Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity Matched Retrospective Cohort Study.

BACKGROUND: Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial. We compared average intraoperative isoflurane/sevoflurane minimum alveolar concentration equivalents between older adults with and without cannabis use. METHODS: The electronic health records of 22,476 surgical patients ≥65 years old at the University of Florida Health System between 2018-2020 were reviewed. The primary exposure was cannabis use within 60 days of surgery, determined via i) a previously published natural language processing algorithm applied to unstructured notes and ii) structured data, including International Classification of Disease codes for cannabis use disorders and poisoning by cannabis, laboratory cannabinoids screening results, and RxNorm codes. The primary outcome was the intraoperative time-weighted average of isoflurane/sevoflurane minimum alveolar concentration equivalents at one-minute resolution. No a priori minimally clinically important difference was established. Patients demonstrating cannabis use were matched 4:1 to non-cannabis use controls using a propensity score. RESULTS: Among 5,118 meeting inclusion criteria, 1,340 patients (268 cannabis users and 1,072 nonusers) remained after propensity score matching. The median and interquartile range (IQR) age was 69 (67, 73) years; 872 (65.0%) were male, and 1,143 (85.3%) were non-Hispanic White. The median (IQR) anesthesia duration was 175 (118, 268) minutes. After matching, all baseline characteristics were well-balanced by exposure. Cannabis users had statistically significantly higher average minimum alveolar concentrations than nonusers [mean±SD: 0.58±0.23 versus 0.54±0.22, respectively; mean difference=0.04; 95% confidence limits, 0.01 to 0.06; p=0.020]. CONCLUSION: Cannabis use was associated with administering statistically significantly higher inhalational anesthetic minimum alveolar concentration equivalents in older adults, but the clinical significance of this difference is unclear. These data do not support the hypothesis that cannabis users require clinically meaningfully higher inhalational anesthetics doses.

Association Between Preoperative Anemia and Cognitive Function in a Large Cohort Study of Older Patients Undergoing Elective Surgery.

BACKGROUND: The etiology of anemia has tremendous overlap with the disease states responsible for cognitive decline. We used data from a perioperative database of older adults undergoing elective surgery with anesthesia to (1) examine relationships among preoperative anemia blood markers, preoperative screeners of cognitive function, and chronic disease status; and (2) examine the relationship of these factors with operative outcomes. The primary goal of this study was to investigate the association between preoperative anemia blood markers and cognition measured by a preoperative cognitive screener. Secondary goals were to (1) examine the relationship between preoperative anemia blood markers and chronic disease states (ie, American Society of Anesthesiologists [ASA] and frailty), and (2) investigate the relationship of preoperative anemia blood markers and cognition with operative outcomes (ie, discharge disposition, 1-year mortality, number of surgical complications, length of hospital stay, and length of intensive care unit [ICU] stay). METHODS: Data were collected at the University of Florida Health Shands Presurgical Center and the Perioperative Cognitive Anesthesia Network clinic within the electronic medical record. Patients 65 years of age or older were included if they had a preoperative hemoglobin (Hgb) value and a preoperative screening. Nonparametric methods were used for bivariate analysis. Logistic regression was used for the simultaneous examination of variables associated with nonhome discharge and 1-year mortality. Primary outcomes were discharge disposition and 1-year mortality. Secondary outcomes were number of surgical complications and length of hospital and ICU stay. RESULTS: Of 14,795 patients cognitively assessed, 8643 met the inclusion criteria. Of these, 26.7% were anemic, with 16.8%, 9.5%, and 0.4% having mild, moderate, and severe anemia, respectively. The Spearman correlation coefficient [95% confidence interval, CI] between the Hgb level and the clock drawing time (CDT) was -.15 [-.17 to -.13] (P < .0001) indicating that a lower Hgb level was associated with cognitive vulnerability. Hgb was also negatively correlated with the ASA physical status classification, patient Fried Frailty Index, and hospital and ICU length of stay. In the multivariable model, age, surgical service, ASA and Fried Frailty Index significantly predicted nonhome discharge. Furthermore, age, surgical service, ASA, Fried Frailty Index, and Hgb independently predicted death within 1 year of surgery. The odds of death, adjusted for ASA, Fried Frailty, and covariates, were 2.7 times higher for those in the mild anemic group compared to those who were not anemic (odds ratio [OR], 2.7, 95% CI, [2.1-3.5]). The odds of death, adjusted for ASA, Fried Frailty, and covariates, were 3.6 times higher for those in the moderate/severe anemic group compared to those who were not anemic (OR, 3.6, 95% CI, [2.7-4.9]). CONCLUSIONS: In this first medicine study, we established relationships among anemia, preoperative markers of frailty and cognition, and chronic disease states in a large cohort of older patients undergoing elective surgery in a large tertiary medical center. We found that anemia, cognitive vulnerability, and chronic health disease states predicted death within 1 year of surgery, and that these preoperative factors negatively contribute to surgical outcomes such as time in the ICU, length of hospital stay, nonhome discharge, and 1-year mortality. The World Health Organization (WHO) and many academic medical societies have urged the adoption of patient blood management (PBM) disciplines, yet anemia is not routinely optimized as a preoperative risk factor. Given the well-defined association between preoperative anemia and postoperative morbidity and mortality, performing elective surgery on an untreated anemic patient should be considered substandard care. With established safe and effective treatment regimens, iron deficiency anemia is a modifiable preoperative risk factor that should be addressed before elective surgery.

Cannabis use and acute postoperative pain outcomes in older adults: a propensity matched retrospective cohort study.

INTRODUCTION: Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery. METHODS: We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020. Of the original cohort, 2577 patients were eligible for propensity-score matching (1:3 cannabis user: non-user). Cannabis use status was determined via natural language processing of clinical notes within 60 days of surgery and structured data. The primary outcomes were average Defense and Veterans Pain Rating Scale (DVPRS) score and total oral morphine equivalents (OME) within 24 hours of surgery. RESULTS: 504 patients were included (126 cannabis users and 378 non-users). The median (IQR) age was 69 (65-72) years; 295 (58.53%) were male, and 442 (87.70%) were non-Hispanic white. Baseline characteristics were well balanced. Cannabis users had significantly higher average DVPRS scores (median (IQR): 4.68 (2.71-5.96) vs 3.88 (2.33, 5.17); difference=0.80; 95% confidence limit (CL), 0.19 to 1.36; p=0.01) and total OME (median (IQR): 42.50 (15.00-60.00) mg vs 30.00 (7.50-60.00) mg; difference=12.5 mg; 95% CL, 3.80 mg to 21.20 mg; p=0.02) than non-users within 24 hours of surgery. DISCUSSION: This study showed that cannabis use in older adults was associated with increased postoperative pain levels and opioid doses.

Association of Sociodemographic Factors With Overtriage, Undertriage, and Value of Care After Major Surgery.

Objective: To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts. Background: In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally. Methods: This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774). K-means clustering identified sociodemographic phenotypes within overtriage and undertriage cohorts. Results: Compared with controls, overtriaged admissions had a predominance of male patients (56.2% vs 43.1%, P < 0.001) and commercial insurance (6.4% vs 2.5%, P < 0.001); undertriaged admissions had a predominance of Black patients (28.4% vs 24.4%, P < 0.001) and greater socioeconomic deprivation. Overtriage was associated with increased total direct costs [$16.2K ($11.4K-$23.5K) vs $14.1K ($9.1K-$20.7K), P < 0.001] and low value of care; undertriage was associated with increased hospital mortality (1.5% vs 0.7%, P = 0.002) and hospice care (2.2% vs 0.6%, P < 0.001) and low value of care. Unique sociodemographic phenotypes within both overtriage and undertriage cohorts had similar outcomes and value of care, suggesting that triage decisions, rather than patient characteristics, drive outcomes and value of care. Conclusions: Postoperative triage decisions should ensure equality across sociodemographic groups by anchoring triage decisions to objective patient acuity assessments, circumventing cognitive shortcuts and mitigating bias.

Development of a Probabilistic Boolean network (PBN) to model intraoperative blood pressure management.

BACKGROUND: Blood pressure is a vital sign for organ perfusion that anesthesiologists measure and modulate during surgery. However, current decision-making processes rely heavily on clinicians' experience, which can lead to variability in treatment across surgeries. With the advent of machine learning, we can now create models to predict the outcomes of interventions and guide perioperative decision-making. The first step in this process involves translating the clinical decision-making process into a framework understood by an algorithm. Probabilistic Boolean networks (PBNs) provide an information-rich approach to this problem. A PBN trends toward a steady state, and its decisions are easily understood via its Boolean predictor functions. We hypothesize that a PBN can be developed that corrects hemodynamic instability in patients by selecting clinical interventions to maintain blood pressure within a given range. METHODS: Data on patients over the age of 65 undergoing surgery with general anesthesia from 2018 to 2020 were drawn from the UF Health PRECEDE data set with IRB approval (IRB201700747). Parameters examined included heart rate, blood pressure, and frequency of medications given 15 min after anesthetic induction and 15 min before awakening. The medication frequency data were truncated into a 66/33 split for the training and validation set used in the PBN. The model was coded using Python 3 and evaluated by comparing the frequency of medications chosen by the program to the values in the testing set via linear regression analysis. RESULTS: The network developed successfully models a hemodynamically unstable patient and corrects the imbalance by administering medications. This is evidenced by the model achieving a stable, steady state matrix in all iterations. However, the model's ability to emulate clinical drug selection was variable. It was successful with its use of vasodilator selection but struggled with the appropriate selection of vasopressors. CONCLUSIONS: The PBN has demonstrated the ability to choose appropriate interventions based on a patient's current vitals. Additional work must be done to have the network emulate the frequency at which drugs are selected from in clinical practice. In its current state, the model provides an understanding of how a PBN behaves in the context of correcting hemodynamic instability and can aid in developing more robust models in the future.

Developing and validating a natural language processing algorithm to extract preoperative cannabis use status documentation from unstructured narrative clinical notes.

OBJECTIVE: This study aimed to develop a natural language processing algorithm (NLP) using machine learning (ML) techniques to identify and classify documentation of preoperative cannabis use status. MATERIALS AND METHODS: We developed and applied a keyword search strategy to identify documentation of preoperative cannabis use status in clinical documentation within 60 days of surgery. We manually reviewed matching notes to classify each documentation into 8 different categories based on context, time, and certainty of cannabis use documentation. We applied 2 conventional ML and 3 deep learning models against manual annotation. We externally validated our model using the MIMIC-III dataset. RESULTS: The tested classifiers achieved classification results close to human performance with up to 93% and 94% precision and 95% recall of preoperative cannabis use status documentation. External validation showed consistent results with up to 94% precision and recall. DISCUSSION: Our NLP model successfully replicated human annotation of preoperative cannabis use documentation, providing a baseline framework for identifying and classifying documentation of cannabis use. We add to NLP methods applied in healthcare for clinical concept extraction and classification, mainly concerning social determinants of health and substance use. Our systematically developed lexicon provides a comprehensive knowledge-based resource covering a wide range of cannabis-related concepts for future NLP applications. CONCLUSION: We demonstrated that documentation of preoperative cannabis use status could be accurately identified using an NLP algorithm. This approach can be employed to identify comparison groups based on cannabis exposure for growing research efforts aiming to guide cannabis-related clinical practices and policies.

Overtriage, Undertriage, and Value of Care after Major Surgery: An Automated, Explainable Deep Learning-Enabled Classification System.

