Drivers of Variation in Opioid Prescribing after Common Surgical Procedures in a Large Multihospital Healthcare System.

BACKGROUND: Misuse of prescription opioids is a well-established contributor to the US opioid epidemic. The primary objective of this study was to identify which level of care delivery (ie patient, prescriber, or hospital) produced the most unwarranted variation in opioid prescribing after common surgical procedures. STUDY DESIGN: Electronic health record data from a large multihospital healthcare system were used in conjunction with random-effect models to examine variation in opioid prescribing practices after similar inpatient and outpatient surgical procedures between October 2019 and September 2021. Unwarranted variation was conceptualized as variation resulting from prescriber behavior unsupported by evidence. Covariates identified as drivers of warranted variation included characteristics known to influence pain levels or patient safety. All other model variables, including prescriber specialty and patient race, ethnicity, and insurance status were characterized as potential drivers of unwarranted variation. RESULTS: Among 25,188 procedures with an opioid prescription at hospital discharge, 53.5% exceeded guideline recommendations, corresponding to 13,228 patients receiving the equivalent of >140,000 excess 5 mg oxycodone tablets after surgical procedures. Prescribing variation was primarily driven by prescriber-level factors, with approximately half of the total variation in morphine milligram equivalents prescribed observed at the prescriber level and not explained by any measured variables. Unwarranted covariates associated with higher prescribed opioid quantity included non-Hispanic Black race, Medicare insurance, smoking history, later hospital discharge times, and prescription by a surgeon rather than a hospitalist or primary care provider. CONCLUSIONS: Given the large proportion of unexplained variation observed at the provider level, targeting prescribers through education and training may be an effective strategy for reducing postoperative opioid prescribing.

Peer Comparison or Guideline-Based Feedback and Postsurgery Opioid Prescriptions: A Randomized Clinical Trial.

Importance: Excess opioid prescribing after surgery can result in prolonged use and diversion. Email feedback based on social norms may reduce the number of pills prescribed. Objective: To assess the effectiveness of 2 social norm-based interventions on reducing guideline-discordant opioid prescribing after surgery. Design, Setting, and Participants: This cluster randomized clinical trial conducted at a large health care delivery system in northern California between October 2021 and October 2022 included general, obstetric/gynecologic, and orthopedic surgeons with patients aged 18 years or older discharged to home with an oral opioid prescription. Interventions: In 19 hospitals, 3 surgical specialties (general, orthopedic, and obstetric/gynecologic) were randomly assigned to a control group or 1 of 2 interventions. The guidelines intervention provided email feedback to surgeons on opioid prescribing relative to institutionally endorsed guidelines; the peer comparison intervention provided email feedback on opioid prescribing relative to that of peer surgeons. Emails were sent to surgeons with at least 2 guideline-discordant prescriptions in the previous month. The control group had no intervention. Main Outcome and Measures: The probability that a discharged patient was prescribed a quantity of opioids above the guideline for the respective procedure during the 12 intervention months. Results: There were 38 235 patients discharged from 640 surgeons during the 12-month intervention period. Control-group surgeons prescribed above guidelines 36.8% of the time during the intervention period compared with 27.5% and 25.4% among surgeons in the peer comparison and guidelines arms, respectively. In adjusted models, the peer comparison intervention reduced guideline-discordant prescribing by 5.8 percentage points (95% CI, -10.5 to -1.1; P = .03) and the guidelines intervention reduced it by 4.7 percentage points (95% CI, -9.4 to -0.1; P = .05). Effects were driven by surgeons who performed more surgeries and had more guideline-discordant prescribing at baseline. There was no significant difference between interventions. Conclusions and Relevance: In this cluster randomized clinical trial, email feedback based on either guidelines or peer comparison reduced opioid prescribing after surgery. Guideline-based feedback was as effective as peer comparison-based feedback. These interventions are simple, low-cost, and scalable, and may reduce downstream opioid misuse. Trial Registration: ClinicalTrials.gov NCT05070338.

Disparities in postoperative opioid prescribing by race and ethnicity: an electronic health records-based observational study from Northern California, 2015-2020.

