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  1. BACKGROUND:

    Classification of perioperative risk is important for patient care, resource allocation, and guiding shared decision-making. Using discriminative features from the electronic health record (EHR), machine-learning algorithms can create digital phenotypes among heterogenous populations, representing distinct patient subpopulations grouped by shared characteristics, from which we can personalize care, anticipate clinical care trajectories, and explore therapies. We hypothesized that digital phenotypes in preoperative settings are associated with postoperative adverse events including in-hospital and 30-day mortality, 30-day surgical redo, intensive care unit (ICU) admission, and hospital length of stay (LOS).

    METHODS:

    We identified all laminectomies, colectomies, and thoracic surgeries performed over a 9-year period from a large hospital system. Seventy-seven readily extractable preoperative features were first selected from clinical consensus, including demographics, medical history, and lab results. Three surgery-specific datasets were built and split into derivation and validation cohorts using chronological occurrence. Consensusk-means clustering was performed independently on each derivation cohort, from which phenotypes’ characteristics were explored. Cluster assignments were used to train a random forest model to assign patient phenotypes in validation cohorts. We reconducted descriptive analyses on validation cohorts to confirm the similarity of patient characteristics with derivation cohorts, and quantified the association of each phenotype with postoperative adverse events by using the area under receiver operating characteristic curve (AUROC). We compared our approach to American Society of Anesthesiologists (ASA) alone and investigated a combination of our phenotypes with the ASA score.

    RESULTS:

    A total of 7251 patients met inclusion criteria, of which 2770 were held out in a validation dataset based on chronological occurrence. Using segmentation metrics and clinical consensus, 3 distinct phenotypes were created for each surgery. The main features used for segmentation included urgency of the procedure, preoperative LOS, age, and comorbidities. The most relevant characteristics varied for each of the 3 surgeries. Low-risk phenotype alpha was the most common (2039 of 2770, 74%), while high-risk phenotype gamma was the rarest (302 of 2770, 11%). Adverse outcomes progressively increased from phenotypes alpha to gamma, including 30-day mortality (0.3%, 2.1%, and 6.0%, respectively), in-hospital mortality (0.2%, 2.3%, and 7.3%), and prolonged hospital LOS (3.4%, 22.1%, and 25.8%). When combined with the ASA score, digital phenotypes achieved higher AUROC than the ASA score alone (hospital mortality: 0.91 vs 0.84; prolonged hospitalization: 0.80 vs 0.71).

    CONCLUSIONS:

    For 3 frequently performed surgeries, we identified 3 digital phenotypes. The typical profiles of each phenotype were described and could be used to anticipate adverse postoperative events.

     
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    Free, publicly-accessible full text available December 5, 2024
  2. Background

    Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening.

    Methods and findings

    For model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis.

    Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables—age, smoking duration, and pack-years—achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts.

    Conclusions

    We present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings.

     
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  3. Importance

    Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence.

    Objective

    To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points.

    Design, Setting, and Participants

    This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021.

    Exposures

    Low-dose CT screening for lung cancer.

    Main Outcomes and Measures

    The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography–CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time.

    Results

    Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69).

    Conclusions and Relevance

    In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.

     
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  4. Abstract

    When aiming to make predictions over targets in the pharmacological setting, a data‐focused approach aims to learn models based on a collection of labeled examples. Unfortunately, data sharing is not always possible, and this can result in many different models trained on disparate populations, leading to the natural question of how best to use and combine them when making a new prediction. Previous work has focused on global model selection or ensembling, with the result of a single final model across the feature space. Machine‐learning models perform notoriously poorly on data outside their training domain, however, due to a problem known as covariate shift, and so we argue that when ensembling models the weightings for individual instances must reflect their respective domains—in other words, models that are more likely to have seen information on that instance should have more attention paid to them. We introduce a method for such an instance‐wise ensembling of models called Synthetic Model Combination (SMC), including a novel representation learning step for handling sparse high‐dimensional domains. We demonstrate the use of SMC on an example with dosing predictions for vancomycin, although emphasize the applicability of the method to any scenario involving the use of multiple models.

     
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  5. Abstract

    Accurate characterization of microcalcifications (MCs) in 2D digital mammography is a necessary step toward reducing the diagnostic uncertainty associated with the callback of indeterminate MCs. Quantitative analysis of MCs can better identify MCs with a higher likelihood of ductal carcinoma in situ or invasive cancer. However, automated identification and segmentation of MCs remain challenging with high false positive rates. We present a two-stage multiscale approach to MC segmentation in 2D full-field digital mammograms (FFDMs) and diagnostic magnification views. Candidate objects are first delineated using blob detection and Hessian analysis. A regression convolutional network, trained to output a function with a higher response near MCs, chooses the objects which constitute actual MCs. The method was trained and validated on 435 screening and diagnostic FFDMs from two separate datasets. We then used our approach to segment MCs on magnification views of 248 cases with amorphous MCs. We modeled the extracted features using gradient tree boosting to classify each case as benign or malignant. Compared to state-of-the-art comparison methods, our approach achieved superior mean intersection over the union (0.670 ± 0.121 per image versus 0.524 ± 0.034 per image), intersection over the union per MC object (0.607 ± 0.250 versus 0.363 ± 0.278) and true positive rate of 0.744 versus 0.581 at 0.4 false positive detections per square centimeter. Features generated using our approach outperformed the comparison method (0.763 versus 0.710 AUC) in distinguishing amorphous calcifications as benign or malignant.

     
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  6. Guillot, Gilles (Ed.)

    Diagnostic and prognostic models are increasingly important in medicine and inform many clinical decisions. Recently, machine learning approaches have shown improvement over conventional modeling techniques by better capturing complex interactions between patient covariates in a data-driven manner. However, the use of machine learning introduces technical and practical challenges that have thus far restricted widespread adoption of such techniques in clinical settings. To address these challenges and empower healthcare professionals, we present an open-source machine learning framework, AutoPrognosis 2.0, to facilitate the development of diagnostic and prognostic models. AutoPrognosis leverages state-of-the-art advances in automated machine learning to develop optimized machine learning pipelines, incorporates model explainability tools, and enables deployment of clinical demonstrators,withoutrequiring significant technical expertise. To demonstrate AutoPrognosis 2.0, we provide an illustrative application where we construct a prognostic risk score for diabetes using the UK Biobank, a prospective study of 502,467 individuals. The models produced by our automated framework achieve greater discrimination for diabetes than expert clinical risk scores. We have implemented our risk score as a web-based decision support tool, which can be publicly accessed by patients and clinicians. By open-sourcing our framework as a tool for the community, we aim to provide clinicians and other medical practitioners with an accessible resource to develop new risk scores, personalized diagnostics, and prognostics using machine learning techniques.

    Software:https://github.com/vanderschaarlab/AutoPrognosis

     
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