 MMEs]). Conclusions and Relevance: In this cross-sectional study of the distribution of postoperative opioid prescribing in the United States, a small number of common procedures accounted for a large proportion of MMEs dispensed after surgery. These findings suggest that the optimal design and targeting of surgical opioid stewardship initiatives in adults undergoing surgery should focus on the procedures that account for the most opioid dispensed following surgery over the life span, such as childbirth and orthopedic procedures. Going forward, systems that provide periodic surveillance of opioid prescribing and associated harms can direct quality improvement initiatives to reduce opioid-related morbidity and mortality.

Pediatric Surgical Opioid Prescribing by Procedure, 2020-2021.

BACKGROUND AND OBJECTIVES: Surgery is one of the most common indications for opioid prescribing to pediatric patients. We identified which procedures account for the most pediatric surgical opioid prescribing. METHODS: We conducted a cross-sectional analysis of commercial and Medicaid claims in the Merative MarketScan Commercial and Multi-State Medicaid Databases. Analyses included surgical procedures for patients aged 0 to 21 years from December 1, 2020, to November 30, 2021. Procedures were identified using a novel crosswalk between 3664 procedure codes and 1082 procedure types. For each procedure type in the crosswalk, we calculated the total amount of opioids in prescriptions dispensed within 3 days of discharge from surgery, as measured in morphine milligram equivalents (MMEs). We then calculated the share of all MMEs accounted for by each procedure type. We conducted analyses separately among patients aged 0 to 11 and 12 to 21 years. RESULTS: Among 107 597 procedures for patients aged 0 to 11 years, the top 3 procedures accounted for 59.1% of MMEs in opioid prescriptions dispensed after surgery: Tonsillectomy and/or adenoidectomy (50.3%), open treatment of upper extremity fracture (5.3%), and removal of deep implants (3.5%). Among 111 406 procedures for patients aged 12 to 21 years, the top 3 procedures accounted for 33.1% of MMEs: Tonsillectomy and/or adenoidectomy (12.7%), knee arthroscopy (12.6%), and cesarean delivery (7.8%). CONCLUSIONS: Pediatric surgical opioid prescribing is concentrated among a small number of procedures. Targeting these procedures in opioid stewardship initiatives could help minimize the risks of opioid prescribing while maintaining effective postoperative pain control.

Worth the Risk? Standardized Screening to Identify Substance Use Among Patients Prior to Surgery.

OBJECTIVE: We sought to compare identification of unhealthy substance use before surgery using The Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS), a standardized 4-item instrument, versus routine clinical documentation in the electronic medical record (EHR). SUMMARY BACKGROUND DATA: Over 20% of individuals exhibit unhealthy substance use before elective surgery. Routine EHR documentation is often based on non-standard questions that may not fully capture the extent of substance use and is subject to bias. In contrast, brief standardized screening could provide a more efficient and systematic approach. METHODS: We conducted a cross-sectional study among adults (≥18 y) at a preoperative clinic from August to September, 2021. Positive screens for unhealthy substances by TAPS were compared to data from the EHR. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were reported. Receiver operating characteristic curves (ROCs) were used to assess diagnostic ability. Multivariable logistic regression was used to estimate the predictors of positive screens by TAPS. RESULTS: The cohort included 240 surgical patients. TAPS screening identified significantly more positive screens than EHR documentation (43.3% vs. 14.2%). Patients with unhealthy substance use were younger (50.8 vs. 56.7 y; P=0.003), and TAPS revealed alcohol misuse in 30.8% of cases, contrasting with 0% in clinician documentation (P<0.001). Of the 104 TAPS-positive patients, 69.2% were missed by EHR documentation. Sensitivity (31%) and accuracy (AUC=0.65) of clinician documentation for any unhealthy substance use were lower compared to TAPS. CONCLUSION: Standardized TAPS screening detected preoperative unhealthy substance use more frequently than routine clinician documentation, emphasizing the need for integrating standardized measures into surgical practice to ensure safer perioperative care and outcomes.

Medicaid Insurance Predicts Increased Postoperative Care Encounters Among Patients on Long-Term Opioid Therapy.

