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Author(s): Lukoye Atwoli 1, Abdullah H. Baqui 2, Thomas Benfield 3, Raffaella Bosurgi 4, Fiona Godlee 5, Stephen Hancocks 6, Richard Horton 7, Laurie Laybourn-Langton 8,*, Carlos Augusto Monteiro 9, [...]

Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. Methods and findings NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of [greater than or equal to]12 and Conclusions The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. Trial registration Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27., Author(s): Brian Lawlor 1,2,*, Ricardo Segurado 3,4, Sean Kennelly 5,6, Marcel G. M. Olde Rikkert 7, Robert Howard 8, Florence Pasquier 9, Anne Börjesson-Hanson 10, Magda Tsolaki 11, Ugo Lucca [...]

Background: Preoperative colorectal cancer care pathways for older patients show considerable practice variation between Dutch hospitals due to differences in interpretation and implementation of guideline-based recommendations. This study aims to report this practice variation in preoperative care between Dutch hospitals in terms of technical efficiency and identifying associated factors. Methods: Data on preoperative involvement of geriatricians, physical therapists and dieticians and the clinicians' judgement on prehabilitation implementation were collected using quality indicators and questionnaires among colorectal cancer surgeons and specialized nurses. These data were combined with registry-based data on postoperative outcomes obtained from the Dutch Surgical Colorectal Audit for patients aged ≥75 years. A two-stage data envelopment analysis (DEA) approach was used to calculate bias-corrected DEA technical efficiency scores, reflecting the extent to which a hospital invests in multidisciplinary preoperative care (input) in relation to postoperative outcomes (output). In the second stage, hospital care characteristics were used in a bootstrap truncated regression to explain variations in measured efficiency scores. Results: Data of 25 Dutch hospitals were analyzed. There was relevant practice variation in bias-corrected technical efficiency scores (ranging from 0.416 to 0.968) regarding preoperative colorectal cancer surgery. The average efficiency score of hospitals was significantly different from the efficient frontier (p = <0.001). After case-mix correction, higher technical efficiency was associated with larger practice size (p = <0.001), surgery performed in a general hospital versus a university hospital (p = <0.001) and implementation of prehabilitation (p = <0.001). Conclusion: This study showed considerable variation in technical efficiency of preoperative colorectal cancer care for older patients as provided by Dutch hospitals. In addition to higher technical efficiency in high-volume hospitals and general hospitals, offering a care pathway that includes prehabilitation was positively related to technical efficiency of hospitals offering colorectal cancer care. [ABSTRACT FROM AUTHOR]

Study objectives: While poor sleep quality has been related to increased risk of Alzheimer's disease, long-time shift workers (maritime pilots) did not manifest evidence of early Alzheimer's disease in a recent study. We explored two hypotheses of possible compensatory mechanisms for sleep disruption: Increased efficiency in generating deep sleep during workweeks (model 1) and rebound sleep during rest weeks (model 2). Methods: We used data from ten male maritime pilots (mean age: 51.6±2.4 years) with a history of approximately 18 years of irregular shift work. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). A single lead EEG-device was used to investigate sleep in the home/work environment, quantifying total sleep time (TST), deep sleep time (DST), and deep sleep time percentage (DST%). Using multilevel models, we studied the sleep architecture of maritime pilots over time, at the transition of a workweek to a rest week. Results: Maritime pilots reported worse sleep quality in workweeks compared to rest weeks (PSQI = 8.2±2.2 vs. 3.9±2.0; p<0.001). Model 1 showed a trend towards an increase in DST% of 0.6% per day during the workweek (p = 0.08). Model 2 did not display an increase in DST% in the rest week (p = 0.87). Conclusions: Our findings indicated that increased efficiency in generating deep sleep during workweeks is a more likely compensatory mechanism for sleep disruption in the maritime pilot cohort than rebound sleep during rest weeks. Compensatory mechanisms for poor sleep quality might mitigate sleep disruption-related risk of developing Alzheimer's disease. These results should be used as a starting point for future studies including larger, more diverse populations of shift workers. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to provide insight into the merits of DementiaNet, a network-based primary care innovation for community-dwelling dementia patients. Methods: Longitudinal mixed methods multiple case study including 13 networks of primary care professionals as cases. Data collection comprised continuously-kept logs; yearly network maturity score (range 0–24), yearly quality of care assessment (quality indicators, 0–100), and in-depth interviews. Results: Networks consisted of median nine professionals (range 5–22) covering medical, care and welfare disciplines. Their follow-up was 1–2 years. Average yearly increase was 2.03 (95%-CI:1.20–2.96) on network maturity and 8.45 (95%-CI:2.80–14.69) on quality indicator score. High primary care practice involvement and strong leadership proved essential in the transition towards more mature networks with better quality of care. Discussion: Progress towards more mature networks favored quality of care improvements. DementiaNet appeared to be effective to realize transition towards network-based care, enhance multidisciplinary collaboration, and improve quality of dementia care. [ABSTRACT FROM AUTHOR]

Background: The number of older cancer patients is rising. Especially in older people, treatment considerations should balance the impact of disease and treatment on quality of life (QOL) and survival. How a cancer diagnosis in older people interacts with concomitant frailty to impact on QOL is largely unknown. We aimed to determine the association between frailty and QOL among community-dwelling older people aged 65 years or above with and without a cancer diagnosis cross-sectionally and at 12 months follow-up. Methods: Data were derived from the TOPICS-MDS database. Frailty was quantified by a frailty index (FI). QOL was measured with the subjective Cantril’s Self Anchoring Ladder (CSAL, range: 0–10) and the health-related EuroQol-5D (EQ-5D, range:-0.33–1.00) at baseline and after 12 months. To determine associations, linear mixed models were used. Results: 7493 older people (78.6±6.4 years, 58.4% female) were included. Dealing with a cancer diagnosis (n = 751) was associated with worse QOL both at baseline (CSAL:-0.25 (95%-CI:-0.36;-0.14), EQ-5D:-0.03 (95%-CI:-0.05;-0.02)) and at follow-up (CSAL:-0.13 (95%-CI:-0.24;-0.02), EQ-5D:-0.02 (95%-CI:-0.03;-0.00)). A ten percent increase in frailty was also associated with a decrease in QOL at baseline (CSAL:-0.35 (95%-CI:-0.38;-0.32), EQ-5D:-0.12 (95%-CI:-0.12;-0.11)) and follow-up (CSAL:-0.27 (95%-CI:-0.30;-0.24), EQ-5D:-0.07 (95%-CI:-0.07;-0.06)). When mutually adjusting for frailty and a cancer diagnosis, associations between a cancer diagnosis and QOL only remained significant for CSAL at baseline (-0.14 (95%-CI:-0.25;-0.03)), whereas associations between frailty and QOL remained significant for all QOL outcomes at baseline and follow-up. No statistical interactions between cancer and frailty in their combined impact on QOL were found. Conclusions: Cancer diagnosis and frailty were associated with worse health-related and self-perceived QOL both at baseline and at follow-up. Differences in QOL between older people with and without a cancer diagnosis were explained to a large extent by differences in frailty levels. This stresses the importance to take into account frailty in routine oncologic care. [ABSTRACT FROM AUTHOR]

Background: Alzheimer’s disease is a neurodegenerative syndrome characterized by multiple dimensions including cognitive decline, decreased daily functioning and psychiatric symptoms. This systematic review aims to investigate the relation between somatic comorbidity burden and progression in late-onset Alzheimer’s disease (LOAD). Methods: We searched four databases for observational studies that examined cross-sectional or longitudinal associations of cognitive or functional or neuropsychiatric outcomes with comorbidity in individuals with LOAD. From the 7966 articles identified originally, 11 studies were included in this review. The Newcastle-Ottawa quality assessment was used. The large variation in progression measures, comorbidity indexes and study designs hampered the ability to perform a meta-analysis. This review was registered with PROSPERO under DIO: 10.15124/CRD42015027046. Results: Nine studies indicated that comorbidity burden was associated with deterioration in at least one of the three dimensions of LOAD examined. Seven out of ten studies investigating cognition found comorbidities to be related to decreased cognitive performance. Five out of the seven studies investigating daily functioning showed an association between comorbidity burden and decreased daily functioning. Neuropsychiatric symptoms (NPS) increased with increasing comorbidity burden in two out of three studies investigating NPS. Associations were predominantly found in studies analyzing the association cross-sectionally, in a time-varying manner or across short follow-up (≤2 years). Rarely baseline comorbidity burden appeared to be associated with outcomes in studies analyzing progression over longer follow-up periods (>2 years). Conclusion: This review provides evidence of an association between somatic comorbidities and multifaceted LOAD progression. Given that time-varying comorbidity burden, but much less so baseline comorbidity burden, was associated with the three dimensions prospectively, this relationship cannot be reduced to a simple cause-effect relation and is more likely to be dynamic. Therefore, both future studies and clinical practice may benefit from regarding comorbidity as a modifiable factor with a possibly fluctuating influence on LOAD. [ABSTRACT FROM AUTHOR]

