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The effect of misclassification errors on case mix measurement.

Case mix systems have been implemented for hospital reimbursement and performance measurement across Europe and North America. Case mix categorizes patients into discrete groups based on clinical information obtained from patient charts in an attempt to identify clinical or cost difference amongst these groups. The diagnosis related group (DRG) case mix system is the most common methodology, with variants adopted in many countries. External validation studies of coding quality have confirmed that widespread variability exists between originally recorded diagnoses and re-abstracted clinical information. DRG assignment errors in hospitals that share patient level cost data for the purpose of establishing cost weights affects cost weight accuracy. The purpose of this study is to estimate bias in cost weights due to measurement error of reported clinical information. DRG assignment error rates are simulated based on recent clinical re-abstraction study results. Our simulation study estimates that 47% of cost weights representing the least severe cases are over weight by 10%, while 32% of cost weights representing the most severe cases are under weight by 10%. Applying the simulated weights to a cross-section of hospitals, we find that teaching hospitals tend to be under weight. Since inaccurate cost weights challenges the ability of case mix systems to accurately reflect patient mix and may lead to potential distortions in hospital funding, bias in hospital case mix measurement highlights the role clinical data quality plays in hospital funding in countries that use DRG-type case mix systems. Quality of clinical information should be carefully considered from hospitals that contribute financial data for establishing cost weights.

Diagnosis-Related Groups↗

CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray.

The ability to use archival tissue to test externally valid hypotheses of carcinogenesis is dependent on the availability of population-based samples of cancer tissue. Tissue microarrays (TMAs) provide an efficient format for developing population-based samples of tissue. A TMA was constructed consisting of archival tissue from patients diagnosed with invasive colorectal cancer in the state of Hawaii in 1995. The population representativeness of the TMA was evaluated by comparing patient and clinical characteristics of TMA cases to that of all cases of colorectal carcinoma diagnosed statewide in 1995. Cytokeratin 20 (CK20) and cytokeratin 7 (CK7) immunohistochemistry was used to validate the utility of the TMA, and the expression of these proteins was correlated with patient and tumor characteristics. The TMA comprised tissue specimens from 286 patients representing 47% of all invasive cases diagnosed statewide in 1995. TMA cases were comparable to all invasive colorectal cases statewide with respect to age, sex, race/ethnicity, anatomic site, and survival. There were some differences between TMA cases and all cases with respect to tumor stage, histological classification, and treatment. There were significant differences in the relative expression of CK20 and CK7 proteins between malignant and normal tissues and by tumor stage. Advanced cancers were more likely to have CK20+/cytokeratin 7+ (CK7+) profiles than early-stage cancers, which were predominantly CK20+/cytokeratin 7- (CK7-). CK7+ expression was not correlated with anatomic location of carcinomas. This well-characterized TMA offers a powerful tool for testing hypotheses regarding colorectal carcinogenesis, including the identification of potential markers of neoplastic development and progression.

Adenocarcinoma↗

ALID score for treatment-effect heterogeneity of adjunctive low-voltage area ablation in persistent atrial fibrillation: A post hoc analysis of SUPPRESS-AF.

BACKGROUND: In persistent atrial fibrillation (AF), the incremental benefit of adjunctive low-voltage area (LVA) ablation beyond pulmonary vein isolation (PVI) remains inconsistent. OBJECTIVE: To examine whether a simple clinical score characterizes treatment-effect heterogeneity of adjunctive LVA ablation among patients with mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 and to perform an exploratory supportive analysis in an independent randomized cohort. METHODS: In this post-hoc analysis of SUPPRESS-AF, which included patients with persistent AF and mapped LVA&#xa0;>&#xa0;5&#xa0;cm2 after PVI, four variables-age&#xa0;&#x2265;&#xa0;75&#xa0;years, left atrial diameter&#xa0;>&#xa0;44&#xa0;mm, estimated glomerular filtration rate&#xa0;<&#xa0;60&#xa0;mL/min/1.73&#xa0;m2, and absence of diabetes-were combined into the ALID score (0-4). Patients were stratified into low (0-1), intermediate (2), and high (3-4) score groups. Because EARNEST-PVI did not use LVA-guided ablation or select patients based on mapped LVA, it was analyzed as an exploratory supportive cohort rather than as an external validation cohort. RESULTS: In SUPPRESS-AF (n&#xa0;=&#xa0;336), a significant treatment-by-score interaction was observed (P&#xa0;<&#xa0;0.001). Adjunctive LVA ablation was associated with increased recurrence in the low-score stratum (HR 3.92; 95% CI 1.50-10.20) and reduced recurrence in the high-score stratum (HR 0.48; 95% CI 0.26-0.86). In EARNEST-PVI (n&#xa0;=&#xa0;494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P&#xa0;=&#xa0;0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5&#xa0;cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.

