Geriatrische Interventie: een klinisch-empirisch onderzoek

In 1986 was ik als klinisch geriater werkzaam op een geriatrische afdeling van een psychiatrisch ziekenhuis (GAPZ) en was ik tevens consulent voor het algemeen ziekenhuis Leyenburg. In de daaropvolgende 4 jaren is mij duidelijk geworden wat de voor- en de nadelen zijn van de behandeling op een geriatrische afdeling versus geriatrische consulten en medebehandeling op andere afdelingen. Toen mijn werkveld naar het algemeen ziekenhuis Leyenburg werd verschoven stond ik voor de opdracht om in dit ziekenhuis de klinische geriatrie verder te ontwikkelen. Op dat ogenblik was er in het ziekenhuis een stijgende vraag naar geriatrische consulten. Geriatrische patienten bleken verspreid over alle afdelingen van het ziekenhuis voor te komen. Het werkelijke aantal geriatrische patienten in het ziekenhuis was op basis van de consulten moeilijk in te schatten. Wanneer een afdeling gedurende een jaar veel aandacht kreeg. steeg het aantal consulten zeer sterk. om daarna weer te dalen wanneer de consultatief werkende afdeling geriatrie er minder actief mee bezig was. Er zijn verschillende organisatorische modellen waarmee geriatrie in ziekenhuizen kan worden bedreven

Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25x10-6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3x10 -9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH