Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires.

BACKGROUND: Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models. METHODS: In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery. RESULTS: A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain. CONCLUSIONS: The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

Postoperative and postdischarge nausea and vomiting following ambulatory eye, head, and neck surgeries: a retrospective cohort study comparing incidence and associated factors.

BACKGROUND: Ambulatory surgery is often followed by the development of nausea and/or vomiting (N/V). Although risk factors for postoperative nausea and vomiting (PONV) are frequently discussed, the distinction between PONV and postdischarge nausea and vomiting (PDNV) is unclear. This is especially troublesome given the potential consequences of postdischarge nausea and vomiting (PDNV), which include major discomfort and hospital readmission. METHODS: In this retrospective cohort study, data from 10,231 adult patients undergoing ambulatory ophthalmology or otolaryngology procedures with general anesthesia were collected and analyzed. Binary and multinomial logistic regression was used to assess the association between patient and anesthetic characteristics (including age, body mass index (BMI), American Society of Anesthesiologists Physical Status (ASA P/S) classification, current smoker status, and intra- and postoperative opioid usage) and the odds ratios of experiencing only PDNV, only PONV, or both PONV and PDNV, as compared to not experiencing N/V at all. RESULTS: We found that 17.8% of all patients developed N/V (PONV and/or PDNV). Patients who experienced PONV had a 2.79 (95% confidence interval 2.24-3.46) times greater risk of reporting PDNV. Binary logistic regression found that younger age, opioid use, and female sex were associated with an increased likelihood of experiencing any N/V. Increased use of nitrous oxide and a higher ASA P/S class was associated with elevated likelihood of PONV, but not PDNV or PONV plus PDNV. CONCLUSIONS: Patients experiencing N/V in the PACU are observed to develop PDNV disproportionately by a factor of 2.79. The patients have distinct predictors, indicating important opportunities for care improvements beyond current guidelines.

The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: a large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL).

ABSTRACT: A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL-Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. We assessed pain among those reaching the end of the VITAL intervention phase using questions from the 2012 National Health Interview Survey. We used ordinal logistic regression to test the effect of vitamin D and omega-3 fatty acids on the odds ratio (OR) and 95% confidence interval [CI] of reporting higher pain prevalence or severity. Overall, 19,611 participants provided complete pain information at the end of the VITAL trial. The ORs for higher pain prevalence or severity for vitamin D and omega-3 supplementation vs placebo were 0.99 ([CI] 0.94-1.05) and 0.99 ([CI] 0.94-1.04), respectively. There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U.S. adults.

Does the Association Between Psychosocial Factors and Opioid Use After Elective Spine Surgery Differ by Sex in Older Adults?

Purpose: Psychosocial disorders have been linked to chronic postoperative opioid use and the development of postoperative pain. The potential interaction between sex and psychosocial factors with respect to opioid use after elective spine surgery in the elderly has not yet been evaluated. Our aim was to assess whether any observed association of anxiety or depression indicators with opioid consumption in the first 72 hours after elective spine surgery varies by sex in adults ≥65 years. Patients and Methods: Secondary analysis of a retrospective cohort of 647 elective spine surgeries performed at Brigham and Women's Hospital, July 1, 2015-March 15, 2017, in patients ≥65. Linear mixed-effects models were used to test whether history of anxiety, anxiolytic use, history of depression, and antidepressant use were associated with opioid consumption 0-24, 24-48, and 48-72 post surgery, and whether these potential associations differed by sex. Results: History of anxiety, anxiolytic use, history of depression, and antidepressant use were more common among women (51.3% of the sample). During the first 24 hours after surgery, men with a preoperative history of anxiety consumed an adjusted mean of 19.5 morphine milligram equivalents (MME) (99.6% CI: 8.1, 31.0) more than men without a history of anxiety; women with a history of anxiety only consumed an adjusted mean 2.9 MME (99.6% CI: -3.1, 8.9) more than women without a history of anxiety (P value for interaction between sex and history of anxiety <0.001). No other interactions were detected between sex and psychosocial factors with respect to opioid use after surgery. Conclusion: Secondary analysis of this retrospective cohort study found minimal evidence that the association between psychosocial factors and opioid consumption after elective spine surgery differs by sex in adults ≥65.

Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine.

BACKGROUND: The dural puncture epidural (DPE) technique has a faster onset, better sacral spread, and improved bilateral coverage when compared to the conventional epidural (EPL) technique. Whether these qualities translate into a lower bupivacaine dose to provide initial analgesia is unknown. We sought to determine the effective dose of bupivacaine to achieve initial (first 30 minutes) labor analgesia in 90% of patients (ED90) with the DPE and EPL techniques, using a biased-coin, sequential allocation method. METHODS: A total of 100 women of mixed parity with term, singleton gestation at ≤5 cm dilation with no major comorbidities were randomized to receive a DPE or an EPL technique. An experienced anesthesiologist performed these techniques and administered an allocated dose of plain bupivacaine diluted with isotonic sterile 0.9% saline to a total volume of 20 mL via the EPL catheter. Bupivacaine doses for each subject were determined by the response of the previous subject, using a biased-coin sequential allocation method, with success defined by a numeric rating scale (NRS) < 3 at 30 minutes. Outcome assessments were performed by an investigator blinded to the technique and bupivacaine dose. Sensory and motor blockade and maternal or fetal side effects were recorded every 5 minutes for the first 30 minutes. The ED90 of bupivacaine with each technique was estimated using centered isotonic regression. RESULTS: A total of 95 women were included in the final analysis. The ED90 of bupivacaine was estimated at 29.30 mg (90% confidence interval [CI], 28.55-31.56) with a DPE technique and 45.25 mg (90% CI, 42.80-52.03) with an EPL technique. CONCLUSIONS: Using a biased-coin, sequential allocation method, the DPE technique requires less bupivacaine to achieve effective initial analgesia (ED90) when compared to the EPL technique.

Multivariable prediction models for atrial fibrillation after cardiac surgery: a systematic review protocol.

INTRODUCTION: Dozens of multivariable prediction models for atrial fibrillation after cardiac surgery (AFACS) have been published, but none have been incorporated into regular clinical practice. One of the reasons for this lack of adoption is poor model performance due to methodological weaknesses in model development. In addition, there has been little external validation of these existing models to evaluate their reproducibility and transportability. The aim of this systematic review is to critically appraise the methodology and risk of bias of papers presenting the development and/or validation of models for AFACS. METHODS: We will identify studies that present the development and/or validation of a multivariable prediction model for AFACS through searches of PubMed, Embase and Web of Science from inception to 31 December 2021. Pairs of reviewers will independently extract model performance measures, assess methodological quality and assess risk of bias of included studies using extraction forms adapted from a combination of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and the Prediction Model Risk of Bias Assessment Tool. Extracted information will be reported by narrative synthesis and descriptive statistics. ETHICS AND DISSEMINATION: This systemic review will only include published aggregate data, so no protected health information will be used. Study findings will be disseminated through peer-reviewed publications and scientific conference presentations. Further, this review will identify weaknesses in past AFACS prediction model development and validation methodology so that subsequent studies can improve upon prior practices and produce a clinically useful risk estimation tool. PROSPERO REGISTRATION NUMBER: CRD42019127329.

Prognostic model for atrial fibrillation after cardiac surgery: a UK cohort study.

OBJECTIVE: To develop a validated clinical prognostic model to determine the risk of atrial fibrillation after cardiac surgery as part of the PARADISE project (NIHR131227). METHODS: Prospective cohort study with linked electronic health records from a cohort of 5.6 million people in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. For model development, we considered a priori candidate predictors including demographics, medical history, medications, and clinical biomarkers. We evaluated associations between covariates and the AF incidence at the end of follow-up using logistic regression with the least absolute shrinkage and selection operator. The model was validated internally with the bootstrap method; subsequent performance was examined by discrimination quantified with the c-statistic and calibration assessed by calibration plots. The study follows TRIPOD guidelines. RESULTS: Between 1998 and 2016, 33,464 patients received cardiac surgery among the 5,601,803 eligible individuals. The final model included 13-predictors at baseline: age, year of index surgery, elevated CHA2DS2-VASc score, congestive heart failure, hypertension, acute coronary syndromes, mitral valve disease, ventricular tachycardia, valve surgery, receiving two combined procedures (e.g., valve replacement + coronary artery bypass grafting), or three combined procedures in the index procedure, statin use, and ethnicity other than white or black (statins and ethnicity were protective). This model had an optimism-corrected C-statistic of 0.68 both for the derivation and validation cohort. Calibration was good. CONCLUSIONS: We developed a model to identify a group of individuals at high risk of AF and adverse outcomes who could benefit from long-term arrhythmia monitoring, risk factor management, rhythm control and/or thromboprophylaxis.

External Validation of a Multivariable Prediction Model for Placenta Accreta Spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is a disorder of abnormal placentation associated with severe postpartum hemorrhage, maternal morbidity, and mortality. Predelivery prediction of this condition is important to determine appropriate delivery location and multidisciplinary planning for operative management. This study aimed to validate a prediction model for PAS developed by Weiniger et al in 2 cohorts who delivered at 2 different United States tertiary centers. METHODS: Cohort A (Brigham and Women's Hospital; N = 253) included patients with risk factors (prior cesarean delivery and placenta previa) and/or ultrasound features of PAS presenting to a tertiary-care hospital. Cohort B (Columbia University Irving Medical Center; N = 99) consisted of patients referred to a tertiary-care hospital specifically because of ultrasound features of PAS. Using the outcome variable of surgical and/or pathological diagnosis of PAS, discrimination (via c-statistic), calibration (via intercept, slope, and flexible calibration curve), and clinical usefulness (via decision curve analysis) were determined. RESULTS: The model c-statistics in cohorts A and B were 0.728 (95% confidence interval [CI], 0.662-0.794) and 0.866 (95% CI, 0.754-0.977) signifying acceptable and excellent discrimination, respectively. The calibration intercept (0.537 [95% CI, 0.154-0.980] for cohort A and 3.001 [95% CI, 1.899- 4.335] for B), slopes (0.342 [95% CI, 0.170-0.532] for cohort A and 0.604 [95% CI, -0.166 to 1.221] for B), and flexible calibration curves in each cohort indicated that the model underestimated true PAS risks on average and that there was evidence of overfitting in both validation cohorts. The use of the model compared to a treat-all strategy by decision curve analysis showed a greater net benefit of the model at a threshold probability of >0.25 in cohort A. However, no net benefit of the model over the treat-all strategy was seen in cohort B at any threshold probability. CONCLUSIONS: The performance of the Weiniger model is variable based on the case-mix of the population with regard to PAS clinical risk factors and ultrasound features, highlighting the importance of spectrum bias when applying this PAS prediction model to distinct populations. The model showed benefit for predicting PAS in populations with substantial case-mix heterogeneity at threshold probability of >25%.

Thrombosis-Related Loss of Arterial Lines in the First Wave of COVID-19 and Non-COVID-19 Intensive Care Unit Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis. Because invasive procedures in patients with COVID-19 may increase the risk for caregiver infection, better defining difficulties in maintaining arterial lines in COVID-19 patients is important. We sought to explore the association between COVID-19 infection and arterial line thrombosis in critically ill patients. METHODS: In this primary exploratory analysis, a multivariable Fine-Gray subdistribution hazard model was used to retrospectively estimate the association between critically ill COVID-19 (versus sepsis/acute respiratory distress syndrome [ARDS]) patients and the risk of arterial line removal for thrombosis (with arterial line removal for any other reason treated as a competing risk). As a sensitivity analysis, we compared the number of arterial line clots per 1000 arterial line days between critically ill COVID-19 and sepsis/ARDS patients using multivariable negative binomial regression. RESULTS: We retrospectively identified 119 patients and 200 arterial line insertions in patients with COVID-19 and 54 patients and 68 arterial line insertions with non-COVID ARDS. Using a Fine-Gray subdistribution hazard model, we found the adjusted subdistribution hazard ratio (95% confidence interval [CI]) for arterial line clot to be 2.18 (1.06-4.46) for arterial lines placed in COVID-19 patients versus non-COVID-19 sepsis/ARDS patients ( P = .034). Patients with COVID-19 had 36.3 arterial line clots per 1000 arterial line days compared to 19.1 arterial line clots per 1000 arterial line days in patients without COVID-19 (adjusted incidence rate ratio [IRR] [95% CI], 1.78 [0.94-3.39]; P = .078). CONCLUSIONS: Our study suggests that arterial line complications due to thrombosis are more likely in COVID-19 patients and supports the need for further research on the association between COVID-19 and arterial line dysfunction requiring replacement.