OBJECTIVE: This study examined the association between insurance type and postoperative unplanned care encounters among patients on long-term opioid therapy prior to surgery. SUMMARY BACKGROUND DATA: Preoperative long-term opioid therapy is associated with unique risks and poorer outcomes following surgery. To date, the extent to which insurance coverage influences postoperative outcomes in this population remains unclear. METHODS: Among individuals receiving a supply of greater than 120 total days or at least 10 opioid prescriptions in the year prior to surgery, we examined patients with Medicaid or private insurance who underwent abdominopelvic surgery from 2017 to 2021 across 70 hospitals in the state of Michigan. The primary outcome was unplanned care encounters, defined as an emergency department visit or unplanned readmission within 30 days of discharge from surgery. Multivariable logistic regression was used to assess the likelihood of acute care events with insurance type as the primary covariate of interest. RESULTS: Among 1212 patients on long-term opioid therapy prior to surgery, 45.6% (n = 553) had Medicaid insurance. Overall, one in eight (n=151) patients met criteria for a postoperative unplanned care encounter within 30 days. The probability of an unplanned encounter was 4.5 percentage points higher among patients with Medicaid insurance compared to private insurance (95% CI: 0.5%, 8.4%). CONCLUSIONS: Among patients on preoperative long-term opioid therapy, unplanned care encounters were higher among patients with Medicaid when compared to private insurance. While this is likely multifactorial, differences by insurance status may point to disparities in underlying social determinants of health and suggest the need for postoperative care pathways that address these gaps.

The Association of Preoperative Opioid Use with Post-Discharge Outcomes: A Cohort Study of the Michigan Surgical Quality Collaborative.

OBJECTIVE: To examine the association of prescription opioid fills over the year prior to surgery with postoperative outcomes. BACKGROUND: Nearly one third of patients report opioid use in the year preceding surgery, yet an understanding of how opioid exposure influences patient-reported outcomes after surgery remains incomplete. Therefore, this study was designed to test the hypothesis that preoperative opioid exposure may impede recovery in the postoperative period. METHODS: This retrospective cohort study used a statewide clinical registry from 70 hospitals linked to opioid fulfillment data from the state's prescription drug monitoring program to categorize patients' preoperative opioid exposure as none (naïve), minimal, intermittent, or chronic. Outcomes were patient-reported pain intensity (primary), as well as 30-day clinical and patient-reported outcomes (secondary). RESULTS: Compared to opioid-naïve patients, opioid exposure was associated with higher reported pain scores at 30 days after surgery. Predicted probabilities was higher among the opioid exposed versus naive group for reporting moderate pain (43.5% [95% CI 42.6 - 44.4%] vs 39.3% [95% CI 38.5 - 40.1%]) and severe pain (13.% [95% CI 12.5 - 14.0%] vs 10.0% [95% CI 9.5 - 10.5%]), and increasing probability was associated increased opioid exposure for both outcomes. Clinical outcomes (incidence of ED visits, readmissions, and reoperation within 30-days) and patient-reported outcomes (reported satisfaction, regret, and quality of life) were also worse with increasing preoperative opioid exposure for most outcomes. CONCLUSIONS: This study is the first to examine the effect of presurgical opioid exposure on both clinical and non-clinical outcomes in a broad cohort of patients, and shows that exposure is associated with worse postsurgical outcomes. A key question to be addressed is whether and to what extent opioid tapering before surgery mitigates these risks after surgery.

