Assessing the diagnostic validity of a structured psychiatric interview in a first-admission hospital sample

The use of structured psychiatric interviews performed by non-clinicians is frequent for research purposes and is becoming increasingly common in clini-cal practice. The validity of such interviews has rarely been evaluated empirically. In this study of a sample of 100 diagnostically heterogeneous, first-admitted inpatients, the results of an assessment with the Structured Clinical Interview for DSM-IV (SCID), yielding a DSM-IV diagnosis and performed by a trained non-clinician, were compared with a consensus lifetime best diagnostic estimate (DSM-IV) by two experienced research clinicians, based on multiple sources of information, which included videotaped comprehensive semi-structured narrative interviews. The overall kappa agreement was 0.18. The sensitivity and specificity for the diagnosis of schizophrenia by SCID were 19% and 100%, respectively. It is concluded that structured interviews performed by non-clinicians are not recommendable for clinical work and should only be used in research with certain precautions. It is suggested that a revival of systematic theoretical and practical training in psychopathology is an obvious way forward in order to improve the validity and therapeutic utility of psychiatric diagnosis.     

Defining the phenotype in human genetic studies: forward genetics and reverse phenotyping

The definition of phenotypes for genetic study is a challenging endeavor. Just as we apply strict quality standards to genotype data, we should expect that phenotypes meet consistently high standards of reproducibility and validity. The methods for achieving accurate phenotype assignment in the research setting--the 'research diagnosis'--are different from the methods used in clinical diagnosis in the patient care setting. We evaluate some of the main challenges of phenotype definition in human genetics, and begin to outline a set of standards to which phenotypes used in genetics studies may aspire with the goal of increasing the quality and reproducibility of linkage and association studies. Revisiting the traditional phenotype definitions through a focus on familial components and heritable endophenotypes is a time-honored approach. Reverse phenotyping, where phenotypes are refined based on genetic marker data, may be a promising new approach. The stakes are high, since the success of gene mapping in genetically complex disorders hinges on the ability to delineate the target phenotype with accuracy and precision.     

The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3

The Marfan syndrome is a common autosomal dominant disorder of connective tissue. Despite many years of intensive investigation, the primary genetic defect has not yet been identified. Reverse genetic methods, targeted at mapping this disease gene, have resulted in an initial report of linkage of the genetic locus for the Marfan phenotype in Finnish families to two polymorphic markers on chromosome 15. We have investigated four large multiplex American families with classic Marfan syndrome using standard genetic linkage methods. Our data confirm the assignment of the Marfan syndrome gene to chromosome 15, but establish a more centromeric location (defined by markers D15S25 and D15S1) as the most probable site for the genetic defect (lod score = 12.1, theta = 0.00). These data should facilitate identification and characterization of the Marfan syndrome gene and, in selected families, have immediate application to diagnosis of equivocal cases or prenatal counseling.     

Impact of integrating clinical and genetic information

To assess the relevance of molecular markers it is required to combine clinical and genetic information. For reliable assessment of parameters relevant to diagnostics and therapy large patient collectives must be characterized both with respect to phenotype and genotype. Matching of genetic data like gene expression profiles, molecular genetics and cytogenetics with clinical data like follow-up, morphological findings and diagnoses involves integration of complex databases. In the context of a nationwide leukemia research network in Germany we designed an integrated database covering both genetic and clinical data of patients. The system contains follow-up data and relevant laboratory modalities, i. e. cytomorphology, cytogenetics, molecular genetics, FISH, immunophenotyping and gene expression profiling. So far 13,541 cases from 7,746 patients treated by 1,225 physicians are documented. The data structure consists of up to 888 variables per case. From our experience, integration of clinical and genetic information requires significant efforts - including data protection issues -, but is feasible and improves data quality leading to faster and more reliable research results for the benefit of the patients.     

Effectiveness of an Animal-Assisted Therapy Program in an Inpatient Psychiatric Unit

Abstract

Proper diagnostic assessment in an inpatient psychiatric setting requires observation of patients under various conditions. Group activities such as animal-assisted therapy (A-AT) can provide an excellent opportunity for assessment—but only if the patient chooses to attend. Retrospective analysis of attendance at a major metropolitan inpatient psychiatric unit indicates that over the course of two years (N= 23 months) the A-AT group attracted the highest percentage of inpatients voluntarily choosing to attend an occupational therapy group. It was found that A-AT was the most effective of all groups offered in attracting isolated individuals regardless of diagnosis. The authors conclude that A-AT is an effective tool for diagnostic observation and assessment.     

Culture,cultural factors and psychiatric diagnosis: review and projections

This paper aims to provide conceptual justifications for the inclusion of culture and cultural factors in psychiatric diagnosis, and logistic suggestions as to the content and use of this approach. A discussion of the scope and limitations of current diagnostic practice, criticisms from different quarters, and the role and relevance of culture in the diagnostic encounter, precede the examination of advantages and disadvantages of the approach. The cultural content of psychiatric diagnosis should include the main, well-recognized cultural variables, adequate family data, explanatory models, and strengths and weaknesses of every individual patient. The practical aspects include the acceptance of “cultural discordances” as a component of an updated definition of mental disorder, and the use of a refurbished cultural formulation. Clinical “telescoping” strategies to obtain relevant cultural data during the diagnostic interview, and areas of future research (including field trials on the cultural formulation and on “culture bound syndromes”), are outlined.     

An evaluation of the multidisciplinary approach to psychiatric diagnosis in elderly people.

OBJECTIVE--To determine the accuracy of psychiatric diagnoses made by two community psychogeriatric teams operating a multidisciplinary assessment procedure. DESIGN--Comparison of team diagnosis with independent formal assessment and consensus diagnosis by research psychiatrists. SETTING--Two community psychogeriatric teams with similar operational policies in an inner London health district. SUBJECTS--100 people aged 65-90 (70 women) newly referred to the teams. MAIN OUTCOME MEASURES--Concordance between team and research diagnoses. RESULTS--Agreement between team and research diagnoses ranged from 90% to 99% for the specific psychiatric disorders studied. There was no significant difference between medical and non-medical team members in their diagnostic performance compared with the research psychiatrists. Increased diagnostic accuracy by team members was associated with longer experience of team working, regardless of the team members'' professional background. CONCLUSIONS--The multidisciplinary approach to the assessment of referrals to these community teams for the elderly is not associated with misdiagnosis of psychiatric disorder.     

Phenotype Characterization and Welfare Assessment of Transgenic Rodents (Mice)

Methods of transgenesis in vertebrate animals in the laboratory involve the stable addition or selective substitution of defined genes into the germline. Although there is a continuous and remarkable development in transgenic technology-the quality of transgenes, gene-targeting vectors, and experimental approaches-the consequences for the phenotype induced by this kind of experimental mutation cannot be completely predicted. This is especially true for the majority of transgenic animals who are generated by pronuclear injection. Randomly integrated foreign DNA may increase the risk of disturbing normal physiological processes, resulting in discomfort possibly crucial to the animals' welfare. Only a careful and comprehensive phenotype and welfare assessment can determine (a) whether apparent and relevant changes of phenotype (genetic burdens) occur and (b) how to deal with them in terms of the 3Rs (replace, reduce, refine). Two structured forms, data record and characterization, have been developed and are proposed for a routine characterization and assessment of newly generated transgenic rodents. Data record form and characterization operate, respectively, at individual (health monitoring) and strain levels (representative sample of individual life histories).     

Phenotype Characterization and Welfare Assessment of Transgenic Rodents (Mice)

Methods of transgenesis in vertebrate animals in the laboratory involve the stable addition or selective substitution of defined genes into the germline. Although there is a continuous and remarkable development in transgenic technology-the quality of transgenes, gene-targeting vectors, and experimental approaches-the consequences for the phenotype induced by this kind of experimental mutation cannot be completely predicted. This is especially true for the majority of transgenic animals who are generated by pronuclear injection. Randomly integrated foreign DNA may increase the risk of disturbing normal physiological processes, resulting in discomfort possibly crucial to the animals' welfare. Only a careful and comprehensive phenotype and welfare assessment can determine (a) whether apparent and relevant changes of phenotype (genetic burdens) occur and (b) how to deal with them in terms of the 3Rs (replace, reduce, refine). Two structured forms, data record and characterization, have been developed and are proposed for a routine characterization and assessment of newly generated transgenic rodents. Data record form and characterization operate, respectively, at individual (health monitoring) and strain levels (representative sample of individual life histories).     

Prenatal diagnosis--principles of diagnostic procedures and genetic counseling

The frequency of inherited malformations as well as genetic disorders in newborns account for around 3-5%. These frequency is much higher in early stages of pregnancy, because serious malformations and genetic disorders usually lead to spontaneous abortion. Prenatal diagnosis allowed identification of malformations and/or some genetic syndromes in fetuses during the first trimester of pregnancy. Thereafter, taking into account the severity of the disorders the decision should be taken in regard of subsequent course of the pregnancy taking into account a possibilities of treatment, parent's acceptation of a handicapped child but also, in some cases the possibility of termination of the pregnancy. In prenatal testing, both screening and diagnostic procedures are included. Screening procedures such as first and second trimester biochemical and/or ultrasound screening, first trimester combined ultrasound/biochemical screening and integrated screening should be widely offered to pregnant women. However, interpretation of screening results requires awareness of both sensitivity and predictive value of these procedures. In prenatal diagnosis ultrasound/MRI searching as well as genetic procedures are offered to pregnant women. A variety of approaches for genetic prenatal analyses are now available, including preimplantation diagnosis, chorion villi sampling, amniocentesis, fetal blood sampling as well as promising experimental procedures (e.g. fetal cell and DNA isolation from maternal blood). An incredible progress in genetic methods opened new possibilities for valuable genetic diagnosis. Although karyotyping is widely accepted as golden standard, the discussion is ongoing throughout Europe concerning shifting to new genetic techniques which allow obtaining rapid results in prenatal diagnosis of aneuploidy (e.g. RAPID-FISH, MLPA, quantitative PCR).     

The Development and Organization of a Children's Psychiatric Hospital

Thistletown Hospital is a children''s psychiatric hospital which was established by the Department of Health of the Province of Ontario. Special legislation permitting control of the admissions procedures was enacted. The administrative organization consists of a series of committees made up of the heads of hospital departments. An advisory board of distinguished psychiatrists and psychologists advises the Minister of Health directly on major policy changes or innovations envisaged for the hospital. Clinical organization is related to four functions: (1) service (treatment and assessment), (2) research, (3) training of staff, and (4) community education.The basic units of the hospital are related to the treatment or research design necessary in special diagnostic categories. A children''s psychiatric hospital should not be restricted to in-patient facilities but should consist of a totally community-oriented service.     

Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment

For an understanding of the aberrant biology seen in mouse mutations and identification of more subtle phenotype variation, there is a need for a full clinical and pathological characterization of the animals. Although there has been some use of sophisticated techniques, the majority of behavioral and functional analyses in mice have been qualitative rather than quantitative in nature. There is, however, no comprehensive routine screening and testing protocol designed to identify and characterize phenotype variation or disorders associated with the mouse genome. We have developed the SHIRPA procedure to characterize the phenotype of mice in three stages. The primary screen utilizes standard methods to provide a behavioral and functional profile by observational assessment. The secondary screen involves a comprehensive behavioral assessment battery and pathological analysis. These protocols provide the framework for a general phenotype assessment that is suitable for a wide range of applications, including the characterization of spontaneous and induced mutants, the analysis of transgenic and gene-targeted phenotypes, and the definition of variation between strains. The tertiary screening stage described is tailored to the assessment of existing or potential models of neurological disease, as well as the assessment of phenotypic variability that may be the result of unknown genetic influences. SHIRPA utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse. These paradigms can be refined to test the function of specific neural pathways, which will, in turn, contribute to a greater understanding of neurological disorders. Received: 3 March 1997 / Accepted: 30 May 1997     

Bladder tissue characterization using probe‐based Raman spectroscopy: Evaluation of tissue heterogeneity and influence on the model prediction

Existing approaches for early‐stage bladder tumor diagnosis largely depend on invasive and time‐consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real‐time tumor diagnosis can enable immediate laser‐based removal of tumors using flexible cystoscopes in the outpatient clinic. Therefore, novel diagnostic modalities are required that can provide real‐time in vivo tumor diagnosis. Raman spectroscopy provides biochemical information of tissue samples ex vivo and in vivo and without the need for complicated sample preparation and staining procedures. For the past decade there has been a rise in applications to diagnose and characterize early cancer in different organs, such as in head and neck, colon and stomach, but also different pathologies, for example, inflammation and atherosclerotic plaques. Bladder pathology has also been studied but only with little attention to aspects that can influence the diagnosis, such as tissue heterogeneity, data preprocessing and model development. The present study presents a clinical investigative study on bladder biopsies to characterize the tumor grading ex vivo, using a compact fiber probe‐based imaging Raman system, as a crucial step towards in vivo Raman endoscopy. Furthermore, this study presents an evaluation of the tissue heterogeneity of highly fluorescent bladder tissues, and the multivariate statistical analysis for discrimination between nontumor tissue, and low‐ and high‐grade tumor.     

The flexible sigmoidoscope as a potential vector of infectious disease, including suggestions for decontamination of the flexible sigmoidoscope

The flexible fiberoptic sigmoidoscope has gained widespread acceptance as a diagnostic tool in the detection and diagnosis of colorectal disease. Since its introduction nearly a decade ago, studies have thus far indicated that in the hands of experienced physicians, flexible sigmoidoscopy is a safe procedure affording greater patient comfort, greater depth of insertion, and a higher yield of neoplastic lesions than rigid sigmoidoscopy, with surprisingly few associated risks. Although reported infrequently, infection is an acknowledged risk of flexible sigmoidoscopy and other endoscopic procedures. The most efficient means of preventing endoscopy-associated infection is uncompromising aseptic practice. Clinical and experimental data obtained from studies designed to investigate endoscopic transmission of infectious organisms and from our own and others' experiences are reviewed. Guidelines for achieving high-level disinfection of the flexible fiberoptic sigmoidoscope are included.     

The utility of metabolomics in natural product and biomarker characterization

BackgroundMetabolomics is a well-established rapidly developing research field involving quantitative and qualitative metabolite assessment within biological systems. Recent improvements in metabolomics technologies reveal the unequivocal value of metabolomics tools in natural products discovery, gene-function analysis, systems biology and diagnostic platforms.Scope of reviewWe review here some of the prominent metabolomics methodologies employed in data acquisition and analysis of natural products and disease-related biomarkers.Major conclusionsThis review demonstrates that metabolomics represents a highly adaptable technology with diverse applications ranging from environmental toxicology to disease diagnosis. Metabolomic analysis is shown to provide a unique snapshot of the functional genetic status of an organism by examining its biochemical profile, with relevance toward resolving phylogenetic associations involving horizontal gene transfer and distinguishing subgroups of genera possessing high genetic homology, as well as an increasing role in both elucidating biosynthetic transformations of natural products and detecting preclinical biomarkers of numerous disease states.General significanceThis review expands the interest in multiplatform combinatorial metabolomic analysis. The applications reviewed range from phylogenetic assignment, biosynthetic transformations of natural products, and the detection of preclinical biomarkers.     

