• Klíčová slova
• Zkoušky klinické, Randomizace,

• Konspekt
• Statistika
• NLK Obory
• statistika, zdravotnická statistika
• diagnostika

Denní stacionáře (DS) představují jednu z alternatív akutní ústavní psychiatrické péče pro pacienty s lehkou až středně těžkou duševní poruchou, která má být stejně účinná a levnější než klasická hospitalizace. Cílem naší studie bylo prověřit toto tvrzení vyplývající ze zahraničních publikací v podmínkách systému české zdravotní péče. Během 20 měsíců náboru do naší studie jsme kontaktovali všech 1543 pacientů odeslaných k přijetí na Psychiatrickou kliniku VFN. Po splnění administrativních kritérií jsme u 944 z nich zvažovali možnost jejich účasti ve studii. Nejčastějšími příčinami jejich nezařazení byla závažnost aktuální psychopatologie, suicidální riziko a závislost na návykových látkách jako hlavní diagnóza. 256 splnilo vstupní a nesplnilo vylučovací kritéria. 210 pacientů s účastí ve studii souhlasilo. 103 z nich bylo randomizováno do denní péče, 107 ke klasické hospitalizaci. Obě skupiny se mezi sebou nelišily ve většině sociodemografických a klinických charakteristik. Je diskutována otázka kapacity denního stacionáře v závislosti na struktuře a kvalitě psychiatrické péče.

Day care represents one of the alternatives of acute psychiatric hospital treatment for patients with mental disorders and it is potentialy as effective and cheaper than standard hospitalisation. The aim of our study was to test this hypothesis in the Czech health care system. During a period of 20 months we contacted all 1543 patients recommended to our Psychiatric hospital VFN. After fulfilling administrative criteria a group of 944 patients emerged to become candidates for participation in the study. The most frequent exclusion reasons were severity of psychopathology, suicidal risk and addictive disorder as main diagnosis. 256 patients fulfilled the inclusion and failed exclusion criteria. 210 agreed to participate in the study. 103 patients were randomized to day care, and 107 to standard hospitalisation. Neither groups differed in their main sociodemographic and clinical characteristics. The question of capacity of day hospitals in relation to structure and quality of psychiatric care has been discussed.

• MeSH
• denní péče o pacienty ekonomika   metody   organizace a řízení   MeSH
• dospělí MeSH
• duševní poruchy diagnóza   ošetřování   terapie   MeSH
• finanční podpora výzkumu jako téma MeSH
• hospitalizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• určení vhodnosti pacienta klasifikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

• MeSH
• biologie MeSH

• Konspekt
• Biologické vědy
• NLK Obory
• biologie
• statistika, zdravotnická statistika

• MeSH
• psychologické testy MeSH
• teoretické modely MeSH
• výuka - hodnocení MeSH

PURPOSE: We combined classical association analyses with one-sample and two-sample Mendelian randomization (MR), to comprehensively assess the causal relation among central corneal thickness (CCT), corneal hysteresis, Fuchs endothelial corneal dystrophy (FECD), and open-angle glaucoma (OAG). METHODS: We analyzed data from a large population-based cohort study (the Rotterdam Study), an FECD case-control study, and genome wide association study summary statistics. We defined OAG as reproducible visual field loss, independent of IOP. Multivariable regression was performed. One-sample MR was performed using the same regression models, with the corresponding genetic risk score (GRS) as independent variable. Two-sample MR was performed using inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods. RESULTS: In total, 303 participants with OAG and 10,598 controls from the Rotterdam Study were included, with 753 FECD cases from the FECD cohort. The odds ratio (OR) 95% confidence interval (CI) of OAG was 0.67 (95% CI = 0.56-0.81) per standard deviation (SD) increase in CCT (P < 0.001). However, one-sample MR showed no significant association between a CCT-GRS and OAG (P = 0.688). Two-sample MR found an OR (95% CI) of 1.23 (95% CI = 1.06-1.42) for each SD increase in the CCT instrumental variable. We observed no association between an FECD-GRS and OAG (P = 0.946). CONCLUSIONS: We found no evidence for a causal link between CCT and OAG. Nevertheless, CCT measurements are still valuable for population-based risk stratification. We found no clear relationship between FECD and OAG.

• MeSH
• celogenomová asociační studie MeSH
• Fuchsova endoteliální dystrofie * genetika   MeSH
• glaukom s otevřeným úhlem * genetika   patofyziologie   diagnóza   epidemiologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mendelovská randomizace * metody   MeSH
• nitrooční tlak fyziologie   MeSH
• rizikové faktory MeSH
• rohovka * patologie   patofyziologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zraková pole fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Glycemic traits-such as hyperinsulinemia, hyperglycemia, and type 2 diabetes-have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type 2 diabetes with colorectal cancer. METHODS: Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type 2 diabetes (n = 268). Using 2-sample MR, we examined these variants in relation to colorectal cancer risk (48 214 case patient and 64 159 control patients). RESULTS: In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD = 1.65, 95% confidence interval [CI] = 1.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86 to 1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88 to 1.23) concentrations on colorectal cancer risk. Genetic liability to type 2 diabetes (OR per 1-unit increase in log odds = 1.04, 95% CI = 1.01 to 1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00 to 1.19) increased colorectal cancer risk, although these findings may have been biased by pleiotropy. Higher HbA1c concentrations increased rectal cancer risk in men (OR per 1-SD = 1.21, 95% CI = 1.05 to 1.40), but not in women. CONCLUSIONS: Our results support a causal effect of higher fasting insulin, but not glucose traits or type 2 diabetes, on increased colorectal cancer risk. This suggests that pharmacological or lifestyle interventions that lower circulating insulin levels may be beneficial in preventing colorectal tumorigenesis.

• MeSH
• celogenomová asociační studie MeSH
• diabetes mellitus 2. typu * komplikace   epidemiologie   genetika   MeSH
• glykovaný hemoglobin analýza   MeSH
• hyperinzulinismus * komplikace   genetika   MeSH
• inzulin MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * komplikace   epidemiologie   genetika   MeSH
• krevní glukóza analýza   genetika   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. METHODS: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). RESULTS: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively). CONCLUSIONS: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. IMPACT: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

• MeSH
• Aspirin farmakologie   terapeutické užití   MeSH
• kolorektální nádory farmakoterapie   MeSH
• lidé MeSH
• mendelovská randomizace metody   MeSH
• proteomika metody   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.

• MeSH
• Aspirin terapeutické užití   MeSH
• celogenomová asociační studie MeSH
• dieta MeSH
• genotypizační techniky MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory krev   epidemiologie   genetika   prevence a kontrola   MeSH
• kyselina salicylová aplikace a dávkování   krev   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mendelovská randomizace metody   MeSH
• nádory hlavy a krku genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tělesná výška genetika   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

BACKGROUND: Mechanistic data indicate the benefit of short-chain fatty acids (SCFA) produced by gut microbial fermentation of fiber on colorectal cancer, but direct epidemiologic evidence is limited. A recent study identified SNPs for two SCFA traits (fecal propionate and butyrate-producing microbiome pathway PWY-5022) in Europeans and showed metabolic benefits. METHODS: We conducted a two-sample Mendelian randomization analysis of the genetic instruments for the two SCFA traits (three SNPs for fecal propionate and nine for PWY-5022) in relation to colorectal cancer risk in three large European genetic consortia of 58,131 colorectal cancer cases and 67,347 controls. We estimated the risk of overall colorectal cancer and conducted subgroup analyses by sex, age, and anatomic subsites of colorectal cancer. RESULTS: We did not observe strong evidence for an association of the genetic predictors for fecal propionate levels and the abundance of PWY-5022 with the risk of overall colorectal cancer, colorectal cancer by sex, or early-onset colorectal cancer (diagnosed at <50 years), with no evidence of heterogeneity or pleiotropy. When assessed by tumor subsites, we found weak evidence for an association between PWY-5022 and risk of rectal cancer (OR per 1-SD, 0.95; 95% confidence intervals, 0.91-0.99; P = 0.03) but it did not surpass multiple testing of subgroup analysis. CONCLUSIONS: Genetic instruments for fecal propionate levels and the abundance of PWY-5022 were not associated with colorectal cancer risk. IMPACT: Fecal propionate and PWY-5022 may not have a substantial influence on colorectal cancer risk. Future research is warranted to comprehensively investigate the effects of SCFA-producing bacteria and SCFAs on colorectal cancer risk.

• MeSH
• butyráty * analýza   metabolismus   MeSH
• feces * chemie   mikrobiologie   MeSH
• kolorektální nádory * epidemiologie   genetika   metabolismus   MeSH
• kyseliny mastné těkavé analýza   genetika   metabolismus   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• propionáty * analýza   metabolismus   MeSH
• riziko MeSH
• střevní mikroflóra * genetika   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Evropa MeSH