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PubMed1981

Classification of depression.

Depression is an aetiologically unspecific reaction pattern of the human organism to psychological or physical changes. It can occur in all forms of psychiatric disorders. The depressive symptomatology in itself does not allow a valid classification. Nosology must take into account aetiology, pathogenesis, and the course. The former two are mostly unknown. Considering the restricted value of all classifications of depressive syndromes the concepts must be validated by external criteria (e.g. genetic, biochemical, neurophysiological criteria, and response to treatment). In this paper a classification based on the course and genetic criteria of depression is proposed. In a preliminary study the clinical diagnoses of 100 depressive patients are compared with the classification based on diagnostic criteria of Feighner et al., Taylor and Abrams, as well as on DSM-III.

Aged↗
PubMed2004

Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes.

Proteochemometrics was applied in the analysis of the binding of organic compounds to wild-type and chimeric melanocortin receptors. Thirteen chimeric melanocortin receptors were designed based on statistical molecular design; each chimera contained parts from three of the MC(1,3-5) receptors. The binding affinities of 18 compounds were determined for these chimeric melanocortin receptors and the four wild-type melanocortin receptors. The data for 14 of these compounds were correlated to the physicochemical and structural descriptors of compounds, binary descriptors of receptor sequences, and cross-terms derived from ligand and receptor descriptors to obtain a proteochemometric model (correlation was performed using partial least-squares projections to latent structures; PLS). A well fitted mathematical model (R(2) = 0.92) with high predictive ability (Q(2) = 0.79) was obtained. In a further validation of the model, the predictive ability for ligands (Q(2)lig = 0.68) and receptors (Q(2)rec = 0.76) was estimated. The model was moreover validated by external prediction by using the data for the four additional compounds that had not at all been included in the proteochemometric model; the analysis yielded a Q(2)ext = 0.73. An interpretation of the results using PLS coefficients revealed the influence of particular properties of organic compounds on their affinity to melanocortin receptors. Three-dimensional models of melanocortin receptors were also created, and physicochemical properties of the amino acids inside the receptors' transmembrane cavity were correlated to the PLS modeling results. The importance of particular amino acids for selective binding of organic compounds was estimated and used to outline the ligand recognition site in the melanocortin receptors.

Base Sequence↗
PubMed2026

Machine learning-driven spleen imaging and genomics uncover a splenic connection to coronary artery disease.

Despite advances in managing traditional risk factors, coronary artery disease (CAD) remains the leading cause of mortality. Circulating hematopoietic cells influence risk for CAD separately from traditional risk factors, but the role of a key regulating organ, the spleen, is unknown. The understudied spleen is a representation of the hematopoietic system optimally suited for unbiased radiologic investigations toward mechanistic insights. Here, we leveraged deep learning to extract 107 splenic radiomic features from abdominal magnetic resonance imaging (MRI) scans of 42,059 UK Biobank participants and of 2745 Mass General Brigham Biobank (MGBB) participants. Of these, 10 features from UK Biobank were associated with CAD. Genome-wide association analysis of CAD-associated features identified 219 loci, including 9p21. Variants at 9p21, the strongest yet mechanistically elusive CAD locus, were associated with splenic features such as run-length nonuniformity, reflecting heterogeneity of continuous texture regions. Research MRI findings were consistent internally, but external clinical validation highlighted challenges in translating analyses of abdominal MRI scans to routine clinical practice because of variability in imaging protocols and greater clinical heterogeneity among patients. Our study, combining deep learning with genomics, presents a framework to uncover potential splenic involvement in CAD and emphasizes translational gaps between research and clinical radiomics.

Humans↗
PubMed2005

Can all neonatal resuscitation be managed by nurse practitioners?

AIM: To assess the ability of nurse practitioners to manage the care of all babies requiring resuscitation at birth in a unit without on site medical assistance. METHOD: A prospective review, and selective external audit, of the case records of all 14 572 babies born in a maternity unit in the north of England during the first eight years after nurse practitioners replaced resident paediatric staff in 1996. RESULTS: Every non-malformed baby with an audible heart beat at the start of delivery was successfully resuscitated. Twenty term babies and 41 preterm babies were intubated at birth. Eight term babies only responded after acidosis or hypovolaemia was corrected following umbilical vein catheterisation; in each case the catheter was in place within six minutes of birth. Early grade 2-3 neonatal encephalopathy occurred with much the same frequency (0.12%) as in other recent studies. Independent external cross validated review found no case of substandard care during the first hour of life. CONCLUSION: The practitioners successfully managed all the problems coming their way from the time of appointment. There was no evidence that their skill decreased over time even though, on average, they only found themselves undertaking laryngeal intubation once a year. It remains to be shown that this level of competence can be replicated in other settings.

Apnea↗
PubMed1994

Methods for quality-of-life studies.

Methodologies involving the use of quality-of-life patient outcomes in observational and interventional studies of health are drawn from a large and diverse field of research methods. The multidimensional way in which quality of life is conceptualized will affect the way it is measured and the complexity of the measurement. At the earliest stages of research, one must rely on methods common to the fields of tests and measurement, survey research, psychometrics and sociometrics to measure constructs that are not directly observable. Indices measuring performance can either focus on the scale's ability to perform in noninterventional, cross-sectional studies or interventional, longitudinal studies. Indices of stability, internal consistency, responsiveness with respect to true changes in quality of life, and sensitivity to treatment effects can be used to assess the scale's adequacy as a dependent variable of interest. Respondent variability can occur due to factors such as different reporters (patient, spouse, physician), the manner and form of administration (long form vs short form; self-administration vs interview) and the assessment environment (clinic, home). Finally, since quality-of-life research often involves inferential statistics and hypothesis testing, the statistical and epidemiologic principles of good study design should be followed. In addition, one should account for the reliability, responsiveness, and the sensitivity of the scale when designing the scientific hypotheses, and should specifically address the meaning of quality-of-life effect sizes by interventional-based validation. Design considerations must address the statistical issues of power, the determination of effect sizes through validation by external criteria, longitudinal data, effects of withdrawal and early termination, ceiling and floor effects, and heterogeneity of responsiveness and sensitivity among individuals. The problem of estimating quality-of-life summary parameters for use in pharmacoeconomic models is receiving increasing attention in this era of health-care reform and fiscal restraint. While medical decision theory has used cost-effectiveness models and quality-adjusted life years since the early 1970s, estimation of population parameters to differentiate among different medical interventions is relatively new. The assessment of the patient outcomes associated with medical interventions in terms of the risks, benefits and costs will clearly be a major focus of health-care reform. Development of new methodologies in quality-of-life research should build upon the strong foundation already established in the areas of clinical research, epidemiology, biostatistics, economics and behavioral science.(ABSTRACT TRUNCATED AT 400 WORDS)

Bias↗
PubMed1990

Latent class analysis of deluded patients.

The internal and external construct validity of 4 severe prognostic psychopathological items is studied in deluded patients. A two-class model of latent structure analysis fits fairly well. One latent class seems to reflect a schizophrenic spectrum while the other class does not include characteristics which are known from one single nosologic entity. Thought disorder is most predictive for schizophrenic class membership, while blunted affect has the least predictive value. This 'schizophrenic' latent class has a fairly high and similar sensitivity to various definitions of schizophrenic disorder. The frequency of the types of delusions differs between the classes.

Affective Symptoms↗
PubMed1995

Factor structure of social support and its relationship to minor psychiatric disorders among Japanese adolescents.

Although social support has been one of the preferred topics in health psychology for the past two decades, there still remains controversy about its construct and the measurement model for it. The People In Your Life (PIYL) scale, a self-report adaptation of Henderson et al.'s Interview Schedule for Social Interactions (1980), appears to be an outgrowth of the recent developments in this domain. We administered PIYL to two samples, 550 and 434 each, of Japanese adolescents and examined its factor structure, its psychometric properties and its concurrent relationship to minor psychiatric disorders. Of the original four subscales, the presence of two subscales called availability of social integration and availability of attachment was confirmed, while the remaining subscales called adequacy of social integration and adequacy of attachment were found to form one general factor of perceived adequacy. Such a three-factor model appeared to fit the data better, psychometrically more sound and externally more valid in accounting for the minor psychiatric disorders.

Adolescent↗
PubMed1991

Activated charcoal and acetylcysteine absorption: issues in interpreting pharmacokinetic data.

Studies determining the effects of activated charcoal on drug absorption frequently use area under the plasma drug concentration versus time curve or drug and metabolite recovery in the urine as endpoints. The considerations in using these endpoints is presented using studies that have evaluated the effects of activated charcoal on acetylcysteine absorption. Acetylcysteine's pharmacokinetics, quantitation of plasma concentrations, and the lack of an identifiable pharmacokinetic-pharmacodynamic relationship all contribute to the difficulties in determining whether activated charcoal inhibits the oral absorption of acetylcysteine, or alters acetylcysteine's efficacy in treating acetaminophen overdoses. The results of these studies should be interpreted cautiously, with consideration of internal and external study validity.

Absorption↗
PubMed2001

2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To update the 1997 clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials. OPTIONS: Six tumor markers for colorectal cancer and eight for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In addition to carcinoembryonic antigen (CEA) and CA 15-3, CA 27.29 was also considered among the serum tumor markers for breast cancer. OUTCOMES: In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used. EVIDENCE: A computerized literature search from 1994 to March 1999 was performed. VALUES: The same values for use, utility, and levels of evidence were used by the committee. BENEFITS, HARMS, AND COSTS: The same benefit, harms, and costs were used. RECOMMENDATION: Changes were recommended (see Appendix). VALIDATION: The updated recommendations were validated by external review by the American Society of Clinical Oncology's (ASCO's) Health Services Research Committee and by ASCO's Board of Directors. SPONSOR: American Society of Clinical Oncology.

Adult↗
PubMed2002

Mathematical model to predict individual survival for patients with renal cell carcinoma.

PURPOSE: To develop a multivariate model and mathematical formula capable of calculating personalized survival for renal cell carcinoma (RCC) patients with clinically available variables. PATIENTS AND METHODS: A total of 477 patients out of 661 undergoing nephrectomy at the University of California Los Angeles between 1989 and 1999 were eligible for evaluation and formed the analyzed cohort for this retrospective study. Time to death was the primary end point assessed. Univariate analysis for 14 to 20 variables was conducted, followed by a multivariate Cox analysis. The variables that provided independent information as to the time of death for metastatic and nonmetastatic patients were coded and incorporated into a function based on the Nadas equation principle. RESULTS: For nonmetastatic patients, the significant variables in the multivariate analysis were Fuhrman's grade and Eastern Cooperative Oncology Group performance status. For the metastatic patients, Fuhrman's grade, 1997 classification T stage, number of symptoms, nodal involvement, and immunotherapy were independent predictors for survival. These variables, based on the Cox multivariate regression model, were implanted into an exponential Nadas equation. The expected survival predicted by use of the Nadas equations faithfully describes the actual survival based on Kaplan-Meier curves. CONCLUSION: We have developed mathematical equations for estimating survival after radical nephrectomy for RCC. The resulting formulas are capable of better tailoring survival estimates for a specific patient and are based on widely accepted clinical prognostic variables. On validation with external data, this type of representation can be used as a tool for the determination of personalized prognosis and may be useful for patient education and counseling.

Carcinoma, Renal Cell↗
PubMed2003

The effect of saddle design on stresses in the perineum during cycling.

PURPOSE: Repetitive internal stress in the perineum has been associated with soft-tissue trauma in bicyclists. Using an engineering approach, the purpose of this study was to quantify the amount of compression exerted in the perineum for a range of saddle widths and orientations. METHODS: Computer tomography was used to create a three-dimensional voxel-based finite element model of the right side of the male perineum-pelvis. For the creation of the saddle model, a commercially available saddle was digitized and the surface manipulated to represent a variety of saddle widths and orientations. The two models were merged, and a static downward load of 189 N was applied to the model at the region representing the sacroiliac joint. For validation purposes, external stresses along the perineum-saddle interface were compared with the results of pressure sensitive film. Good agreement was found for these external stresses. The saddles were then stretched and rotated, and the magnitude and location of maximum stresses within the perineum were both recorded. In all cases, the model of the pelvis-perineum was held in an upright position. RESULTS: Stresses within the perineum were reduced when the saddle was sufficiently wide to support both ischial tuberosities. This supporting mechanism was best achieved when the saddle was at least two times wider than the bi-ischial width of the cyclist. Stresses in the anterior of the perineum were reduced when the saddle was tilted downward, whereas stresses in the posterior were reduced when the saddle was tilted upward. CONCLUSIONS: Recommendations that saddles should be sufficiently wide to support the ischial tuberosities appear to be well founded. Recommendations that saddles be tilted downward (i.e., nose down) are supported by the model, but with caution, given the limitations of the model.

Animals↗
PubMed2004

Discriminating different classes of toxicants by transcript profiling.

Male rats were treated with various model compounds or the appropriate vehicle controls. Most substances were either well-known hepatotoxicants or showed hepatotoxicity during preclinical testing. The aim of the present study was to determine if biological samples from rats treated with various compounds can be classified based on gene expression profiles. In addition to gene expression analysis using microarrays, a complete serum chemistry profile and liver and kidney histopathology were performed. We analyzed hepatic gene expression profiles using a supervised learning method (support vector machines; SVMs) to generate classification rules and combined this with recursive feature elimination to improve classification performance and to identify a compact subset of probe sets with potential use as biomarkers. Two different SVM algorithms were tested, and the models obtained were validated with a compound-based external cross-validation approach. Our predictive models were able to discriminate between hepatotoxic and nonhepatotoxic compounds. Furthermore, they predicted the correct class of hepatotoxicant in most cases. We provide an example showing that a predictive model built on transcript profiles from one rat strain can successfully classify profiles from another rat strain. In addition, we demonstrate that the predictive models identify nonresponders and are able to discriminate between gene changes related to pharmacology and toxicity. This work confirms the hypothesis that compound classification based on gene expression data is feasible.

