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

Over oude mensen en een jong specialisme

De wijze waarop in Nederland de specialistische medische zorg voor oude mensen is ingericht, moet verbeterd worden. Dit is nodig om de kwaliteit te waarborgen en om aan de toenemende vraag aan gespecialiseerde ouderenzorg te kunnen voldoen. Dit vereist een andere manier van werken en denken, waarbij geriaters over de grenzen van hun eigen specialisme heenkijken.

A desire for death is a living desire

De Nederlandse euthanasiepraktijk ondergaat al langere tijd een proces van onderzoek en evaluatie. In het huidige debat worden cruciale begrippen als zelfbeschikking, individualiteit, rationaliteit, onafhankelijkheid en zelfredzaamheid voornamelijk normerend en als dragende begrippen gehanteerd. Eén van de problematische aspecten in dit cluster is de suggestie dat een leven begrepen kan worden vanuit een autonoom besluit, zonder zich te voegen in de samenhang van het concrete menselijk leven als relationeel, contextueel en historisch-belichaamd. Omdat het ‘ervaren’ lijden binnen de persoonscontext en de gebezigde argumentatie vaker verwoord worden vanuit een existentieel kader dan vanuit de medische situatie, zou het kader van de euthanasievraag moeten gaan om de onderkenning ervan als ‘zorgvraag’, en wel door de euthanasievraag ‘vanuit het leven’ te begrijpen. Een euthanasievraag vanuit het leven begrijpen, betekent dat de zelfbeschikking ‘binnen de relatie’ als een relationeel proces voor de patiënt inhoud en betekenis kan krijgen. De inhoudelijke behandeling van het verzoek vindt daarbinnen plaats. ‘Hoe’ er kennis van het uitzichtloos ondraaglijk lijden wordt verkregen is een epistemische vraag evenals ‘wie’ er van dit lijden kennisneemt. De wet gaat er nu van uit dat de hoofdbehandelaar zelfstandig kennis opdoet binnen het uitzichtloos ondraaglijk lijden, waar de consultatie door de tweede, onafhankelijk arts overwegend procedureel van aard is. De leidende gedachte achter deze studie is het zoeken naar verbindingen tussen de wettelijke zorgvuldigheidsvoorwaarden enerzijds en een hermeneutisch, relationeel proces tussen arts(en) en patiënt anderzijds, gebaseerd op het concrete menselijk leven. Dit artikel schetst de thematiek vanuit de levensechte praktijk met intermitterende reflecties op die praktijk, met als bedoeling de complexiteit van een dergelijk proces weer te geven. Het betreft geen standpuntbepaling of een voorschrift van ‘wat er zou moeten gebeuren’; het betreft een levensecht verslag van ‘wat zich kan tonen’ binnen een per definitie moeilijk proces naar euthanasie. Het vinden van een ethische route binnen de schijnbaar strijdige uitgangspunten vormt een wezenlijke opgave

The effectiveness of a bibliotherapy in increasing the self-management ability of slightly to moderately frail older people

Objective: Self-management ability (SMA) is the ability to obtain those resources necessary for the production of well-being.With age, SMA becomes increasingly important, if one has a large variety of resources, physical and psychosocial losses due to the aging process can be substituted or compensated for. This study examined whether an increase in SMA would ensure sustainable levels of positive well-being among slightly to moderately frail older people. Methods: A bibliotherapy was developed to increase the SMA of slightly to moderaterly frail older people, and to help these persons to sustain a certain level of well-being. The effectiveness of this bibliotherapy was examined by comparing the SMA, mastery, and subjective well-being of 97 older people participating in the bibliotherapy to those of 96 older people in a delayed-treatment control condition. Results: The bibliotherapy resulted in a significant increase in SMA and mastery compared to the delayed-treatment control condition, and for SMA, this effect still existed 6 months after the intervention. The increase in SMA among older people who received the bibliotherapy prevented a decline in well-being as expected, but only in the short-term. Conclusion: The current findings show that it is possible to counteract an age-related decline in well-being, even with only slight to moderate levels of frailty. Practice implications: Cheap and easily accessible interventions, like the self-management bibliotherapy described in this article, may provide a useful addition to more traditional gerontological interventions.

