Objective Negative effects (NEs) in group treatments remain an under-researched area. This study aimed to explore the prevalence of various types of NEs in a multicomponent group-based treatment and to determine their predictors. Method: A total of 330 patients participating in a multicomponent group-based treatment were recruited across seven clinical sites. At the end of treatment, the Negative Effects Questionnaire (NEQ) was used to measure NEs. Item-level descriptive analysis was conducted to explore the prevalence of various types of NEs, and structural equation modeling was used to determine predictors of these NEs. Results: The most frequently reported type of NEs was the worsening of symptoms, and the single most frequently reported item was the resurfacing of unpleasant memories. Predictors of NEs included the overall distress level, alexithymia, attachment avoidance, low working alliance, problem actuation, and worse outcomes; psychological mindedness was a protective factor. Conclusion: Patients who experience higher levels of distress at the beginning of treatment, who perceive the group working alliance as problematic, and who experience high in-session emotional arousal related to their problem seem to be especially prone to reporting NEs. Furthermore, the findings do not support the assumption that NEs are a prerequisite for therapeutic change.Trial registration: ISRCTN.org identifier: ISRCTN13532466.

• MeSH
• deprese * psychologie   MeSH
• lidé MeSH
• prevalence MeSH
• průzkumy a dotazníky MeSH
• psychický stres * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dekubity epidemiologie   MeSH
• dráždivá dermatitida epidemiologie   MeSH
• fekální inkontinence komplikace   MeSH
• hospitalizace MeSH
• inkontinence moči komplikace   MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• multicentrická studie MeSH

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

• MeSH
• big data MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   MeSH
• neurozobrazování MeSH
• posttraumatická stresová porucha * diagnostické zobrazování   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Hallucinatory experiences can occur in both clinical and nonclinical groups. However, in previous studies of the general population, investigations of the cognitive mechanisms underlying hallucinatory experiences have yielded inconsistent results. We ran a large-scale preregistered multisite study, in which general-population participants (N = 1,394 across 11 data-collection sites and online) completed assessments of hallucinatory experiences, a measure of adverse childhood experiences, and four tasks: source memory, dichotic listening, backward digit span, and auditory signal detection. We found that hallucinatory experiences were associated with a higher false-alarm rate on the signal detection task and a greater number of reported adverse childhood experiences but not with any of the other cognitive measures employed. These findings are an important step in improving reproducibility in hallucinations research and suggest that the replicability of some findings regarding cognition in clinical samples needs to be investigated.

• MeSH
• halucinace * MeSH
• kognice * MeSH
• lidé MeSH
• reprodukovatelnost výsledků MeSH
• sluchová percepce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: Biventricular pacing (BVP) from multiple left ventricular (LV) sites could enhance the efficacy of cardiac resynchronization therapy (CRT) by engaging a greater myocardial mass. OBJECTIVES: The goal of this study was to evaluate the acute hemodynamic effect of various multisite pacing (MSP) configurations against conventional BVP. METHODS: Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block (mean age: 59 ± 14 years; LV ejection fraction: 27% ± 6%; native QRS: 171 ± 16 milliseconds) were investigated during a routine CRT implant procedure. In addition to conventional right atrial and right ventricular leads, 2 quadripolar leads were placed in the distant coronary venous branches. LV hemodynamics was evaluated by using a micromanometer-tipped catheter during atrioventricular BVP with 4 LV lead configurations: single-lead conventional BVP; single-lead multipoint pacing; triventricular pacing from distal dipoles of 2 LV leads; and maximum MSP (MSP-Max) from 4 dipoles of 2 LV leads. RESULTS: Compared with right atrial pacing, any BVP configuration produced a significant increase in the maximal LV diastolic pressure rise (LVdP/dTMax) (a median relative increase of 28% [IQR: 8%-45%], 25% [IQR: 18%-46%], 36% [IQR: 18%-54%], and 38% [IQR: 28%-58%], respectively; all, P < 0.001). MSP-Max but no other multisite BVP generated a significant increase of the maximal LVdP/dTMax than conventional BVP (P = 0.041). Increased LVdP/dTMax during MSP-Max was associated with greater LV diameter and lower LV ejection fraction, independently of the QRS width. CONCLUSIONS: The study shows the hemodynamic advantage of a novel dual-vein MSP-Max configuration that could be useful for CRT in patients with advanced LV remodeling.

• MeSH
• fibrilace síní * MeSH
• funkce levé komory srdeční MeSH
• hemodynamika MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• srdeční resynchronizační terapie * metody   MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

• MeSH
• astrocyty metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proteiny tau metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí patologie   MeSH
• stupeň závažnosti nemoci MeSH
• tauopatie patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

GOALS: To test the hypothesis that water exchange (WE) significantly increases adenoma detection rates (ADR) compared with water immersion (WI). BACKGROUND: Low ADR was linked to increased risk for interval colorectal cancers and related deaths. Two recent randomized controlled trials of head-to-head comparison of WE, WI, and traditional air insufflation (AI) each showed that WE achieved significantly higher ADR than AI, but not WI. The data were pooled from these 2 studies to test the above hypothesis. STUDY: Two trials (5 sites, 14 colonoscopists) that randomized 1875 patients 1:1:1 to AI, WI, or WE were pooled and analyzed with ADR as the primary outcome. RESULTS: The ADR of AI (39.5%) and WI (42.4%) were comparable, significantly lower than that of WE (49.6%) (vs. AI P=0.001; vs. WI P=0.033). WE insertion time was 3 minutes longer than that of AI (P<0.001). WE showed significantly higher detection rate (vs. AI) of the >10 mm advanced adenomas. Right colon combined advanced and sessile serrated ADR of AI (3.4%) and WI (5%) were comparable and were significantly lower than that of WE (8.5%) (vs. AI P<0.001; vs. WI P=0.039). CONCLUSIONS: Compared with AI and WI, the superior ADR of WE offsets the drawback of a significantly longer insertion time. For quality improvement focused on increasing adenoma detection, WE is preferred over WI. The hypothesis that WE could lower the risk of interval colorectal cancers and related deaths should be tested.

• MeSH
• adenom diagnóza   MeSH
• insuflace MeSH
• kolonoskopie metody   MeSH
• kolorektální nádory diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Moderními metodami genetického výzkumu schizofrenie jsou celogenomové asociační studie a hledání mikrodelecí/mikroduplikací DNA. Takto mohou být významné geny či polymorfizmy nalezeny, neznáme však jejich roli v patogenezi onemocnění. Proto se pozornost obrací ke genetickému vyšetřování endofenotypů schizofrenie. Endofenotyp je nejčastěji neurobiologická či neuropsychologická charakteristika asociovaná s danou nemocí, je dědičná a celoživotní a vyskytuje se také u duševně zdravých příbuzných pacienta. U schizofrenie jsou studovány zejména endofenotypy neurofyziologické, neuromotorické, neurokognitivní, neuroanatomické a neurologické. V tomto přehledovém článku jsou nejvýznamnější endofenotypy schizofrenie popsány, zmíněn je jejich biologický podklad a možné významné genetické nálezy. Problémem popisovaného výzkumu je zejména skutečnost, že schizofrenie je klinicky velmi heterogenní a výskyt endofenotypů se u jejích jednotlivých podskupin může významně lišit. Budoucnost má multicentrický mezinárodní genetický výzkum endofenotypů schizofrenie, kdy však veškeré procedury musejí být prováděny jednotně. Nalezení a vysvětlení genetického podkladu schizofrenie může sloužit její léčbě, prevenci i destigmatizaci onemocnění.

Genome-wide association studies and studies of DNA microdeletions/microduplications represent modern genetic research methods applied in schizophrenia. It is possible to find important genes and their polymorphisms by these procedures, but the findings do not clarify schizophrenia pathogenesis. That is why the genetic research into schizophrenia endophenotypes has recently been emphas ized. Endophenotype is usually a neurobiological or neuropsychological marker associated with a certain disease, heritable and life-l ong, and also occurs in healthy relatives of the patients. Neurophysiological, neuromotoric, neurocognitive, neuroanatomical and neurolo gical endophenotypes are studied in schizophrenia most frequently. In this review article, we mention the most important schizophreni a endophenotypes including their biological background, and relevant genetic findings. The problem is that schizophrenia is a cli nically heterogenous mental disorder, so the appearance of individual endophenotypes in particular subgroups may be significantly diffe rent. A multisite international genetic research into schizophrenia endophenotypes seems to be promising, but the procedures must be performed uniformly in all centers. The finding and elucidation of the genetic background of schizophrenia may help in its trea tment, prevention, and destigmatization.

• Klíčová slova
• etiopatogeneze,
• MeSH
• endofenotypy MeSH
• genetická predispozice k nemoci genetika   MeSH
• genetické asociační studie MeSH
• genetika MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• schizofrenie etiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

INTRODUCTION: At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap. METHODS AND ANALYSIS: This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56-80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences-Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery. ETHICS AND DISSEMINATION: The study received the following approvals: South Central-Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN93895792.

• MeSH
• dostupnost zdravotnických služeb MeSH
• duševní poruchy * terapie   MeSH
• kognitivně behaviorální terapie * metody   MeSH
• lidé MeSH
• primární zdravotní péče MeSH
• psychotické poruchy * terapie   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• protokol klinické studie MeSH

Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.73 m2, and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg/d were later reduced to 200 mg/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg/d versus placebo (1.63% versus 4.74%, respectively; P=0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively; P<0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified. (ClinicalTrials.gov: NCT01233869).

• MeSH
• aniliny škodlivé účinky   terapeutické užití   MeSH
• chinoliny škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nitrily škodlivé účinky   terapeutické užití   MeSH
• polycystické ledviny autozomálně dominantní farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH