Machine Learning-Based Pre-Test Risk Stratification for PCR-Confirmed Chlamydia Using Patient-Reported Data and Urine Biomarkers

Background: Pregnancy-associated thrombotic microangiopathy (P-TMA) is rare but life-threatening. Early risk prediction before overt clinical presentation remains challenging, as the associated laboratory abnormalities are subtle, multidimensional, and frequently masked by common physiological changes such as gestational thrombocytopenia and pregnancy-related proteinuria, thus overlapping heavily with benign obstetric and renal conditions. This complexity is poorly captured by univariate or rule-based approaches; however, it is addressable by machine learning, which can extract latent, time-dependent risk signatures from longitudinal clinical tests. Methods: This retrospective study included 300 pregnancies comprising 142 P-TMA cases and 158 controls. After exclusion of identifiers and non-informative variables, 146 longitudinal laboratory predictors were retained. Participants were divided into a training cohort (80%) and a held-out test cohort (20%) using stratified sampling. Five algorithms were evaluated: logistic regression, support vector machine with radial basis function kernel, random forest, extra trees, and gradient boosting. The final model was selected by mean cross-validated AUROC, refitted on the full training cohort, and evaluated once in the held-out test cohort. Interpretability analyses examined global feature importance and distributional patterns of leading predictors. Results: Gradient boosting was prespecified by cross-validation in the training cohort. The model achieved an AUROC of 0.872 (95% CI: 0.769-0.952) and an AUPRC of 0.883 (95% CI: 0.780-0.959) in a held-out test cohort, with sensitivity of 0.750 and specificity of 0.812. Conclusions: Longitudinal clinical laboratory tests obtained during routine care contained informative and clinically plausible signals for P-TMA risk. Notably, cystatin C at week 6 showed promise as an early monitoring indicator.

Machine learning models for chronic kidney disease (CKD) risk prediction often post strong discrimination scores on internal test sets. Calibration and uncertainty quantification get far less attention, leaving clinicians without reliable information about whether the probability outputs are accurate. We trained five classifiers on the UCI CKD dataset (400 patients, 62.5% CKD prevalence): logistic regression, random forest, XGBoost, SVM with Platt scaling, and Gaussian naive Bayes. We evaluated each across calibration quality, conformal prediction coverage, and an eight-criterion deployment readiness framework. A distributional stress-test applied the best-calibrated variant of each model to the open-access MIMIC-IV demo cohort (97 patients, 23.7% CKD) to assess behaviour under prevalence shift and feature missingness. We measured calibration before and after Platt scaling and isotonic regression using Expected Calibration Error and Brier Score, and quantified uncertainty through split conformal prediction targeting 90% marginal coverage. All five models reached AUROC 1.00 on the UCI test set. Isotonic recalibration reduced internal ECE to 0.000-0.022. On MIMIC-IV, AUROC fell to 0.48-0.58, ECE rose to 0.68-0.76, and conformal coverage dropped from 0.80-0.98 to 0.21-0.25 against a 90% target. No model scored above 4 out of 16 on the deployment readiness checklist. Near-perfect internal performance did not transfer. Calibration stability and conformal coverage should be evaluated on external data before any clinical prediction model moves toward deployment.

Data leakage -- contamination of a model with information unavailable at baseline -- is the dominant reproducibility failure in machine-learning-based science, yet detection tools require training code, external data, or domain expertise. None operates on the artifact an auditor most often holds: the model's output. We ask what can be decided about leakage from predictions and outcomes alone. We give a decision-theoretic framework in which leakage diagnostics are functionals of the predicted-risk/outcome law, parameterized by a threshold-weighting linked to proper scoring rules and decision-curve analysis. We prove a sharp impossibility: a recalibrated leak matching an honest model's calibration and discrimination is indistinguishable from honest performance by \emph{any} function of the predictions, so the broad class is detectable only against an externally supplied ceiling on achievable discrimination. We then prove what leakage cannot hide: a near-deterministic subgroup -- the signature of a near-label leak -- produces a sustained unit-purity head that no legitimate predictor of a non-deterministic outcome can manufacture, yielding a prior-free test. These results organize leakage into a trichotomy -- miscalibrated, broad-calibrated, and deterministic -- each with a matched detector and failure mode. We validate on UK Biobank using time-windowed comorbidity leakage with known, graded severity, measuring a detection floor of $Δ\cstar \approx 0.007$ on this endpoint, below which residual leakage is undetectable from output and too small to alter conclusions. The numerical floor is cohort- and endpoint-specific; the structural lesson is general: output-only detection fails where residual leakage is indistinguishable from an honestly stronger predictor. The test returns a verdict on a prediction vector in under a second on commodity hardware.