A Tutorial on Generative Adversarial Networks with Application to Classification of Imbalanced Data.

A challenge unique to classification model development is imbalanced data. In a binary classification problem, class imbalance occurs when one class, the minority group, contains significantly fewer samples than the other class, the majority group. In imbalanced data, the minority class is often the class of interest (e.g., patients with disease). However, when training a classifier on imbalanced data, the model will exhibit bias towards the majority class and, in extreme cases, may ignore the minority class completely. A common strategy for addressing class imbalance is data augmentation. However, traditional data augmentation methods are associated with overfitting, where the model is fit to the noise in the data. In this tutorial we introduce an advanced method for data augmentation: Generative Adversarial Networks (GANs). The advantages of GANs over traditional data augmentation methods are illustrated using the Breast Cancer Wisconsin study. To promote the adoption of GANs for data augmentation, we present an end-to-end pipeline that encompasses the complete life cycle of a machine learning project along with alternatives and good practices both in the paper and in a separate video. Our code, data, full results and video tutorial are publicly available in the paper's github repository.

A survey of pregnant patients' perspectives on the implementation of artificial intelligence in clinical care.

OBJECTIVE: To evaluate and understand pregnant patients' perspectives on the implementation of artificial intelligence (AI) in clinical care with a focus on opportunities to improve healthcare technologies and healthcare delivery. MATERIALS AND METHODS: We developed an anonymous survey and enrolled patients presenting to the labor and delivery unit at a tertiary care center September 2019-June 2020. We investigated the role and interplay of patient demographic factors, healthcare literacy, understanding of AI, comfort levels with various AI scenarios, and preferences for AI use in clinical care. RESULTS: Of the 349 parturients, 57.6% were between the ages of 25-34 years, 90.1% reported college or graduate education and 69.2% believed the benefits of AI use in clinical care outweighed the risks. Cluster analysis revealed 2 distinct groups: patients more comfortable with clinical AI use (Pro-AI) and those who preferred physician presence (AI-Cautious). Pro-AI patients had a higher degree of education, were more knowledgeable about AI use in their daily lives and saw AI use as a significant advancement in medicine. AI-Cautious patients reported a lack of human qualities and low trust in the technology as detriments to AI use. DISCUSSION: Patient trust and the preservation of the human physician-patient relationship are critical in moving forward with AI implementation in healthcare. Pregnant individuals are cautiously optimistic about AI use in their care. CONCLUSION: Our findings provide insights into the status of AI use in perinatal care and provide a platform for driving patient-centered innovations.

COVID-19 increases the risk for the onset of atrial fibrillation in hospitalized patients.

COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.

Factors Associated With Prescription Opioid Abuse and Dependence Among Those Reporting Prescription Opioid Misuse: A Retrospective Cross-Sectional Study.

BACKGROUND: Prescription opioid misuse is an ongoing epidemic in the United States. Though the number of people misusing prescription opioids is declining, the prevalence of abuse and dependence remains stable. This highlights the need to identify and intervene in factors leading to the escalation of prescription opioid misuse. OBJECTIVES: The aim of this study was to explore the association of prescription opioid-specific misuse factors such as pill source, misuse motivation, and misuse habits with abuse and dependence. STUDY DESIGN: A retrospective cross-sectional study. SETTING: Participants in the 2015 to 2018 National Survey on Drug Use and Health (NSDUH) reporting prescription opioid misuse in the past 12 months. METHODS: Simple and multivariable logistic regression were used to estimate the association of prescription opioid-specific misuse factors with prescription opioid abuse and dependence, which were determined by participant responses to screening questions according to DSM-IV criteria. RESULTS: After multivariable adjustment, prescription opioid abuse was associated with use in greater amounts than prescribed and misuse for 3-19 days in the past month, whereas dependence was associated with use in greater amounts and more often than prescribed, and misuse for 6 or more days in the past month. Initiating misuse in the past year and misuse without one's own prescription in the past year were associated with lower odds of opioid dependence. LIMITATIONS: Only associations and not causal relationships can be claimed between the factors and outcomes. Second, the survey relies on self-reported data, and there is likely both underreporting and overreporting, leading to bias towards the null. The survey target population was civilian, so it excluded individuals living in institutional group quarters such as hospitals, treatment facilities, nursing homes, and prisons. This study does not differentiate between prescription opioids used for acute versus chronic pain. CONCLUSIONS: Study results suggest the importance of the frequency of prescription opioid misuse as a possible risk factor for dependence and emphasize the need to monitor for misuse even in instances of acute pain.

