Acetaminophen for self-reported sleep problems in an elderly population (ASLEEP): Study protocol of a randomized placebo-controlled double-blind trial

Background: The prevalence of sleep disorders increases with age. Sleep disorders may have serious health implications and may be related to serious underlying diseases. Many older people use hypnotics, like benzodiazepines, although these medications have serious side effects and often lead to habituation. Acetaminophen is one of the most frequently used off-label drugs for sleep disorders, although little is known about its effects. Our objective is to investigate whether acetaminophen is effective in treating self-reported sleep disorders in older people. Methods/Design: Participants, aged 65 years or older (n = 150), who have sleep disorders will be randomized for treatment with either acetaminophen 1000 mg or placebo, once daily at bedtime in a double-blind design. Eligible patients should be able to give informed consent, should not be cognitively impaired (Minimal Mental State Examination (MMSE) score ≥ 20), should not have pain, and should not use acetaminophen on a regular basis because of pain complaints. The study will take three weeks to complete. During these three weeks, the participants register their sleep behavior in a sleep diary. The participants will use the study medication during the second and third week. The primary endpoint will be the self-reported sleep disorders at the end of week three, as measured by means of the Insomnia Severity Index (ISI). To validate these subjective sleep parameters against objectively measured indices of the sleep-wake pattern, we will measure the periods of wakefulness and sleep in a subgroup of participants, using an actigraph worn on the wrist during the entire study period. Discussion: The proposed study will contribute to our knowledge about the treatment of sleep disorders in an older population. There is a need for treatments for sleep disorders without serious adverse effects. Acetaminophen might be a simple and inexpensive alternative for the regimes that are currently used with older people. Trial registration: The Netherlands National Trial Register NTR2747

Examining the construct and known-group validity of a composite endpoint for the Older Persons and Informal Caregivers Survey Minimum Data Set (TOPICS-MDS); A largescale data sharing initiative

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

Measurement properties of the EQ-5D across four major geriatric conditions: Findings from TOPICS-MDS

Background: As populations age, chronic geriatric conditions linked to progressive organ failure jeopardize health-related quality of life (HRQoL). Thus, this research assessed the validity and applicability of the EQ-5D (a common HRQoL instrument) across four major chronic geriatric conditions: hearing issues, joint damage, urinary incontinence, or dizziness with falls. Methods: The study sample comprised 25,637 community-dwelling persons aged 65 years and older residing in the Netherlands (Data source: TOPICS-MDS, www.topics-mds.eu ). Floor and ceiling effects were examined. To assess convergent validity, random effects meta-correlations (Spearman's rho) were derived between individual EQ-5D domains and related survey items. To further examine construct validity, the association between sociodemographic characteristics and EQ-5D summary scores were assessed using linear mixed models. Outcomes were compared to the overall study population as well as a 'healthy' subgroup reporting no major chronic conditions. Results: Whereas ceiling effects were observed in the overall study population and the 'healthy' subgroup, such was not the case in the geriatric condition subgroups. The majority of hypotheses regarding correlations between survey items and sociodemographic associations were supported. EQ-5D summary scores were lower in respondents who were older, female, widowed/single, lower educated, and living alone. Increasing co-morbidity had a clear negative effect on EQ-5D scores. Conclusion: This study supported the construct validity of the EQ-5D across four major geriatric conditions. For older persons who are generally healthy, i.e. reporting few to no chronic conditions, the EQ-5D confers poor discriminative ability due to ceiling effects. Although the overall dataset initially suggested poor discriminative ability for the EQ-5D, such was not the case within subgroups presenting with major geriatric conditions

Fear of falling: measurement strategy, prevalence, risk factors and consequences among older persons: a systematic review.

BACKGROUND: fear of falling (FOF) is a major health problem among the elderly living in communities, present in older people who have fallen but also in older people who have never experienced a fall. The aims of this study were 4-fold: first, to study methods to measure FOF; second, to study the prevalence of FOF among fallers and non-fallers; third, to identify factors related to FOF; and last, to investigate the relationship between FOF and possible consequences among community-dwelling older persons. METHODS: several databases were systematically searched, and selected articles were cross-checked for other relevant publications. RESULTS: a systematic review identified 28 relevant studies among the community-dwelling elderly. Due to the many different kinds of measurements used, the reported prevalence of FOF varied between 3 and 85%. The main risk factors for developing FOF are at least one fall, being female and being older. The main consequences were identified as a decline in physical and mental performance, an increased risk of falling and progressive loss of health-related quality of life. CONCLUSION: this review shows that there is great variation in the reported prevalence of FOF in older people and that there are multiple associated factors. Knowledge of risk factors of FOF may be useful in developing multidimensional strategies to decrease FOF and improve quality of life. However, the only identified modifiable risk factor of FOF is a previous fall. In order to measure the impact of interventions, a uniform measurement strategy for FOF should be adopted, and follow-up studies should be conducted

Neuroinflammation in delirium: a postmortem case-control study

Delirium can be hypothesized to be an extreme manifestation of sickness behavior in elderly persons with neurodegenerative disease. The purpose of this study was to investigate whether increased cerebral inflammation with microglial, astrocyte, and cytokine activation exists in patients with delirium compared to nondelirious patients. Postmortem brain tissue from 9 cases with delirium was compared to 6 age-matched controls without delirium. Human leukocyte antigen-DR (HLA-DR) and CD68 cell count and glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), IL-6,β-amyloid, and tau protein immunoreactivity were determined in hippocampus, frontal cortex, and white matter. There were no significant differences in the patients with delirium compared to the controls with respect to age 73 versus 70.5 years (p=0.72) or dementia (22% versus 0%, p=0.22). Both markers for microglial activity showed significantly higher scores in delirium brain specimens than controls in the total brain score (HLA-DR 129 vs. 20 and CD68 30 vs. 8.5) as well as in the various brain areas separately. The immunoreactivity of astrocyte activity (GFAP) was higher in the total brain score in patients with delirium (5.2 vs. 4.0, p=0.05), but in the various brain areas this was only significant in the dentate gyrus. IL-6 immunoreactivity was higher in patients with delirium in all brain areas and IL-1β was not detectable. Coexisting infectious disease or dementia did not influence the overall results. These preliminary study results show an association between human brain activity of microglia, astrocytes, and IL-6 and delirium in elderly patients and add to the accumulating evidence that inflammatory mechanisms are involved in deliriu