BACKGROUND: In single-institution studies, overtriaging low-risk postoperative patients to ICUs has been associated with a low value of care; undertriaging high-risk postoperative patients to general wards has been associated with increased mortality and morbidity. This study tested the reproducibility of an automated postoperative triage classification system to generating an actionable, explainable decision support system. STUDY DESIGN: This longitudinal cohort study included adults undergoing inpatient surgery at two university hospitals. Triage classifications were generated by an explainable deep learning model using preoperative and intraoperative electronic health record features. Nearest neighbor algorithms identified risk-matched controls. Primary outcomes were mortality, morbidity, and value of care (inverted risk-adjusted mortality/total direct costs). RESULTS: Among 4,669 ICU admissions, 237 (5.1%) were overtriaged. Compared with 1,021 control ward admissions, overtriaged admissions had similar outcomes but higher costs ($15.9K [interquartile range $9.8K to $22.3K] vs $10.7K [$7.0K to $17.6K], p < 0.001) and lower value of care (0.2 [0.1 to 0.3] vs 1.5 [0.9 to 2.2], p < 0.001). Among 8,594 ward admissions, 1,029 (12.0%) were undertriaged. Compared with 2,498 control ICU admissions, undertriaged admissions had longer hospital length-of-stays (6.4 [3.4 to 12.4] vs 5.4 [2.6 to 10.4] days, p < 0.001); greater incidence of hospital mortality (1.7% vs 0.7%, p = 0.03), cardiac arrest (1.4% vs 0.5%, p = 0.04), and persistent acute kidney injury without renal recovery (5.2% vs 2.8%, p = 0.002); similar costs ($21.8K [$13.3K to $34.9K] vs $21.9K [$13.1K to $36.3K]); and lower value of care (0.8 [0.5 to 1.3] vs 1.2 [0.7 to 2.0], p < 0.001). CONCLUSIONS: Overtriage was associated with low value of care; undertriage was associated with both low value of care and increased mortality and morbidity. The proposed framework for generating automated postoperative triage classifications is reproducible.

Building an automated, machine learning-enabled platform for predicting post-operative complications.

Objective. In 2019, the University of Florida College of Medicine launched theMySurgeryRiskalgorithm to predict eight major post-operative complications using automatically extracted data from the electronic health record.Approach. This project was developed in parallel with our Intelligent Critical Care Center and represents a culmination of efforts to build an efficient and accurate model for data processing and predictive analytics.Main Results and Significance. This paper discusses how our model was constructed and improved upon. We highlight the consolidation of the database, processing of fixed and time-series physiologic measurements, development and training of predictive models, and expansion of those models into different aspects of patient assessment and treatment. We end by discussing future directions of the model.

Cysteine-Selective Modification of Peptides and Proteins via Desulfurative C-C Bond Formation.

The site-selective modification of peptides and proteins facilitates the preparation of targeted therapeutic agents and tools to interrogate biochemical pathways. Among the numerous bioconjugation techniques developed to install groups of interest, those that generate C(sp3 )-C(sp3 ) bonds are significantly underrepresented despite affording proteolytically stable, biogenic linkages. Herein, a visible-light-mediated reaction is described that enables the site-selective modification of peptides and proteins via desulfurative C(sp3 )-C(sp3 ) bond formation. The reaction is rapid and high yielding in peptide systems, with comparable translation to proteins. Using this chemistry, a range of moieties is installed into model systems and an effective PTM-mimic is successfully integrated into a recombinantly expressed histone.

Early reduction in postoperative pain is associated with improved long-term function after shoulder arthroplasty: a retrospective case series.

PURPOSE: Mixed modalities are frequently utilized in total shoulder arthroplasty (TSA) to control pain, improve patient satisfaction, reduce narcotics use and facilitate earlier discharge. We investigate the relationship between early postoperative pain control and long-term functional outcomes after shoulder arthroplasty. METHODS: A retrospective review identified 294 patients (314 shoulders) who underwent anatomic or reverse TSA and received a continuous cervical paravertebral nerve block perioperatively. Opioid and non-opioid analgesics were also available to the patients in an "as needed" capacity to augment perioperative pain control. In addition to demographic and surgical characteristics, the impact on functional outcomes of relative pain (i.e., a patient's subjective pain relative to the entire cohort), pain gradient (i.e., the slope of a patient's subjective pain), and opioid consumption during the first 24 h postoperatively were assessed. Shoulder function was assessed using validated outcome measures collected at 2 year follow-up. Outcomes were measured using American Shoulder and Elbow Surgeons questionnaire (ASES), Shoulder Pain and Disability Index (SPADI), SPADI-130, Raw and Normalized Constant Score, SST-12 and UCLA score. RESULTS: Patients younger than 65, females, reverse TSA, revisions, and preoperative opioid users had worse functional outcomes. On univariate analysis, increased pain perioperatively (> 50% percentile relative pain) was associated with decreased function at 2 years when analyzed with all seven outcome scores (P < .001 for all), reaching minimal clinically important difference (MCID) using the Constant Score. On multivariate analysis, increased pain in the first 24 h postoperatively (assessed on a continuous scale) was independently associated with worse ASES, SPADI, and SPADI-130 scores. Intraoperative ketamine administration and opioid consumption in the 24 h postoperative period did not influence long-term shoulder function. CONCLUSION: Patients reporting reduced pain after TSA demonstrated improved shoulder function with the Constant score at 2 years postoperatively in both univariate and multivariate analysis. Larger-scale investigation may be warranted to see if this is true for other functional outcome measures. LEVEL OF EVIDENCE: III, treatment study.

Postoperative Overtriage to an Intensive Care Unit Is Associated With Low Value of Care.

OBJECTIVE: We test the hypothesis that for low-acuity surgical patients, postoperative intensive care unit (ICU) admission is associated with lower value of care compared with ward admission. BACKGROUND: Overtriaging low-acuity patients to ICU consumes valuable resources and may not confer better patient outcomes. Associations among postoperative overtriage, patient outcomes, costs, and value of care have not been previously reported. METHODS: In this longitudinal cohort study, postoperative ICU admissions were classified as overtriaged or appropriately triaged according to machine learning-based patient acuity assessments and requirements for immediate postoperative mechanical ventilation or vasopressor support. The nearest neighbors algorithm identified risk-matched control ward admissions. The primary outcome was value of care, calculated as inverse observed-to-expected mortality ratios divided by total costs. RESULTS: Acuity assessments had an area under the receiver operating characteristic curve of 0.92 in generating predictions for triage classifications. Of 8592 postoperative ICU admissions, 423 (4.9%) were overtriaged. These were matched with 2155 control ward admissions with similar comorbidities, incidence of emergent surgery, immediate postoperative vital signs, and do not resuscitate order placement and rescindment patterns. Compared with controls, overtraiged admissions did not have a lower incidence of any measured complications. Total costs for admission were $16.4K for overtriage and $15.9K for controls ( P =0.03). Value of care was lower for overtriaged admissions [2.9 (2.0-4.0)] compared with controls [24.2 (14.1-34.5), P <0.001]. CONCLUSIONS: Low-acuity postoperative patients who were overtriaged to ICUs had increased total costs, no improvements in outcomes, and received low-value care.

Long-Term Postoperative Pain Prediction Using Higher-Order Singular Value Decomposition of Intraoperative Physiological Responses: Prospective Cohort Study.

BACKGROUND: Long-term postoperative pain (POP) and patient responses to pain relief medications are not yet fully understood. Although recent studies have developed an index for the nociception level of patients under general anesthesia based on multiple physiological parameters, it remains unclear whether these parameters correlate with long-term POP outcomes. OBJECTIVE: This study aims to extract unbiased and interpretable descriptions of how the dynamics of physiological parameters change over time and across patients in response to surgical procedures and intraoperative medications using a multivariate-temporal analysis. We demonstrated that there is an association (correlation) between the main features of intraoperative physiological responses and long-term POP, which has a predictive value, even without claiming causality. METHODS: We proposed a complex higher-order singular value decomposition method to accurately decompose patients' physiological responses into multivariate structures evolving over time. We used intraoperative vital signs of 175 patients from a mixed surgical cohort to extract three interconnected, low-dimensional, complex-valued descriptions of patients' physiological responses: multivariate factors, reflecting subphysiological parameters; temporal factors, reflecting common intrasurgery temporal dynamics; and patients' factors, describing interpatient changes in physiological responses. RESULTS: Adoption of the complex higher-order singular value decomposition method allowed us to clarify the dynamic correlation structure included in the intraoperative physiological responses. Instantaneous phases of the complex-valued physiological responses of 242 patients within the subspace of principal descriptors enabled us to discriminate between mild and not-mild (moderate-severe) levels of pain at postoperative days 30 and 90. Following rotation of physiological responses before projection to align with the common multivariate-temporal dynamic, the method achieved an area under curve for postoperative day 30 and 90 outcomes of 0.81 and 0.89 for thoracic surgery, 0.87 and 0.83 for orthopedic surgery, 0.87 and 0.88 for urological surgery, 0.86 and 1 for colorectal surgery, 1 and 1 for transplant surgery, and 0.83 and 0.92 for pancreatic surgery, respectively. CONCLUSIONS: By categorizing patients into different surgical groups, we identified significant surgery-related principal descriptors. Each of them potentially encodes different surgical stimulation. The dynamics of patients' physiological responses to these surgical events were linked to long-term POP development.

