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

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

The role of abiotic and biotic factors in the unequal body shape diversification of a Gondwanan fish radiation (Otophysi: Characiformes).

Understanding why some clades diversify greatly while others do not is a major goal of evolutionary biology. Both abiotic and biotic factors are important in driving unequal morphological diversity across the tree of life. However, few studies have quantified how abiotic habitat and community composition differences influence unequal morphological diversification in spatiotemporally diffuse radiations. We use geometric morphometrics, abiotic habitat data generated by Geographic Information Systems (GIS) analyses, evolutionary simulations, and phylogenetic comparative methods to determine whether random evolution, habitat variation, competition for niches, or a combination of factors influenced the unequal body shape diversity of a Gondwanan freshwater fish radiation. We find that Neotropical characiform lineages, which exhibit substantially more body shape diversity than their African counterparts, occupy significantly more slope and elevation habitats than African lineages. Differences in habitat occupation between the continental radiations occur through a combination of likely competition with cypriniform fishes in Africa restricting access to higher slope and elevation habitats and significantly more low-elevation and slope habitats available in the Neotropics. Our findings suggest that spatiotemporally widespread radiations, like Characiformes, do not diversify across homogenized habitats and biotic assemblages, with differences in community structure and physical habitat playing an important role in driving unequal morphological diversification.

Diadromy Drives Elevated Rates of Trait Evolution and Ecomorphological Convergence in Clupeiformes (Herring, Shad, and Anchovies).

AbstractMigration can have a profound influence on rates and patterns of phenotypic evolution. Diadromy is the migration between marine and freshwater habitats for feeding and reproduction that can require individuals to travel tens to thousands of kilometers. The high energetic demands of diadromy are predicted to select for ecomorphological traits that maximize swimming and locomotor efficiency. Intraspecific studies have shown repeated instances of divergence among diadromous and nondiadromous populations in locomotor and foraging traits, which suggests that at a macroevolutionary scale diadromous lineages may experience convergent evolution onto one or multiple adaptive optima. We tested for differences in rates and patterns of phenotypic evolution among diadromous and nondiadromous lineages in Clupeiformes, a clade that has evolved diadromy more than 10 times. Our results show that diadromous clupeiforms show convergent evolution for some locomotor traits and faster rates of evolution, which we propose are adaptive responses to the locomotor demands of migration. We also find evidence that diadromous lineages show convergence into multiple regions of multivariate trait space and suggest that these respective trait spaces are associated with differences in migration and trophic ecology. However, not all locomotor traits and no trophic traits show evidence of convergence or elevated rates of evolution associated with diadromy. Our results show that long-distance migration influences the tempo and patterns of phenotypic evolution at macroevolutionary scales, but there is not a single diadromous syndrome.

Revisiting the Landscape of Potential Small and Drug Substance Related Nitrosamines in Pharmaceuticals.

N-Nitrosamines are a class of indirect acting mutagens, as their metabolic degradation leads to the formation of the DNA-alkylating diazonium ion. Following up on the in-silico identification of thousands of nitrosamines that can potentially be derived from small molecule drugs and their known impurities described in a previous publication, we have now re-analyzed this dataset to apply EMA's Carcinogenic Potency Categorization Approach (CPCA) introduced with the 16th revision of their Q&A document for Marketing Authorization Holders. We find that the majority of potential nitrosamines from secondary amine precursors belongs to potency categories 4 and 5, corresponding to an acceptable daily intake of 1500 ng, whereas nitrosamines from tertiary amine precursors distribute more evenly among all categories, resulting in a substantial number of structures that are assigned the more challenging acceptable intakes of 18 ng/day and 100 ng/day for potency categories 1 and 2, respectively. However, the nitrosative dealkylation pathway for tertiary amine is generally far slower than the direct nitrosation on secondary amines, with a direct nitrosation mechanism suspected only for structures featuring electron-rich (hetero)aromatic substituents. This allows for greater focus towards those structures that require further review, and we demonstrate that their number is not substantial. In addition, we reflect on the nitrosamine risk posed by secondary amine API impurities and demonstrate that based on the ICH Q3A/B identification threshold unknown impurities may exist that could be transformed to relevant amounts of NA. We also demonstrate that the analytical sensitivity required for the quantification of high potency nitrosamines can be problematic especially for high dose APIs. In summary, the regulatory framework rolled out with the latest Q&A document represents a substantial improvement compared with the previous situation, but further refinement through interaction between manufacturers, regulators, not-for-profit and academic institutions will be required to ensure patient access to vital medicines without compromising safety.

Integrating current analyses of the breast cancer microbiome.

Many cancer types have significant associations with their resident microbial communities-emerging evidence suggests that breast cancers also interact with the local tissue-associated microbiota. Microbiome research advances rapidly and analysis pipelines and databases are updated frequently. This dynamic environment makes comparative evaluations challenging. Here, we have integrated all publicly available studies related to breast cancer and the mammary microbiome in light of advances in this rapidly progressing field. Based on alpha diversity, beta diversity, proportional abundance, and statistical analyses, we observed differences between our modern analytical approaches and the original findings. We were able to classify and identify additional taxa across samples through abundance analyses and identify previously unidentified statistically significant taxa. In our updated analyses there were more taxa identified as statistically significant in comparison to the original studies' results. In the re-analysis for The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease by Hieken et al., there were twelve statistically significant differentially abundant taxa identified in breast tissue microbiota in benign and invasive cancer disease states. In the re-analysis for The Microbiota of Breast Tissue and Its Association with Breast Cancer by Urbaniak et al., there were 18 taxa identified as statistically significant. In the re-analysis for Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors by Chan et al., there were three genera identified as statistically significant in the skin and fluid samples. Our work has discovered that reanalyses are necessary for microbiome studies, especially older 16S studies. Through our re-analysis, we classified and identified more phyla and genera across studies, which supports the notion that reanalyses provide new insights to the microbiome field and help to assess robusticity of previously published findings by using new and updated tools and databases.

Simultaneous integration and modularity underlie the exceptional body shape diversification of characiform fishes.

Evolutionary biology has long striven to understand why some lineages diversify exceptionally while others do not. Most studies have focused on how extrinsic factors can promote differences in diversification dynamics, but a clade's intrinsic modularity and integration can also catalyze or restrict its evolution. Here, we integrate geometric morphometrics, phylogenetic comparative methods and visualizations of covariance to infer the presence of distinct modules in the body plan of Characiformes, an ecomorphologically diverse fish radiation. Strong covariances reveal a cranial module, and more subtle patterns support a statistically significant subdivision of the postcranium into anterior (precaudal) and posterior (caudal) modules. We uncover substantial covariation among cranial and postcranial landmarks, indicating body-wide evolutionary integration as lineages transition between compressiform and fusiform body shapes. A novel method of matrix subdivision reveals that within- and among-module covariation contributes substantially to the overall eigenstructure of characiform morphospace, and that both phenomena led to biologically important divergence among characiform lineages. Functional integration between the cranium and post-cranial skeleton appears to have allowed lineages to optimize the aspect ratio of their bodies for locomotion, while the capacity for independent change in the head, body and tail likely eased adaptation to diverse dietary and hydrological regimes. These results reinforce a growing consensus that modularity and integration synergize to promote diversification.

The Landscape of Potential Small and Drug Substance Related Nitrosamines in Pharmaceuticals.

This article reports the outcome of an in silico analysis of more than 12,000 small molecule drugs and drug impurities, identifying the nitrosatable structures, assessing their potential to form nitrosamines under relevant conditions and the challenges to determine compound-specific AIs based on data available or read-across approaches for these nitrosamines and their acceptance by health authorities. Our data indicate that the presence of nitrosamines in pharmaceuticals is likely more prevalent than originally expected. In total, 40.4 % of the analyzed APIs and 29.6 % of the API impurities are potential nitrosamine precursors. Most structures identified through our workflow could form complex API-related nitrosamines, so-called nitrosamine drug substance related impurities (NDSRIs), although we also found structures that could release the well-known small and potent nitrosamines NDMA, NDEA, and others. Due to common structural motifs including secondary or tertiary amine moieties, whole essential drug classes such as beta blockers and ACE inhibitors are at risk. To avoid the risk of drug shortages or even the complete loss of therapeutic options, it will be essential that the well-established ICH M7 principles remain applicable for nitrosamines and that that the industry and regulatory authorities keep an open communication not only about the science but also to make sure there is a good balance between risk and benefit to patients.

Retrospective analysis of sepsis in cutaneous T-cell lymphoma reveals significantly greater risk in Black patients.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and resource utilization among patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVE: To characterize the demographic, clinical, and microbial attributes distinguishing patients with CTCL sepsis from other patients with non-Hodgkin lymphoma (NHL) sepsis and patients with CTCL in general. METHODS: Two-part retrospective cohort study at an academic medical center from 2001-2019 involving patients with CTCL (n = 97) and non-CTCL NHL (n = 88) admitted with sepsis, and a same-institution CTCL patient database (n = 1094). Overall survival was estimated by Kaplan-Meier analyses. RESULTS: Patients with CTCL sepsis were more likely to be older, Black, experience more sepsis episodes, die or be readmitted within 30 days of an inpatient sepsis episode, and develop Gram-positive bacteremia than patients with non-CTCL NHL sepsis. Staphylococcus aureus and Escherichia coli were the most frequently speciated organisms in CTCL (26%) and non-CTCL NHL (14%), respectively. No between-group differences were identified regarding sex, presence of central line, chemotherapy use, or disease stage. Compared with general patients with CTCL, patients with sepsis were Black and exhibited advanced-stage disease, higher body surface area involvement, and higher lactate dehydrogenase levels. LIMITATIONS: Single institution, retrospective nature may limit generalizability. CONCLUSION: Awareness of CTCL-specific risk factors is crucial for guiding sepsis prevention and improving patient outcomes.

Relugolix: Five Reasons Why the US Food and Drug Administration Should Have Exercised Restraint.

We highlight concerns regarding the approval of relugolix for patients with prostate cancer. These include the unsuitable comparator arm and primary endpoint in the HERO trial, as well as potential selection bias and the poor representativeness of the trial population. Dosing adherence to a daily tablet may also be an issue in comparison to injections at 3-mo intervals. Rigorous postmarketing trials of relugolix assessing clinically meaningful endpoints for these patients are needed.

Gut microbiota analyses of cutaneous T-cell lymphoma patients undergoing narrowband ultraviolet B therapy reveal alterations associated with disease treatment.

Recent studies have shown a close relationship between cutaneous T-cell lymphoma (CTCL) and its microbiome. CTCL disease progression is associated with gut dysbiosis and alterations in bacterial taxa parallel those observed in immunologically similar atopic dermatitis. Moreover, the microbial profile of lesional skin may predict response to narrowband ultraviolet B (nbUVB), a common skin-directed therapy. However, the relationship between the gut microbiome, an immunologically vital niche, and nbUVB remains unexplored in CTCL. Herein, we performed 16S rRNA sequencing and PICRUSt2 predictive metagenomics on DNA extracted from stool swabs of 13 CTCL patients treated with nbUVB, 8 non-treated patients, and 13 healthy controls. Disease response was assessed with modified Severity Weighted Assessment Tool (mSWAT); of nbUVB-treated patients, 6 improved (decreased mSWAT), 2 remained stable, and 5 worsened (increased mSWAT). Protective commensal bacteria including Lactobacillaceae and Erysipelatoclostridiaceae were significantly less abundant in CTCL patients compared to controls. With treatment, the CTCL gut microbiome exhibited decreased phylogenetic diversity and lower relative abundance of pro-inflammatory Sutterellaceae. Sutterellaceae was also significantly more abundant in patients who worsened, and Eggerthellaceae and Erysipelotrichaceae trended higher in patients who improved. Finally, PICRUSt2 functional predictions based on shifts in abundance of bacterial sequences repeatedly identified alterations in inositol degradation, which plays a key role in host immunomodulation, including inositol phospholipid signaling relevant to T-cell survival and proliferation. Our results bolster the paradigm of gut dysbiosis in CTCL and its functional implications in disease pathogenesis, and further delineate bacterial taxa associated with nbUVB response and with nbUVB treatment itself.

Machine Learning for the Prediction of Procedural Case Durations Developed Using a Large Multicenter Database: Algorithm Development and Validation Study.

BACKGROUND: Accurate projections of procedural case durations are complex but critical to the planning of perioperative staffing, operating room resources, and patient communication. Nonlinear prediction models using machine learning methods may provide opportunities for hospitals to improve upon current estimates of procedure duration. OBJECTIVE: The aim of this study was to determine whether a machine learning algorithm scalable across multiple centers could make estimations of case duration within a tolerance limit because there are substantial resources required for operating room functioning that relate to case duration. METHODS: Deep learning, gradient boosting, and ensemble machine learning models were generated using perioperative data available at 3 distinct time points: the time of scheduling, the time of patient arrival to the operating or procedure room (primary model), and the time of surgical incision or procedure start. The primary outcome was procedure duration, defined by the time between the arrival and the departure of the patient from the procedure room. Model performance was assessed by mean absolute error (MAE), the proportion of predictions falling within 20% of the actual duration, and other standard metrics. Performance was compared with a baseline method of historical means within a linear regression model. Model features driving predictions were assessed using Shapley additive explanations values and permutation feature importance. RESULTS: A total of 1,177,893 procedures from 13 academic and private hospitals between 2016 and 2019 were used. Across all procedures, the median procedure duration was 94 (IQR 50-167) minutes. In estimating the procedure duration, the gradient boosting machine was the best-performing model, demonstrating an MAE of 34 (SD 47) minutes, with 46% of the predictions falling within 20% of the actual duration in the test data set. This represented a statistically and clinically significant improvement in predictions compared with a baseline linear regression model (MAE 43 min; P<.001; 39% of the predictions falling within 20% of the actual duration). The most important features in model training were historical procedure duration by surgeon, the word "free" within the procedure text, and the time of day. CONCLUSIONS: Nonlinear models using machine learning techniques may be used to generate high-performing, automatable, explainable, and scalable prediction models for procedure duration.

Development and Testing of a Data Capture Device for Use With Clinical Incentive Spirometers: Testing and Usability Study.

BACKGROUND: The incentive spirometer is a basic and common medical device from which electronic health care data cannot be directly collected. As a result, despite numerous studies investigating clinical use, there remains little consensus on optimal device use and sparse evidence supporting its intended benefits such as prevention of postoperative respiratory complications. OBJECTIVE: The aim of the study is to develop and test an add-on hardware device for data capture of the incentive spirometer. METHODS: An add-on device was designed, built, and tested using reflective optical sensors to identify the real-time location of the volume piston and flow bobbin of a common incentive spirometer. Investigators manually tested sensor level accuracies and triggering range calibrations using a digital flowmeter. A valid breath classification algorithm was created and tested to determine valid from invalid breath attempts. To assess real-time use, a video game was developed using the incentive spirometer and add-on device as a controller using the Apple iPad. RESULTS: In user testing, sensor locations were captured at an accuracy of 99% (SD 1.4%) for volume and 100% accuracy for flow. Median and average volumes were within 7.5% (SD 6%) of target volume sensor levels, and maximum sensor triggering values seldom exceeded intended sensor levels, showing a good correlation to placement on 2 similar but distinct incentive spirometer designs. The breath classification algorithm displayed a 100% sensitivity and a 99% specificity on user testing, and the device operated as a video game controller in real time without noticeable interference or delay. CONCLUSIONS: An effective and reusable add-on device for the incentive spirometer was created to allow the collection of previously inaccessible incentive spirometer data and demonstrate Internet-of-Things use on a common hospital device. This design showed high sensor accuracies and the ability to use data in real-time applications, showing promise in the ability to capture currently inaccessible clinical data. Further use of this device could facilitate improved research into the incentive spirometer to improve adoption, incentivize adherence, and investigate the clinical effectiveness to help guide clinical care.

Narrowband ultraviolet B response in cutaneous T-cell lymphoma is characterized by increased bacterial diversity and reduced Staphylococcus aureus and Staphylococcus lugdunensis.

Skin microbiota have been linked to disease activity in cutaneous T-cell lymphoma (CTCL). As the skin microbiome has been shown to change after exposure to narrowband ultraviolet B (nbUVB) phototherapy, a common treatment modality used for CTCL, we performed a longitudinal analysis of the skin microbiome in CTCL patients treated with nbUVB. 16S V4 rRNA gene amplicon sequencing for genus-level taxonomic resolution, tuf2 amplicon next generation sequencing for staphylococcal speciation, and bioinformatics were performed on DNA extracted from skin swabs taken from lesional and non-lesional skin of 25 CTCL patients receiving nbUVB and 15 CTCL patients not receiving nbUVB from the same geographical region. Disease responsiveness to nbUVB was determined using the modified Severity Weighted Assessment Tool: 14 (56%) patients responded to nbUVB while 11 (44%) patients had progressive disease. Microbial α-diversity increased in nbUVB-responders after phototherapy. The relative abundance of Staphylococcus, Corynebacterium, Acinetobacter, Streptococcus, and Anaerococcus differentiated nbUVB responders and non-responders after treatment (q<0.05). Microbial signatures of nbUVB-treated patients demonstrated significant post-exposure depletion of S. aureus (q=0.024) and S. lugdunensis (q=0.004) relative abundances. Before nbUVB, responder lesional skin harboured higher levels of S. capitis (q=0.028) and S. warneri (q=0.026) than non-responder lesional skin. S. capitis relative abundance increased in the lesional skin of responders (q=0.05) after phototherapy; a similar upward trend was observed in non-responders (q=0.09). Post-treatment skin of responders exhibited significantly reduced S. aureus (q=0.008) and significantly increased S. hominis (q=0.006), S. pettenkoferi (q=0.021), and S. warneri (q=0.029) relative abundances compared to that of no-nbUVB patients. Staphylococcus species abundance was more similar between non-responders and no-nbUVB patients than between responders and no-nbUVB patients. In sum, the skin microbiome of CTCL patients who respond to nbUVB is different from that of non-responders and untreated patients, and is characterized by shifts in S. aureus and S. lugdunensis. Non-responsiveness to phototherapy may reflect more aggressive disease at baseline.

Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria.

The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.

Understanding How Older Adults with Communication Difficulties Access Health Services: What We Can Learn from the National Health and Aging Trends Study (NHATS).

People with communication disorders face barriers to accessing safe and respectful healthcare. These barriers result in increased healthcare complications and inefficiencies, both of which contribute to increased healthcare costs. One obstacle to advocating for accommodations that could improve healthcare for this population is the absence of cost effectiveness studies of such accommodations specifically, as well as a paucity of data defining the needs of this population in general. The purpose of this study was to explore how people with communication and swallowing difficulties are characterized in the National Health and Aging Trends Study (NHATS), a nationally representative survey of Medicare beneficiaries aged 65 and older, and how they manage their healthcare. Cross-sectional data from the NHATS rounds 5 to 9 (2015-2019) resulted in 8,038 unique respondents, 3,243 of who reported speech, memory, hearing, and/or swallowing difficulties. More than 90% of respondents with communication difficulties reported having a regular doctor. Less than 60% of respondents with communication difficulties had a family member or caregiver go to medical appointments with them, and around 70% of that subset of participants received help from that caregiver with communication during appointments. Fewer than 15% of respondents with communication difficulties used the internet for healthcare communication or information. Less than 5% of respondents across all communication difficulty categories had received rehabilitation services for communication in the year prior to their survey responses. While the information gleaned from NHATS points to likely gaps between the needs people with communication disorders may have for safe and accessible healthcare, and the support available, future research is needed to improve and clarify how communication disorders are defined and characterized in large-scale surveys to generate more interpretable data. These stronger empirical foundations are needed to support cost-effectiveness analyses to advocate for better communication accessibility of healthcare settings.

Association of Anesthesiologist Staffing Ratio With Surgical Patient Morbidity and Mortality.

Importance: Recent studies have investigated the effect of overlapping surgeon responsibilities or nurse to patient staffing ratios on patient outcomes, but the association of overlapping anesthesiologist responsibilities with patient outcomes remains unexplored to our knowledge. Objective: To examine the association between different levels of anesthesiologist staffing ratios and surgical patient morbidity and mortality. Design, Setting, and Participants: A retrospective, matched cohort study consisting of major noncardiac inpatient surgical procedures performed from January 1, 2010, to October 31, 2017, was conducted in 23 US academic and private hospitals. A total of 866 453 adult patients (aged ≥18 years) undergoing major inpatient surgery within the Multicenter Perioperative Outcomes Group electronic health record registry were included. Anesthesiologist sign-in and sign-out times were used to calculate a continuous time-weighted average staffing ratio variable for each operation. Propensity score-matching methods were applied to create balanced sample groups with respect to patient-, operative-, and hospital-level confounders and resulted in 4 groups based on anesthesiologist staffing ratio. Groups consisted of patients receiving care from an anesthesiologist covering 1 operation (group 1), more than 1 to no more than 2 overlapping operations (group 1-2), more than 2 to no more than 3 overlapping operations (group 2-3), and more than 3 to no more than 4 overlapping operations (group 3-4). Data analysis was performed from October 2019 to October 2021. Exposure: Undergoing a major inpatient surgical operation that involved an anesthesiologist providing care for up to 4 overlapping operations. Main Outcomes and Measures: The primary composite outcome was 30-day mortality and 6 major surgical morbidities (cardiac, respiratory, gastrointestinal, urinary, bleeding, and infectious complications) derived from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision discharge diagnosis codes. Results: In all, 578 815 adult patients (mean [SD] age, 55.7 [16.2] years; 55.1% female) were analyzed. After matching operations according to anesthesiologist staffing ratio, 48 555 patients were in group 1; 247 057, group 1-2; 216 193, group 2-3; and 67 010, group 3-4. Increasing anesthesiologist coverage responsibilities was associated with an increase in risk-adjusted surgical patient morbidity and mortality. Compared with patients in group 1-2, those in group 2-3 had a 4% relative increase in risk-adjusted mortality and morbidity (5.06% vs 5.25%; adjusted odds ratio [AOR], 1.04; 95% CI, 1.01-1.08; P = .02) and those in group 3-4 had a 14% increase in risk-adjusted mortality and morbidity (5.06% vs 5.75%; AOR, 1.15; 95% CI, 1.09-1.21; P < .001). Conclusions and Relevance: This study's findings suggest that increasing overlapping coverage by anesthesiologists is associated with increased surgical patient morbidity and mortality. Therefore, the potential effects of staffing ratios in perioperative team models should be considered in clinical coverage efforts.