Humans↗

Modelling the growth of Leuconostoc mesenteroides by Artificial Neural Networks.

The combined effect of temperature (10.5 to 24.5 degrees C), pH level (5.5 to 7.5), sodium chloride level (0.25% to 6.25%) and sodium nitrite level (0 to 200 ppm) on the predicted specific growth rate (Gr), lag-time (Lag) and maximum population density (yEnd) of Leuconostoc mesenteroides under aerobic and anaerobic conditions, was studied using an Artificial Neural Network-based model (ANN) in comparison with Response Surface Methodology (RS). For both aerobic and anaerobic conditions, two types of ANN model were elaborated, unidimensional for each of the growth parameters, and multidimensional in which the three parameters Gr, Lag, and yEnd are combined. Although in general no significant statistical differences were observed between both types of model, we opted for the unidimensional model, because it obtained the lowest mean value for the standard error of prediction for generalisation. The ANN models developed provided reliable estimates for the three kinetic parameters studied; the SEP values in aerobic conditions ranged from between 2.82% for Gr, 6.05% for Lag and 10% for yEnd, a higher degree accuracy than those of the RS model (Gr: 9.54%; Lag: 8.89%; yEnd: 10.27%). Similar results were observed for anaerobic conditions. During external validation, a higher degree of accuracy (Af) and bias (Bf) were observed for the ANN model compared with the RS model. ANN predictive growth models are a valuable tool, enabling swift determination of L. mesenteroides growth parameters.

Dose-Response Relationship, Drug↗

Subtypes of female juvenile offenders: a cluster analysis of the Millon Adolescent Clinical Inventory.

The current study sought to explore subtypes of adolescents within a sample of female juvenile offenders. Using the Millon Adolescent Clinical Inventory with 101 female juvenile offenders, a two-step cluster analysis was performed beginning with a Ward's method hierarchical cluster analysis followed by a K-Means iterative partitioning cluster analysis. The results suggest an optimal three-cluster solution, with cluster profiles leading to the following group labels: Externalizing Problems, Depressed/Interpersonally Ambivalent, and Anxious Prosocial. Analysis along the factors of age, race, offense typology and offense chronicity were conducted to further understand the nature of found clusters. Only the effect for race was significant with the Anxious Prosocial and Depressed Intepersonally Ambivalent clusters appearing disproportionately comprised of African American girls. To establish external validity, clusters were compared across scales of the Behavioral Assessment System for Children - Self Report of Personality, and corroborative distinctions between clusters were found here.

Adolescent↗

Application of the transtheoretical model to identify psychological constructs influencing exercise behavior: a questionnaire survey.

BACKGROUND: Current research on exercise behavior has largely been attempted to identify the relationship between psychological attributes and the initiation or adherence of exercise behavior based on psychological theories. A limited data are available on the psychological predictors of exercise behavior in public health. OBJECTIVES: The present study examined the theorized association of TTM of behavior change constructs by stage of change for exercise behavior. METHODS: A total of 228 college students selected from 2 universities in Seoul were surveyed. Four Korean-version questionnaires were used to identify the stage of exercise behavior and psychological attributes of adolescents. Data were analyzed by frequency analysis, MANOVA, correlation analysis, and discriminant function analysis. RESULTS: Multivariate F-test indicated that behavioral and cognitive processes of change, exercise efficacy, and pros differentiated participants across the stages of exercise behavior. Furthermore, exercise behavior was significantly correlated with the TTM constructs, and that overall classification accuracy across the stages of change was 61.0%. CONCLUSIONS: The present study supports the internal and external validity of the Transtheoretical Model for explaining exercise behavior. As this study highlights, dissemination must increase awareness but also influences perceptions regarding theoretically based and practically important exercise strategies for public health professionals.

Adolescent↗

Artificial intelligence in treatment prediction for skeletal Class III malocclusion: A systematic review.

In skeletal Class III patients, treatment options range from orthodontics to orthognathic surgery. Choosing the optimal approach requires a comprehensive clinical evaluation, which may be supported by AI tools. The aim of this study was to assess the performance of AI models in predicting the need for orthognathic surgery and in identifying predictors influencing treatment decisions. A PRISMA-guided electronic database search (PubMed, Web of Science; 2009-2024; English/French) was performed to identify studies using machine learning (ML) or deep learning (DL) on cephalometric and clinical data. After screening and assessment for eligibility, 15 studies were critically appraised. Model performance was summarized using accuracy, sensitivity, specificity, and the area under the curve (AUC). ML algorithms (particularly Random Forest and XGBoost) and DL models (ResNet-based convolutional neural networks (CNNs)) achieved high accuracy for predicting surgical need. Frequently selected predictors included Wits appraisal, ANB angle, the maxillomandibular ratio (Mx/Md), overjet, and the divergence of the lower gonial angle. AI methods show promise for assisting treatment decisions in Class III malocclusion, with Random Forest and XGBoost performing well on tabular cephalometric data and CNNs on imaging. Larger, multicentre datasets and external validation are needed to improve reliability, address bias, and support clinical implementation.

Humans↗

Spatial and temporal transmission risk of Dirofilaria immitis in Argentina.

The aim of this work was to assess spatial and seasonal Dirofilaria immitis transmission risk throughout Argentina with models based on the temperature threshold below which filarial development will not proceed in the mosquito (i.e. 14 degrees C), the occurrence and the number of potential vector mosquito species, and the Heartworm Development Units derived from the degree-days concept. The four models showed a similar increasing southwest-northeast tendency and correlated significantly with canine prevalences used as external validation data. About one-third of Argentina would be suitable for heartworm transmission and the highest risk areas include the north-eastern provinces. According to our models, heartworm transmission is markedly seasonal with peaks in January and February; no region would support transmission throughout the year. To improve the present models, it is necessary to know which mosquito species are competent rather than potential vectors in the country. We believe the present study provides the first risk assessment maps for D. immitis transmission in the Southern Hemisphere and provides a useful guide for heartworm prevention during the transmission periods in different regions of Argentina.

Animals↗

Predictors of aortic stenosis in homozygous familial hypercholesterolemia: A study from the Canadian HoFH registry.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. This disease is associated with a major risk of both atherosclerotic cardiovascular disease and aortic stenosis (AS). The predictors of AS in this population are not well established. OBJECTIVE: To investigate the univariable and multivariable predictors of AS in patients from the Canadian HoFH registry. METHODS: Individuals from the Canadian HoFH registry were included in this retrospective longitudinal study. Clinical data were obtained from the treating physicians using a standardized questionnaire. Cox proportional hazards models were used to investigate the predictors of AS. The observed lifetime risk of AS was calculated using Kaplan-Meier estimates. RESULTS: Among the 67 patients with HoFH, 25 (37%) developed AS. The mean age at baseline was 22&#xa0;&#xb1;&#xa0;17 years and women represented 57% of the cohort. The independent predictors of AS were the baseline LDL-C (hazard ratio [HR] 1.22 [1.09-1.35], P&#xa0;=&#xa0;.0003) as well as the presence of at least 1 null genetic variant (HR 3.73 [1.41-9.86], P&#xa0;=&#xa0;.008). Having a baseline LDL-C value above 13&#xa0;mmol/L was associated with an observed lifelong risk of developing AS approaching 100% within this cohort, whereas having a value below this threshold was associated with a risk of 27% (P&#xa0;=&#xa0;.0002). CONCLUSION: This is the first systematic evaluation within a national HoFH registry to report the univariable and multivariable predictors of AS in patients with HoFH. An external validation of our results in an international cohort of HoFH is warranted.

Aortic stenosis↗

Is "relationship fear" unique to Japan? Symptom factors and patient clusters of social anxiety disorder among the Japanese clinical population.

BACKGROUND: There have been only a limited number of cross-cultural studies of social anxiety disorder (SAD), especially as diagnosed with modern operationalized diagnostic criteria and as measured with recently developed assessment instruments. We examined the symptomatological structure and clinical subtypes of patients with DSM-IV SAD among the Japanese clinical population. METHODS: We performed confirmatory and exploratory factor analyses of the joint Social Interaction Anxiety Scale and Social Phobia Scale from 149 psychiatric patients diagnosed with SAD. Based on the derived symptom factors, we further ran cluster analysis to identify patient subgroups. RESULTS: Factor analyses revealed three factors which were named "scrutiny fears", "conversation fears" and "relationship fears". The first two appeared common to Western clinical populations but the third appeared unique to the Japanese. Cluster analysis based on these three factor scores yielded three subgroups, which were externally validated and which overall corresponded with mild, moderate and pervasive subtypes of social phobia. LIMITATIONS: Both factor analysis and cluster analysis employed in the present study are exploratory in nature. Further empirical examination in different settings and cultures is necessary to provide definitive answers. CONCLUSIONS: It is suggested that we may need three symptom subscales and three subtypes in order to better account for cultural variations in the presentation of SAD.

Adolescent↗

An electrophysiological endophenotype of hypomanic and hyperthymic personality.

BACKGROUND: Hyperthymic Temperament (HYT) and a closely related trait, Hypomanic Personality (HYP), have both been related to bipolar affective disorder (BAD). Intensity dependence of auditory evoked potentials (IAEP) is a suggested inverse indicator of serotonergic neurotransmission and has been found to be elevated in BAD. Therefore the present study explored for the first time whether subclinical variance of HYT/HYP is also associated with IAEP in a healthy sample. As several traits from biological personality research are correlated with HYT/HYP and also with BAD, the specificity of results against these traits was further analyzed by calculating multiple regression analyses. METHODS: Evoked potentials were recorded from a sample (N=87) homogenous for confounding variables influencing IAEP. For this reason, only 19 to 27-year-old non-smoker psychiatrically healthy male students were included. RESULTS: Significant correlations were found between IAEP and both HYP and HYT. Including Sensation or Novelty Seeking and Extraversion in Regression Analyses did not weaken the associations of HYP with IAEP much, but did affect those of HYT. However, these competing biological personality traits were hardly able to predict IAEP themselves. Impulsivity, though, was able to reduce the predictive power of HYP and HYT and to explain unique IAEP-variance. This was even more the case for Behavioral-Activation-System-Sensitivity (BAS) subscale Fun Seeking clearly dominating all regression analyses. LIMITATIONS: Homogeneity of sample. CONCLUSIONS: The impact of BAS is in agreement with the assumption that heightened BAS-sensitivity is an underlying biological cause for HYP/HYT and for BAD. Future studies on BAD should include BAS and Impulsivity besides HYP/HYT to further explore uniqueness of the latter and to develop questionnaires based on those items of a hyperthymic-hypomanic-impulsive-funseeking item pool, which possess the most external validity.

Adult↗

Mass spectrometric separation and quantitation of overlapping isotopologues. H2O/HOD/D2O and H2Se/HDSe/D2Se mixtures.

