A cluster randomized controlled trial on the effects and costs of advance care planning in elderly care: Study protocol

Background: Currently, health care and medical decision-making at the end of life for older people are often insufficiently patient-centred. In this trial we study the effects of Advance Care Planning (ACP), a formalised process of timely communication about care preferences at the end of life, for frail older people. Methods/Design: We will conduct a cluster randomised controlled trial among older people residing in care homes or receiving home care in the Netherlands. The intervention group will receive the ACP program Respecting Choices® in addition to usual care. The control group will receive usual care only. Participants in both groups will fill out questionnaires at baseline and after 12 months. We hypothesize that ACP will lead to better patient activation in medical decision making and quality of life, while reducing the number of medical interventions and thus health care costs. Multivariate analysis will be used to compare differences between the intervention group and the control group at baseline and to compare differences in changes after 12 months following the inclusion. Discussion: Our study can contribute to more understanding of the effects of ACP on patient activation and quality of life in frail older people. Further, we will gain insight in the costs and cost-effectiveness of ACP. This study will facilitate ACP policy for older people in the Netherlands. Trial registration: Nederlands Trial Register: NTR4454

Low patient activation levels in frail older adults: a cross-sectional study

Abstract Background Frail older adults are increasingly expected to self-manage their health and healthcare. We assessed the extent to which this group is able to take up this responsibility by measuring their level of activation as patients (i.e. their knowledge, skills and confidence to self-manage their health and healthcare). Further, we studied which characteristics of older adults were associated with patient activation. Methods In this cross-sectional study 200 frail, competent adults (median age 87 years) participated. Participants were community-dwelling adults who received home care and residents of care homes. Data were collected via personal interviews in participants’ homes. The main outcome measure was patient activation assessed by the short version of the Patient Activation Measure (PAM-13; range: 0–100). The PAM distinguishes four levels of increasing activation with level 1 indicating poor patient activation and level 4 adequate patient activation. Other studied variables were: multimorbidity, type of residency, frailty (Tilburg Frailty Index), mental competence (Mini Mental State Examination), health-related quality of life (SF-12), satisfaction with healthcare (subscale Patient Satisfaction Questionnaire) and personal characteristics (age, gender, marital status, educational level). Regression analyses were performed to investigate which variables were associated with patient activation. Results Participants had a median PAM score of 51. Thirty-nine percent had level 1 activation, 31% level 2, 26% level 3 and 5% level 4. Fifty-nine percent of community dwelling adults had level 1 or 2 activation versus 81% of care home residents (p = 0.007). Mental competence (Effect: 0.52, CI: 0.03–1.01, p = 0.04) and health-related quality of life (Effect: 0.15, CI: 0.01–0.30, p = 0.04 for physical health; Effect: 0.20, CI: 0.07–0.34, p = 0.003 for mental health) were positively associated with patient activation. Frailty (Effect: -1.06, CI: -1.75 – -0.36, p = 0.003) was negatively associated with patient activation. Conclusions The majority of this frail and very old study population, especially those with a lower health-related quality of life, may be unable to self-manage their health and healthcare to the level expected from them. The increasing population of frail older adults may need help in managing their health and healthcare

Gastrointestinal zygomycosis due to Rhizopus microsporus var. rhizopodiformis as a manifestation of chronic granulomatous disease.

Contains fulltext : 70218.pdf (publisher's version ) (Closed access)A case of gastrointestinal zygomycosis in a 10-month-old boy with chronic granulomatous disease (CGD) is presented. Zygomycetes are an uncommon cause of fungal disease in CGD patients and gastrointestinal zygomycosis has not been previously described in individuals with CGD. To improve outcome, a timely and correct diagnosis is of utmost importance

Induced expression of expanded CGG RNA causes mitochondrial dysfunction in vivo

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting carriers of premutation forms of the FMR1 gene, resulting in a progressive development of tremor, ataxia and neuropsychological problems. The disease is caused by an expanded CGG repeat in the FMR1 gene, leading to an RNA gain-of-function toxicity mechanism. In order to study the pathogenesis of FXTAS, new inducible transgenic mouse models have been developed that expresses either 11CGGs or 90CGGs at the RNA level under control of a Tet-On promoter. When bred to an hnRNP-rtTA driver line, doxycycline (dox) induced expression of the transgene could be found in almost all tissues. Dox exposure resulted in loss of weight and death within 5 d for the 90CGG RNA expressing mice. Immunohistochemical examination of tissues of these mice revealed steatosis and apoptosis in the liver. Decreased expression of GPX1 and increased expression of cytochrome C is found. These effects were not seen in mice expressing a normal sized 11CGG repeat. In conclusion, we were able to show in vivo that expression of an expanded CGG-repeat rather than overexpression of a normal CGG-repeat causes pathology. In addition, we have shown that expanded CGG RNA expression can cause mitochondrial dysfunction by regulating expression levels of several markers. Although FTXAS patients do not display liver abnormalities, our findings contribute to understanding of the molecular mechanisms underlying toxicity of CGG repeat RNA expression in an animal model. In addition, the dox inducible mouse lines offer new opportunities to study therapeutic interventions for FXTAS

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-beta pathway that is essential for TGF-beta signal transmission(1-3). SMAD3 mutations lead to increased aortic expression of several key players in the TGF-beta pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-beta pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis

Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice

Item does not contain fulltextFragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder generally presenting with intention tremor and gait ataxia, but with a growing list of co-morbid medical conditions including hypothyroidism, hypertension, peripheral neuropathy, and cognitive decline. The pathological hallmark of FXTAS is the presence of intranuclear inclusions in both neurons and astroglia. However, it is unknown to what extent such inclusions are present outside the central nervous system (CNS). To address this issue, we surveyed non-CNS organs in ten human cases with FXTAS and in a CGG repeat knock-in (CGG KI) mouse model known to possess neuronal and astroglial inclusions. We find inclusions in multiple tissues from FXTAS cases and CGG KI mice, including pancreas, thyroid, adrenal gland, gastrointestinal, pituitary gland, pineal gland, heart, and mitral valve, as well as throughout the associated autonomic ganglia. Inclusions were observed in the testes, epididymis, and kidney of FXTAS cases, but were not observed in mice. These observations demonstrate extensive involvement of the peripheral nervous system and systemic organs. The finding of intranuclear inclusions in non-CNS somatic organ systems, throughout the PNS, and in the enteric nervous system of both FXTAS cases as well as CGG KI mice suggests that these tissues may serve as potential sites to evaluate early intervention strategies or be used as diagnostic factors