Перспективи використання теорії катастроф у дослідженні економічних криз

OBJECTIVE: To assess in-hospital and long-term mortality of Dutch ICU patients admitted with an acute intoxication. DESIGN: Cohort of ICU admissions from a national ICU registry linked to records from an insurance claims database. SETTING: Eighty-one ICUs (85% of all Dutch ICUs). PATIENTS: Seven thousand three hundred thirty-one admissions between January 1, 2008, and October 1, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier curves were used to compare the unadjusted mortality of the total intoxicated population and for specific intoxication subgroups based on the Acute Physiology and Chronic Health Evaluation IV reasons for admission: 1) alcohol(s), 2) analgesics, 3) antidepressants, 4) street drugs, 5) sedatives, 6) poisoning (carbon monoxide, arsenic, or cyanide), 7) other toxins, and 8) combinations. The case-mix adjusted mortality was assessed by the odds ratio adjusted for age, gender, severity of illness, intubation status, recurrent intoxication, and several comorbidities. The ICU mortality was 1.2%, and the in-hospital mortality was 2.1%. The mortality 1, 3, 6, 12, and 24 months after ICU admission was 2.8%, 4.1%, 5.2%, 6.5%, and 9.3%, respectively. Street drugs had the highest mortality 2 years after ICU admission (12.3%); a combination of different intoxications had the lowest (6.3%). The adjusted observed mortality showed that intoxications with street drugs and "other toxins" have a significant higher mortality 1 month after ICU admission (odds ratio adj = 1.63 and odds ratioadj= 1.73, respectively). Intoxications with alcohol or antidepressants have a significant lower mortality 1 month after ICU admission (odds ratioadj = 0.50 and odds ratioadj = 0.46, respectively). These differences were not found in the adjusted mortality 3 months upward of ICU admission. CONCLUSIONS: Overall, the mortality 2 years after ICU admission is relatively low compared with other ICU admissions. The first 3 months after ICU admission there is a difference in mortality between the subgroups, not thereafter. Still, the difference between the in-hospital mortality and the mortality after 2 years is substantial

Rhabdomyolysis in Clozapine Overdose

CONTEXT: Clozapine is used for decennia for the treatment of schizophrenia. Agranulocytosis, diabetic ketoacidosis, gastrointestinal hypomotility, and myocarditis are well-known adverse effects of clozapine, which are sometimes life threatening. Here we report a case of rhabdomyolysis upon an acute overdose of clozapine. CASE: A male patient, 36 years, with elevated creatinine kinase levels (9899 U/l), developed rhabdomyolysis afterafter admission to the emergency department. Approximately 2–4 h earlier he had intoxicated himself with his maintenance oral medication clozapine 125 mg, temazepam 20 mg and lorazepam 1.5 mg. Co-medications, and physical and laboratory examinations did not reveal other risk factors for rhabdomyolysis. According to the Naranjo probability scale there was a probable relation between clozapine dose and symptoms, that developed approximately 2–4 h after the auto-intoxication of 125 mg tablets. At day 5 of hospitalization, clozapine and creatinine kinase levels returned to normal and the patient was discharged with no somatic sequelae. CONCLUSIONS: Elevated creatinine kinase levels in acute clozapine intoxication may be an indicator that rhabdomyolysis may be involved

Sport, sex and age increase risk of illness at the Rio 2016 Summer Paralympic Games: a prospective cohort study of 51 198 athlete days

OBJECTIVETo describe the epidemiology of illness at the Rio 2016 Summer Paralympic Games. METHODS A total of 3657 athletes from 78 countries, representing 83.5% of all athletes at the Games, were monitored on the web-based injury and illness surveillance system (WEB-IISS) over 51 198 athlete days during the Rio 2016 Summer Paralympic Games. Illness data were obtained daily from teams with their own medical support through the WEB-IISS electronic data capturing systems. RESULTSThe total number of illnesses was 511, with an illness incidence rate (IR) of 10.0 per 1000 athlete days (12.4%). The highest IRs were reported for wheelchair fencing (14.9), para swimming (12.6) and wheelchair basketball (12.5) (p<0.05). Female athletes and older athletes (35–75 years) were also at higher risk of illness (both p<0.01). Illnesses in the respiratory, skin and subcutaneous and digestive systems were the most common (IRs of 3.3, 1.8 and 1.3, respectively). CONCLUSION (1) The rate of illness was lower than that reported for the London 2012 Summer Paralympic Games; (2) the sports with the highest risk were wheelchair fencing, para swimming and wheelchair basketball; (3) female and older athletes (35–75 years) were at increased risk of illness; and (4) the respiratory system, skin and subcutaneous system and digestive system were most affected by illness. These results allow for comparison at future Games

Vitamin D receptor gene polymorphisms have negligible effect on human height.

Human height is a highly heritable trait, with genetic factors explaining up to 90% of phenotypic variation. Vitamin D levels are known to influence several physiological processes, including skeletal growth. The vitamin D receptor (VDR) gene has been reported as contributing to variation in height. A meta-analysis of 13607 adult individuals found a small but significant association with the rs1544410 (Bsml) polymorphism. In contrast, the meta-analysis found no effect in a sample of 550 children. Two recent studies reported variants with large effect on height elsewhere in VDR (rs10735810 [Fokl] and rs7139166 [-1521] polymorphisms). We genotyped large Caucasian samples from Australia (N = 3906) and the Netherlands (N = 1689) for polymorphisms in VDR. The Australian samples were twin families with height measures from 3 time points throughout adolescence. The Dutch samples were adult twins. We use the available family data to perform both within and between family tests of association. We found no significant associations for any of the genotyped variants after multiple testing correction. The (non-significant) effect of rs1544410 in the Australian adolescent cohort was in the same direction and of similar magnitude (additive effect 0.3cm) to the effect observed in the published adult meta-analysis. An effect of this size explains similar to 0.1% of the phenotypic variance in height - this implies that many, probably hundreds, of such variants are responsible for the observed genetic variation. Our results did not support any role for two other regions (rs10735810, rs7139166) of VDR in explaining variation in height

Chromosome 9: linkage for borderline personality disorder features.

Objective A large-scale twin study implicated genetic influences on borderline personality disorder (BPO) features, with a heritability estimate of 42%. To date, no genome-wide linkage study has been conducted to identify the genomic region(s) containing the quantitative trait loci that influence the manifestation of BPD features. Methods We conducted a family-based linkage study using Merlin regress. The participating families were drawn from the community-based Netherlands Twin Register. The sample consisted of 711 sibling pairs with phenotype and genotype data, and 561 additional parents with genotype data. BPD features were assessed on a quantitative scale. Results Evidence for linkage was found on chromosomes 1, 4, 9, and 18. The highest linkage peak was found on chromosome 9p at marker D9S286 with a logarithm of odds score of 3.548 (empirical P= 0.0001). Conclusion To our knowledge, this is the first linkage study on BPD features and shows that chromosome 9 is the richest candidate for genes influencing BPD. The results of this study will move the field closer to determining the genetic etiology of BPD and may have important implications for treatment programs in the future. Association studies in this region are, however, warranted to detect the actual genes. © 2008 Wolters Kluwer Health|Lippincott Williams & Wilkins

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets