Search

Abstract Background Random forests have become popular for clinical risk prediction modeling. In a case study on predicting ovarian malignancy, we observed training AUCs close to 1. Although this suggests overfitting, performance was competitive on test data. We aimed to understand the behavior of random forests for probability estimation by (1) visualizing data space in three real-world case studies and (2) a simulation study. Methods For the case studies, multinomial risk estimates were visualized using heatmaps in a 2-dimensional subspace. The simulation study included 48 logistic data-generating mechanisms (DGM), varying the predictor distribution, the number of predictors, the correlation between predictors, the true AUC, and the strength of true predictors. For each DGM, 1000 training datasets of size 200 or 4000 with binary outcomes were simulated, and random forest models were trained with minimum node size 2 or 20 using the ranger R package, resulting in 192 scenarios in total. Model performance was evaluated on large test datasets (N = 100,000). Results The visualizations suggested that the model learned “spikes of probability” around events in the training set. A cluster of events created a bigger peak or plateau (signal), isolated events local peaks (noise). In the simulation study, median training AUCs were between 0.97 and 1 unless there were 4 binary predictors or 16 binary predictors with a minimum node size of 20. The median discrimination loss, i.e., the difference between the median test AUC and the true AUC, was 0.025 (range 0.00 to 0.13). Median training AUCs had Spearman correlations of around 0.70 with discrimination loss. Median test AUCs were higher with higher events per variable, higher minimum node size, and binary predictors. Median training calibration slopes were always above 1 and were not correlated with median test slopes across scenarios (Spearman correlation − 0.11). Median test slopes were higher with higher true AUC, higher minimum node size, and higher sample size. Conclusions Random forests learn local probability peaks that often yield near perfect training AUCs without strongly affecting AUCs on test data. When the aim is probability estimation, the simulation results go against the common recommendation to use fully grown trees in random forest models.

Objectives To conduct a systematic review of studies externally validating the ADNEX (Assessment of Different Neoplasias in the adnexa) model for diagnosis of ovarian cancer and to present a meta-analysis of its performance.Design Systematic review and meta-analysis of external validation studiesData sources Medline, Embase, Web of Science, Scopus, and Europe PMC, from 15 October 2014 to 15 May 2023.Eligibility criteria for selecting studies All external validation studies of the performance of ADNEX, with any study design and any study population of patients with an adnexal mass. Two independent reviewers extracted the data. Disagreements were resolved by discussion. Reporting quality of the studies was scored with the TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) reporting guideline, and methodological conduct and risk of bias with PROBAST (Prediction model Risk Of Bias Assessment Tool). Random effects meta-analysis of the area under the receiver operating characteristic curve (AUC), sensitivity and specificity at the 10% risk of malignancy threshold, and net benefit and relative utility at the 10% risk of malignancy threshold were performed.Results 47 studies (17 007 tumours) were included, with a median study sample size of 261 (range 24-4905). On average, 61% of TRIPOD items were reported. Handling of missing data, justification of sample size, and model calibration were rarely described. 91% of validations were at high risk of bias, mainly because of the unexplained exclusion of incomplete cases, small sample size, or no assessment of calibration. The summary AUC to distinguish benign from malignant tumours in patients who underwent surgery was 0.93 (95% confidence interval 0.92 to 0.94, 95% prediction interval 0.85 to 0.98) for ADNEX with the serum biomarker, cancer antigen 125 (CA125), as a predictor (9202 tumours, 43 centres, 18 countries, and 21 studies) and 0.93 (95% confidence interval 0.91 to 0.94, 95% prediction interval 0.85 to 0.98) for ADNEX without CA125 (6309 tumours, 31 centres, 13 countries, and 12 studies). The estimated probability that the model has use clinically in a new centre was 95% (with CA125) and 91% (without CA125). When restricting analysis to studies with a low risk of bias, summary AUC values were 0.93 (with CA125) and 0.91 (without CA125), and estimated probabilities that the model has use clinically were 89% (with CA125) and 87% (without CA125).Conclusions The results of the meta-analysis indicated that ADNEX performed well in distinguishing between benign and malignant tumours in populations from different countries and settings, regardless of whether the serum biomarker, CA125, was used as a predictor. A key limitation was that calibration was rarely assessed.Systematic review registration PROSPERO CRD42022373182.

Abstract Background Assessing malignancy risk is important to choose appropriate management of ovarian tumors. We compared six algorithms to estimate the probabilities that an ovarian tumor is benign, borderline malignant, stage I primary invasive, stage II-IV primary invasive, or secondary metastatic. Methods This retrospective cohort study used 5909 patients recruited from 1999 to 2012 for model development, and 3199 patients recruited from 2012 to 2015 for model validation. Patients were recruited at oncology referral or general centers and underwent an ultrasound examination and surgery ≤ 120 days later. We developed models using standard multinomial logistic regression (MLR), Ridge MLR, random forest (RF), XGBoost, neural networks (NN), and support vector machines (SVM). We used nine clinical and ultrasound predictors but developed models with or without CA125. Results Most tumors were benign (3980 in development and 1688 in validation data), secondary metastatic tumors were least common (246 and 172). The c-statistic (AUROC) to discriminate benign from any type of malignant tumor ranged from 0.89 to 0.92 for models with CA125, from 0.89 to 0.91 for models without. The multiclass c-statistic ranged from 0.41 (SVM) to 0.55 (XGBoost) for models with CA125, and from 0.42 (SVM) to 0.51 (standard MLR) for models without. Multiclass calibration was best for RF and XGBoost. Estimated probabilities for a benign tumor in the same patient often differed by more than 0.2 (20% points) depending on the model. Net Benefit for diagnosing malignancy was similar for algorithms at the commonly used 10% risk threshold, but was slightly higher for RF at higher thresholds. Comparing models, between 3% (XGBoost vs. NN, with CA125) and 30% (NN vs. SVM, without CA125) of patients fell on opposite sides of the 10% threshold. Conclusion Although several models had similarly good performance, individual probability estimates varied substantially.

Background While patients with COPD often cite weather conditions as a reason for inactivity, little is known about the relationship between physical activity (PA) and weather conditions. The present study investigated the association of day-to-day weather changes on PA in patients with COPD and investigated patient characteristics related to being more or less influenced by weather conditions. Methods In this longitudinal analysis, device-based day-by-day step counts were objectively measured in COPD patients for up to 12 months. Daily meteorological data (temperature, precipitation, wind speed, hours of sunlight and daylight) were linked to the daily step count and individual and multivariable relationships were investigated using mixed-model effects. Individual R2 was calculated for every subject to investigate the estimated influence of weather conditions on a patient level and its relationship with patient characteristics. Results We included 50 patients with a mean±sd follow-up time of 282±93 days, totalling 14 117 patient-days. Daily temperature showed a positive linear pattern up until an inflexion point, after which a negative association with increasing temperature was observed (p

Abstract Background Clinical prediction models should be validated before implementation in clinical practice. But is favorable performance at internal validation or one external validation sufficient to claim that a prediction model works well in the intended clinical context? Main body We argue to the contrary because (1) patient populations vary, (2) measurement procedures vary, and (3) populations and measurements change over time. Hence, we have to expect heterogeneity in model performance between locations and settings, and across time. It follows that prediction models are never truly validated. This does not imply that validation is not important. Rather, the current focus on developing new models should shift to a focus on more extensive, well-conducted, and well-reported validation studies of promising models. Conclusion Principled validation strategies are needed to understand and quantify heterogeneity, monitor performance over time, and update prediction models when appropriate. Such strategies will help to ensure that prediction models stay up-to-date and safe to support clinical decision-making.

The generalizability of predictive algorithms is of key relevance to application in clinical practice. We provide an overview of three types of generalizability, based on existing literature: temporal, geographical, and domain generalizability. These generalizability types are linked to their associated goals, methodology, and stakeholders.