OBJECTIVES: To examine racial and ethnic disparities in postoperative opioid prescribing. DATA SOURCES: Electronic health records (EHR) data across 24 hospitals from a healthcare delivery system in Northern California from January 1, 2015 to February 2, 2020 (study period). STUDY DESIGN: Cross-sectional, secondary data analyses were conducted to examine differences by race and ethnicity in opioid prescribing, measured as morphine milligram equivalents (MME), among patients who underwent select, but commonly performed, surgical procedures. Linear regression models included adjustment for factors that would likely influence prescribing decisions and race and ethnicity-specific propensity weights. Opioid prescribing, overall and by race and ethnicity, was also compared to postoperative opioid guidelines. DATA EXTRACTION: Data were extracted from the EHR on adult patients undergoing a procedure during the study period, discharged to home with an opioid prescription. PRINCIPAL FINDINGS: Among 61,564 patients, on adjusted regression analysis, non-Hispanic Black (NHB) patients received prescriptions with higher mean MME than non-Hispanic white (NHW) patients (+ 6.4% [95% confidence interval: 4.4%, 8.3%]), whereas Hispanic and non-Hispanic Asian patients received lower mean MME (-4.2% [-5.1%, -3.2%] and - 3.6% [-4.8%, -2.3%], respectively). Nevertheless, 72.8% of all patients received prescriptions above guidelines, ranging from 71.0 to 80.3% by race and ethnicity. Disparities in prescribing were eliminated among Hispanic and NHB patients versus NHW patients when prescriptions were written within guideline recommendations. CONCLUSIONS: Racial and ethnic disparities in opioid prescribing exist in the postoperative setting, yet all groups received prescriptions above guideline recommendations. Policies encouraging guideline-based prescribing may reduce disparities and overall excess prescribing.

Lifestyle change program engagement in real-world clinical practice: a mixed-methods analysis.

Participant engagement in structured lifestyle change programs (LCPs) is essential for adopting behaviors that promote weight loss; however, the challenges to, and facilitators that promote, engagement with such programs are not well understood. We conducted a mixed-methods study among real-world LCP participants to assess factors associated with program engagement and to examine the reasons for withdrawal. Using electronic health records (EHR), we identified LCP eligible participants between 2010 and 2017. Multivariable logistic regression was used to assess associations between program engagement and baseline characteristics. Semi-structured interviews with LCP participants were conducted and thematically analyzed to examine reasons for withdrawal. A total of 1,813 LCP participants were included. The median number of sessions attended was 10 of 21-25 sessions. Highest LCP engagement was associated with factors potentially related to self-efficacy/motivation, such as older age, higher baseline weight, prior healthcare utilization and an absence of a history of smoking or depression. Engagement was also negatively associated with being Non-Hispanic Black versus White. The qualitative analysis of the interviews revealed four general themes pertaining to participants' withdrawal: competing priorities, perceived program effectiveness, characteristics of the program, and facilitator-related factors. Taken together, results from this mixed-methods study suggest that motivation and self-efficacy are important for program engagement; future LCP enhancements should incorporate flexible formats that may help participants manage competing priorities and maximize personal and cultural relevance for all racial/ethnic groups, especially those who have not benefitted fully. Furthermore, participants should be encouraged to set realistic goals to manage expectations.

Engaging in a structured lifestyle change program (LCP) is essential to learn healthy behaviors, however, it is not well understood. This study examined factors associated with program engagement and reasons for program withdrawal at a large healthcare system. Highest LCP engagement was found to be associated to factors potentially related to self-efficacy/motivation including older age, higher initial weight, and prior healthcare utilization. Non-Hispanic Black, history of smoking, and prior diagnosis of depression were found to be negatively associated with LCP engagement. Program withdrawal was related to four themes: competing priorities, perceived program effectiveness, characteristics of the program, and facilitator-related factors. These findings suggest that motivation and self-efficacy are important for behavior change program engagement.

Evaluating the effectiveness of email-based nudges to reduce postoperative opioid prescribing: study protocol of a randomised controlled trial.