Opioid Consumption After Discharge From Total Knee and Hip Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Pain is challenging after recovery from total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures, and patients often receive prescription opioids. However, opioid consumption by patients remains unclear, and unused opioids may lead to risks including misuse and diversion. The objective of this systematic review and meta-analysis was to compare prescription size versus patient-reported consumption of opioids after discharge following TKA and THA. METHODS: PubMed and Embase were systematically searched for publications published between 2015 and 2022 on patient-reported consumption of opioids after TKA and THA. The primary outcome was opioid use in oxycodone 5-mg equivalents. Team members independently reviewed studies for screening, inclusion, data extraction, and risk of bias. RESULTS: Among the 17 included studies (15 TKA and 11 THA), discharge opioid prescribing exceeded consumption for both TKA (88.4 versus 65.0 pills at 6 weeks) and THA (64.0 versus 29.8 pills at 12 weeks). For both TKA and THA, the range of opioids prescribed varied significantly, by 1.6-fold for TKA and 2.8-fold for THA. Most studies reported pain outcomes (89%) and the use of nonopioid medications (72%). Of the 4 studies offering prescribing recommendations, the amounts ranged from 50 to 104 pills for TKA and 30 to 45 pills for THA. CONCLUSIONS: Opioid prescribing exceeds the amount consumed following TKA and THA. These findings serve as a call to action to tailor prescribing guidelines to how much patients actually consume while emphasizing the use of nonopioid medications to better optimize recovery from surgery.

Comparison of methods to identify individuals prescribed opioid analgesics for pain.

INTRODUCTION: While identifying opioid prescriptions in claims data has been instrumental in informing best practises, studies have not evaluated whether certain methods of identifying opioid prescriptions yield better results. We compared three common approaches to identify opioid prescriptions in large, nationally representative databases. METHODS: We performed a retrospective cohort study, analyzing MarketScan, Optum, and Medicare claims to compare three methods of opioid classification: claims database-specific classifications, National Drug Codes (NDC) from the Centers for Disease Control and Prevention (CDC), or NDC from Overdose Prevention Engagement Network (OPEN). The primary outcome was discrimination by area under the curve (AUC), with secondary outcomes including the number of opioid prescriptions identified by experts but not identified by each method. RESULTS: All methods had high discrimination (AUC>0.99). For MarketScan (n=70,162,157), prescriptions that were not identified totalled 42,068 (0.06%) for the CDC list, 2,067,613 (2.9%) for database-specific categories, and 0 (0%) for the OPEN list. For Optum (n=61,554,852), opioid prescriptions not identified totalled 9,774 (0.02%) for the CDC list, 83,700 (0.14%) for database-specific categories, and 0 (0%) for the OPEN list. In Medicare claims (n=92,781,299), the number of opioid prescriptions not identified totalled 8,694 (0.01%) for the CDC file and 0 (0%) for the OPEN list. DISCUSSION: This analysis found that identifying opioid prescriptions using methods from CDC and OPEN were similar and superior to prespecified database-specific categories. Overall, this study shows the importance of carefully selecting the approach to identify opioid prescriptions when investigating claims data.

Variation in Intraoperative Opioid Administration by Patient, Clinician, and Hospital Contribution.

Importance: The opioid crisis has led to scrutiny of opioid exposures before and after surgical procedures. However, the extent of intraoperative opioid variation and the sources and contributing factors associated with it are unclear. Objective: To analyze attributable variance of intraoperative opioid administration for patient-, clinician-, and hospital-level factors across surgical and analgesic categories. Design, Setting, and Participants: This cohort study was conducted using electronic health record data collected from a national quality collaborative database. The cohort consisted of 1 011 268 surgical procedures at 46 hospitals across the US involving 2911 anesthesiologists, 2291 surgeons, and 8 surgical and 4 analgesic categories. Patients without ambulatory opioid prescriptions or use history undergoing an elective surgical procedure between January 1, 2014, and September 11, 2020, were included. Data were analyzed from January 2022 to July 2023. Main Outcomes and Measures: The rate of intraoperative opioid administration as a continuous measure of oral morphine equivalents (OMEs) normalized to patient weight and case duration was assessed. Attributable variance was estimated in a hierarchical structure using patient, clinician, and hospital levels and adjusted intraclass correlations (ICCs). Results: Among 1 011 268 surgical procedures (mean [SD] age of patients, 55.9 [16.2] years; 604 057 surgical procedures among females [59.7%]), the mean (SD) rate of intraoperative opioid administration was 0.3 [0.2] OME/kg/h. Together, clinician and hospital levels contributed to 20% or more of variability in intraoperative opioid administration across all analgesic and surgical categories (adjusting for surgical or analgesic category, ICCs ranged from 0.57-0.79 for the patient, 0.04-0.22 for the anesthesiologist, and 0.09-0.26 for the hospital, with the lowest ICC combination 0.21 for anesthesiologist and hosptial [0.12 for the anesthesiologist and 0.09 for the hospital for opioid only]). Comparing the 95th and fifth percentiles of opioid administration, variation was 3.3-fold among anesthesiologists (surgical category range, 2.7-fold to 7.7-fold), 4.3-fold among surgeons (surgical category range, 3.4-fold to 8.0-fold), and 2.2-fold among hospitals (surgical category range, 2.2-fold to 4.3-fold). When adjusted for patient and surgical characteristics, mean (square error mean) administration was highest for cardiac surgical procedures (0.54 [0.56-0.52 OME/kg/h]) and lowest for orthopedic knee surgical procedures (0.19 [0.17-0.21 OME/kg/h]). Peripheral and neuraxial analgesic techniques were associated with reduced administration in orthopedic hip (51.6% [95% CI, 51.4%-51.8%] and 60.7% [95% CI, 60.5%-60.9%] reductions, respectively) and knee (48.3% [95% CI, 48.0%-48.5%] and 60.9% [95% CI, 60.7%-61.1%] reductions, respectively) surgical procedures, but reduction was less substantial in other surgical categories (mean [SD] reduction, 13.3% [8.8%] for peripheral and 17.6% [9.9%] for neuraxial techniques). Conclusions and Relevance: In this cohort study, clinician-, hospital-, and patient-level factors had important contributions to substantial variation of opioid administrations during surgical procedures. These findings suggest the need for a broadened focus across multiple factors when developing and implementing opioid-reducing strategies in collaborative quality-improvement programs.

The Association of Cannabis Use After Discharge From Surgery With Opioid Consumption and Patient-reported Outcomes.

OBJECTIVE: To compare outcomes of patients using versus not using cannabis as a treatment for pain after discharge from surgery. BACKGROUND: Cannabis is increasingly available and is often taken by patients to relieve pain. However, it is unclear whether cannabis use for pain after surgery impacts opioid consumption and postoperative outcomes. METHODS: Using Michigan Surgical Quality Collaborative registry data at 69 hospitals, we analyzed a cohort of patients undergoing 16 procedure types between January 1, 2021, and October 31, 2021. The key exposure was cannabis use for pain after surgery. Outcomes included postdischarge opioid consumption (primary) and patient-reported outcomes of pain, satisfaction, quality of life, and regret to undergo surgery (secondary). RESULTS: Of 11,314 included patients (58% females, mean age: 55.1 years), 581 (5.1%) reported using cannabis to treat pain after surgery. In adjusted models, patients who used cannabis consumed an additional 1.0 (95% CI: 0.4-1.5) opioid pills after surgery. Patients who used cannabis were more likely to report moderate-to-severe surgical site pain at 1 week (adjusted odds ratio: 1.7, 95% CIL 1.4-2.1) and 1 month (adjusted odds ratio: 2.1, 95% CI: 1.7-2.7) after surgery. Patients who used cannabis were less likely to endorse high satisfaction (72.1% vs 82.6%), best quality of life (46.7% vs 63.0%), and no regret (87.6% vs 92.7%) (all P < 0.001). CONCLUSIONS: Patient-reported cannabis use, to treat postoperative pain, was associated with increased opioid consumption after discharge from surgery that was of clinically insignificant amounts, but worse pain and other postoperative patient-reported outcomes.

Cohort study of new off-label gabapentin prescribing in chronic opioid users.