Factors associated with heroin use among those reporting -prescription opioid misuse: Results from a nationally -representative sample.

OBJECTIVE: The present investigation aims to identify characteristics associated with heroin use among those reporting prescription opioid misuse from a nationally representative sample, and how these characteristics vary by urbanicity. DESIGN: A cross-sectional analysis. SETTING: Pooled 2015-2018 data from the National Survey on Drug Use and Health (NSDUH), the leading source for nationally representative substance use, mental health, and other health-related data and trends in the United States. PATIENTS AND PARTICIPANTS: 23,719 participants (12,109 male and 11,610 female) reporting previous prescription opioid misuse in the 2015-2018 NSDUH data. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Univariable and multivariable logistic regressions were used to assess the association of characteristics with heroin use, stratified by urbanicity. RESULTS: After multivariable adjustment, factors associated with heroin use among prescription opioid misusers were male sex, non-Hispanic White race, low educational attainment, recent nonopioid illicit drug use, and recent nonopioid prescription drug misuse. Commercial health insurance was associated with lower odds of heroin use among both rural and urban prescription opioid misusers, but an observed association between Medicaid and greater odds of heroin use was stronger among urban versus rural participants. In contrast, observed associations between illicit drug use other than marijuana in the past year and greater odds of heroin use were stronger among rural vs urban participants. CONCLUSION: Important differences exist between factors associated with heroin use among urban and rural prescription opioid misusers, and there is a need to consider broader polysubstance use trends and barriers to mental healthcare access to adequately address heroin use.

Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status.

BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE: This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 µg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN: In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS: The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 µg/mL. All patients had a plasma concentration >10 µg/mL for 1 hour after infusion. Plasma concentration was >10 µg/mL in more than half of the patients at 3 hours and fell <10 µg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION: After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 µg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

Frequency and Risk Factors for Difficult Intubation in Women Undergoing General Anesthesia for Cesarean Delivery: A Multicenter Retrospective Cohort Analysis.

BACKGROUND: Estimates for the incidence of difficult intubation in the obstetric population vary widely, although previous studies reporting rates of difficult intubation in obstetrics are older and limited by smaller samples. The goals of this study were to provide a contemporary estimate of the frequency of difficult and failed intubation in women undergoing general anesthesia for cesarean delivery and to elucidate risk factors for difficult intubation in women undergoing general anesthesia for cesarean delivery. METHODS: This is a multicenter, retrospective cohort study utilizing the Multicenter Perioperative Outcomes Group database. The study population included women aged 15 to 44 yr undergoing general anesthesia for cesarean delivery between 2004 and 2019 at 1 of 45 medical centers. Coprimary outcomes included the frequencies of difficult and failed intubation. Difficult intubation was defined as Cormack-Lehane view of 3 or greater, three or more intubation attempts, rescue fiberoptic intubation, rescue supraglottic airway, or surgical airway. Failed intubation was defined as any attempt at intubation without successful endotracheal tube placement. The rates of difficult and failed intubation were assessed. Several patient demographic, anatomical, and obstetric factors were evaluated for potential associations with difficult intubation. RESULTS: This study identified 14,748 cases of cesarean delivery performed under general anesthesia. There were 295 cases of difficult intubation, with a frequency of 1:49 (95% CI, 1:55 to 1:44; n = 14,531). There were 18 cases of failed intubation, with a frequency of 1:808 (95% CI, 1:1,276 to 1:511; n = 14,537). Factors with the highest point estimates for the odds of difficult intubation included increased body mass index, Mallampati score III or IV, small hyoid-to-mentum distance, limited jaw protrusion, limited mouth opening, and cervical spine limitations. CONCLUSIONS: In this large, multicenter, contemporary study of more than 14,000 general anesthetics for cesarean delivery, an overall risk of difficult intubation of 1:49 and a risk of failed intubation of 1:808 were observed. Most risk factors for difficult intubation were nonobstetric in nature. These data demonstrate that difficult intubation in obstetrics remains an ongoing concern.