Background: Preference-weighted multi-faceted endpoints have the potential to facilitate comparative effectiveness research that incorporates patient preferences. The Older Persons and Informal Caregivers Survey—Composite endpoint (TOPICS-CEP) is potentially a valuable outcome measure for evaluating interventions in geriatric care as it combines multiple outcomes relevant to older persons in a single metric. The objective of this study was to validate TOPICS-CEP across different study settings (general population, primary care and hospital). Methods: Data were extracted from TOPICS Minimum Dataset (MDS), a pooled public-access national database with information on older persons throughout the Netherlands. Data of 17,603 older persons were used. Meta-correlations were performed between TOPICS-CEP indexed scores, EuroQol5-D utility scores and Cantril’s ladder life satisfaction scores. Mixed linear regression analyses were performed to compare TOPICS-CEP indexed scores between known groups, e.g. persons with versus without depression. Results: In the complete sample and when stratified by study setting TOPICS-CEP and Cantril’s ladder were moderately correlated, whereas TOPICS-CEP and EQ-5D were highly correlated. Higher mean TOPICS-CEP scores were found in persons who were: married, lived independently and had an education at university level. Moreover, higher mean TOPICS-CEP scores were found in persons without dementia, depression, and dizziness with falls, respectively. Similar results were found when stratified by subgroup. Conclusion: This study supports that TOPICS-CEP is a robust measure which can potentially be used in broad settings to identify the effect of intervention or of prevention in elderly care. [ABSTRACT FROM AUTHOR]

Background: The Older Persons and Informal Caregivers Survey—Minimum Dataset (TOPICS-MDS) collects uniform information from research projects funded under the Dutch National Care for the Elderly Programme. To compare the effectiveness of these projects a preference-weighted outcome measure that combined multidimensional TOPICS-MDS outcomes into a composite endpoint (TOPICS-CEP) was developed based on the health state preferences of older persons and informal caregivers. Objectives: To derive preference weights for TOPICS-CEP’s components based on health state preferences of healthcare professionals and to investigate whether these weights differ between disciplines and differ from those of older persons and informal caregivers. Materials and Methods: Vignette studies were conducted. Participants assessed the general wellbeing of older persons described in vignettes on a scale (0-10). Mixed linear analyses were used to obtain and compare the preference weights of the eight TOPICS-CEP components: morbidities, functional limitations, emotional wellbeing, pain experience, cognitive problems, social functioning, self-perceived health, and self-perceived quality of life (QOL). Results: Overall, 330 healthcare professionals, 124 older persons and 76 informal caregivers participated. The preference weights were not significantly different between disciplines. However, the professionals’ preference weights differed significantly from those of older persons and informal caregivers. Morbidities and functional limitations were given more weight by older persons and informal caregivers than by healthcare professionals [difference between preference weights: 0.12 and 0.07] while the opposite was true for pain experience, social functioning, and self-perceived QOL [difference between preference weights: 0.13, 0.15 and 0.26]. Conclusion: It is important to recognize the discrepancies between the health state preferences of various stakeholders to (1) correctly interpret results when studying the effectiveness of interventions in elderly care and (2) establish appropriate healthcare policies. Furthermore, we should strive to include older persons in our decision making process through a shared decision making approach. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost-effectiveness of post-diagnosis dementia treatment and coordination of care by memory clinics compared to general practitioners’ care. Methods: A multicentre randomised trial with 175 community dwelling patients newly diagnosed with mild to moderate dementia, and their informal caregivers, with twelve months’ follow-up. Cost-effectiveness was evaluated from a societal point of view and presented as incremental cost per quality adjusted life year. To establish cost-effectiveness, a cost-utility analysis was conducted using utilities based on the EQ-5D. Uncertainty surrounding the incremental cost-effectiveness ratio (difference in costs divided by difference in effects) was calculated by bootstrapping from the original data. Results: Compared to general practitioners’ care, treatment by the memory clinics was on average €1024 (95% CI: −€7723 to €5674) cheaper, and showed a non-significant decrease of 0.025 (95% CI: −0.114 to 0.064) quality adjusted life years. The incremental cost-effectiveness point estimate from the bootstrap simulation was € 41 442 per QALY lost if one would use memory clinic care instead of general practitioner care. Conclusion: No evidence was found that memory clinics were more cost-effective compared to general practitioners with regard to post-diagnosis treatment and coordination of care of patients with dementia in the first year after diagnosis. Trial Registration: ClinicalTrials.gov NCT00554047 [ABSTRACT FROM AUTHOR]

Introduction:In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons’ health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu). Materials and Methods:A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden). Results:Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. Discussion:TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations), standardised dataset pooled from various study protocols with different sampling frameworks. This unique implementation strategy improves efficiency and facilitates individual-level data meta-analysis. [ABSTRACT FROM AUTHOR]

Carotid sinus hypersensitivity has a high prevalence in the elderly and is a possible cause of falls. In carotid sinus hypersensitivity, external triggers cause sudden reductions in blood pressure, leading to dizziness or syncope, resulting in falls. Turning of the head is considered an important example of such an external trigger in everyday life, wherein rotation of the neck is thought to manipulate the hypersensitive carotid sinus. However, direct evidence for this is lacking. The aim of this study was to investigate the effects of head turning in elderly with carotid sinus hypersensitivity. We performed a prospective, observational study in 105 elderly patients who visited a geriatric falls clinic in a university teaching hospital and in 25 community dwelling healthy elderly subjects. Continuous measurements of blood pressure and heart rate (Finapres) were performed before, during, and after head turning. Head turning-induced hypotension was defined as a drop in systolic blood pressure of at least 20 mmHg during head turning. Carotid sinus hypersensitivity was examined with carotid sinus massage. We also tested for two other common geriatric hypotensive syndromes, orthostatic hypotension and post prandial hypotension, using active standing and a meal test. All three hypotensive syndromes were defined using consensus definitions. Head turning resulted in hypotension in 39% of patients (mean systolic blood pressure drop 36 mm Hg) and in 44% of the healthy elderly, irrespective of the direction of the head movement. Carotid sinus hypersensitivity was associated with head-turning induced hypotension (OR= 3.5, 95% CI= 1.48 to 8.35). We conclude that head turning is indeed an important cause of sudden drops in blood pressure in elderly with carotid sinus hypersensitivity. [ABSTRACT FROM AUTHOR]

Working memory is sensitive to aging-related decline. Evidence exists that aging is accompanied by a reorganization of the working-memory circuitry, but the underlying neurocognitive mechanisms are unclear. In this study, we examined aging-related changes in prefrontal activation during working-memory performance using functional Near-Infrared Spectroscopy (fNIRS), a noninvasive neuroimaging technique. Seventeen healthy young (21-32 years) and 17 healthy older adults (64-81 years) performed a verbal working-memory task (n-back). Oxygenated and deoxygenated hemoglobin concentration changes were registered by two fNIRS channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition in older adults, but not in young participants. In both young and older adults, prefrontal activation increased with rising working-memory load. Young adults showed slight right-hemispheric dominance at low levels of working-memory load, while no hemispheric differences were apparent in older adults. Analysis of the time-activation curve during the high working-memory load condition revealed a continuous increase of the hemodynamic response in the young. In contrast to that, a quadratic pattern of activation was found in the older participants. Based on these results it could be hypothesized that young adults were better able to keep the prefrontal cortex recruited over a prolonged period of time. To conclude, already at low levels of working-memory load do older adults recruit both hemispheres, possibly in an attempt to compensate for the observed aging-related decline in performance. Also, our study shows that aging effects on the time course of the hemodynamic response must be taken into account in the interpretation of the results of neuroimaging studies that rely on blood oxygen levels, such as fMRI.