Evaluation of the chronic disease self-management program (CDSMP) among chronically ill older people in the Netherlands

Many chronically ill older patients in the Netherlands have a combination of more than one chronic disease. There is therefore a need for self-management programs that address general management problems, rather than the problems related to a specific disease. The Chronic Disease Self-Management Program (CDSMP) seems to be very suitable for this purpose. In evaluations of the program that have been carried out in the United States and China, positive effects were found on self-management behaviour and health status. However, the program has not yet been evaluated in the Netherlands. Therefore, the aim of this study was to evaluate the short-term and longer-term effects of the program among chronically ill older people in the Netherlands. One hundred and thirty-nine people aged 59 or older, with a lung disease, a heart disease, diabetes, or arthritis were randomly assigned to an intervention group (CDSMP) or a control group (care-asusual). Demographic data and data on self-efficacy, self-management behaviour and health status were collected at three measurement moments (baseline, after 6 weeks, and after 6 months). The patients who participated rated the program with a mean of 8.5 points (range 0–10), and only one dropped out. However, our study did not yield any evidence for the effectiveness of the CDSMP on self-efficacy, self-management behaviour or health status of older patients in the Netherlands. Because the patients who participated were very enthusiastic, which was also indicated by very high mean attendance (5.6 out of 6 sessions) and only one dropout, it seems too early to conclude that the program is not beneficial for these patients.

Evaluation of the chronic disease self-management program (CDSMP) among chronically ill older people in the Netherlands

Many chronically ill older patients in the Netherlands have a combination of more than one chronic disease. There is therefore a need for self-management programs that address general management problems, rather than the problems related to a specific disease. The Chronic Disease Self-Management Program (CDSMP) seems to be very suitable for this purpose. In evaluations of the program that have been carried out in the United States and China, positive effects were found on self-management behaviour and health status. However, the program has not yet been evaluated in the Netherlands. Therefore, the aim of this study was to evaluate the short-term and longer-term effects of the program among chronically ill older people in the Netherlands. One hundred and thirty-nine people aged 59 or older, with a lung disease, a heart disease, diabetes, or arthritis were randomly assigned to an intervention group (CDSMP) or a control group (care-as-usual). Demographic data and data on self-efficacy, self-management behaviour and health status were collected at three measurement moments (baseline, after 6 weeks, and after 6 months). The patients who participated rated the program with a mean of 8.5 points (range 0-10), and only one dropped out. However, our study did not yield any evidence for the effectiveness of the CDSMP on self-efficacy, self-management behaviour or health status of older patients in the Netherlands. Because the patients who participated were very enthusiastic, which was also indicated by very high mean attendance (5.6 out of 6 sessions) and only one dropout, it seems too early to conclude that the program is not beneficial for these patients.Self management Elderly Chronic disease Randomized trial The Netherlands

INTERMED: a clinical instrument for biopsychosocial assessment

Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrome P450 isozymes. Eight patients were phenotyped with dextromethorphan (CYP2D6), mephenytoin (CYP2C19), and caffeine (CYP1A2) before and after the introduction of risperidone. Before risperidone, all eight patients were phenotyped as being extensive metabolizers of CYP2D6 and CYP2C19. Risperidone at dosages between 2 and 6 mg/d does not appear to significantly inhibit CYP1A2 and CYP2C19 in vivo (median plasma paraxanthine/caffeine ratios before and after risperidone: 0.65, 0.69; p = 0.89; median urinary (S)/(R) mephenytoin ratios before and after risperidone:0.11, 0.12; p = 0.75). Although dextromethorphan metabolic ratio is significantly increased by risperidone (median urinary dextromethorphan/dextrorphan ratios before and after risperidone: 0.010, 0.018; p = 0.042), risperidone can be considered a weak in vivo CYP2D6 inhibitor, as this increase is modest and none of the eight patients was changed from an extensive to a poor metabolizer. The reported increase of clozapine concentrations by risperidone can therefore not be explained by an inhibition of CYP1A2, CYP2D6, CYP2C19 or by any combination of the three UR - http://psy.psychiatryonline.org/cgi/content/abstract/42/2/10