Preparing for future pandemics: frailty associates with mortality in hospitalised older people during the entire COVID-19 pandemic, a Dutch multicentre cohort study.

PURPOSE: Viral mutations and improved prevention or treatment options may have changed the association of frailty with mortality throughout the COVID-19 pandemic. We investigated how associations of frailty with in-hospital mortality changed throughout the pandemic in older people hospitalised for COVID-19. METHODS: The COVID-OLD study included COVID-19 patients aged ≥ 70 years hospitalised during the first (early 2020), second (late 2020), third (late 2021) or fourth wave (early 2022). Based on the clinical frailty scale, patients were categorised as fit (1-3), pre-frail (4-5) or frail (6-9). Associations of frailty with in-hospital mortality were assessed with pairwise comparisons with fit as reference category and modelled using binary logistic regression adjusted for age and sex. RESULTS: This study included 2362 patients (mean age 79.7 years, 60% men). In the first wave, in-hospital mortality was 46% in patients with frailty and 27% in fit patients. In-hospital mortality decreased in each subsequent wave to 25% in patients with frailty and 11% in fit patients in the fourth wave. After adjustments, an overall higher risk of in-hospital mortality was found in frail (OR 2.26, 95% CI: 1.66-3.07) and pre-frail (OR 1.73, 95% CI: 1.27-2.35) patients compared to fit patients, which did not change over time (p for interaction = 0.74). CONCLUSIONS: Frailty remained associated with a higher risk of in-hospital mortality throughout the entire COVID-19 pandemic, although overall in-hospital mortality rates decreased. Frailty therefore remains a relevant risk factor in all stages of a pandemic and is important to consider in prevention and treatment guidelines for future pandemics.

Differences in characteristics and outcomes of older patients hospitalized for COVID-19 after introduction of vaccination.

PURPOSE: The aim of the present study was to investigate characteristics and outcomes in vaccinated and unvaccinated older patients hospitalized for COVID-19 infection. METHODS: A retrospective multicentre cohort study among patients aged ≥70 years hospitalized for COVID-19 infection. RESULTS: 263 vaccinated and 82 unvaccinated patients were included. Vaccinated patients were older (median age 79 vs. 76 years; p < 0.001), more patients were male (66.2% vs. 53.7%; p = 0.040), had more comorbidities [median Charlson Comorbidity Index (CCI) 2 vs. 1; p 0.016] and were frailer [Clinical Frailty Scale (CFS) ≥ 4 68% vs. 49%; p 0.015]. Vaccinated patients were admitted earlier after symptom onset (median 5 days vs. 7 days) but were equally ill at time of hospital admission. After correction for frailty, comorbidity and disease severity, risk of in-hospital mortality was three times lower for vaccinated patients (HR 0.30 95% CI 0.16-0.56; p < 0.001) compared to unvaccinated patients. CONCLUSION: Vaccinated patients had lower risk of in-hospital mortality than unvaccinated patients with COVID-19 infection. These findings suggest that vaccinated patients benefit from the protective effect of the vaccine against death during hospital stay, outweighing the increased mortality risk that is associated with older age, greater frailty and more numerous comorbidities. This could be an encouragement for older people to receive age-appropriate vaccines, although no definite conclusions can be drawn for this was no intervention study.

Delirium in older COVID-19 patients: Evaluating risk factors and outcomes.

