Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer's Disease in Clinical Practice: An Illustration with 3 Case Reports

Analysis of the brain specific biomarkers amyloid β42 (Aβ42) and total tau (t-tau) protein in cerebrospinal fluid (CSF) has a sensitivity and specificity of more than 85% for differentiating Alzheimer's Disease (AD) from non-demented controls. International guidelines are contradictory in their advice on the use of CSF biomarkers in AD diagnostics, resulting in a lack of consistency in clinical practice. We present three case reports that illustrate clinical practice according to the Dutch and European guidelines and portray the value of CSF biomarker analysis as an add-on diagnostic to the standard diagnostic workup for AD

The predictive value of the 'VMS frail older patients' for adverse outcomes in geriatric inpatients

Background/Objective: The Dutch Safety Management system (VMS) screening for frail older patients is used as a predictor for adverse outcomes. We aimed to determine the predictive value of the VMS for adverse outcomes in geriatric inpatients. Design: Retrospective cohort study in geriatric inpatients. Outcomes were institutionalization, readmission and mortality (3- and 12-months). Logistic regression analysis was performed to assess the predictive value of the number of positive VMS domains, a VMS score >= 1, and individual domains for adverse outcomes. Results: We included 477 patients. Median age was 85 years (54-99) and 37% were male. Eighty-seven % scored positive on delirium risk, 57% on fall risk, 39% on malnutrition and 64% on physical impairment. One-hundredthirty-five patients (28%) were institutionalized, 78 patients (16%) were readmitted and mortality rate was 127 (27%) at 3 months and 184 (39%) at one year. The VMS was not predictive for readmission (OR 1.6; 95%-CI 0.213.7) and mortality, (OR 0.6 95%-CI 0.2-2.0 and OR 1.1; 95%-CI 0.3-3.7). For institutionalization, delirium risk (OR 2.2; 95%-CI 1.1-4.4), physical impairment (OR 1.8; 95%-CI 1.1-2.9) and a positive score on all four domains were predictive (OR 12.1 95%-CI-1.4-101.7). Malnutrition was predictive for readmission (OR 1.74; 95%-CI 1.05-2.91) and three-month mortality (OR 1.69; 95%-CI 1.11-2.57), delirium risk for one -year mortality (OR 2.0; 95%-CI 1.0-4.0) . Conclusions: Almost all geriatric inpatients scored positive on at least one domain of the VMS. The number of positive VMS domains had some predictive value for institutionalization. Individual domains were able to predict adverse outcomes

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

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

The Comparative Risk of Delirium with Different Opioids:A Systematic Review

There is substantial evidence that the use of opioids increases the risk of adverse outcomes such as delirium, but whether this risk differs between the various opioids remains controversial. In this systematic review, we evaluate and discuss possible differences in the risk of delirium from the use of various types of opioids in older patients. We performed a search in MEDLINE by combining search terms on delirium and opioids. A specific search filter for use in geriatric medicine was used. Quality was scored according to the quality assessment for cohort studies of the Dutch Cochrane Institute. Six studies were included, all performed in surgical departments and all observational. No study was rated high quality, one was rated moderate quality, and five were rated low quality. Information about dose, route, and timing of administration of the opioid was frequently missing. Pain and other important risk factors of delirium were often not taken into account. Use of tramadol or meperidine was associated with an increased risk of delirium, whereas the use of morphine, fentanyl, oxycodone, and codeine were not, when compared with no opioid. Meperidine was also associated with an increased risk of delirium compared with other opioids, whereas tramadol was not. The risk of delirium appeared to be lower with hydromorphone or fentanyl, compared with other opioids. Numbers used for comparisons were small. Some data suggest that meperidine may lead to a higher perioperative risk for delirium; however, high-quality studies that compare different opioids are lacking. Further comparative research is neede

Geriatric rehabilitation of patients selected at the emergency department:Patient factors related to rehabilitation outcome

In the Netherlands geriatric rehabilitation is possible (among others) for patients who are selected by a geriatrician at the emergency department of a hospital. The aim of this study was to investigate the rehabilitation trajectory of patients who were selected for geriatric rehabilitation at the emergency department after a single contact with the geriatrician and to identify patient factors related to rehabilitation outcome. Successful rehabilitation was defined as discharge to home or a residential care facility after a maximum of 6 months. All patients who in 2016 were selected for geriatric rehabilitation were included. Data were collected retrospectively from electronic patient files. 74 patients were included (mean age 84.7 years). 84% were successfully discharged home or to a residential care facility within six months. The presentation with a fall and the absence of a partner at home was higher in the unsuccessful group. In the successful group more patients lived independent and without professional help prior to rehabilitation. Noteworthy is that the analysed patient group is a frail group, considering the high one-year mortality (21,6%) and overall functional decline despite geriatric rehabilitation

The Comparative Risk of Delirium with Different Opioids: A Systematic Review

Objective There is substantial evidence that the use of opioids increases the risk of adverse outcomes such as delirium, but whether this risk differs between the various opioids remains controversial. In this systematic review, we evaluate and discuss possible differences in the risk of deliriumfromthe use of various types of opioids in older patients. Methods We performed a search in MEDLINE by combining search terms on delirium and opioids. A specific search filter for use in geriatric medicine was used. Quality was scored according to the quality assessment for cohort studies of the Dutch Cochrane Institute. Results Six studies were included, all performed in surgical departments and all observational. No study was rated high quality, one was rated moderate quality, and five were rated low quality. Information about dose, route, and timing of administration of the opioid was frequently missing. Pain and other important risk factors of delirium were often not taken into account. Use of tramadol or meperidine was associated with an increased risk of delirium, whereas the use of morphine, fentanyl, oxycodone, and codeine were not, when compared with no opioid. Meperidine was also associated with an increased risk of delirium compared with other opioids, whereas tramadol was not. The risk of delirium appeared to be lower with hydromorphone or fentanyl, compared with other opioids. Numbers used for comparisons were small. Conclusion Some data suggest that meperidine may lead to a higher perioperative risk for delirium; however, highquality studies that compare different opioids are lacking. Further comparative research is needed

Orthostatic blood pressure recovery in older males using alpha-blockers for lower urinary tract symptoms, an explorative study in a urology outpatient clinic

What is known and objective Alpha-blockers have been associated with orthostatic hypotension (OH). We aimed to assess the prevalence of OH measured with beat-to-beat blood pressure monitoring in older male outpatients who used alpha-blockers for lower urinary tract symptoms (LUTS). In addition, we investigated associations of OH with duration of alpha-blocker use, concomitant medication use and comorbidity. Methods Cross-sectional explorative study in a urology outpatient clinic. Older white males >= 65 years using alpha-blockers for LUTS were included. Blood pressure responses to standing up from supine were recorded using a validated beat-to-beat blood pressure device (Finapres). Prevalence rates were derived from the beat-to-beat data to include OH measured between 60-110 s (OH), impaired recovery OH at 40 s (OH[40]), initial OH (IOH) and normal orthostatic response. Subgroups were defined based on duration of alpha-blocker use, polypharmacy, and Charlson comorbidity index (CCI), to obtain relative risks. Results and discussion Sixty-five patients were included. Median age was 75 years (range 65-92). The prevalence of OH was 7.7% (n = 5). The prevalence of OH(40) was 16.9% (n = 11) and of IOH 38.5% (n = 25). Thirty-six patients (55.4%) had a normal orthostatic response. The relative risk of OH for the subgroup using >=$$\ge$$ 10 medications (n = 13) was 6.0 (95%CI 1.1-32.3). For the subgroup with multimorbidity (CCI >= 3, n = 11) this was 7.4 (95%CI 1.4-39.0). Recent initiation of alpha-blocker use

Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes

Purpose: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. Methods: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. Results: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76–86 years; versus 79 years, IQR 74–84, p = 0.044) and were more often classified as severely frail (CFS 6–9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34–1.0); p = 0.058]. Conclusions: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes