Hereditary trichilemmal cysts: a proposal for the assessment of diagnostic clinical criteria

Trichilemmal cysts (TCs) can occur as sporadic lesions or in hereditary–familial settings with autosomal dominant transmission. These entities have not been widely analyzed in their peculiar aspects yet. The aim of this study was to describe a cohort of patients with diagnosis of TCs through a clinical and biomolecular characterization, intended to highlight some effective diagnostic criteria for their identification. Among 149 cases of this study, 24 cases of TCs (16.1%) arose in patients with at least one first‐degree relative with diagnosis of TCs. Peculiar findings concerning hereditary lesions included the multiple presentation with an early onset age. On the basis of clinical evaluation, we propose a panel of clinical and histologic criteria for the diagnosis of hereditary TCs, which includes: (i) the diagnosis of TCs in at least two first‐degree relatives or in three first‐ or second‐degree relatives in two consecutive generations; (ii) at least one of the patients with TCs diagnosed <45 years; and (iii) the diagnosis of multiple or giant (>5‐cm lesions) or rare histopathologic features (proliferating and ossifying) TCs.     

Posttraumatic stress disorder: diagnostic data analysis by data mining methodology

Aim

To use data mining methods in assessing diagnostic symptoms in posttraumatic stress disorder (PTSD)

Methods

The study included 102 inpatients: 51 with a diagnosis of PTSD and 51 with psychiatric diagnoses other than PTSD. Several models for predicting diagnosis were built using the random forest classifier, one of the intelligent data analysis methods. The first prediction model was based on a structured psychiatric interview, the second on psychiatric scales (Clinician-administered PTSD Scale – CAPS, Positive and Negative Syndrome Scale – PANSS, Hamilton Anxiety Scale – HAMA, and Hamilton Depression Scale – HAMD), and the third on combined data from both sources. Additional models placing more weight on one of the classes (PTSD or non-PTSD) were trained, and prototypes representing subgroups in the classes constructed.

Results

The first model was the most relevant for distinguishing PTSD diagnosis from comorbid diagnoses such as neurotic, stress-related, and somatoform disorders. The second model pointed out the scores obtained on the Clinician-administered PTSD Scale (CAPS) and additional Positive and Negative Syndrome Scale (PANSS) scales, together with comorbid diagnoses of neurotic, stress-related, and somatoform disorders as most relevant. In the third model, psychiatric scales and the same group of comorbid diagnoses were found to be most relevant. Specialized models placing more weight on either the PTSD or non-PTSD class were able to better predict their targeted diagnoses at some expense of overall accuracy. Class subgroup prototypes mainly differed in values achieved on psychiatric scales and frequency of comorbid diagnoses.

Conclusion

Our work demonstrated the applicability of data mining methods for the analysis of structured psychiatric data for PTSD. In all models, the group of comorbid diagnoses, including neurotic, stress-related, and somatoform disorders, surfaced as important. The important attributes of the data, based on the structured psychiatric interview, were the current symptoms and conditions such as presence and degree of disability, hospitalizations, and duration of military service during the war, while CAPS total scores, symptoms of increased arousal, and PANSS additional criteria scores were indicated as relevant from the psychiatric symptom scales.Posttraumatic stress disorder (PTSD) is characterized by the symptoms of re-experiencing the traumatic event, avoidance symptoms, and increased arousal (1), but differences can be found in clinical presentations of symptoms between survivors of different traumas (2). Various comorbid diagnoses can be identified in these patients: alcohol abuse, depression, anxiety disorders, panic disorder and phobia, psychosomatic disorder, personality disorder, psychotic disorders, drug abuse, and dementia (3). Furthermore, PTSD is commonly misdiagnosed, resulting in inappropriate treatment (4).Many authors reported various difficulties in estimating symptom severity in PTSD patients, especially if the diagnostic process was related to compensation seeking (3,5-8). It has also been shown that clinicians have a more subjective approach to patients who demand compensation (9).Because of these adverse factors, the process of diagnosing PTSD is a complex one, and defining accurate diagnostic methods for PTSD is important in both clinical and forensic practice.As some studies have shown (10,11), various data collected from the patient, such as short medical history, laboratory tests, specialist findings, or examination results could be analyzed with specialized “data mining” algorithms. Such algorithms can be used for finding intercorrelations between different parameters and exploring possibilities of using the acquired data for deriving rules and conditions useful in making faster diagnostic procedures and more targeted therapeutic interventions (12).Data mining is defined as “nontrivial extraction of implicit, previously unknown, and potentially useful information from data” (13) and “the science of extracting useful information from large data sets or databases” (14). The term “data mining” includes both statistical techniques and algorithms developed for machine learning applications. Machine learning is a part of the artificial intelligence field in computer science, dealing with algorithms that can identify important structural features and seek non-obvious patterns in available data (15), in order to improve their performance in future, previously unseen situations. Especially relevant for data mining are those machine learning approaches which represent the acquired knowledge in an explicit form understandable to humans.Since one of the major conditions for applying data mining techniques is the existence of uniform data sets (16), such methods are mostly used in biomedical research efforts, such as gene expression and regulation, protein structure, mutation research (17-19), and less frequently in everyday clinical work. The aim of our study was to demonstrate that data mining techniques can assist in the diagnostic process of PTSD. To demonstrate that data mining techniques can assist in the diagnostic process of PTSD, we investigated the feasibility of a data mining approach applied to medical information acquired on psychiatric patients in the Department of Psychiatry of the Dubrava University Hospital, with the assistance of the experts from Ruđer Bošković Institute.     