OBJECTIVES: A high incidence of delirium has been reported in older patients with Coronavirus disease 2019 (COVID-19). We aimed to identify determinants of delirium, including the Clinical Frailty Scale, in hospitalized older patients with COVID-19. Furthermore, we aimed to study the association of delirium independent of frailty with in-hospital outcomes in older COVID-19 patients. METHODS: This study was performed within the framework of the multi-center COVID-OLD cohort study and included patients aged ≥60 years who were admitted to the general ward because of COVID-19 in the Netherlands between February and May 2020. Data were collected on demographics, co-morbidity, disease severity, and geriatric parameters. Prevalence of delirium during hospital admission was recorded based on delirium screening using the Delirium Observation Screening Scale (DOSS) which was scored three times daily. A DOSS score ≥3 was followed by a delirium assessment by the ward physician In-hospital outcomes included length of stay, discharge destination, and mortality. RESULTS: A total of 412 patients were included (median age 76, 58% male). Delirium was present in 82 patients. In multivariable analysis, previous episode of delirium (Odds ratio [OR] 8.9 [95% CI 2.3-33.6] p = 0.001), and pre-existent memory problems (OR 7.6 [95% CI 3.1-22.5] p < 0.001) were associated with increased delirium risk. Clinical Frailty Scale was associated with increased delirium risk (OR 1.63 [95%CI 1.40-1.90] p < 0.001) in univariable analysis, but not in multivariable analysis. Patients who developed delirium had a shorter symptom duration and lower levels of C-reactive protein upon presentation, whereas vital parameters did not differ. Patients who developed a delirium had a longer hospital stay and were more often discharged to a nursing home. Delirium was associated with mortality (OR 2.84 [95% CI1.71-4.72] p < 0.001), but not in multivariable analyses. CONCLUSIONS: A previous delirium and pre-existent memory problems were associated with delirium risk in COVID-19. Delirium was not an independent predictor of mortality after adjustment for frailty.

Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands: the COVID-OLD study.

BACKGROUND: as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. OBJECTIVE: to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. METHODS: this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. RESULTS: a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28-51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. CONCLUSIONS: compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.

Identifying relevant outcomes in the progression of Alzheimer's disease; what do patients and care partners want to know about prognosis?

BACKGROUND: Prognostic studies in the context of Alzheimer's disease (AD) mainly predicted time to dementia. However, it is questionable whether onset of dementia is the most relevant outcome along the AD disease trajectory from the perspective of patients and their care partners. Therefore, we aimed to identify the most relevant outcomes from the viewpoint of patients and care partners. METHODS: We used a two-step, mixed-methods approach. As a first step we conducted four focus groups in the Netherlands to elicit a comprehensive list of outcomes considered important by patients (n = 12) and care partners (n = 14) in the prognosis of AD. The focus groups resulted in a list of 59 items, divided into five categories. Next, in an online European survey, we asked participants (n = 232; 99 patients, 133 care partners) to rate the importance of all 59 items (5-point Likert scale). As participants were likely to rate a large number of outcomes as "important" (4) or "very important" (5), we subsequently asked them to select the three items they considered most important. RESULTS: The top-10 lists of items most frequently mentioned as "most important" by patients and care partners were merged into one core outcome list, comprising 13 items. Both patients and care partners selected outcomes from the category "cognition" most often, followed by items in the categories "functioning and dependency" and "physical health." No items from the category "behavior and neuropsychiatry" and "social environment" ended up in our core list of relevant outcomes. CONCLUSION: We identified a core list of outcomes relevant to patients and care partner, and found that prognostic information related to cognitive decline, dependency, and physical health are considered most relevant by both patients and their care partners.

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs.

BACKGROUND AND OBJECTIVE: Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the associations between cardiovascular medications and fall risk in older adults. METHODS: Design: A systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and PsycINFO. Key search concepts were "fall," "aged," "causality," and "medication." Studies that investigated cardiovascular medications as risk factors for falls in participants ≥60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately. RESULTS: In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed. CONCLUSION: Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play a role. Thus, studies addressing these issues are warranted to obtain a better understanding of drug-related falls.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others.

BACKGROUND AND OBJECTIVE: The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications. METHODS AND DESIGN: A systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately. RESULTS: In a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association). CONCLUSION: Opioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitations.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: II. Psychotropics.

BACKGROUND AND OBJECTIVE: Falls are a major public health problem in older adults. Earlier studies showed that psychotropic medication use increases the risk of falls. The aim of this study is to update the current knowledge by providing a comprehensive systematic review and meta-analysis on psychotropic medication use and falls in older adults. METHODS AND DESIGN: This study is a systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated psychotropics (antipsychotics, antidepressants, anxiolytics, sedatives, and hypnotics) as risk factors for falls in participants ≥60 years of age or participants with a mean age of ≥70 years. Meta-analyses were performed using generic inverse variance method pooling unadjusted and adjusted odds ratio (OR) estimates separately. RESULTS: In total, 248 studies met the inclusion criteria for qualitative synthesis. Meta-analyses using adjusted data showed the following pooled ORs: antipsychotics 1.54 [95% confidence interval (CI) 1.28-1.85], antidepressants 1.57 (95% Cl 1.43-1.74), tricyclic antidepressants 1.41 (95% CI 1.07-1.86), selective serotonin reuptake inhibitors 2.02 (95% CI 1.85-2.20), benzodiazepines 1.42 (95%, CI 1.22-1.65), long-acting benzodiazepines 1.81 (95%, CI 1.05-3.16), and short-acting benzodiazepines 1.27 (95%, CI 1.04-1.56) Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and healthcare setting. CONCLUSIONS: Antipsychotics, antidepressants, and benzodiazepines are consistently associated with a higher risk of falls. It is unclear whether specific subgroups such as short-acting benzodiazepines and selective serotonin reuptake inhibitors are safer in terms of fall risk. Prescription bias could not be accounted for. Future studies need to address pharmacologic subgroups as fall risk may differ depending on specific medication properties. Precise and uniform classification of target medication (Anatomical Therapeutic Chemical Classification) is essential for valid comparisons between studies.

[SDM supports better application of EBM in geriatric patients]. / Gezamenlijke besluitvorming zorgt voor een betere toepassing van evidence-based medicine in de geriatrische patiënt.

Evidence based medicine (EBM) is the integration of the best research evidence, clinical expertise and patient values in the decision making process for patient care. However, elderly people are often excluded from participating in scientific studies and they often have multiple morbidities, which complicates the application of EBM. Shared decision making (SDM), a process where clinicians and patients share the best available evidence when faced with the task of making decisions, and where patients are supported to consider options, to achieve appropriate treatment can help to shape EBM for this group of patients.In this article, we provide tools for finding relevant literature for the geriatric patient population and for shaping the SDM process to achieve personalized care.

Estimating the Time to Benefit for Preventive Drugs with the Statistical Process Control Method: An Example with Alendronate.

BACKGROUND: For physicians dealing with patients with a limited life expectancy, knowing the time to benefit (TTB) of preventive medication is essential to support treatment decisions. OBJECTIVE: The aim of this study was to investigate the usefulness of statistical process control (SPC) for determining the TTB in relation to fracture risk with alendronate versus placebo in postmenopausal women. METHODS: We performed a post hoc analysis of the Fracture Intervention Trial (FIT), a randomized, controlled trial that investigated the effect of alendronate versus placebo on fracture risk in postmenopausal women. We used SPC, a statistical method used for monitoring processes for quality control, to determine if and when the intervention group benefited significantly more than the control group. SPC discriminated between the normal variations over time in the numbers of fractures in both groups and the variations that were attributable to alendronate. The TTB was defined as the time point from which the cumulative difference in the number of clinical fractures remained greater than the upper control limit on the SPC chart. RESULTS: For the total group, the TTB was defined as 11 months. For patients aged ≥70 years, the TTB was 8 months [absolute risk reduction (ARR) = 1.4%]; for patients aged <70 years, it was 19 months (ARR = 0.7%). CONCLUSION: SPC is a clear and understandable graphical method to determine the TTB. Its main advantage is that there is no need to define a prespecified time point, as is the case in traditional survival analyses. Prescribing alendronate to patients who are aged ≥70 years is useful because the TTB shows that they will benefit after 8 months. Investigators should report the TTB to simplify clinical decision making.

Comorbidity and favorable neurologic outcome after out-of-hospital cardiac arrest in patients of 70 years and older.