INTRODUCTION: Gabapentin is commonly prescribed as an off-label adjunct to opioids because of its safer risk profile. Recent evidence has shown an increased risk of mortality when coprescribed with opioids. Therefore, we aimed to evaluate whether the addition of off-label gabapentin in patients with chronic opioid use is associated with a reduction in opioid dosage. METHODS: We performed a retrospective cohort study of patients with chronic opioid use with a new off-label gabapentin prescription (2010-2019). Our primary outcome of interest was a reduction in opioid dosage measured via oral morphine equivalents (OME) per day after the addition of a new off-label gabapentin prescription. RESULTS: In our cohort of 172,607 patients, a new off-label gabapentin prescription was associated with a decrease in opioid dosage in 67,016 patients (38.8%) (median OME/day reduction:13.8), with no change in opioid dosage in 24,468 patients (14.2%), and an increase in opioid dosage in 81,123 patients (47.0%) (median OME/day increase: 14.3). A history of substance/alcohol use disorders was associated with a decrease in opioid dosage after the addition of a new off-label gabapentin (aOR 1.20, 95% CI 1.16 to 1.23). A history of pain disorders was associated with a decrease in opioid dosage after the initiation of a new gabapentin prescription including arthritis (aOR 1.12, 95% CI 1.09 to 1.15), back pain (aOR 1.10, 95% CI 1.07 to 1.12), and other pain conditions (aOR 1.08, 95% CI 1.06 to 1.10). CONCLUSIONS: In this study of patients with chronic opioid use, an off-label gabapentin prescription did not reduce opioid dosage in the majority of patients. The coprescribing of these medications should be critically evaluated to ensure optimal patient safety.

What evidence is needed to inform postoperative opioid consumption guidelines? A cohort study of the Michigan Surgical Quality Collaborative.

INTRODUCTION: To balance adequate pain management while minimizing opioid-related harms after surgery, opioid prescribing guidelines rely on patient-reported use after surgery. However, it is unclear how many patients are required to develop precise guidelines. We aimed to compare patterns of use, required sample size, and the precision for patient-reported opioid consumption after common surgical procedures. METHODS: We analyzed procedure-specific 30-day opioid consumption data reported after discharge from 15 common surgical procedures between January 2018 and May 2019 across 65 hospitals in the Michigan Surgical Quality Collaborative. We calculated proportions of patients using no pills and the estimated number of pills meeting most patients' needs, defined as the 75th percentile of consumption. We compared several methods to model consumption patterns. Using the best method (Tweedie), we calculated sample sizes required to identify opioid consumption within a 5-pill interval and estimates of pills to meet most patients' needs by calculating the width of 95% CIs. RESULTS: In a cohort of 10,688 patients, many patients did not consume any opioids after all types of procedures (range 20%-40%). Most patients' needs were met with 4 pills (thyroidectomy) to 13 pills (abdominal hysterectomy). Sample sizes required to estimate opioid consumption within a 5-pill wide 95% CI ranged from 48 for laparoscopic appendectomy to 188 for open colectomy. The 95% CI width for estimates ranged from 0.7 pills for laparoscopic cholecystectomy to 7.0 pills for ileostomy/colostomy. CONCLUSIONS: This study demonstrates that profiles of opioid consumption share more similarities than differences for certain surgical procedures. Future investigations on patient-reported consumption are required for procedures not currently included in prescribing guidelines to ensure surgeons and perioperative providers can appropriately tailor recommendations to the postoperative needs of patients.

Opioid Prescribing by US Surgeons, 2016-2022.

This cross-sectional study investigates the rate and dosing of opioid prescriptions among US surgeons from 2016 to 2022.

Perioperative opioid prescribing and iatrogenic opioid use disorder and overdose: a state-of-the-art narrative review.

BACKGROUND/IMPORTANCE: Considerable attention has been paid to identifying and mitigating perioperative opioid-related harms. However, rates of postsurgical opioid use disorder (OUD) and overdose, along with associated risk factors, have not been clearly defined. OBJECTIVE: Evaluate the evidence connecting perioperative opioid prescribing with postoperative OUD and overdose, compare these data with evidence from the addiction literature, discuss the clinical impact of these conditions, and make recommendations for further study. EVIDENCE REVIEW: State-of-the-art narrative review. FINDINGS: Nearly all evidence is from large retrospective studies of insurance claims and Veterans Health Administration (VHA) data. Incidence rates of new OUD within the first year after surgery ranged from 0.1% to 0.8%, while rates of overdose events ranged from 0.01% to 0.8%. Higher rates were seen among VHA patients, which may reflect differences in data completeness and/or risk factors. Identified risk factors included those related to substance use (preoperative opioid use; non-opioid substance use disorders; preoperative sedative, anxiolytic, antidepressant, and gabapentinoid use; and postoperative new persistent opioid use (NPOU)); demographic attributes (chiefly male sex, younger age, white race, and Medicaid or no insurance coverage); psychiatric comorbidities such as depression, bipolar disorder, and PTSD; and certain medical and surgical factors. Several challenges related to the use of administrative claims data were identified; there is a need for more granular retrospective studies and, ideally, prospective cohorts to assess postoperative OUD and overdose incidence with greater accuracy. CONCLUSIONS: Retrospective data suggest an incidence of new postoperative OUD and overdose of up to 0.8% during the first year after surgery, but prospective studies are lacking.