INTRODUCTION: Surgical patients are commonly prescribed more opioids at discharge than needed to manage their postoperative pain. These excess opioids increase the risks of new persistent opioid use, opioid-induced ventilatory impairment and opioid diversion. This study tests the effectiveness of two behavioural nudges, one based on peer behaviour and one based on best practice guidelines, in reducing excessive postoperative opioid prescriptions. METHODS AND ANALYSIS: The study will be conducted at 19 hospitals within a large healthcare delivery system in northern California, USA. Three surgical specialties (general surgery, orthopaedic surgery and obstetric/gynaecological surgery) at each hospital will be randomised either to a control group or to one of two active intervention arms. One intervention is grounded in the theory of injunctive norms, and provides feedback to surgeons on their postoperative opioid prescribing relative to prescribing guidelines endorsed by their institution. The other intervention draws from the theory of descriptive norms, and provides feedback similar to the first intervention but using peers' behaviour rather than guidelines as the benchmark for the surgeon's prescribing behaviour. The interventions will be delivered by a monthly email. Both interventions will be active for twelve months. The effects of each intervention relative to the control group and to each other will be tested using a four-level hierarchical model adjusted for multiple hypothesis testing. ETHICS AND DISSEMINATION: Using behavioural nudges rather than rigid policy changes allows us to target excessive prescribing without preventing clinicians from using their clinical judgement to address patient pain. All study activities have been approved by the RAND Human Subjects Protection Committee (ID 2018-0988). Findings will be disseminated through conference presentations, peer-reviewed publications and social media accounts. TRIAL REGISTRATION NUMBER: NCT05070338.

Assessment of Postoperative Opioid Prescriptions Before and After Implementation of a Mandatory Prescription Drug Monitoring Program.

Importance: Legislation mandating consultation with a prescription drug monitoring program (PDMP) was implemented in California on October 2, 2018. This mandate requires PDMP consultation before prescribing a controlled substance and integrates electronic health record (EHR)-based alerts; prescribers are exempt from the mandate if they prescribe no more than a 5-day postoperative opioid supply. Although previous studies have examined the consequences of mandated PDMP consultation, few have specifically analyzed changes in postoperative opioid prescribing after mandate implementation. Objective: To examine whether the implementation of mandatory PDMP consultation with concurrent EHR-based alerts was associated with changes in postoperative opioid quantities prescribed at discharge. Design Setting and Participants: This cross-sectional study performed an interrupted time series analysis of opioid prescribing patterns within a large health care system (Sutter Health) in northern California between January 1, 2015, and February 1, 2020. A total of 93 760 adult patients who received an opioid prescription at discharge after undergoing general, obstetric and gynecologic (obstetric/gynecologic), or orthopedic surgery were included. Exposures: Mandatory PDMP consultation before opioid prescribing, with concurrent integration of an EHR alert. Prescribers are exempt from this mandate if prescribing no more than a 5-day opioid supply postoperatively. Main Outcomes and Measures: The primary outcome was the total quantity of opioid medications (morphine milligram equivalents [MMEs] and number of opioid tablets) prescribed at discharge before and after implementation of the PDMP mandate, with separate analyses by surgical specialty (general, obstetric/gynecologic, and orthopedic) and most common surgical procedure within each specialty (laparoscopic cholecystectomy, cesarean delivery, and knee arthroscopy). The secondary outcome was the proportion of prescriptions with a duration of longer than 5 days. Results: Of 93 760 patients (mean [SD] age, 46.7 [17.6] years; 67.9% female) who received an opioid prescription at discharge, 65 911 received prescriptions before PDMP mandate implementation, and 27 849 received prescriptions after implementation. Most patients received general or obstetric/gynecologic surgery (48.6% and 30.1%, respectively), did not have diabetes (90.3%), and had never smoked (66.0%). Before the PDMP mandate was implemented, a decreasing pattern in opioid prescribing quantities was already occurring. During the quarter of implementation, total MMEs prescribed at discharge further decreased for all 3 surgical specialties (eg, medians for general surgery: ß = -10.00 [95% CI, -19.52 to -0.48]; obstetric/gynecologic surgery: ß = -18.65 [95% CI, -22.00 to -15.30]; and orthopedic surgery: ß = -30.59 [95% CI, -40.19 to -21.00]) after adjusting for the preimplementation prescribing pattern. The total number of tablets prescribed also decreased across specialties (eg, medians for general surgery: ß = -3.02 [95% CI, -3.47 to -2.57]; obstetric/gynecologic surgery: ß = -4.86 [95% CI, -5.38 to -4.34]; and orthopedic surgery: ß = -4.06 [95% CI, -5.07 to -3.04]) compared with the quarters before implementation. These reductions were not consistent across the most common surgical procedures. For cesarean delivery, the median number of tablets prescribed decreased during the quarter of implementation (ß = -10.00; 95% CI, -10.10 to -9.90), but median MMEs did not (ß = 0; 95% CI, -9.97 to 9.97), whereas decreases were observed in both median MMEs and number of tablets prescribed (MMEs: ß = -33.33 [95% CI, -38.48 to -28.19]; tablets: ß = -10.00 [95% CI, -11.17 to -8.82]) for laparoscopic cholecystectomy. For knee arthroscopy, no decreases were found in either median MMEs or number of tablets prescribed (MMEs: ß = 10.00 [95% CI, -22.33 to 42.33; tablets: ß = 0.83; 95% CI, -3.39 to 5.05). The proportion of prescriptions written for longer than 5 days also decreased significantly during the quarter of implementation across all 3 surgical specialties. Conclusions and Relevance: In this cross-sectional study, the implementation of mandatory PDMP consultation with a concurrent EHR-based alert was associated with an immediate decrease in opioid prescribing across the 3 surgical specialties. These findings might be explained by prescribers' attempts to meet the mandate exemption and bypass PDMP consultation rather than the PDMP consultation itself. Although policies coupled with EHR alerts may be associated with changes in postoperative opioid prescribing behavior, they need to be well designed to optimize evidence-based opioid prescribing.

Validity of an Automated Algorithm to Identify Cirrhosis Using Electronic Health Records in Patients with Primary Biliary Cholangitis.

BACKGROUND: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients. METHODS: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis. RESULTS: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively). CONCLUSION: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

Insulin-like growth factor-I-stimulated Akt phosphorylation and oligodendrocyte progenitor cell survival require cholesterol-enriched membranes.

Previously we showed that insulin-like growth factor-I (IGF-I) promotes sustained phosphorylation of Akt in oligodendrocyte progenitor cells (OPCs) and that Akt phosphorylation is required for survival of these cells. The direct mechanisms, however, by which IGF-I promotes Akt phosphorylation are currently undefined. Recently, cholesterol-enriched membranes (CEMs) have been implicated in regulation of growth factor-mediated activation of the PI3K/Akt pathway and survival of mature oligodendrocytes; however, less is know about their role in OPC survival. In the present study, we investigate the role of CEMs in IGF-I-mediated Akt phosphorylation and OPC survival. We report that acute disruption of membrane cholesterol with methyl-beta-cyclodextrin results in altered OPC morphology and inhibition of IGF-I-mediated Akt phosphorylation. We also report that long-term inhibition of cholesterol biosynthesis with 25-hydroxycholesterol blocks IGF-I stimulated Akt phosphorylation and cell survival. Moreover, we show that the PI3K regulatory subunit, p85, Akt, and the IGF-IR are sequestered within cholesterol-enriched fractions in steady-state stimulation of the IGF-IR and that phosphorylated Akt and IGF-IR are present in cholesterol-enriched fractions with IGF-I stimulation. Together, the results of these studies support a role for CEMs or "lipid rafts" in IGF-I-mediated Akt phosphorylation and provide a better understanding of the mechanisms by which IGF-I promotes OPC survival.

Insulin-like growth factor type-I receptor internalization and recycling mediate the sustained phosphorylation of Akt.

Previously we demonstrated that insulin-like growth factor-I mediates the sustained phosphorylation of Akt, which is essential for long term survival and protection of glial progenitors from glutamate toxicity. These prosurvival effects correlated with prolonged activation and stability of the insulin-like growth factor type-I receptor. In the present study, we investigated the mechanisms whereby insulin-like growth factor-I signaling, through the insulin-like growth factor type-I receptor, mediates the sustained phosphorylation of Akt. We showed that insulin-like growth factor-I stimulation induced loss of receptors from the cell surface but that surface receptors recovered over time. Blocking receptor internalization inhibited Akt phosphorylation, whereas inhibition of receptor trafficking blocked receptor recovery at the cell surface and the sustained phosphorylation of Akt. Moreover the insulin-like growth factor type-I receptor localized with the transferrin receptor and Rab11-positive endosomes in a ligand-dependent manner, further supporting the conclusion that this receptor follows a recycling pathway. Our results provide evidence that ligand stimulation leads to internalization of the insulin-like growth factor type-I receptor, which mediates Akt phosphorylation, and that receptor recycling sustains Akt phosphorylation in glial progenitors. Mathematical modeling of receptor trafficking further supports these results and predicts an additional kinetic state of the receptor consistent with sustained Akt phosphorylation.