Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: a machine-learning study.

BACKGROUND: Early diagnosis of schizophrenia could improve the outcomes and limit the negative effects of untreated illness. Although participants with schizophrenia show aberrant functional connectivity in brain networks, these between-group differences have a limited diagnostic utility. Novel methods of magnetic resonance imaging (MRI) analyses, such as machine learning (ML), may help bring neuroimaging from the bench to the bedside. Here, we used ML to differentiate participants with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls based on resting-state functional connectivity (rsFC). METHOD: We acquired resting-state functional MRI data from 63 patients with FES who were individually matched by age and sex to 63 healthy controls. We applied linear kernel support vector machines (SVM) to rsFC within the default mode network, the salience network and the central executive network. RESULTS: The SVM applied to the rsFC within the salience network distinguished the FES from the control participants with an accuracy of 73.0% (p = 0.001), specificity of 71.4% and sensitivity of 74.6%. The classification accuracy was not significantly affected by medication dose, or by the presence of psychotic symptoms. The functional connectivity within the default mode or the central executive networks did not yield classification accuracies above chance level. CONCLUSIONS: Seed-based functional connectivity maps can be utilized for diagnostic classification, even early in the course of schizophrenia. The classification was probably based on trait rather than state markers, as symptoms or medications were not significantly associated with classification accuracy. Our results support the role of the anterior insula/salience network in the pathophysiology of FES.

Psychiatrist's adherence: a new factor in relapse prevention of schizophrenia. A randomized controlled study on relapse control through telemedicine system.

ACCESSIBLE SUMMARY: Exposure to psychotic states has detrimental effects on the long-term outcome of schizophrenia and brain integrity. Therefore, improving relapse prevention is a key component of long-term management of schizophrenia. Previous studies using continuous monitoring of an individual's early signs of relapse and adopting preventative pharmacological interventions, when early signs are detected, showed promising clinical results in terms of relapse risk reduction. This 18-month multi-centre parallel randomized controlled, open label, trial with telemedicine relapse prevention programme ITAREPS failed to show superiority of maintenance plus prodrome-based targeted medication strategy over treatment as usual. The study, marked by low investigator's adherence, confirmed that absence of pharmacological intervention at early stage of prodrome, critically influenced the risk of relapse. This and previous randomized controlled trials with telemedicine programme ITAREPS suggested that substantial improvement in relapse prevention in schizophrenia is likely to be unattainable under current clinical settings. Future preventive strategies in schizophrenia would require rapid pharmacological intervention upon occurrence of subclinical prodromal symptoms that are undetectable under conventional outpatient practice. Studies with ITAREPS suggested that integration of telemedicine relapse prevention systems and visiting nurse service might together represent practical solution capable to address those requirements. ABSTRACT: The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) presents a telemedicine solution for weekly monitoring and management of schizophrenia. This study aims to evaluate the effectiveness of the programme in reducing the number of hospitalizations during the 18-month multi-centre parallel randomized controlled, open label, trial. Outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n = 74) or control group (n = 72). In the active arm, investigators increased the antipsychotic dose upon occurrence of prodrome announced by the system. Intention-to-treat analysis showed no between-group difference in the hospitalization-free survival rate [Kaplan-Meier method; hazard ratio (HR) = 1.21, 95% confidence interval (CI): 0.56-2.61, P = 0.6). In a post hoc multivariate Cox proportional hazards model, out of 13 potential predictors, only ITAREPS-related variables (number of alerts without pharmacological intervention/HR = 1.38, P = 0.042/ and patient non-adherence with ITAREPS /HR = 1.08, P = 0.009/) increased the risk of hospitalization. In this trial ITAREPS was not effective. The results in context with previous ITAREPS studies suggest non-adherence of both psychiatrists and patients as the main reasons for the failure of this preventive strategy. Tertiary prevention in schizophrenia have to be regarded a major challenge, warranting the need for implementation of strategies with more active participation of both patient and treating psychiatrist.

[Treatment options in sarcoidosis]. / Soucasné moznosti lécby sarkoidózy.

When to start the treatment of sarcoidosis and what are the optimal treatment methods? The curative of the first choice are glucocorticoids used in indicated cases in general administration, as inhalation therapy or locally in the skin manifestations. Frequently used are also immunosuppressives, cytostatics and antimalarics. The newest trend in the treatment of this multi-organ granulomatose disease of unknown origin is the use of TNF inhibitors--pentoxifyllin, infliximab, adalimumab, leflunomid, thalidomid.

[Tuberculosis in patients with chronic kidney failure]. / Tuberkulóza u pacientu s chronickým selháním ledvin.

BACKGROUND: In a retrospective study we analysed the incidence of tuberculosis (tb) in end-stage renal disease patients undergoing dialysis treatment at the Department of Medicine Strahov, General University Hospital, 1st Medical Faculty, Charles University, Prague. Study included patients who died and were autopsied from 1991 till 2000. METHODS AND RESULTS: Active tb was found in 11 cases (4 men and 7 women, age 56 to 84 years) from the total of 275 patients, i.e. in 4%. The results confirmed the increased risk of tb in our group as compared to general population. Tuberculosis was diagnosed of in 2 patients before they died and in 3 patients there was a suspicion of tb before the death. In 6 cases tb was found during autopsy. Unlike the non-dialysed population, where pulmonary tb has the highest incidence (in Czech republic 75%), in the studied group extrapulmonary forms of tb were predominant (9 patients, i.e. 81.8% had some form of extrapulmonary tb). Miliary tb was found in 8 cases (72.7%). Because the symptoms of tb are unspecific and they are not pathognomonic, they were masked by other, already known diseases in patients with multiple co-morbidities. The low number of cases of tb diagnosed before death represents a serious problem. Obviously, it is difficult to prove tb unambiguously, even when such possibility is taken into account. CONCLUSIONS: In differential diagnosis, we always have to bear in mind the possibility of the patient having tb. In examination algorithm we have to concentrate on both pulmonary and extra-pulmonary forms of tb.

[Endobronchial neurofibroma]. / Endobronchiální neurofibrom.

Neurofibroma belongs to the benign tumors and it is categorised as neuroectodermal tumor. Neurofibromas are most frequently found in the posterior mediastinum, their endobronchial localisation is rather rare. Our paper presents two cases of endobronchial neurofibromas with diverse clinical and X-ray symptomatology. Both patients underwent surgery and the etiology of tumours was assessed by histological examination of the preoperative biopsy.

[Lymphangioleiomyomatosis in a menopausal woman]. / Lymfangioleiomyomatóza u zeny v menopauze.

Lymphagioleiomyomatosis is a rare pulmonary disease which affects mainly women of childbearing age. An observation of lymphangiomyomatosis in a menopausal woman or in men is considered very unusual. We report a case of lymphagioleiomyomatosis in a 60-year-old woman.

[Chiral compounds and their pharmacologic effects]. / Chirálne zlúceniny a ich farmakologické úcinky.

The present contribution to the problems of the stereochemistry of drugs is an attempt at stressing the importance of a stereochemical view of pharmacology and at informing about the advances of "chiral pharmacology" within the framework of the contemporary knowledge of selective effects of drugs. There are no simple solutions in the "racemates versus enantiomers" problems and each substance must be considered and tested individually, i.e. on the case-by-case principle. For many racemates available at present there exist relatively few items of knowledge concerning the pharmacological, toxicological and pharmacokinetic properties of their individual enantiomers, or concerning the influence of age, health condition, sex and genetic factors on biological availability and response of the organism to the drug. Additional testing of the enantiomers of the racemates used in practice can lead to the discovery of new indications of the original drug, improve its clinical use and result in increasing its safety and efficacy. If it is so, in this case the "chiral meditations" in pharmacology are double worth the problems they pose.

Waldenström's macroglobulinemia with pulmonary amyloidosis.

We present a case of AL-type amyloidosis involving pulmonary parenchyma and hilar and mediastinal lymph nodes in a patient with Waldenström's macroglobulinemia. Direct infiltration of pulmonary parenchyma by lymphocytes and plasma cells is an important factor in the etiology and pathogenesis of pulmonary manifestations of the disease. Despite detailed examination, we did not find amyloid depositions in any extrapulmonary site.

[Minor glomerular abnormalities in chronic tubulointerstitial nephritis]. / Malé abnormality glomerulov pri chronických tubulointersticiálnych nefritídach.

The authors examined consecutive renal biopsies from 43 patients with minor glomerular abnormalities and from 35 patients with chronic tubulointerstitial nephritis (in the least affected glomeruli). The findings were evaluated according to WHO criteria of minor abnormalities. They found that significantly more frequently lipid drops were found in minor abnormalities (6:0), as well as changes in the capillaries of glomeruli (breakdown 1:7), wrinkling (15:29-highly significant even after correction of p)) in tubulointerstitial nephritis. The incidence in another 15 compared indicators there was not significantly different. With regard to the assembled results the authors consider the morphological finding of minor glomerular abnormalities as non-specific changes, and adaptational glomerular changes in response to various noxious substances. Therefore it is necessary to evaluate purely morphological findings of minor abnormalities carefully and in a differentiated manner, in particular in conjunction with treatment.