Perioperative Use of Gabapentinoids and Risk for Postoperative Long-Term Opioid Use in Older Adults Undergoing Total Knee or Hip Arthroplasty.

BACKGROUND: Gabapentinoids are recommended by guidelines as a component of multimodal analgesia to manage postoperative pain and reduce opioid use. It remains unknown whether perioperative use of gabapentinoids is associated with a reduced or increased risk of postoperative long-term opioid use (LTOU) after total knee or hip arthroplasty (TKA/THA). METHODS: Using Medicare claims data from 2011 to 2018, we identified fee-for-service beneficiaries aged ≥ 65 years who were hospitalized for a primary TKA/THA and had no LTOU before the surgery. Perioperative use of gabapentinoids was measured from 7 days preadmission through 7 days postdischarge. Patients were required to receive opioids during the perioperative period and were followed from day 7 postdischarge for 180 days to assess postoperative LTOU (ie, ≥90 consecutive days). A modified Poisson regression was used to estimate the relative risk (RR) of postoperative LTOU in patients with versus without perioperative use of gabapentinoids, adjusting for confounders through propensity score weighting. RESULTS: Of 52,788 eligible Medicare older beneficiaries (mean standard deviation [SD] age 72.7 [5.3]; 62.5% females; 89.7% White), 3,967 (7.5%) received gabapentinoids during the perioperative period. Postoperative LTOU was 3.8% in patients with and 4.0% in those without perioperative gabapentinoids. After adjusting for confounders, the risk of postoperative LTOU was similar comparing patients with versus without perioperative gabapentinoids (RR = 1.07; 95% confidence interval [CI] = 0.91-1.26, P = .408). Sensitivity and bias analyses yielded consistent results. CONCLUSION: Among older Medicare beneficiaries undergoing a primary TKA/THA, perioperative use of gabapentinoids was not associated with a reduced or increased risk for postoperative LTOU.

Concurrent use of prescription gabapentinoids with opioids and risk for fall-related injury among older US Medicare beneficiaries with chronic noncancer pain: A population-based cohort study.

BACKGROUND: Gabapentinoids are increasingly prescribed to manage chronic noncancer pain (CNCP) in older adults. When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentinoids with opioids compared with use of opioids alone is associated with an increased risk of fall-related injury among older adults with CNCP. METHODS AND FINDINGS: We conducted a population-based cohort study using a 5% national sample of Medicare beneficiaries in the United States between 2011 and 2018. Study sample consisted of fee-for-service (FFS) beneficiaries aged ≥65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days' supply overlapping for ≥1 day and designated first day of concurrency as the index date. We created 2 cohorts based on whether concurrent users initiated gabapentinoids on the day of opioid initiation (Cohort 1) or after opioid initiation (Cohort 2). Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0.005). Limitations of this study included confounding due to unmeasured factors, unavailable information on gabapentinoids' indication, potential misclassification, and limited generalizability beyond older adults insured by Medicare FFS program. CONCLUSIONS: In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not significantly associated with risk for fall-related injury. However, addition of gabapentinoids to an existing opioid regimen was associated with increased risks for fall. Mechanisms for the observed excess risk, whether pharmacological or because of channeling of combination therapy to high-risk patients, require further investigation. Clinicians should consider the risk-benefit of combination therapy when prescribing gabapentinoids concurrently with opioids.

Fairness in the prediction of acute postoperative pain using machine learning models.

Introduction: Overall performance of machine learning-based prediction models is promising; however, their generalizability and fairness must be vigorously investigated to ensure they perform sufficiently well for all patients. Objective: This study aimed to evaluate prediction bias in machine learning models used for predicting acute postoperative pain. Method: We conducted a retrospective review of electronic health records for patients undergoing orthopedic surgery from June 1, 2011, to June 30, 2019, at the University of Florida Health system/Shands Hospital. CatBoost machine learning models were trained for predicting the binary outcome of low (≤4) and high pain (>4). Model biases were assessed against seven protected attributes of age, sex, race, area deprivation index (ADI), speaking language, health literacy, and insurance type. Reweighing of protected attributes was investigated for reducing model bias compared with base models. Fairness metrics of equal opportunity, predictive parity, predictive equality, statistical parity, and overall accuracy equality were examined. Results: The final dataset included 14,263 patients [age: 60.72 (16.03) years, 53.87% female, 39.13% low acute postoperative pain]. The machine learning model (area under the curve, 0.71) was biased in terms of age, race, ADI, and insurance type, but not in terms of sex, language, and health literacy. Despite promising overall performance in predicting acute postoperative pain, machine learning-based prediction models may be biased with respect to protected attributes. Conclusion: These findings show the need to evaluate fairness in machine learning models involved in perioperative pain before they are implemented as clinical decision support tools.

Executive summary of the artificial intelligence in surgery series.

As opportunities for artificial intelligence to augment surgical care expand, the accompanying surge in published literature has generated both substantial enthusiasm and grave concern regarding the safety and efficacy of artificial intelligence in surgery. For surgeons and surgical data scientists, it is increasingly important to understand the state-of-the-art, recognize knowledge and technology gaps, and critically evaluate the deluge of literature accordingly. This article summarizes the experiences and perspectives of a global, multi-disciplinary group of experts who have faced development and implementation challenges, overcome them, and produced incipient evidence thereof. Collectively, evidence suggests that artificial intelligence has the potential to augment surgeons via decision-support, technical skill assessment, and the semi-autonomous performance of tasks ranging from resource allocation to patching foregut defects. Most applications remain in preclinical phases. As technologies and their implementations improve and positive evidence accumulates, surgeons will face professional imperatives to lead the safe, effective clinical implementation of artificial intelligence in surgery. Substantial challenges remain; recent progress in using artificial intelligence to achieve performance advantages in surgery suggests that remaining challenges can and will be overcome.

Concurrent Use of Prescription Opioids and Gabapentinoids in Older Adults.

INTRODUCTION: Concurrent use of prescription opioids with gabapentinoids may pose risks of serious drug interactions. Yet, little is known about the trends in and patient characteristics associated with concurrent opioid-gabapentinoid use among older Medicare opioid users with chronic noncancer pain. METHODS: A cross-sectional study was conducted among Medicare older beneficiaries (aged ≥65 years) with chronic noncancer pain who filled ≥1 opioid prescription within 3 months after a randomly selected chronic noncancer pain diagnosis (index date) in a calendar year between 2011 and 2018. Patient characteristics were measured in the 6-month baseline before the index date, and concurrent opioid-gabapentinoid use for ≥1 day was measured in the 3-month follow-up after the index date. Multivariable modified Poisson regression hwas used to assess the trends and characteristics of concurrent opioid-gabapentinoid use. Analyses were conducted from January to June 2021. RESULTS: Among 464,721 eligible older beneficiaries with chronic noncancer pain and prescription opioids, the prevalence of concurrent opioid-gabapentinoid use increased from 17.0% in 2011 to 23.5% in 2018 (adjusted prevalence ratio=1.48, 95% CI=1.45, 1.53). Concurrent users versus opioid-only users tended to be non-Black, low-income subsidy recipients, and Southern residents. The clinical factors associated with concurrent opioid-gabapentinoid use included having a diagnosis of neuropathic pain, polypharmacy, and risk factors for opioid-related adverse events. CONCLUSIONS: Concurrent opioid-gabapentinoid use among older Medicare beneficiaries with chronic noncancer pain and prescription opioids has increased significantly between 2011 and 2018. Future studies are warranted to investigate the impact of concurrent use on outcomes in older patients. Interventions that reduce inappropriate concurrent use may target older patients with identified characteristics.