Algorithms↗
PubMed2001

Comparative binding energy (COMBINE) analysis of human neutrophil elastase inhibition by pyridone-containing trifluoromethylketones.

The complexes of human neutrophil elastase with a series of 40 N3-substituted trifluoromethylketone-based pyridone inhibitors have been modelled. The series spans three orders of magnitude in inhibition constants despite the fact that it was originally developed in an attempt to improve the oral activity of a lead compound. Ligand-receptor interaction energies calculated using molecular mechanics did not correlate well with the experimental activities. A good correlation with activity was found, however, when a COMBINE analysis of the same data was carried out, which allowed a quantitative interpretation of the modelled complexes. The essence of this method is to partition the ligand-receptor interaction energies into individual residue-based van der Waals and electrostatic contributions, and to subject the resulting energy matrix to partial least squares analysis. Incorporation of two additional descriptors representing the electrostatic energy contributions to the partial desolvation of both the receptor and the ligands improved the QSAR model, as did the replacement of the distance-dependent electrostatic contributions with solvent-screened electrostatic interactions calculated by numerically solving the Poisson-Boltzmann equation. The model was validated both internally (cross-validation) and externally, using a set of twelve 6-phenyl-pyridopyrimidine analogs. The analysis reveals the subtle interplay of binding forces which occurs within the enzyme active site and provides objective information that can be interpreted in the light of the receptor structure. This information, gained from a series of real compounds, can be easily translated into 3D real or virtual database queries in the search for more active derivatives.

Humans↗
PubMed2026

Enterocutaneous Fistula-Associated Sepsis and Mortality: Development and Validation of a Multimodal Artificial Intelligence Prediction Model.

BACKGROUND: Predicting enterocutaneous fistula (ECF)-associated sepsis and mortality poses significant challenges in digital health care due to the disease's complexity and heterogeneous clinical manifestations. Current approaches that rely on single-modal data or traditional scoring systems often fail to capture the intricate immune-inflammatory dynamics and multisystem involvement in patients with ECF. OBJECTIVE: This study aims to develop an artificial intelligence (AI)-driven multimodal fusion model integrating clinical, imaging, and transcriptomic data for early prediction of ECF-associated sepsis and 28-day mortality, addressing the limitations of conventional single-dimensional models. METHODS: This study leveraged publicly available datasets (Medical Information Mart for Intensive Care III [MIMIC-III], electronic Intensive Care Unit [eICU], and The Cancer Genome Atlas) to construct a multimodal framework. Clinical parameters were processed using Extreme Gradient Boosting, abdominal imaging features were extracted via convolutional neural networks, and transcriptomic profiles were analyzed with variational autoencoders. A Transformer-based fusion network was employed for joint prediction and validated through cross-validation and external testing. Key features were identified using Shapley Additive Explanations and Local Interpretable Model-Agnostic Explanations interpretability algorithms, while immune regulatory mechanisms were explored via weighted gene co-expression network analysis. RESULTS: The multimodal model achieved an area under the curve (AUC) of 0.89 for predicting sepsis and 28-day mortality, outperforming unimodal models (clinical-only model, AUC 0.72, and imaging-only model, AUC 0.78). Critical predictors included Sequential Organ Failure Assessment score, lactate levels, intra-abdominal free fluid on imaging, and immunoregulatory genes (programmed death-ligand 1 [PD-L1] and indoleamine 2,3-dioxygenase 1 [IDO1]). Mechanistic analysis revealed distinct immune reprogramming in patients with sepsis, characterized by increased regulatory T cells and M2 macrophages, along with downregulated cluster of differentiation 8+ (CD8+) T cells. CONCLUSIONS: This multimodal AI model offers an innovative digital solution in medical informatics, enabling precise early risk stratification for ECF-associated sepsis. By integrating multisource data and providing interpretable insights into immune-inflammatory pathways, the model enhances health care quality for patients with ECF and paves the way for personalized intervention strategies.

Humans↗
PubMed2001

Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome.