Three conceptually different mathematical methods are presented for accurate mass spectrometric determination of H2O/HOD/D2O and H2Se/HDSe/D2Se concentrations from mixtures. These are alternating least-squares, weighted two-band target entropy minimization, and a statistical mass balance model. The otherwise nonmeasurable mass spectra of partially deuterated isotopologues (HOD and HDSe) are mathematically constructed. Any recorded isotopologue mixture mass spectra are then deconvoluted by least-squares into their components. This approach is used to study the H2O/D2O exchange reaction, and is externally validated gravimetrically. The H2O/D2O exchange equilibrium constant is also measured from the deconvoluted 70 eV electron impact GC/MS data (K = 3.85 +/- 0.03).

Algorithms↗

Models developed by three techniques did not achieve acceptable prediction of binary trauma outcomes.

BACKGROUND AND OBJECTIVES: To develop prediction models for outcomes following trauma that met prespecified performance criteria. To compare three methods of developing prediction models: logistic regression, classification trees, and artificial neural networks. METHODS: Models were developed using a 1996-2001 dataset from a major trauma center in Victoria, Australia. Developed models were subjected to external validation using the first year of data collection, 2001-2002, from a state-wide trauma registry for Victoria. Different authors developed models for each method. All authors were blinded to the validation dataset when developing models. RESULTS: Prediction models were developed for an intensive care unit stay following trauma (prevalence 23%) using information collected at the scene of the injury. None of the three methods gave a model that satisfied the performance criteria of sensitivity >80%, positive predictive value >50% in the validation dataset. Prediction models were also developed for death (prevalence 2.9%) using hospital-collected information. The performance criteria of sensitivity >95%, specificity >20% in the validation dataset were not satisfied by any model. CONCLUSION: No statistical method of model development was optimal. Prespecified performance criteria provide useful guides to interpreting the performance of developed models.

Adult↗

Artificial intelligence for dental caries detection: An umbrella review.

Artificial intelligence (AI) has been proposed as a tool to improve dental caries detection across imaging modalities; however, its clinical value remains uncertain. This umbrella review aimed to synthesize and critically appraise systematic reviews evaluating AI for caries detection and diagnosis. An umbrella review was conducted following PRIOR guidance (PROSPERO CRD420261340728). Searches were performed in MEDLINE, Embase, Scopus, Web of Science, and Google Scholar up to 15 March 2026. Methodological quality was assessed using AMSTAR 2, and overlap of primary studies was quantified using the corrected covered area (CCA). Seventeen systematic reviews were included, of which five reported diagnostic test accuracy meta-analyses using bivariate or HSROC models. Across these meta-analyses, pooled sensitivity ranged from 0.76 to 0.94 and specificity from 0.85 to 0.91. Most systems were based on deep learning models applied to bitewing radiographs and intraoral photographs. However, substantial heterogeneity was observed in imaging modalities, lesion thresholds, analytical tasks, and evaluation metrics. In addition, a high degree of overlap across reviews and recurrent methodological limitations, including reliance on retrospective datasets, limited external validation, and inconsistent reporting, substantially weaken the reliability of the evidence. Although AI models demonstrate high diagnostic performance under experimental conditions, current evidence does not support their use as stand-alone diagnostic tools. Their clinical applicability remains limited, and implementation should be restricted to decision-support contexts until robust prospective validation demonstrates meaningful impact on clinical decision-making and patient outcomes.

Dental Caries↗

3D-QSAR comparative molecular field analysis on delta opioid receptor agonist SNC80 and its analogs.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) for a series of delta opioid receptor agonists: SNC80 analogs. Quantum chemical calculations on SNC80 show that protonation is preferred at the basic N4 atom over the alternative N1 atom, accordingly N4 protonation may contribute significantly to ligand-receptor interactions under physiologically relevant conditions. Statistically significant and predictive CoMFA models were achieved by pooling biological data from independent published sources, including compounds with both alphaR and alphaS benzylic configurations. Improved CoMFA models were obtained when the compounds were considered as N4-protonated species rather than neutral compounds. The influence of various atomic partial-charge formalisms, alignment schemes and additional molecular descriptors was evaluated in order to produce the highest quality models. In addition, separate CoMFA models were generated for compounds with only the alphaR benzylic configuration. These CoMFA models showed excellent internal predictability and consistency, and external validation using test-set compounds yielded predicted pIC50 values within 1log unit of the corresponding experimentally measured values. Key insights into the structure-activity relationship derived from the CoMFA analysis concur with experimentally observed data, thus the CoMFA models presented here find utility for predicting the binding affinity, and guiding the design, of novel SNC80 analogs and related delta opioid receptor agonists.

