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Decision curve analysis: a novel method for evaluating prediction models.

BACKGROUND: Diagnostic and prognostic models are typically evaluated with measures of accuracy that do not address clinical consequences. Decision-analytic techniques allow assessment of clinical outcomes but often require collection of additional information and may be cumbersome to apply to models that yield a continuous result. The authors sought a method for evaluating and comparing prediction models that incorporates clinical consequences,requires only the data set on which the models are tested,and can be applied to models that have either continuous or dichotomous results. METHOD: The authors describe decision curve analysis, a simple, novel method of evaluating predictive models. They start by assuming that the threshold probability of a disease or event at which a patient would opt for treatment is informative of how the patient weighs the relative harms of a false-positive and a false-negative prediction. This theoretical relationship is then used to derive the net benefit of the model across different threshold probabilities. Plotting net benefit against threshold probability yields the "decision curve." The authors apply the method to models for the prediction of seminal vesicle invasion in prostate cancer patients. Decision curve analysis identified the range of threshold probabilities in which a model was of value, the magnitude of benefit, and which of several models was optimal. CONCLUSION: Decision curve analysis is a suitable method for evaluating alternative diagnostic and prognostic strategies that has advantages over other commonly used measures and techniques.

Decision Support Techniques↗

Application of treatment thresholds to diagnostic-test evaluation: an alternative to the comparison of areas under receiver operating characteristic curves.

Diagnostic tests are often evaluated by comparison of the areas under receiver operating characteristic (ROC) curves. In this study the authors compared this approach with a more direct method that takes into account consequences of a diagnosis. Data from a prospective study of diagnosis of pulmonary embolism were used for a motivating example. Using multivariable logistic regression analysis, three diagnostic models were built and compared based on their ROC curves. Although model 1 (0.706) and model 2 (0.702) had the same ROC-curve area, they performed differently when risks and benefits of subsequent decisions were considered by applying the treatment probability threshold. Models 1 and 3 (0.611) had substantially different ROC-curve areas but performed similarly taking into account the therapeutic consequences. This demonstrates that comparison of diagnostic tests using the areas under the ROC curves may lead to erroneous conclusions about therapeutic usefulness. To correspond to daily practice, it would be more appropriate to also consider the clinical implications in evaluating diagnostic tests. This is made feasible by explicit definition and application of a treatment threshold.

Decision Support Techniques↗

Multiple imputation for model checking: completed-data plots with missing and latent data.

In problems with missing or latent data, a standard approach is to first impute the unobserved data, then perform all statistical analyses on the completed dataset--corresponding to the observed data and imputed unobserved data--using standard procedures for complete-data inference. Here, we extend this approach to model checking by demonstrating the advantages of the use of completed-data model diagnostics on imputed completed datasets. The approach is set in the theoretical framework of Bayesian posterior predictive checks (but, as with missing-data imputation, our methods of missing-data model checking can also be interpreted as "predictive inference" in a non-Bayesian context). We consider the graphical diagnostics within this framework. Advantages of the completed-data approach include: (1) One can often check model fit in terms of quantities that are of key substantive interest in a natural way, which is not always possible using observed data alone. (2) In problems with missing data, checks may be devised that do not require to model the missingness or inclusion mechanism; the latter is useful for the analysis of ignorable but unknown data collection mechanisms, such as are often assumed in the analysis of sample surveys and observational studies. (3) In many problems with latent data, it is possible to check qualitative features of the model (for example, independence of two variables) that can be naturally formalized with the help of the latent data. We illustrate with several applied examples.

Animals↗

Lumbar puncture first: an alternative model for the investigation of lone acute sudden headache.

Subarachnoid hemorrhage (SAH) is a diagnosis often considered in patients presenting to the ED with acute sudden headaches, but with normal physical examinations. Standard of care today is for these patients to be investigated by noncontrast CT scan followed by lumbar puncture (LP) for negative CTs. However, given that most investigated patients have benign headaches, most of the CT and LP results are normal. The authors studied, by means of a theoretical analysis, the impact of an alternative diagnostic model, in which LP would be the first (and, in most cases, only) diagnostic test for patients suspected of SAH who met lone acute sudden headache (LASH) criteria. Given reasonable assumptions, for every 100 patients investigated, the "LP-first" model would result in 79 to 83 fewer CT scans and only seven to 11 additional LPs, as compared with traditional strategies. Among ED headache patients meeting LASH criteria, the authors believe use of this model could result in more efficient use of resources, minimal additional morbidity, and equal diagnostic accuracy for SAH.

