Wiley series in probability and statistics
1st ed. xvii, 259 s.
- Keywords
- Zkoušky klinické, Randomizace,
- Conspectus
- Statistika
- NML Fields
- 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
- Day Care, Medical economics methods organization & administration MeSH
- Adult MeSH
- Mental Disorders diagnosis nursing therapy MeSH
- Research Support as Topic MeSH
- Hospitalization MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Surveys and Questionnaires MeSH
- Aged MeSH
- Socioeconomic Factors MeSH
- Eligibility Determination classification MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
Texts in statistical science
2nd ed. xix, 399 s.
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 therapeutic use MeSH
- Genome-Wide Association Study MeSH
- Diet MeSH
- Genotyping Techniques MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms blood epidemiology genetics prevention & control MeSH
- Salicylic Acid administration & dosage blood MeSH
- Humans MeSH
- Mendelian Randomization Analysis MeSH
- Risk Factors MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article 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
- Genome-Wide Association Study MeSH
- Diabetes Mellitus, Type 2 * complications epidemiology genetics MeSH
- Glycated Hemoglobin analysis MeSH
- Hyperinsulinism * complications genetics MeSH
- Insulin MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms * complications epidemiology genetics MeSH
- Blood Glucose analysis genetics MeSH
- Humans MeSH
- Mendelian Randomization Analysis MeSH
- Risk Factors MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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 pharmacology therapeutic use MeSH
- Colorectal Neoplasms drug therapy MeSH
- Humans MeSH
- Mendelian Randomization Analysis methods MeSH
- Proteomics methods MeSH
- Risk Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural 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
- Genome-Wide Association Study MeSH
- Genetic Predisposition to Disease MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Mendelian Randomization Analysis methods MeSH
- Head and Neck Neoplasms genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Body Height genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Body Mass Index * MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Mendelian Randomization Analysis * MeSH
- Mutation * MeSH
- Breast Neoplasms etiology pathology MeSH
- Prognosis MeSH
- BRCA1 Protein genetics MeSH
- BRCA2 Protein genetics MeSH
- Risk Factors MeSH
- Body Height * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Přes významné zlepšování metodologie epidemiologických studií a analýz zdravotnických databází, zůstávají v observačních epidemiologických studiích asociace mezi ovlivnitelnými expozicemi a nemocí do určité míry zkresleny. Princip mendelovské randomizace, tj. náhodné rozdělení rodičovských genů potomkům v meiose během formování gamet a při koncepci, představuje jednu z šancí metodologie hodnocení příčinné povahy některých zevních příčin nemocí. Při využití tohoto přístupu je zjištěná asociace mezi nemocí a studovaným genetickým polymorfizmem, který odráží biologickou spojitost mezi podezřelou expozicí a nemocí, obecně méně náchylná k fenoménu zavádění nebo k zpětnému zapříčinění, které může zkreslit interpretaci výsledků konvenčních pozorovacích studií. Autoři ilustrují explanační možnosti mendelovské randomizace na příkladech vztahů folát – homocystein – ICHS a izothiokyanát versus karcinom plic. I když využití principu mendelovské randomizace má svá omezení, poskytuje nové možnosti jak testovat příčinnou souvislost dějů a jasně ukazuje, jak prostředky vložené do projektu lidského genomu mohou přispět k poznání a potenciálním možnostem prevence nepříznivých účinků ovlivnitelných expozic na lidské zdraví.
Though the methodology and designs of epidemiological studies and analyses of medical databases have improved, associations between modifiable exposures and the disease in observational epidemiological studies remain partly biased. Mendelian randomization principle, which is the random distribution of parental genes to offspring in meiosis during gametogeneis and at conception, represents a chance for methodology of evaluation of the causal relations between the external cause and the disease. The use of this principle assumes the association between the disease and the genetic polymorphism which reflects the biological relation between the suspected exposure and the disease, and is generally less prone to the phenomenon of confounding and reverse causation that can impair the interpretation of results in conventional observational studies. Authors describe explanatory options of the Mendelian randomization principle using examples in folic acid – homocysteine – coronary heart disease, and isothiocyanate versus lung carcinoma. Though the use of Mendelian randomization principle has its limitations, it offers new possibilities to test causal relations and clearly shows that means invested into the Human genome project can contribute to the understanding and prevention of adverse effects of modifiable exposure to the human health.