Covert genetic selections to optimize phenotypes

In many high complexity systems (cells, organisms, institutions, societies, economies, etc.), it is unclear which components should be regulated to affect overall performance. To identify and prioritize molecular targets which impact cellular phenotypes, we have developed a selection procedure ("SPI"-single promoting/inhibiting target identification) which monitors the abundance of ectopic cDNAs. We have used this approach to identify growth regulators. For this purpose, complex pools of S. cerevisiae cDNA transformants were established and we quantitated the evolution of the spectrum of cDNAs which was initially present. These data emphasized the importance of translation initiation and ER-Golgi traffic for growth. SPI provides functional insight into the stability of cellular phenotypes under circumstances in which established genetic approaches cannot be implemented. It provides a functional "synthetic genetic signature" for each state of the cell (i.e. genotype and environment) by surveying complex genetic libraries, and does not require specialized arrays of cDNAs/shRNAs, deletion strains, direct assessment of clonal growth or even a conditional phenotype. Moreover, it establishes a hierarchy of importance of those targets which can contribute, either positively or negatively, to modify the prevailing phenotype. Extensions of these proof-of-principle experiments to other cell types should provide a novel and powerful approach to analyze multiple aspects of the basic biology of yeast and animal cells as well as clinically-relevant issues.     

Assessing the power of informative subsets of loci for population assignment: standard methods are upwardly biased

It is well known that statistical classification procedures should be assessed using data that are separate from those used to train the classifier. This principle is commonly overlooked when the classification procedure in question is population assignment using a set of genetic markers that were chosen specifically on the basis of their allele frequencies from amongst a larger number of candidate markers. This oversight leads to a systematic upward bias in the predicted accuracy of the chosen set of markers for population assignment. Three widely used software programs for selecting markers informative for population assignment suffer from this bias. The extent of this bias is documented through a small set of simulations. The relative effect of the bias is largest when screening many candidate loci from poorly differentiated populations. Simple unbiased methods are presented and their use encouraged.     

Psychiatrists' attitudes regarding genetic testing and patient safeguards: a preliminary study

AIMS: A probability sample of U.S. psychiatrists (n = 93) was invited to complete a mail survey regarding the likely impact of genetic testing on psychiatry; the clinical utility of pharmacogenetic, diagnostic, and susceptibility genetic testing; and 14 proposed ethical and legal safeguards for clinical genetic testing. RESULTS: Forty-five psychiatrists participated in the survey (response rate = 48%). The majority (80% and 60%, respectively) believed that genetic testing would benefit many psychiatric patients and would dramatically change the way psychiatry is practiced. Many psychiatrists (73-85%) also stated that pharmacogenetic, diagnostic, and susceptibility tests for common psychiatric disorders would be somewhat useful or extremely useful in the clinical setting. Nearly all (98-100%) believed that psychiatrists should obtain informed consent before genetic testing, should keep test results confidential, should provide pre- and posttest counseling, and should demonstrate competence in interpreting test results. Nearly all (96-100%) supported laws and regulations to prevent discrimination based on genetic test results and to protect consumers from misleading advertisements for testing. Ninety-one percent endorsed restrictions on the sale of genetic tests directly to consumers. CONCLUSIONS: This probability sample of U.S. psychiatrists expressed a strongly positive view of genetic testing in psychiatry, while voicing nearly unanimous support for seven ethical and legal safeguards.     

Interpreting Images: Diagnostic Skill In The Genetics Clinic

The diagnosis of rare genetic disorders involves classifying patients on the basis of clinical understandings of the relationship between visible, measurable characteristics (the phenotype) and an underlying genetic characterization (the genotype). Diagnosis is performed through the routine ritual observation and interpretation of images of patients in relation to their clinical features and test results. In this process, which is mediated by senior clinicians, the experience of the effect of a patient's image is integral to the skilful elicitation of a diagnosis. Such skill develops over time, through regular participation in diagnostic performances. I suggest that, from this perspective, genetic diagnosis is a clinical process rather than a form of genetic reductionism and that assumptions about 'geneticization' require further exploration. The article also shows that participant observation and a cross-cultural mode of analysis can contribute to documenting and interpreting these processes.