INTRODUCTION: Advanced age is reported to be associated with lower survival after out-of-hospital cardiac arrest (OHCA). We aimed to establish survival rate and neurological outcome at hospital discharge after OHCA in older patients and evaluated whether pre-OHCA comorbidity was associated with favorable neurologic outcome. METHODS: From a prospective registry of all cardiopulmonary resuscitation (CPR) attempts after OHCA, we established survival in 1332 patients aged ≥ 70 years in whom resuscitation with non-traumatic etiology was attempted in 2009-2011. Pre-OHCA factors (age, gender, residing in long-term care institution, Charlson Comorbidity Index [CCI] score) and resuscitation parameters (initial rhythm, bystander witnessed, bystander CPR and time to defibrillator connection) with survival at hospital discharge with favorable neurologic outcome were regressed in the 851 patients of whom CCI was known. RESULTS: We found a 12% survival to discharge rate in patients aged ≥ 70 years (70-79 years: 16%; ≥ 80 years: 8%, p=0.001). Among surviving patients, 90% survived with favorable neurologic outcome. In a model with only pre-OHCA factors age was significantly associated with outcome (age OR 0.94, 95%CI 0.91-0.98), p = 0.003). High CCI score (≥ 4) was not statistically significant when associated with survival (7% vs. 12%, OR 0.53, 95%CI (0.25-1.13), p = 0.10). When adjusted for resuscitation parameters, OR for high CCI was 0.71 (95% CI 0.28-1.80, p = 0.47), also none of the other pre-OHCA factors remained statistically significant. CONCLUSION: In the Netherlands, the survival rate in older patients was 12%; the great majority survived with favorable neurologic outcome. Resuscitation-related factors and not comorbidity determine outcome after OHCA in older patients.

Reviews of individual patient data (IPD) are useful for geriatrics: an overview of available IPD reviews.

OBJECTIVES: To determine how many individual patient data (IPD) reviews that included older people were available in MEDLINE and whether the effectiveness of treatments differed between older and younger individuals. DESIGN: Overview of IPD reviews. SETTING: A MEDLINE search was conducted for IPD reviews of randomized controlled trials published before July 2012. PARTICIPANTS: IPD reviews that presented a regression model that included age as a factor or a subgroup analysis of individuals aged 70 and older or in which all participants were aged 70 and older. MEASUREMENTS: Whether the IPD reviews reported similar conclusions for the younger and older populations was evaluated. RESULTS: Twenty-six IPD reviews with a subgroup of older individuals and eight reviews with only older individuals were included (median N = 3,351). The most important reason for choosing an IPD review was the ability to perform a subgroup analysis in the older population. Fourteen IPD reviews suggested that older people should receive different treatments from younger people because of differences in effectiveness, six of which indicated that the investigated treatment(s) should be avoided in older adults. CONCLUSION: IPD review is a valuable approach for generating evidence in older adults. Treatment effects frequently differed between older and younger individuals. Still, IPD results should be applied to older adults cautiously, because they are often excluded from primary trials. The collaborative sharing of raw data should be promoted to improve evidence-based decisions for this group.

The chance of survival and the functional outcome after in-hospital cardiopulmonary resuscitation in older people: a systematic review.

BACKGROUND: physicians are frequently confronted with the question whether cardiopulmonary resuscitation (CPR) is a medically appropriate treatment for older people. For physicians, patients and relatives, it is important to know the chance of survival and the functional outcome after CPR in order to make an informed decision. METHODS: a systematic search was performed in MEDLINE, Embase and Cochrane up to November 2012. Studies that were included described the chance of survival, the social status and functional outcome after in-hospital CPR in older people aged 70 years and above. RESULTS: we identified 11,377 publications of which 29 were included in this review; 38.6% of the patients who were 70 years and older had a return of spontaneous circulation. More than half of the patients who initially survived resuscitation died in the hospital before hospital discharge. The pooled survival to discharge after in-hospital CPR was 18.7% for patients between 70 and 79 years old, 15.4% for patients between 80 and 89 years old and 11.6% for patients of 90 years and older. Data on social and functional outcome after surviving CPR were scarce and contradictory. CONCLUSIONS: the chance of survival to hospital discharge for in-hospital CPR in older people is low to moderate (11.6-18.7%) and decreases with age. However, evidence about functional or social outcomes after surviving CPR is scarce. Prospective studies are needed to address this issue and to identify pre-arrest factors that can predict survival in the older people in order to define subgroups that could benefit from CPR.

Underrepresentation of patients with pre-existing cognitive impairment in pharmaceutical trials on prophylactic or therapeutic treatments for delirium: a systematic review.

OBJECTIVE: Representation of hospitalized patients with pre-existing cognitive impairment in pharmaceutical delirium trials is important because these patients are at high risk for developing delirium. The aim of this systematic review is to investigate whether patients with cognitive impairment were included in studies on pharmacological prophylaxis or treatment of delirium and to explore the motivations for their exclusion (if they were excluded). STUDY DESIGN: This study was a systematic review. A MEDLINE search was performed for publications dated from 1 January 1985 to 15 November 2012. Randomized and non-randomized controlled trials that investigated medication to prevent or treat delirium were included. The number of patients with cognitive impairment was counted, and if they were excluded, motivations were noted. RESULTS: The search yielded 4293 hits, ultimately resulting in 31 studies that met the inclusion criteria. Of these, five studies explicitly mentioned the percentage of patients with cognitive impairment that were included. These patients comprised a total of 8% (n = 279 patients) of the 3476 patients included in all 31 studies. Ten studies might have included cognitively impaired patients but did not mention the exact percentage, and sixteen studies excluded all patients with cognitive impairment. The motivations for exclusion varied, but most were related to the influence of dementia on delirium. CONCLUSION: The exclusion of patients with pre-existing cognitive impairment hampers the generalizability of the results of these trials and leaves clinicians with limited evidence about the pharmacological treatment of this group of vulnerable patients who have an increased risk of side effects.

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.

Pharmacological treatment of dementia: a scoping review of systematic reviews.

BACKGROUND: Until now, multiple reviews on the pharmacological treatment of dementia have been published. METHODS: We performed a scoping review to summarize research findings and to identify gaps in the existing literature. We searched the literature and assessed the risk of bias of the included reviews. A team of clinical experts assessed the fields in which more research is necessary. Fifty-five reviews with a low risk of bias were included, most of them concerning the treatment of cognitive decline (n = 16) and behavioral symptoms (n = 10) in Alzheimer's disease (AD). For cognitive impairment, cholinesterase inhibitors (n = 13) and memantine (n = 7) were described most frequently. Little information was found about the treatment of depression in dementia. CONCLUSIONS: For many current treatments, there is sufficient evidence. New research should focus on the symptomatic treatment of the earliest and most salient complaints in AD as well as on disease-modifying interventions acting at the level of the amyloid cascade.

Pre-arrest predictors of survival after resuscitation from out-of-hospital cardiac arrest in the elderly a systematic review.

BACKGROUND: To enable older people to make decisions about the appropriateness of cardiopulmonary resuscitation (CPR), information is needed about the predictive value of pre-arrest factors such as comorbidity, functional and cognitive status on survival and quality of life of survivors. We systematically reviewed the literature to identify pre-arrest predictors for survival, quality of life and functional outcomes after out-of-hospital (OHC) CPR in the elderly. METHODS: We searched MEDLINE (through May 2011) and included studies that described adults aged 70 years and over needing CPR after OHC cardiac arrest. Prognostic factors associated with survival to discharge and quality of life of survivors were extracted. Two authors independently appraised the quality of each of the included studies. When possible a meta-analysis of odd's ratios was performed. RESULTS: Twenty-three studies were included (n = 44,582). There was substantial clinical and statistical heterogeneity and reporting was often inadequate. The pooled survival to discharge in patients >70 years was 4.1% (95% CI 3.0-5.6%). Several studies showed that increasing age was significantly associated with worse survival, but the predictive value of comorbidity was investigated in only one study. In another study, nursing home residency was independently associated with decreased chances of survival. Only a few small studies showed that age is negatively associated with a good quality of life of survivors. We were unable to perform a meta-analysis of possible predictors due to a wide variety in reporting and statistical methods. CONCLUSIONS: Although older patients have a lower chance of survival after CPR in univariate analysis (i.e. 4.1%), older age alone does not seem to be a good criterion for denying patients CPR. Evidence for the predictive value of comorbidities and for the predictive value of age on quality of life of survivors is scarce. Future studies should use uniform methods for reporting data and pre-arrest factors to increase the available evidence about pre arrest factors on the chance of survival. Furthermore, patient-specific outcomes such as quality of life and post-arrest cognitive function should be investigated too.