PURPOSE: We analyzed the effects of the change in TNM classification from the 1987 to the 1997 version and suggest a modified tumor size cutoff point between T stages 1 and 2 for renal cell carcinoma. MATERIALS AND METHODS: We evaluated a database containing the records of 661 patients who underwent nephrectomy between 1989 and 1999. The effect of the change in TNM classification on the distribution of patients between stages, the rates of M+ and N+ disease, and the local and distant recurrence rates were outlined for 280 patients with T stages 1 and 2 disease. The Cox model was used to identify the optimal cutoff point between T1 and T2 disease, and the resulting effect of adopting this cutoff was outlined. RESULTS: A total of 174 and 128 cases were down staged from 1987 version stage T2 to 1997 version stage T1 and from 1987 TNM stage II to 1997 TNM stage I, respectively. Survival was not significantly different in patients with 1997 TNM stages I and II disease due to a lack of survival difference during the first 2 years of followup. Stage shift also caused an increase in average tumor size, the proportion of patients with high grade cancer, and M+ and N+ disease at diagnosis in 1997 stages T1 and T2 as well as an increase in the proportion of 1997 stage T2N0M0 cases at diagnosis with systemic failure. Analysis of 11 potential cutoff points between 1 and 10 cm. revealed that 4.5 cm. was most predictive of patients survival (hazards ratio 4.99, p = 0.0001). Using this cutoff resulted in improved discriminatory power of the TNM classification and a moderating effect on the distribution of patients, average tumor size, high grade disease, M+ and N+ disease at diagnosis, and systemic failure between T(14.5) and T(24.5) compared with 1997 T1 and T2. CONCLUSIONS: Our data imply that the current cutoff point of 7 cm. between stages T1 and T2 tumors is too high. Lowering the cutoff to 4.5 cm. resulted in better discriminatory power of the TNM classification in our dataset. This observation should be further validated by external data.

Adult↗
PubMed2003

[Guidelines: state of the art and peculiar aspects in pediatric emergency].

In recent years pediatric guidelines have increasingly become part of clinical practice, in Italy too. Aim of the present work is, on the basis of a review of national and international literature, to focus on the Italian situation about the use of guidelines in pediatric emergency, with particular respect to methodology, correct use, and related risks and benefits. The developing of efficient guidelines is achieved in different steps: 1) identifying and refining the topic for guidelines, in order to obtain an improvement of healthcare; 2) correct developing strategies, based on scientific evidence, leading to production of recommendations validated by external review; 3) adequate implementation and diffusion in local settings; 4) application with sensible and appropriate clinical discretion. Benefits obtained with the correct use of efficient pediatric guidelines, can be identified at different levels: patients' care (outcome improvement, increased patients' consciousness, influence on public healthcare policy); healthcare professionals (improving quality of clinical decisions, agreement on clinical and therapeutic strategies; medicolegal protection, representing a reference for prospective and retrospective audits); healthcare systems (standardising care, improving efficacy of care; optimising costs). Personal experience in systematic development of emergency pediatric guidelines, applied in a second level Emergency Department is also presented.

Child↗
PubMed1992

The prediction of total body water from body impedance in young obese subjects.

Almost all formulae for the prediction of total body water (TBW) from body impedance are based on the assumption of a constant conductor configuration--i.e. a constant subject section. In this paper we report on data obtained for a group of 19 young obese subjects (relative weight greater than 120%) and 10 young normal subjects (relative weight 80-110%). In obese subjects, the application of two different formulae generated from normal children gave biased results and led to an underestimation of TBW with respect to the reference value obtained by deuterium oxide dilution. Body mass index accounted for more than 40% of the inter-individual variability, suggesting that body size was not taken sufficiently into consideration by the predictive formulae used. We have used the body surface area as the anthropometrical parameter for the prediction of TBW from body impedance. The regression formula that we propose (TBW = 1.156 x (surface area/body impedance) - 2.356; R = 0.96), although requiring further validation on external populations, seems to provide a more realistic assessment of TBW in young obese subjects. We therefore suggest that the assessment of TBW in young obese subjects requires specifically designed prediction formulae.

Adolescent↗
PubMed1992

[Quality assurance in the public health office].

Quality is assured not only by long-standing experience; it must be continually safeguarded. Preconditions are as follows: qualified training with scientific background and continual scientific supervision; regular continuing education via exchange of experience; standardising of methods on a intra-office level and by inter-office exchange on Lander level; internal and external cooperation; validity and plausibility controls; interdisciplinary cooperation. These principles are discussed by means of examples of health protection--health protection on environmental protection principles--expertising--medical statistics/health planning--health care aid/health advisory service.

Delivery of Health Care↗