Association of cannabis use with patient-reported pain measures among adults with chronic pain in US states with medical cannabis programs.

INTRODUCTION: Most Americans live in a state that has legalized cannabis as a medical treatment for pain, but it is unclear how chronic pain intensity relates to cannabis use. Our objective was to examine the association between patient-reported pain measures and cannabis among adults with chronic pain. METHODS: This cross-sectional study of a representative sample of adults reporting chronic non-cancer pain in 36 states and DC with active medical cannabis programs from March to April 2022 assessed cannabis use for chronic pain, categorized as active (within 30 days), past (>31 days), or never use (referent). Measures were pain intensity (primary) and interference, Widespread Pain Index, and number of chronic pain diagnoses. RESULTS: Among 1628 participants (57% female, 69% white), 352 (22%) actively used cannabis to treat chronic pain, 137 (8%) reported past cannabis use, and 1139 (70%) never used cannabis. In adjusted models, active cannabis use was associated with higher scores for pain intensity (score difference 1.03, 95% CI 0.05 to 2.02) and pain interference (score difference 1.82, 95% CI 0.99 to 2.65) compared with never use. Persons who actively used cannabis had higher Widespread Pain Index scores (score difference 0.56, 95% CI 0.26 to 0.86) and more chronic pain diagnoses (difference 0.45, 95% CI 0.06 to 0.83). CONCLUSION: People with chronic non-cancer pain who used cannabis for pain reported non-clinically meaningful worse pain measures and greater burden of chronic pain conditions than their counterparts who never used cannabis. Alternatively, those with worse pain and greater burden of pain appear more likely to use cannabis.

Association of Genetic Variants with Postsurgical Pain: A Systematic Review and Meta-analyses.

BACKGROUND: Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants of interest will help investigators understand the potential effects of genetic variation. METHODS: This article is a systematic review of genetic variants associated with postsurgical pain in humans, assessing association with postsurgical pain scores and opioid use in both acute (0 to 48 h postoperatively) and chronic (at least 3 months postoperatively) settings. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from 2000 to 2022 for studies using search terms related to genetic variants and postsurgical pain in humans. English-language studies in adult patients examining associations of one or more genetic variants with postsurgical pain were included. The primary outcome was association of genetic variants with either acute or chronic postsurgical pain. Pain was measured by patient-reported pain score or analgesic or opioid consumption. RESULTS: A total of 163 studies were included, evaluating 129 unique genes and 594 unique genetic variants. Many of the reported significant associations fail to be replicated in other studies. Meta-analyses were performed for seven variants for which there was sufficient data (OPRM1 rs1799971; COMT rs4680, rs4818, rs4633, and rs6269; and ABCB1 rs1045642 and rs2032582). Only two variants were associated with small differences in postsurgical pain: OPRM1 rs1799971 (for acute postsurgical opioid use standard mean difference = 0.25; 95% CI, 0.16 to 0.35; cohort size, 8,227; acute postsurgical pain score standard mean difference = 0.20; 95% CI, 0.09 to 0.31; cohort size, 4,619) and COMT rs4680 (chronic postsurgical pain score standard mean difference = 0.26; 95% CI, 0.08 to 0.44; cohort size, 1,726). CONCLUSIONS: Despite much published data, only two alleles have a small association with postsurgical pain. Small sample sizes, potential confounding variables, and inconsistent findings underscore the need to examine larger cohorts with consistent outcome measures.