Aligning Patient Acuity With Resource Intensity After Major Surgery: A Scoping Review.

OBJECTIVE: Develop unifying definitions and paradigms for data-driven methods to augment postoperative resource intensity decisions. SUMMARY BACKGROUND DATA: Postoperative level-of-care assignments and frequency of vital sign and laboratory measurements (ie, resource intensity) should align with patient acuity. Effective, data-driven decision-support platforms could improve value of care for millions of patients annually, but their development is hindered by the lack of salient definitions and paradigms. METHODS: Embase, PubMed, and Web of Science were searched for articles describing patient acuity and resource intensity after inpatient surgery. Study quality was assessed using validated tools. Thirty-five studies were included and assimilated according to PRISMA guidelines. RESULTS: Perioperative patient acuity is accurately represented by combinations of demographic, physiologic, and hospital-system variables as input features in models that capture complex, non-linear relationships. Intraoperative physiologic data enriche these representations. Triaging high-acuity patients to low-intensity care is associated with increased risk for mortality; triaging low-acuity patients to intensive care units (ICUs) has low value and imparts harm when other, valid requests for ICU admission are denied due to resource limitations, increasing their risk for unrecognized decompensation and failure-to-rescue. Providing high-intensity care for low-acuity patients may also confer harm through unnecessary testing and subsequent treatment of incidental findings, but there is insufficient evidence to evaluate this hypothesis. Compared with data-driven models, clinicians exhibit volatile performance in predicting complications and making postoperative resource intensity decisions. CONCLUSION: To optimize value, postoperative resource intensity decisions should align with precise, data-driven patient acuity assessments augmented by models that accurately represent complex, non-linear relationships among risk factors.

Mimicking Native Display of CD0873 on Liposomes Augments Its Potency as an Oral Vaccine against Clostridioides difficile.

Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally to hamsters induces neutralising antibodies locally as well as systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was to determine whether displaying CD0873 on liposomes, mimicking native presentation, would drive a stronger antibody response. The recombinant form we previously tested resembles the naturally cleaved lipoprotein commencing with a cysteine but lacking lipid modification. A synthetic lipid (DHPPA-Mal) was designed for conjugation of this protein via its N-terminal cysteine to the maleimide headgroup. DHPPA-Mal was first formulated with liposomes to produce MalLipo; then, CD0873 was conjugated to headgroups protruding from the outer envelope to generate CD0873-MalLipo. The immunogenicity of CD0873-MalLipo was compared to CD0873 in hamsters. Intestinal sIgA and CD0873-specific serum IgG were induced in all vaccinated animals; however, neutralising activity was greatest for the CD0873-MalLipo group. Our data hold great promise for development of a novel oral vaccine platform driving intestinal and systemic immune responses.

Machine Learning Applications in Solid Organ Transplantation and Related Complications.

The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable postoperative graft survival to equitable allocation of scarce organs, machine learning promises to inform clinical decision making by deciphering prodigious amounts of available data. This paper reviews current research describing how algorithms have the potential to augment clinical practice in solid organ transplantation. We provide a general introduction to different machine learning techniques, describing their strengths, limitations, and barriers to clinical implementation. We summarize emerging evidence that recent advances that allow machine learning algorithms to predict acute post-surgical and long-term outcomes, classify biopsy and radiographic data, augment pharmacologic decision making, and accurately represent the complexity of host immune response. Yet, many of these applications exist in pre-clinical form only, supported primarily by evidence of single-center, retrospective studies. Prospective investigation of these technologies has the potential to unlock the potential of machine learning to augment solid organ transplantation clinical care and health care delivery systems.