Low-Dose Perioperative Corticosteroids Can Be Administered Without Additional Morbidity in Patients Undergoing Bilateral Total Knee Replacement: A Retrospective Follow-up Study of a Randomized Controlled Trial.

Background: Short-term benefits of perioperative corticosteroid injections (CSIs) for bilateral total knee replacement (BTKR) include suppressed inflammation, improved knee motion, and reduced pain. Very little is known about the long-term benefits, complications, and safety of corticosteroids administered in the perioperative period. Purpose: We sought to compare 3-year follow-up outcomes of BTKR patients who received perioperative CSI with those who received placebo. We hypothesized that there would be no statistically significant differences in functional outcomes or adverse events based on whether or not CSIs were administered in the perioperative period. Methods: We conducted a retrospective review of chart and registry data of BTKR patients from a prior randomized controlled trial to compare outcomes in patients who received hydrocortisone vs placebo injections after BTKR (ClinicalTrials.gov: NCT01399268 and NCT01815918). Outcomes were compared at 6 and 12 weeks and at 1, 2, and 3 years. The Knee Injury and Osteoarthritis Outcome Scores (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to evaluate clinical outcomes. Cochran-Mantel-Haenszel tests were used to compare the risk of complications between treatments after adjustment for trial. When possible, summary relative risk estimates were calculated using the Mantel-Haenszel method. Results: No BTKR patients in the treatment group developed an infection. The risk of complications did not increase in patients who received CSI compared with those who received placebo. Patients in the CSI group experienced greater reductions in pain and stiffness, though these results were not statistically significant. There were no statistically significant differences in the KOOS-Symptoms, KOOS-Activities of Daily Living, KOOS-Sports, KOOS-Quality of Life, or WOMAC Function scores. Conclusions: Low-dose corticosteroids can be administered in selected patients who undergo BTKR without increasing the risk of adverse events. At 3-year follow-up, administration of low-dose corticosteroids did not result in superior clinical outcomes scores when compared with placebo.

Inconsistent Methodology as a Barrier to Meaningful Research Outputs From Studies of Atrial Fibrillation After Cardiac Surgery.

Atrial fibrillation after cardiac surgery (AFACS) is a serious postoperative complication. There is significant research interest in this field but also relevant heterogeneity in reported AFACS definitions and approaches used for its identification. Few data exist on the extent of this variation in clinical studies. The authors reviewed the literature since 2001 and included manuscripts reporting outcomes of AFACS in adults. They excluded smaller studies and studies in which patients did not undergo a sternotomy. The documented protocol in each manuscript was analyzed according to six different categories to determine how AFACS was defined, which techniques were used to identify it, and the inclusion and/or exclusion criteria. They also noted when a category was not described in the documented protocol. The authors identified 302 studies, of which 92 were included. Sixty-two percent of studies were randomized controlled trials. There was significant heterogeneity in the manuscripts, including the exclusion of patients with preoperative AF, the definition and duration of AF needed to meet the primary endpoint, the type of screening approach (continuous, episodic, or opportunistic), the duration of monitoring during the study period in days, the diagnosis with predefined electrocardiogram criteria, and the requirement for independent confirmation by study investigators. Furthermore, the definitions of these criteria frequently were not described. Consistent reporting standards for AFACS research are needed to advance scientific progress in the field. The authors here propose pragmatic standards for trial design and reporting standards. These include adequate sample size estimation, a clear definition of the AFACS endpoints, and a protocol for AFACS detection.