Generalized anxiety disorder: clinical presentation, diagnostic features, and guidelines for clinical practice

Generalized anxiety disorder (GAD) is a prevalent and disabling disorder characterised by persistent worrying, anxiety symptoms, and tension. General practitioners and mental healthcare professionals frequently misdiagnose the presenting symptoms. This article addresses the clinical presentation of GAD and provides guidelines for discriminating GAD from other disorders, based on theoretical considerations and clinical experience. Debate relating to the validity of the definition of GAD is discussed, and suggestions are made for improving the criteria for GAD, which may guide future versions of classification systems such as the Diagnostic and Statistical Manual.     

Restless legs syndrome in childhood: A consensus proposal for diagnostic criteria

Summary No previous studies have explicitly addressed the issue of diagnostic criteria for restless legs syndrome (RLS) in children. Diagnosis of RLS in adults is primarily based on the ­patient's history. Children may exhibit and report symptoms of RLS differently from adults, depending on the child's chronological and developmental age and on the child's ability at verbal expression. Members of the study groups 'Movement Disorder' and 'Paediatrics' of the German Sleep Society have therefore elaborated a consensus proposal for diagnostic criteria of RLS in childhood by adapting and modifying the criteria of the International Restless Legs Syndrome Study Group used in adults. As minimal criteria for the diagnosis of RLS in childhood we propose: 1) The desire to move the legs is associated with sensations like discomfort or pain in the legs; 2) Increase in dysaesthesiae in the legs at rest and decrease due to motor activity; 3) The dysaesthesiae of the legs are worse during the even­ing and at night; 4) The child obviously suffers from the symptomatology; and 5) The symptoms described should persist for at least 6 months. Additional clinical features proposed include: 6) Sleep disturbance and its consequences; 7) Involuntary movements of the legs while awake and at rest or periodic leg movements in sleep; 8) Normal neurological examination; and 9) Positive family history.     

IDH1 mutation analysis in low cellularity specimen: A limitation of diagnostic accuracy and a proposal for the diagnostic procedure

Recently, new techniques for detecting IDH1 mutations have been developed. Most studies assessed the mutation status in glioma tissue without consideration of the size of the samples. We assessed the mutation status of IDH1 in simulated small biopsied tissue from 5 low grade gliomas, prepared by grid cutting procedure with direct sequencing, IDH1 immunohistochemistry (IHC), multiplex PCR with single base extension (SBE) assay and PNA-clamping method, and then analyzed the agreement between the methods. Kappa values were 0.53 (direct sequencing), 0.59 (multiplex PCR with SBE assay), and 0.69 (PNA-clamping method). Discrepant results between the methods were observed in lower cellularity samples. Twelve out of 25 cases were classified as wild type by direct sequencing, even with IDH1 IHC-positive cells, whereas 6, 8, and 11 of IHC-negative cases were classified as mutant cases by other 3 methods. In conclusion, newly developed sensitive methods, such as the PNA-clamping method and multiplex PCR with SBE assay, are practically useful in addition to the conventional IDH1 IHC in small biopsied samples.     

Reliability and validity of the DSM-IV diagnostic category of schizoaffective disorder: preliminary data

BACKGROUND: Concerns have been expressed about the reliability and validity of the DSM-IV criteria for schizoaffective disorder, but no systematic study has been published up to now. METHODS: The Cohen's kappa for the individual items of the DSM-IV definition of schizoaffective disorder, manic episode and major depressive episode was evaluated in 150 patients independently interviewed by two psychiatrists using the Composite International Diagnostic Interview. The two-year outcome of patients with a consensus DSM-IV diagnosis of schizoaffective disorder was compared to that of patients with DSM-IV schizophrenia and schizophreniform disorder, using the Strauss-Carpenter Outcome Scale. RESULTS: The Cohen's kappa was 0.22 for the diagnosis of schizoaffective disorder, 0.71 for that of manic episode, and 0.82 for that of major depressive episode. Schizoaffective patients had a significantly better outcome than those with schizophrenia but a worse outcome than those with schizophreniform disorder. CONCLUSIONS: The inter-rater reliability of the DSM-IV criteria for schizoaffective disorder is not satisfactory. The better outcome of DSM-IV schizoaffective disorder compared with schizophrenia seems to depend more on the inclusion, in the definition of schizophrenia but not in that of schizoaffective disorder, of the six-month duration and functional impairment criteria than on the different symptomatological patterns of the two conditions. LIMITATION: The size of the sample of patients fulfilling DSM-IV criteria for schizoaffective disorder was small. CLINICAL RELEVANCE: The study suggests that the clinical implications of the currently problematic diagnosis of schizoaffective disorder may be modest.     

EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA‐DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new ‘gold standard’ for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.     

Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis

Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator‐related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator‐related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25–30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of ‘occult’ mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow‐up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.     

Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP)

Background: This paper presents the methodology and clinical data in mid-stream from a French multi-center study (EPIDEP) in progress on a national sample of patients with DSM-IV major depressive episode (MDE). The aim of EPIDEP is to show the feasibility of validating the spectrum of soft bipolar disorders by practising clinicians. In this report, we focus on bipolar II (BP-II). Method: EPIDEP involves training 48 French psychiatrists in 15 sites; construction of a common protocol based on the criteria of DSM-IV and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Evaluation of Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal), family history (Research Diagnostic Criteria); and prospective follow-up. Results: Results are presented on 250 (of the 537) MDE patients studied thus far during the acute phase. The rate of BP-II disorder which was 22% at initial evaluation, nearly doubled (40%) by systematic evaluation. As expected from the selection of MDE by uniform criteria, inter-group comparison between BP-II vs unipolar showed no differences on the majority of socio-demographic parameters, clinical presentation and global intensity of depression. Despite such uniformity, key characteristics significantly differentiated BP-II from unipolar: younger age at onset of first depression, higher frequency of suicidal thoughts and hypersomnia during index episode, higher scores on Hypomania Checklist and cyclothymic and irritable temperaments, and higher switching rate under current treatment. Eighty-eight percent of cases assigned to cyclothymic temperament by clinicians (with a cut-off of 10/21 items on self-rated cyclothymia) were recognized as BP-II. Evaluation of this temperament by clinician and patient correlated at a highly significant level (r=0.73; p<0.0001). Cyclothymia and hypomania were also correlated significantly (r=0.51; p<0.001). Limitation: In a study conducted in diverse clinical settings, it was not possible to assure that clinicians making affective diagnoses were blind to the various temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. Conclusion: With a systematic search for hypomania, 40% of major depressive episodes were classified as BP-II, of which only half were known to the clinicians at study entry. Cyclothymic temperamental dysregulation emerged as a robust clinical marker of BP-II disorder. These data indicate that clinicians in diverse practice settings can be trained to recognize soft bipolarity, leading to changes in diagnostic practice at a national level.     

Cognitive-behavioral therapy for intermittent explosive disorder: a pilot randomized clinical trial

No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized clinical trial among adults with IED (N = 45). Aggression, anger, and associated symptoms were assessed at baseline, midtreatment, posttreatment, and 3-month follow-up. Group and individual cognitive-behavioral therapy tended not to differ, with each reducing aggression, anger, hostile thinking, and depressive symptoms, while improving anger control relative to wait-list participants. Posttreatment effect sizes were large. These effects were maintained at 3-month follow-up. Findings provide initial support for the use of multicomponent cognitive-behavioral therapy in the treatment of IED.     

Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria.

Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops through a multistep histopathologic sequence. Premalignant or non-invasive neoplastic lesions of bile ducts have been historically called biliary dysplasia or atypical biliary epithelium. To this date, no standard terminology or classification system has been offered for these lesions. In 2005, a conceptual framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN) were proposed using the livers of patients with hepatolithiasis. We report herein an international interobserver agreement study on the diagnosis of biliary non-invasive neoplastic lesions with the goal to obtain a consensus on the terminology and grading. Seventeen pathologists from the United States, Europe and Asia participated in this study. They shared a digital file containing histological pictures of 30 foci of non-invasive neoplastic lesions selected from the biliary system of patients suffering from primary sclerosing cholangitis, choledochal cyst or hepatolithiasis. In the criteria, we proposed in 2005, BilIN was classified into three categories based on the degree of atypia: BilIN-1, BilIN-2 and BilIN-3. In this study, consensus was reached for the terminology of BilIN and the three-grade classification system. Interobserver agreement on the diagnosis was moderate (kappa-value=0.45). On the basis of the suggestions and opinions obtained from the 17 participants, the original criteria for BilIN were revised. We now propose a new consensus classification of BilIN that may assist in allowing a more uniform terminology for the diagnosis of biliary non-invasive neoplastic lesions. This classification should help to advance clinical and research applications.