Abstract Background Prognostic models are used widely in the oncology domain to guide medical decision-making. Little is known about the risk of bias of prognostic models developed using machine learning and the barriers to their clinical uptake in the oncology domain. Methods We conducted a systematic review and searched MEDLINE and EMBASE databases for oncology-related studies developing a prognostic model using machine learning methods published between 01/01/2019 and 05/09/2019. The primary outcome was risk of bias, judged using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). We described risk of bias overall and for each domain, by development and validation analyses separately. Results We included 62 publications (48 development-only; 14 development with validation). 152 models were developed across all publications and 37 models were validated. 84% (95% CI: 77 to 89) of developed models and 51% (95% CI: 35 to 67) of validated models were at overall high risk of bias. Bias introduced in the analysis was the largest contributor to the overall risk of bias judgement for model development and validation. 123 (81%, 95% CI: 73.8 to 86.4) developed models and 19 (51%, 95% CI: 35.1 to 67.3) validated models were at high risk of bias due to their analysis, mostly due to shortcomings in the analysis including insufficient sample size and split-sample internal validation. Conclusions The quality of machine learning based prognostic models in the oncology domain is poor and most models have a high risk of bias, contraindicating their use in clinical practice. Adherence to better standards is urgently needed, with a focus on sample size estimation and analysis methods, to improve the quality of these models.

Abstract Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling was subsequently applied to capture these deviations in a per sample nucleosome footprint score. Validation was performed in 271 cfDNAs pre-surgically collected from women with an adnexal mass. We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses.

Abstract Background Describe and evaluate the methodological conduct of prognostic prediction models developed using machine learning methods in oncology. Methods We conducted a systematic review in MEDLINE and Embase between 01/01/2019 and 05/09/2019, for studies developing a prognostic prediction model using machine learning methods in oncology. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Prediction model Risk Of Bias ASsessment Tool (PROBAST) and CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) to assess the methodological conduct of included publications. Results were summarised by modelling type: regression-, non-regression-based and ensemble machine learning models. Results Sixty-two publications met inclusion criteria developing 152 models across all publications. Forty-two models were regression-based, 71 were non-regression-based and 39 were ensemble models. A median of 647 individuals (IQR: 203 to 4059) and 195 events (IQR: 38 to 1269) were used for model development, and 553 individuals (IQR: 69 to 3069) and 50 events (IQR: 17.5 to 326.5) for model validation. A higher number of events per predictor was used for developing regression-based models (median: 8, IQR: 7.1 to 23.5), compared to alternative machine learning (median: 3.4, IQR: 1.1 to 19.1) and ensemble models (median: 1.7, IQR: 1.1 to 6). Sample size was rarely justified (n = 5/62; 8%). Some or all continuous predictors were categorised before modelling in 24 studies (39%). 46% (n = 24/62) of models reporting predictor selection before modelling used univariable analyses, and common method across all modelling types. Ten out of 24 models for time-to-event outcomes accounted for censoring (42%). A split sample approach was the most popular method for internal validation (n = 25/62, 40%). Calibration was reported in 11 studies. Less than half of models were reported or made available. Conclusions The methodological conduct of machine learning based clinical prediction models is poor. Guidance is urgently needed, with increased awareness and education of minimum prediction modelling standards. Particular focus is needed on sample size estimation, development and validation analysis methods, and ensuring the model is available for independent validation, to improve quality of machine learning based clinical prediction models.

Abstract Background We suggest an adaptive sample size calculation method for developing clinical prediction models, in which model performance is monitored sequentially as new data comes in. Methods We illustrate the approach using data for the diagnosis of ovarian cancer (n = 5914, 33% event fraction) and obstructive coronary artery disease (CAD; n = 4888, 44% event fraction). We used logistic regression to develop a prediction model consisting only of a priori selected predictors and assumed linear relations for continuous predictors. We mimicked prospective patient recruitment by developing the model on 100 randomly selected patients, and we used bootstrapping to internally validate the model. We sequentially added 50 random new patients until we reached a sample size of 3000 and re-estimated model performance at each step. We examined the required sample size for satisfying the following stopping rule: obtaining a calibration slope ≥ 0.9 and optimism in the c-statistic (or AUC) < = 0.02 at two consecutive sample sizes. This procedure was repeated 500 times. We also investigated the impact of alternative modeling strategies: modeling nonlinear relations for continuous predictors and correcting for bias on the model estimates (Firth’s correction). Results Better discrimination was achieved in the ovarian cancer data (c-statistic 0.9 with 7 predictors) than in the CAD data (c-statistic 0.7 with 11 predictors). Adequate calibration and limited optimism in discrimination was achieved after a median of 450 patients (interquartile range 450–500) for the ovarian cancer data (22 events per parameter (EPP), 20–24) and 850 patients (750–900) for the CAD data (33 EPP, 30–35). A stricter criterion, requiring AUC optimism < = 0.01, was met with a median of 500 (23 EPP) and 1500 (59 EPP) patients, respectively. These sample sizes were much higher than the well-known 10 EPP rule of thumb and slightly higher than a recently published fixed sample size calculation method by Riley et al. Higher sample sizes were required when nonlinear relationships were modeled, and lower sample sizes when Firth’s correction was used. Conclusions Adaptive sample size determination can be a useful supplement to fixed a priori sample size calculations, because it allows to tailor the sample size to the specific prediction modeling context in a dynamic fashion.