Algorithms↗

Computer graphics representation of a statistical model used with computer-aided diagnosis.

A description of computer graphics of a multidimensional model that is used with computer-aided diagnosis or prognosis is presented. The model is discussed and computer graphics of the model are developed. The computer graphics are suitable as visual supplements for presenting the computer-aided diagnostic model to individuals who may be inexperienced in multivariate statistics.

Animals↗

An evaluation of DSM-III-R and ICD-10 benzodiazepine dependence criteria using Rasch modelling.

AIMS: To evaluate the homogeneity of the elements of the Substance Dependence Syndrome (SDS) as applied to benzodiazepines (BZDs) by Rasch modelling. MEASUREMENTS: The Rasch scaling model was applied to data obtained by administering the SCAN (Schedules for Clinical Assessments in Neuropsychiatry) substance dependence sections. Subsequently, Rasch-homogeneous sets of DSM-III-R and ICD-10 BZD dependence criteria were assessed for subject and item discriminability. To support their construct validity a theoretical rationale was formulated based on the Rasch scale values. PARTICIPANTS: A heterogeneous sample of 599 outpatient BZD users. FINDINGS: Only particular subsets of the DSM-III-R and ICD-10 BZD dependence criteria met the requirements for Rasch-homogeneity, which appears to be due to medical aspects of BZD use. The subject and item discriminability results were sufficiently good. CONCLUSIONS: The DSM-III-R and ICD-10 BZD dependence constructs may need to be redefined. The use of a BZD dependence severity model based on a Rasch-homogeneous scale appears to have greater clinical value than a dichotomous diagnostic model based on an arbitrary cut-off point. We recommend Rasch modelling to investigate the homogeneity of the elements of the SDS across other psychoactive substances.

Adolescent↗

Doppler ultrasonographic findings on hepatic arterial vasospasm early after liver transplantation.

OBJECTIVE: Hepatic arterial vasospasm has not been well recognized clinically as a post-liver transplant vascular complication because of the lack of sufficient data and diagnostic standards. The goal of this study was to provide new evidence and a diagnostic model for the clinical appreciation of hepatic arterial vasospasm and evaluate the role of ultrasonography in the diagnostic process. METHODS: Nine post-orthotopic liver transplant cases were retrospectively reviewed. Multiple clinical measurements were analyzed. Routine Doppler ultrasonography was performed within 24 hours, and additional ultrasonographic examinations were conducted as indicated. Each of the 9 patients was given a single 10 mg dose of nifedipine sublingually and monitored by ultrasonography when vasospasm was suspected on the basis of the Doppler ultrasonographic results. RESULTS: Doppler ultrasonography showed high-resistance hepatic arterial flow with absence of antegrade flow and even reversal of flow during diastole both extrahepatically and intrahepatically in all cases. Ten to 45 minutes after administration of the vasodilator, antegrade diastolic flow was observed along the course of the main hepatic artery and its intrahepatic branches with the resistive indices decreasing on average from 1.0 to 0.76. In addition, the peak systolic velocities increased from 57 cm/s before nifedipine administration to 77 cm/s after administration. CONCLUSIONS: High-resistance hepatic arterial flow (resistive index = 1) early after liver transplantation is indicative of hepatic arterial vasospasm if it responds to vasodilators. Doppler ultrasonography is a useful tool for the diagnosis of this vascular complication.

Adult↗

Multi-locus allelic architecture underlying natural variation in leaf rolling in japonica rice.

Leaf rolling is a key component of rice canopy architecture that affects light interception, microclimate formation, and planting density. The contribution of naturally occurring allelic variation to quantitative variation in leaf rolling within cultivated rice remains poorly understood, while extreme leaf rolling caused by loss-of-function mutations often results in detrimental pleiotropic effects. Herein, we examined how multi-locus allelic variation contributes to natural variation in leaf rolling within japonica rice. Leaf rolling was quantified based on the leaf rolling index (LRI) using a panel of 201 japonica accessions. The phenotype was transformed using the Yeo-Johnson method to reduce strong right skewness and improve the distributional properties of the data, thereby facilitating subsequent regression modeling. Haplotype analyses were performed for previously reported leaf rolling-associated genes and genome-wide association study (GWAS) lead loci, leading to the identification of five loci exhibiting substantial haplotype-dependent phenotypic variation. Phenotypically defined allelic groups represented these loci were subsequently evaluated using multiple linear regression (MLR), with the first two principal components derived from genome-wide SNP data included as covariates to account for population structure. The final MLR model identified four loci (qALR1, OsYABBY1, OsSLL2, and OsSRL10) as the independent contributors to leaf rolling variation, collectively explaining 21% of the variance in the transformed phenotype after accounting for population structure. Model diagnostics and ten-fold cross-validation supported the statistical validity of the framework and indicated stable model performance across validation folds. Analysis of multi-locus allelic combinations showed 13 distinct configurations that clustered into three phenotypically differentiated groups. This reflected the cumulative dosage of high-leaf rolling alleles. Thus, the natural variation in leaf rolling in japonica rice is governed by the additive effects of multiple moderate-impact loci. The multi-locus allelic framework established here provides a statistically sound and biologically interpretable basis for dissecting polygenic canopy traits and practical guidance for developing genetic materials aimed at optimizing rice plant architecture.

cross-validation↗

Aspects of climate change prediction relevant to crop productivity.

Projected changes in surface climate are reviewed at a range of temporal scales, with an emphasis on tropical northern Africa--a region considered to be particularly vulnerable to climate change. Noting the key aspects of 'weather' affecting crop yield, we then consider relevant and projected change using output from a range of state of the art global climate models (GCMs), and for different future emission scenarios. The outputs from the models reveal significant inter-model variation in the change expected by the end of the twenty-first century for even the lowest IPCC emission scenario. We provide a set of recommendations on future model diagnostics, configurations and ease of use to close further the gap between GCMs and smaller-scale crop models. This has the potential to empower countries to make their own assessments of vulnerability to climate change induced periods of food scarcity.

Africa, Northern↗

[Role of intravenous cholangio-cholecystography in the diagnosis of asymptomatic choledocholithiasis].

INTRODUCTION: Standard diagnostic procedures (anamnesis, physical examination, laboratory analyses, ultrasound diagnosis), commonly used in diagnosis and preparation for surgical intervention of patients with cholelithiasis, are in most cases a reliable indicator for evaluation of the disease and conditions planned for surgery. DISCUSSION: In some cases by application of these narrow diagnostic models, some conditions, anatomic variations and biliary tract malformations remain unrecognized. Asymptomatic ("silent") choledocholithiasis (2.02%) represents a special diagnostic and therapeutic problem. CONCLUSION: Our extended diagnostic protocol includes routine intravenous cholangio-cholecystography as a standard diagnostic procedure for evaluation of cholecysto-choledocholithiasis prior planning cholecystectomy.

Cholangiography↗

[Determination of somatotype of man in cranio-facial personality identification].

On the basis of their independent research and through the analysis of published data the authors suggested quantitative criteria for the diagnosis of a somatotype of man by the dimensional features of the face and skull. M. A. Negasheva method, based on the discriminative analysis of 7 measurement features, was used in the individual diagnosis of a somatotype by V. V. Bunaka scheme (somatotypes-pectoral, muscular, abdominal and indefinite). The authors suggest 2 diagnostic models based on the linear and discriminative analysis of 11 and 7 measurement features for the skull. The diagnostic accuracy in case of main male som-atotypes makes 87 and 64.4%, respectively, with the canonic correlations of 0.574 and 0.292. The designed methods can be used in forensic medicine for the cranio-facial and portrait expertise.

Cephalometry↗

Diagnostic power of aortic elastic properties in young patients with Marfan syndrome.

BACKGROUND: In patients with Marfan syndrome, progressive aortic dilation implicates a still-unpredictable risk of life-threatening aortic dissection and rupture. We sought to quantify aortic wall dysfunction noninvasively, determine the diagnostic power of various aortic parameters, and establish a diagnostic model for the early detection of aortic abnormalities associated with Marfan syndrome. METHODS: In 19 patients with Marfan syndrome (age, 17.7 +/- 9.5 years) and 19 age- and sex-matched healthy control subjects, computerized ascending and abdominal aortic wall contour analysis with continuous determination of aortic diameters was performed out of transthoracic M-mode echocardiographic tracings. After simultaneous oscillometric blood pressure measurement, aortic elastic properties were determined automatically. RESULTS: The following ascending aortic elastic parameters showed statistically significant differences between the Marfan group and the control group: (1) decreased aortic distensibility ( P < .001), (2) increased wall stiffness index ( P < .01), (3) decreased systolic diameter increase ( P < .01), and (4) decreased maximum systolic area increase ( P < .001). The diagnostic power of all investigated parameters was tested by single logistic regression models. A multiple logistic regression model including solely aortic parameters yielded a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: In young patients with Marfan syndrome, a computerized image-analyzing technique revealed decreased aortic elastic properties expressed by parameters showing high diagnostic power. A multiple logistic regression model including merely aortic parameters can serve as useful predictor for Marfan syndrome.

Adolescent↗

[Neuropathic pain syndromes: from their diagnosis to the return to work. Proposal of a model for rapid evaluation and therapy based on their pathogenic mechanisms].

The therapeutic approach to neuropathic pain differs significantly among physicians. This is in large part because of the relative paucity of randomized clinical trials and the scarcity of comparative studies with different drugs. Clinical studies on the efficacy of a drug or a technique are generally referred to the pathologic diagnosis and not to the pain mechanism. We have learned from animal models the different pain mechanisms which may be involved in the peripheral nerves and the spinal cord. Unfortunately, one mechanism could be responsible for many different symptoms, while the same symptom can be caused by different mechanisms. The authors propose a simple model to evaluate the patients in order to define the mechanisms involved an to select the treatment strategy. The diagnostic model allows classification of the patient into four groups according to pain mechanism (spinal neurons sensitization due to deafferentation, ectopic discharges in peripheral nociceptive C fibers, spinal neurons sensitization due to ectopic discharges in peripheral nociceptive C fibers, spinal neurons sensitization due to nociceptors sensitization). The authors propose also a second step in which a fifth mechanism, adrenosensitivity, is evaluated. Treatment options may target any of the mechanisms discussed. Drugs and analgesic techniques can be classified according to their action on pain mechanisms. The authors identify in the literature some drugs and techniques which can be tested in each defined groups. A complementary and multidisciplinary rehabilitative approach of chronic pain patients is recommended.

Adrenergic alpha-Agonists↗

The future of biostatistics: expecting the unexpected.

The paper explores the future of (clinical) biostatistics. In the first part of the paper important trends in biostatistics are reviewed: new applications and more complex data; causal models for observational data; cross-validation-based model building; graphical chain and random effect models; faster computing and new algorithms as Markov chain Monte Carlo; generalized estimating equations and pseudo-likelihood; pooled data sets for meta-analysis and prognostic modelling. In the second part some dreams and nightmares of the author are sketched. Dreams are: implementation of prognostic and diagnostic models in the clinic; an instantaneous numeric integrator; much more and better organized follow-up data; disease mapping in space and time. 'Nightmares', that is, issues which it is hoped will go out of use in the future, are: P-value; rank tests; exact methods; meta-analysis; matched case-control studies.

Biometry↗

Application of serum protein fingerprinting coupled with artificial neural network model in diagnosis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma tends to present at a late clinical stage with poor prognosis. Therefore, it is urgent to explore and develop a simple, rapid diagnostic method, which has high sensitivity and specificity for hepatocellular carcinoma at an early stage. In this study, the serum proteins in patients with hepatocellular carcinoma or liver cirrhosis and in normal controls were analysed. Surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF-MS) spectrometry was used to fingerprint serum protein using the protein chip technique and explore the value of the fingerprint, coupled with artificial neural network, to diagnose hepatocellular carcinoma. METHODS: Of the 106 serum samples obtained, 52 were from patients with hepatocellular carcinoma, 22 from patients with liver cirrhosis and 32 from healthy volunteers. The samples were randomly assigned into a training group (n = 70, 35 patients with hepatocellular carcinoma, 14 with liver cirrhosis, and 21 normal controls) and a testing group (n = 36, 17 patients with hepatocellular carcinoma, 8 with liver cirrhosis, and 11 normal controls). An artificial neural network was trained on data from 70 individuals in the training group to develop an artificial neural network diagnostic model and this model was tested. The 36 sera in the testing group were analysed with blind prediction by using the same flowchart and procedure of data collection. The 36 serum protein spectra were clustered with the preset clustering method and the same mass/charge (M/Z) peak values as those in the training group. Matrix transfer was performed after data were output. Then the data were input into the previously built artificial neural network model to get the prediction value. The M/Z peaks of the samples with more than 2000 M/Z were normalized with biomarker wizard of ProteinChip Software version 3.1 for noise filtering. The first threshold for noise filtering was set at 5, and the second was set at 2. The 10% was the minimum threshold for clustering. The statistical analysis of the data of serum protein mass spectrum was performed in the groups (normal vs. hepatocellular carcinoma, and liver cirrhosis vs. hepatocellular carcinoma) with the t test. RESULTS: Comparison between the groups of hepatocellular carcinoma and normal control: The mass spectra from 56 samples (hepatocellular carcinoma and normal controls) in the training group were analysed and 241 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and normal controls (P < 0.01). Only 2 peaks at 3015 M/Z and 5900 M/Z were selected with significant difference (P < 10 (-9)). A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and normal controls. The sensitivity was 100% (17/17), and the specificity was 100% (11/11). Comparison between the groups of hepatocellular carcinoma and liver cirrhosis: The mass spectra from 49 samples in the training group (including patients with hepatocellular carcinoma and liver cirrhosis) were analysed and 208 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis (P < 0.01). Only 2 peaks at 7759 M/Z, 13134 M/Z were selected with significant difference (P < 10 (-9)). A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis. The sensitivity was 88.2% (15/17), and the specificity was 100% (8/8). CONCLUSIONS: The specific biomarkers selected with the SELDI technology could be used for early diagnosis of hepatocellular carcinoma.

Adult↗

[The diagnosis of aspirin-induced asthma by using a functional model].

The analysis of case history, clinical, laboratory and instrumental findings, objectively characterizing the patient's condition in two alternative groups (nonaspirin and aspirin bronchial asthma) enabled the authors to create a functional diagnostic model for aspirin bronchial asthma. The model-based computer program designed by the authors can perform early diagnosis of aspirin asthma outpatiently without any risk for the patients.

Adult↗

Use of preoperative magnetic resonance imaging to predict rotator cuff tear pattern and method of repair.

PURPOSE: To determine the magnetic resonance imaging (MRI) criteria for predicting rotator cuff tear pattern and method of repair. TYPE OF STUDY: Retrospective MRI/arthroscopy correlation. METHODS: Sixty-six preoperative MRI scans were evaluated. The maximum medial to lateral length (L) of the tear was measured on T2-weighted coronal cuts. The maximum anterior to posterior width (W) was measured on T2-weighted sagittal cuts. The cases were divided into 3 groups: group 1, short-wide tears, L < or = W, L < 2 cm; group 2, long-narrow tears, L > W, W < 2 cm; and group 3, long-wide tears, L > or = 2 cm, W > or = 2 cm. RESULTS: Of the 66 MRI scans, 55 were adequate for standardized measurement. Group 1, 16 cases: 15 were found at arthroscopy to be crescent-shaped tears repaired end-to-bone; 1 was repaired with interval slides. Group 2, 22 cases: all 22 were repaired side-to-side/margin convergence. Group 3, 17 cases: 12 required interval slides, 1 partial repair was performed, and 4 were repaired side-to-side/margin convergence. CONCLUSIONS: Tear pattern and method of repair can be predicted on high-quality MRI scan. Group 1, L < or = W and L < 2 cm, predicts a crescent-shaped tear and end-to-bone repair (positive predictive value, 93.8%). Group 2, L > W and W < 2 cm, predicts a longitudinal tear and side-to-side/margin convergence repair (positive predictive value 100%). Group 3, L > or = 2 cm and W > or = 2 cm, predicts a massive contracted tear and that primary end-to-bone or side-to-side repairs are usually not possible and that interval slides or partial repair may be necessary (positive predictive value, 76.5%). The overall diagnostic model based on usable MRI scans significantly predicted arthroscopic findings (P < .001 for chi-square test). LEVEL OF EVIDENCE: Level III, development of diagnostic criteria with universally applied reference (nonconsecutive patients).

Adult↗

Survival ensembles.

We propose a unified and flexible framework for ensemble learning in the presence of censoring. For right-censored data, we introduce a random forest algorithm and a generic gradient boosting algorithm for the construction of prognostic and diagnostic models. The methodology is utilized for predicting the survival time of patients suffering from acute myeloid leukemia based on clinical and genetic covariates. Furthermore, we compare the diagnostic capabilities of the proposed censored data random forest and boosting methods, applied to the recurrence-free survival time of node-positive breast cancer patients, with previously published findings.

Algorithms↗