Economic considerations of Alzheimer's disease and related disorders

Economic analyses of geriatric syndromes are seldom performed. However, demographic and epidemiological imperatives have led to significant interest in the evaluation of AD-related costs. Over 300 papers devoted to economic considerations of Alzheimer's disease have been published in peer-reviewed journals, within the last five years. In these papers, the chosen perspective (costs to society or to specific payers) is important. Analytical methods are still evolving and remain complex. Unresolved methodological issues will need to be addressed to further our understanding of long-term economic consequences. At present, it is clear that diagnostic and drug costs are low compared to the major cost of institutionalization. Thus, directing efforts at early diagnosis and delaying nursing home placement are two key cost-containment interventions. In this respect, the need to support informal care should not be underestimate

Early markers of prolonged hospital stay in demented inpatients: A multicentre and prospective study

Background: Dementia is a serious, chronic, and costly public health problem. Prior studies have described dementia as increasing length of hospital stay, but so far no explanations have been proposed. Methods: To identify early markers for prolonged hospital stay in demented elderly inpatients, 178 community-dwelling or institutionalized subjects aged 75+, hospitalized through an emergency department in 9 teaching hospitals in France, were analyzed. Prolonged hospital stays were defined according a limit adjusted for Diagnosis Related Group. All patients underwent a comprehensive geriatric assessment at admission. Logistic regression multifactorial mixed model was performed. Center effect was considered as a random effect. Results: Of the 178 stays, 52 were prolonged. Most concerned community-dwelling patients (86%). Multifactor analysis demonstrated that demographic variables had no influence on the length of stay, while diagnosis of delirium (OR 2.31; 95% CI 1.77-2.91), walking difficulties (OR 1.94; 95% CI 1.62-2.43) and report by the informal caregiver of moderate or severe burden (OR 1.52; 95% CI 1.19-1.86) or low social quality-of-life score (OR 1.25; 95% CI 1.03-1.40), according to the Zarit's Burden Inventory short scale (12 items) and the Duke's Health Profile respectively, were identified as early markers for prolonged hospital stays. Conclusion: At the time of the rising incidence of cognitive disorders, these results suggest that preventive approaches might be possible. In a hospital setting as well as in a community-dwelling population, more specific, specialized and coordinated care, using the expertise of multiple disciplines appears as a probable effective measure to limit prolonged hospital stay. Such approaches require (i) clear patient-oriented goal definition, (ii) understanding and appreciation of roles among various health care and social disciplines and, (iii) cooperation between partners in patient's management. However, the cost- and health-effectiveness of such approaches should be evaluate

Swiss Frailty Network and Repository: protocol of a Swiss Personalized Health Network's driver project observational study.

Early identification of frailty by clinical instruments or accumulation of deficit indexes can contribute to improve healthcare for older adults, including the prevention of negative outcomes in acute care. However, conflicting evidence exists on how to best capture frailty in this setting. Simultaneously, the increasing utilisation of electronic health records (EHRs) opens up new possibilities for research and patient care, including frailty. The Swiss Frailty Network and Repository (SFNR) primarily aims to develop an electronic Frailty Index (eFI) from routinely available EHR data in order to investigate its predictive value against length of stay and in-hospital mortality as two important clinical outcomes in a study sample of 1000-1500 hospital patients aged 65 years and older. In addition, we will examine the correlation between the eFI and a test-based clinical Frailty Instrument to compare both concepts in Swiss older adults in acute care settings. As a Swiss Personalized Health Network (SPHN) driver project, our study will report on the characteristics and usability of the first nationwide eFI in Switzerland connecting all five Swiss University Hospitals' Geriatric Departments with a representative sample of patients aged 65 years and older admitted to acute care. The study protocol was approved by the competent ethics committee of the Canton of Zurich (BASEC-ID 2019-00445). All acquired data will be handled according to SPHN's ethical framework for responsible data processing in personalised health research. Analyses will be performed within the secure BioMedIT environment, a national infrastructure to enable secure biomedical data processing, an integral part of SPHN. NCT04516642

Use it or lose it! Cognitive activity as a protec-tive factor for cognitive decline associated with Alzheimer's disease.

Because of the worldwide aging of populations, Alzheimer's disease and other dementias constitute a devastating experience for patients and families as well as a major social and economic burden for both healthcare systems and society. Multiple potentially modifiable cardiovascular and lifestyle risk factors have been associated with this disease. Thus, modifying these risk factors and identifying protective factors represent important strategies to prevent and delay disease onset and to decrease the social burden. Based on the cognitive reserve hypothesis, evidence from epidemiological studies shows that low education and cognitive inactivity constitute major risk factors for dementia. This indicates that a cognitively active lifestyle may protect against cognitive decline or delay the onset of dementia. We describe a newly developed preventive programme, based on this evidence, to stimulate and increase cognitive activity in older adults at risk for cognitive decline. This programme, called "BrainCoach", includes the technique of "motivational interviewing" to foster behaviour change. If the planned feasibility study is successful, we propose to add BrainCoach as a module to the already existing "Health Coaching" programme, a Swiss preventive programme to address multiple risk factors in primary care

Malignant perivascular epithelioid cell tumor of the uterus

Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors arising in a wide array of anatomic locations and characterized by a myomelanocytic phenotype. PEComas which occur in non-classic anatomic distributions are known as perivascular epithelioid cell tumor-not otherwise specified (PEComa-NOS), and one of the most common primary sites for PEComa-NOS is the uterus. The risk of aggressive behavior of these tumors has been linked to a number of factors evaluable on pathologic review following initial surgical resection. We report a case of PEComa-NOS of the uterus with multiple high-risk features, including frank vascular invasion, with no evidence of recurrent disease 18 months following initial surgical resection

Factors influencing the participation of gastroenterologists and hepatologists in clinical research

<p>Abstract</p> <p>Background</p> <p>Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.</p> <p>Methods</p> <p>We surveyed 1050 members of the American Association for the Study of Liver Diseases regarding their participation in clinical research. We compared the survey responses by specialty and level of clinical trial experience.</p> <p>Results</p> <p>A majority of the respondents (71.6%) reported involvement in research activities. Factors most influential in clinical trial participation included funding and compensation (88.3%) and intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n = 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced (n = 159) clinical researchers. These barriers included uncompensated research costs and lack of specialized support. Industry marketing was a greater influence among respondents with less trial experience, compared to those with extensive experience (15.7% vs 1.6%; <it>P </it>< .01). Hepatologists and respondents with extensive clinical trial experience tended to be more interested in phase 1 and 2 studies, whereas gastroenterologists and less experienced investigators were more interested in phase 4 studies.</p> <p>Conclusion</p> <p>This study suggests that the greatest barrier to participation in clinical research is lack of adequate resources. Respondents also favored industry-sponsored research with less complex trial protocols and studies of relatively short duration.</p

Interventions that support the creation of dementia friendly environments in health care : protocol for a realist review

© 2016 Handley et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedImproving health-care outcomes for people living with dementia when they are admitted to hospital is a policy priority. Dementia friendly interventions in health care promote inclusion of patients and carers in decision-making and adapt practices and environments to be appropriate to the needs of people with cognitive impairment. While there has been a wealth of activity, the number of studies evaluating interventions is limited, and the majority focuses on reporting staff and organisational outcomes. By focusing on patient and carer outcomes, this review will aim to develop an explanatory account of how and in what circumstances dementia friendly environments in health care work for people living with dementia and with what outcomesPeer reviewe

Study Protocol: The Behaviour and Pain in Dementia Study (BePAID)

<p>Abstract</p> <p>Background</p> <p>People with dementia admitted to the acute hospital often receive poor quality care particularly with regards to management of behavioural and psychiatric symptoms of dementia (BPSD) and of pain. There have been no UK studies on the prevalence and type of pain or BPSD in people with dementia in this setting, or on how these may impact on patients, carers, staff and costs of care.</p> <p>Methods/Design</p> <p>We shall recruit older people with dementia who have unplanned acute medical admissions and measure the prevalence of BPSD using the Behave-AD (Behaviour in Alzheimer's Disease) and the CMAI (Cohen Mansfield Agitation Inventory). Pain prevalence and severity will be assessed by the PAINAD (Pain Assessment in Advanced Dementia) and the FACES pain scale. We will then analyse how these impact on a variety of outcomes and test the hypothesis that poor management of pain is associated with worsening of BPSD.</p> <p>Discussion</p> <p>By demonstrating the costs of BPSD to individuals with dementia and the health service this study will provide important evidence to drive improvements in care. We can then develop effective training for acute hospital staff and alternative treatment strategies for BPSD in this setting.</p

Co-morbidity and drug treatment in Alzheimer's disease. A cross sectional study of participants in the Dementia Study in Northern Norway

Inappropriate medical treatment of co-morbidities in Alzheimer’s disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway. Setting: Nine rural municipalities with 70 000 inhabitants in Northern Norway. Participants: Participants with and without AD recruited in general practice and by population based screening. 187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t-test, chi-square, ANCOVA and logistic regression. A co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1 ± 3.6 and 2.9 ± 2.4 respectively, p < 0.001 age and gender adjusted), also when adjusted for co-morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9 ± 3.9 and 4.5 ± 3.3, respectively, p < 0.001). AD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors

Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons

Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer’s disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ₄₂ activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ₄₂-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1. Aβ₄₂-induced neurotoxicity was also inhibited by treatment with TPEN used as a Zn²⁺-specific chelator. Cell imaging revealed that Aβ₄₂-induced lysosomal dysfunction, cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS. These effects were suppressed by TRPM2-KO, inhibition of TRPM2 or PARP-1, or treatment with TPEN. Bafilomycin-induced lysosomal dysfunction also resulted in TRPM2-dependent cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, and mitochondrial generation of ROS, supporting that lysosomal dysfunction and accompanying Zn²⁺ release trigger mitochondrial Zn²⁺ accumulation and generation of ROS. Aβ₄₂-induced effects on lysosomal and mitochondrial functions besides neurotoxicity were also suppressed by inhibition of PKC and NOX. Furthermore, Aβ₄₂-induced neurotoxicity was prevented by inhibition of MEK/ERK. Therefore, our study reveals multiple molecular mechanisms, including PKC/NOX-mediated generation of ROS, activation of MEK/ERK and PARP-1, lysosomal dysfunction and Zn²⁺ release, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS, are critically engaged in forming a positive feedback loop that drives Aβ₄₂-induced activation of the TRPM2 channel and neurotoxicity in hippocampal neurons. These findings shed novel and mechanistic insights into AD pathogenesis