Objectives To investigate prognostic factors for anxiety, depression and post-traumatic stress (PTS) symptoms 1 month after early pregnancy loss (EPL).Design A prospective cohort study. Consecutive women were recruited, and demographic and clinical data were collected. Surveys containing the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Diagnostic Scale (PDS) were emailed 1 month after a loss. Univariable logistic regression was performed to link factors with caseness of anxiety, depression or PTS according to screening measures.Setting Early pregnancy units of three central London hospitals.Participants 737/1116 eligible women with an EPL were recruited. 492 responded to HADS and 487 to PDS.Primary and secondary outcome measures Primary outcome is the area under the curve (AUC) to predict any psychological morbidity (defined as moderate/severe anxiety or depression, or meeting screening criteria for PTS) for each variable. Further outcomes are explained variation (R2) and p value for any morbidity, and AUC, explained variation, and p value for each morbidity separately.Results Women who had a past diagnosis of a psychiatric condition were more likely to meet criteria for anxiety, depression or PTS (75% for current diagnosis vs 55% for past vs 30% for no diagnosis; AUC 0.61; R2 8.4%; p

Introduction The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) were both published to improve the reporting and critical appraisal of prediction model studies for diagnosis and prognosis. This paper describes the processes and methods that will be used to develop an extension to the TRIPOD statement (TRIPOD-artificial intelligence, AI) and the PROBAST (PROBAST-AI) tool for prediction model studies that applied machine learning techniques.Methods and analysis TRIPOD-AI and PROBAST-AI will be developed following published guidance from the EQUATOR Network, and will comprise five stages. Stage 1 will comprise two systematic reviews (across all medical fields and specifically in oncology) to examine the quality of reporting in published machine-learning-based prediction model studies. In stage 2, we will consult a diverse group of key stakeholders using a Delphi process to identify items to be considered for inclusion in TRIPOD-AI and PROBAST-AI. Stage 3 will be virtual consensus meetings to consolidate and prioritise key items to be included in TRIPOD-AI and PROBAST-AI. Stage 4 will involve developing the TRIPOD-AI checklist and the PROBAST-AI tool, and writing the accompanying explanation and elaboration papers. In the final stage, stage 5, we will disseminate TRIPOD-AI and PROBAST-AI via journals, conferences, blogs, websites (including TRIPOD, PROBAST and EQUATOR Network) and social media. TRIPOD-AI will provide researchers working on prediction model studies based on machine learning with a reporting guideline that can help them report key details that readers need to evaluate the study quality and interpret its findings, potentially reducing research waste. We anticipate PROBAST-AI will help researchers, clinicians, systematic reviewers and policymakers critically appraise the design, conduct and analysis of machine learning based prediction model studies, with a robust standardised tool for bias evaluation.Ethics and dissemination Ethical approval has been granted by the Central University Research Ethics Committee, University of Oxford on 10-December-2020 (R73034/RE001). Findings from this study will be disseminated through peer-review publications.PROSPERO registration number CRD42019140361 and CRD42019161764.

Abstract Background The assessment of calibration performance of risk prediction models based on regression or more flexible machine learning algorithms receives little attention. Main text Herein, we argue that this needs to change immediately because poorly calibrated algorithms can be misleading and potentially harmful for clinical decision-making. We summarize how to avoid poor calibration at algorithm development and how to assess calibration at algorithm validation, emphasizing balance between model complexity and the available sample size. At external validation, calibration curves require sufficiently large samples. Algorithm updating should be considered for appropriate support of clinical practice. Conclusion Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated. The ultimate aim is to optimize the utility of predictive analytics for shared decision-making and patient counseling.

