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
- lidé MeSH
- podpůrné srdeční systémy * MeSH
- srdce MeSH
- srdeční selhání * chirurgie MeSH
- transplantace plic * MeSH
- transplantace srdce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
- MeSH
- houby účinky léků genetika izolace a purifikace fyziologie MeSH
- lidé MeSH
- management nemoci MeSH
- mykologie MeSH
- mykózy diagnóza farmakoterapie mikrobiologie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- společnosti lékařské MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. METHODS AND RESULTS: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). CONCLUSIONS: GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
- MeSH
- funkce levé komory srdeční účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- močovina analogy a deriváty terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- senioři MeSH
- srdeční selhání * farmakoterapie patofyziologie MeSH
- tepový objem účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper.
- MeSH
- diabetes mellitus 2. typu genetika MeSH
- genetické testování MeSH
- HDL-cholesterol metabolismus MeSH
- hydroxymethylglutaryl-CoA-reduktasy genetika MeSH
- index tělesné hmotnosti MeSH
- jednonukleotidový polymorfismus genetika MeSH
- LDL-cholesterol metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- rizikové faktory MeSH
- senioři MeSH
- statiny škodlivé účinky MeSH
- tělesná hmotnost genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Klíčová slova
- vliv uzemění na fyziologické a patofyziologické procesy,
- MeSH
- cirkadiánní rytmus fyziologie imunologie účinky léků MeSH
- elektřina * škodlivé účinky MeSH
- financování organizované MeSH
- hydrokortison fyziologie izolace a purifikace MeSH
- krevní glukóza fyziologie metabolismus účinky léků MeSH
- krevní oběh fyziologie účinky léků MeSH
- krevní tlak fyziologie účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- spánek fyziologie účinky léků MeSH
- statická elektřina * škodlivé účinky MeSH
- statistika jako téma MeSH
- testosteron fyziologie izolace a purifikace MeSH
- únava etiologie patofyziologie patologie MeSH
- warfarin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- délka lunárního dne je 24.84 h, lidské biologické rytmy během a po izolaci v podzemí,
- MeSH
- chronobiologické jevy fyziologie genetika imunologie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- endokrinní systém fyziologie MeSH
- experimenty na lidech MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- kardiovaskulární systém patofyziologie MeSH
- lidé MeSH
- Měsíc MeSH
- metaanalýza jako téma MeSH
- planetární evoluce * MeSH
- příliv a odliv * dějiny klasifikace MeSH
- sociální izolace MeSH
- spánková medicína metody MeSH
- statistika jako téma MeSH
- tělesná teplota fyziologie MeSH
- únava etiologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Klíčová slova
- cirkadiánní poruchy endokrinního systému,
- MeSH
- cirkadiánní rytmus * fyziologie genetika imunologie MeSH
- dehydroepiandrosteron fyziologie metabolismus MeSH
- depresivní poruchy enzymologie etiologie komplikace MeSH
- endokrinní systém * abnormality enzymologie patofyziologie MeSH
- estradiol izolace a purifikace metabolismus MeSH
- financování organizované MeSH
- hormony izolace a purifikace metabolismus MeSH
- hydrokortison fyziologie metabolismus MeSH
- krevní oběh - doba MeSH
- krevní tlak fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- melatonin fyziologie izolace a purifikace metabolismus MeSH
- selen metabolismus MeSH
- statistika jako téma MeSH
- testosteron fyziologie izolace a purifikace metabolismus MeSH
- únava enzymologie etiologie komplikace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- lunární cyklus, cirkasemidiánní cyklus,
- MeSH
- ambulantní monitorování * MeSH
- biologické hodiny fyziologie MeSH
- chronobiologické jevy * fyziologie MeSH
- cirkadiánní rytmus fyziologie MeSH
- dospělí MeSH
- financování organizované MeSH
- lidé MeSH
- měření krevního tlaku metody využití MeSH
- poruchy cirkadiánního rytmu (spánek) * etiologie MeSH
- statistika jako téma MeSH
- určení tepové frekvence metody využití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
We analyzed cycles with periods, tau, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the tau range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) tau of 1.39 years; the 95% confidence interval (CI) of the tau extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a tau and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's tau overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a tau of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a tau with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly tau and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The taus are only candidate transyears; the 95% CIs of their taus overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's tau no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a tau between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities.
- MeSH
- chronobiologické jevy * MeSH
- infarkt myokardu epidemiologie MeSH
- lidé MeSH
- náhlá srdeční smrt epidemiologie MeSH
- sluneční aktivita * MeSH
- zeměpis MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přednášky MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
- Gruzie epidemiologie MeSH
- Hongkong epidemiologie MeSH
- Spojené státy americké epidemiologie MeSH