Animals↗

Online measurement of motivational processes: introducing the Continuous Delay Aversion Test (ConDAT).

The Continuous Delay Aversion Test (ConDAT), a new computer task for online monitoring and continuously measuring delay aversion (DA), is introduced. DA is a motivational style related to a shortened delay gradient which is proposed as a major endophenotype of attention deficit hyperactivity disorder (ADHD). It is characterised by avoiding or escaping from delay-rich situations despite the prospects of a reward. In each ConDAT trial the rapidly diminishing reward/delay ratio, which tends asymptotically towards zero, is visually presented on the computer screen. The test subject is permanently confronted with the question whether to quit or to continue the trial in the face of the deteriorating reward/time ratio. An elaborated control of stimuli and responses, including the sending of trigger codes to external recording devices, makes the task useful for neurophysiological or brain imaging experiments. Compared to existing tasks, the ConDAT is more flexible and sensitive due to its asymptotic open-ended trials and the interval-scaled output measure. Pilot data give evidence for satisfactory reliability and external validity of the task.

Attention Deficit Disorder with Hyperactivity↗

McKenzie classification of mechanical spinal pain: profile of syndromes and directions of preference.

The purpose of this study was to develop a profile of the use of McKenzie classifications of diagnosis and treatment, by physiotherapists credentialed in the McKenzie method in New Zealand. This system has been in common use for more than 20 years and the inter-rater reliability of the assessment has been previously established for therapists at this level of training. Prior studies identifying the classification of patients according to syndrome and directional preference have been mainly for the lumbar spine. The 34 participants for this study each assessed and classified 10 consecutive spinal patients during a 10-week period. Of the 340 patients assessed, 19 were excluded. Of those with pain arising from the lumbar spine; 140/187 were classified as reducible derangement syndrome, 11/187 were classified as irreducible derangement, 11/187 as dysfunction syndrome, 1/187 as posture syndrome and 24/187 as 'other'. For treatment in the reducible derangement syndrome; 98/140 were given extension, 8/140 were given flexion and 34/140 were given lateral movements of either side gliding or rotation. Classifications and treatment for the cervical and thoracic spine groups followed similar patterns. These findings add to the external validity of the McKenzie method, and support mechanical evaluation of spinal patients according to directional preference.

Adult↗

The prevalence of house dust mite (HDM) allergy and the use of HDM-impermeable bed covers in a primary care population of patients with persistent asthma in the Netherlands.

BACKGROUND: : House dust mite (HDM) allergen is one of the most common allergens to which asthma patients are sensitised. Prevalence of HDM allergy varies in the literature. Use of HDM-impermeable bed covers reduces exposure to HDM allergen. The aim of this study was to assess the prevalence of HDM allergy in a primary care population of asthma patients, as well as the use of HDM-impermeable bed covers by these patients. METHODS: : A random sample of asthma patients between 16 and 60 years old was taken from general practices. Allergy was assessed with a radio allegro sorbent test (RAST). A questionnaire was used to identify demographic characteristics and the actual use of bed covers. RESULTS: : 534 patients were invited and 160 patients participated. 53 patients not willing to participate were randomly selected to test the external validity of our findings. The sample was representative for the primary care asthma population. 48.8% of the asthma population was sensitised to HDM allergen. 25.6% of the HDM-allergic asthma patients were using HDM-impermeable bed covers. CONCLUSION: : Almost half of the patients with asthma were sensitised to HDM allergen. Only a minority of the patients used HDM-impermeable bed covers.

Journal Article↗