Abstract Background Decision curve analysis is a method to evaluate prediction models and diagnostic tests that was introduced in a 2006 publication. Decision curves are now commonly reported in the literature, but there remains widespread misunderstanding of and confusion about what they mean. Summary of commentary In this paper, we present a didactic, step-by-step introduction to interpreting a decision curve analysis and answer some common questions about the method. We argue that many of the difficulties with interpreting decision curves can be solved by relabeling the y-axis as “benefit” and the x-axis as “preference.” A model or test can be recommended for clinical use if it has the highest level of benefit across a range of clinically reasonable preferences. Conclusion Decision curves are readily interpretable if readers and authors follow a few simple guidelines.

Abstract Background Clinical prediction models are useful in estimating a patient’s risk of having a certain disease or experiencing an event in the future based on their current characteristics. Defining an appropriate risk threshold to recommend intervention is a key challenge in bringing a risk prediction model to clinical application; such risk thresholds are often defined in an ad hoc way. This is problematic because tacitly assumed costs of false positive and false negative classifications may not be clinically sensible. For example, when choosing the risk threshold that maximizes the proportion of patients correctly classified, false positives and false negatives are assumed equally costly. Furthermore, small to moderate sample sizes may lead to unstable optimal thresholds, which requires a particularly cautious interpretation of results. Main text We discuss how three common myths about risk thresholds often lead to inappropriate risk stratification of patients. First, we point out the contexts of counseling and shared decision-making in which a continuous risk estimate is more useful than risk stratification. Second, we argue that threshold selection should reflect the consequences of the decisions made following risk stratification. Third, we emphasize that there is usually no universally optimal threshold but rather that a plausible risk threshold depends on the clinical context. Consequently, we recommend to present results for multiple risk thresholds when developing or validating a prediction model. Conclusion Bearing in mind these three considerations can avoid inappropriate allocation (and non-allocation) of interventions. Using discriminating and well-calibrated models will generate better clinical outcomes if context-dependent thresholds are used.

Objectives To determine the prevalence of burnout in doctors practising obstetrics and gynaecology, and assess the association with defensive medical practice and self-reported well-being.Design Nationwide online cross-sectional survey study; December 2017–March 2018.Setting Hospitals in the UK.Participants 5661 practising obstetrics and gynaecology consultants, specialty and associate specialist doctors and trainees registered with the Royal College of Obstetricians and Gynaecologists.Primary and secondary outcome measures Prevalence of burnout using the Maslach Burnout Inventory and defensive medical practice (avoiding cases or procedures, overprescribing, over-referral) using a 12-item questionnaire. The odds ratios (OR) of burnout with defensive medical practice and self-reported well-being.Results 3102/5661 doctors (55%) completed the survey. 3073/3102 (99%) met the inclusion criteria (1462 consultants, 1357 trainees and 254 specialty and associate specialist doctors). 1116/3073 (36%) doctors met the burnout criteria, with levels highest amongst trainees (580/1357 (43%)). 258/1116 (23%) doctors with burnout reported increased defensive practice compared with 142/1957 (7%) without (adjusted OR 4.35, 95% CI 3.46 to 5.49). ORs of burnout with well-being items varied between 1.38 and 6.37, and were highest for anxiety (3.59, 95% CI 3.07 to 4.21), depression (4.05, 95% CI 3.26 to 5.04) and suicidal thoughts (6.37, 95% CI 95% CI 3.95 to 10.7). In multivariable logistic regression, being of younger age, white or ‘other’ ethnicity, and graduating with a medical degree from the UK or Ireland had the strongest associations with burnout.Conclusions High levels of burnout were observed in obstetricians and gynaecologists and particularly among trainees. Burnout was associated with both increased defensive medical practice and worse doctor well-being. These findings have implications for the well-being and retention of doctors as well as the quality of patient care, and may help to inform the content of future interventions aimed at preventing burnout and improving patient safety.

Introduction Infertility and in vitro fertilisation (IVF; with or without intracytoplasmic sperm injection) result in considerable emotional and financial burden. Increasing evidence suggests that lifestyle factors, including diet, physical activity and personal well-being, are associated with IVF-success rates. Currently, IVF is not routinely combined with a lifestyle programme. The preconception lifestyle (PreLiFe) randomised controlled trial (RCT) assesses the effects of a new mobile PreLiFe programme in couples undergoing IVF.Methods and analysis A multicentre RCT including 460 heterosexual couples starting IVF in Belgian fertility clinics. IVF couples are randomised between an attention control group or the PreLiFe programme for a period of 12 months or until an ongoing pregnancy is confirmed by ultrasound. The attention control programme includes a mobile application with treatment information (ie, appointments and medication instructions) in addition to standard care. The PreLiFe programme includes a mobile application with the same treatment information in combination with a lifestyle programme. This new lifestyle programme includes tailored advice and skills training on diet, physical activity and mindfulness in combination with text messages and telephone interaction with a healthcare professional trained in motivational interviewing. The primary outcome of this RCT is the cumulative ongoing pregnancy rate within 12 months after randomisation. Secondary outcomes include changes in diet, physical activity, emotional distress, body mass index, waist circumference, quality of life and other reproductive outcomes including IVF discontinuation, clinical pregnancy rate and time to pregnancy. Additionally, partner support and the feasibility (use and acceptability) of the PreLiFe programme will be evaluated in the intervention group. Analysis will be according to intention to treat.Ethics and dissemination This study has been approved by the Medical Ethical Committee of the Leuven University Hospital (Belgium) and the other recruiting clinics. The findings of this RCT will be disseminated through presentations at international scientific meetings and peer-reviewed publications.Trial registration number NCT03790449; Pre-results.

PROBLEM SETTING:Support vector machines (SVMs) are very popular tools for classification, regression and other problems. Due to the large choice of kernels they can be applied with, a large variety of data can be analysed using these tools. Machine learning thanks its popularity to the good performance of the resulting models. However, interpreting the models is far from obvious, especially when non-linear kernels are used. Hence, the methods are used as black boxes. As a consequence, the use of SVMs is less supported in areas where interpretability is important and where people are held responsible for the decisions made by models. OBJECTIVE:In this work, we investigate whether SVMs using linear, polynomial and RBF kernels can be explained such that interpretations for model-based decisions can be provided. We further indicate when SVMs can be explained and in which situations interpretation of SVMs is (hitherto) not possible. Here, explainability is defined as the ability to produce the final decision based on a sum of contributions which depend on one single or at most two input variables. RESULTS:Our experiments on simulated and real-life data show that explainability of an SVM depends on the chosen parameter values (degree of polynomial kernel, width of RBF kernel and regularization constant). When several combinations of parameter values yield the same cross-validation performance, combinations with a lower polynomial degree or a larger kernel width have a higher chance of being explainable. CONCLUSIONS:This work summarizes SVM classifiers obtained with linear, polynomial and RBF kernels in a single plot. Linear and polynomial kernels up to the second degree are represented exactly. For other kernels an indication of the reliability of the approximation is presented. The complete methodology is available as an R package and two apps and a movie are provided to illustrate the possibilities offered by the method.

Risk prediction models can assist clinicians in making decisions. To boost the uptake of these models in clinical practice, it is important that end-users understand how the model works and can efficiently communicate its results. We introduce novel methods for interpretable model visualization.The proposed visualization techniques are applied to two prediction models from the Framingham Heart Study for the prediction of intermittent claudication and stroke after atrial fibrillation. We represent models using color bars, and visualize the risk estimation process for a specific patient using patient-specific contribution charts.The color-based model representations provide users with an attractive tool to instantly gauge the relative importance of the predictors. The patient-specific representations allow users to understand the relative contribution of each predictor to the patient's estimated risk, potentially providing insightful information on which to base further patient management. Extensions towards non-linear models and interactions are illustrated on an artificial dataset.The proposed methods summarize risk prediction models and risk predictions for specific patients in an alternative way. These representations may facilitate communication between clinicians and patients.

Over time, methods for the development of clinical decision support (CDS) systems have evolved from interpretable and easy-to-use scoring systems to very complex and non-interpretable mathematical models. In order to accomplish effective decision support, CDS systems should provide information on how the model arrives at a certain decision. To address the issue of incompatibility between performance, interpretability and applicability of CDS systems, this paper proposes an innovative model structure, automatically leading to interpretable and easily applicable models. The resulting models can be used to guide clinicians when deciding upon the appropriate treatment, estimating patient-specific risks and to improve communication with patients.We propose the interval coded scoring (ICS) system, which imposes that the effect of each variable on the estimated risk is constant within consecutive intervals. The number and position of the intervals are automatically obtained by solving an optimization problem, which additionally performs variable selection. The resulting model can be visualised by means of appealing scoring tables and color bars. ICS models can be used within software packages, in smartphone applications, or on paper, which is particularly useful for bedside medicine and home-monitoring. The ICS approach is illustrated on two gynecological problems: diagnosis of malignancy of ovarian tumors using a dataset containing 3,511 patients, and prediction of first trimester viability of pregnancies using a dataset of 1,435 women. Comparison of the performance of the ICS approach with a range of prediction models proposed in the literature illustrates the ability of ICS to combine optimal performance with the interpretability of simple scoring systems.The ICS approach can improve patient-clinician communication and will provide additional insights in the importance and influence of available variables. Future challenges include extensions of the proposed methodology towards automated detection of interaction effects, multi-class decision support systems, prognosis and high-dimensional data.

Background: Treatment of cervical cancer during pregnancy is often complex and challenging. This study aimed to analyze current patterns of practice in the management of pregnant patients diagnosed with cervical cancer. Methods: This was a matched cohort study comprising patients managed for cervical cancer during pregnancy from six European centers. Patient information was retrieved from the dataset of the International Network for Cancer, Infertility and Pregnancy from 1990 to 2012. Each center matched its patients with two non-pregnant controls for age (±5 years) and International Federation of Gynecology and Obstetrics (FIGO) 2009 stage. Information on age, histological type, grade, lymphovascular space invasion, stage, tumor size, method of diagnosis, site of recurrence, delivery, date of recurrence, and date of death was recorded. Progression-free survival was compared using multivariable Cox proportional hazards regression. Results: A total of 132 pregnant patients and 256 controls were analyzed. The pregnant patients (median age 34 years, range 21–43) were diagnosed at a median gestational age of 18.4 weeks of pregnancy (range 7–39). Stage distribution during pregnancy was 14.4% for stage IA, 47.0% for IB1, 18.9% for IB2, and 19.7% for II-IV. For treatment during pregnancy, 17.4% of the patients underwent surgery, 16.7% received neoadjuvant chemotherapy, 26.5% delayed their treatment, 12.9% had a premature delivery, and 26.5% had their pregnancy terminated. Median follow-up was 84 months (67 months for pregnant and 95 months for non-pregnant patients). The unadjusted hazard ratio of pregnancy for progression-free survival was 1.18 (95% confidence interval 0.74 to 1.88). Conclusion: Surgery and chemotherapy is increasingly used in the management of pregnant patients with cervical cancer and prognosis is similar to that of non-pregnant patients. [ABSTRACT FROM AUTHOR]

: BACKGROUND To determine whether hCG ratio at 48 h can predict ultimate viability of intrauterine pregnancies of uncertain viability (IPUVs) in the pregnancy of unknown location (PUL) population. : METHODS Prospective observational study from June 2001 to October 2004. All women classified with PUL had serum hCG levels measured at 0 and 48 h to calculate hCG ratio (hCG 48/hCG 0 h). All women were followed up until final diagnosis: failing PUL, viable and non-viable intrauterine pregnancy (IUP), ectopic pregnancy. Those PULs found to have an IPUV at follow-up transvaginal ultrasound scan (TVS) were included in final analysis. : RESULTS During the study period, 12 572 consecutive first trimester women were scanned. One thousand and three (8%) women were classified PULs. Three hundred and seventy-nine (37.8%) PULs were confirmed IPUVs at follow-up scan. Complete data from 334 IPUVs were analyzed: 82.6% (276/334) viable IUPs and 17.4% (58/334) non-viable IUPs. Median hCG ratio was greater in viable IUPs [2.32, inter-quartile range (IQR) 1.16–4.77] compared with non-viable IUPs 1.83 (IQR 0.97–4.60). Sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratios of an hCG ratio >2.00 for the prediction of a viable IUP are 77.2%, 95.8%, 86.6%, 90.9%, 15.5, 0.24, respectively. In our population, an hCG ratio >2.00 increases the odds for a viable IUP from 0.42 to 6.46 post-test. : CONCLUSIONS The hCG ratio is significantly higher in those IPUVs which become viable IUPs compared with non-viable IUPs. New cut-offs for the hCG ratio need to be evaluated for the prediction of viability in the IPUV group of PULs. [ABSTRACT FROM AUTHOR]