Does a bicycle accident as the cause of proximal femur fracture indicate that geriatric co-management is superfluous? A retrospective cohort study.

BACKGROUND: Deployment of geriatric care would be more sustainable if we could limit geriatric co-management to older hip fracture patients who benefit most from it. We assumed that riding a bicycle is a proxy of good health and hypothesized that older patients with a hip fracture due to a bicycle accident have a more favorable prognosis than patients whose hip fracture was caused by another type of accident. METHODS: Retrospective cohort study of hip fracture patients ≥ 70 years admitted to hospital. Nursing home residents were excluded. Primary outcome was length of hospital stay (LOS). Secondary outcomes were delirium, infection, blood transfusion, intensive care unit stay and death during hospitalization. The group with a bicycle accident (BA) was compared to the non-bicycle accident (NBA) group using linear and logistic regression  models, with correction for age and sex. RESULTS: Of the 875 patients included, 102 (11.7%) had a bicycle accident. BA patients were younger (79.8 versus 83.9 years, p < 0.001), less often female (54.9 versus 71.2%, p = 0.001) and lived independently more often (100 versus 85.1%, p < 0.001). Median LOS in the BA group was 0.91 times the median LOS in the NBA group (p = 0.125). For none of the secondary outcomes the odds ratio favored the BA group, except for infection during hospital stay (OR = 0.53, 95%CI 0.28-0.99; p = 0.048). CONCLUSIONS: Although older hip fracture patients who had a bicycle accident appeared more healthy than other older hip fracture patients, their clinical course was not more favorable. Based on this study, a bicycle accident is not an indicator that geriatric co-management can be omitted.

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.

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 ≥ 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 (<3 months) did not increase OH risk (RR 0.6 [95%CI 0.1-5.1]). WHAT IS NEW AND CONCLUSION: The overall prevalence of OH was low and comparable to age-matched population prevalence, suggesting that the relative contribution of alpha-blockers to OH was small. However, OH risk significantly increased in patients with multimorbidity or polypharmacy. For these patients, the benefits of starting alpha-blockers for LUTS should be weighed against the increased risk of OH.

[Sensory impairments and dementia]. / Zintuiglijke beperkingen en dementie.

In recent years, research has consistently reported an association between hearing- and vision loss and mental health outcomes. Whether treating these condition in elders improves cognition has been addressed by several studies. Observational data suggest that treatment positively impacts cognition, even though more research is needed. Nevertheless, because hearing loss is suspected to account for 9% of dementia cases, and also because these factors are one of the few potentially modifiable factors from a dementia prevention perspective, the need to stimulate research to have clearer knowledge about the benefits of treating hearing and/or vision loss on cognitive outcomes is urgent.

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.

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-hundred-thirty-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 0.2-13.7) 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.

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.

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 delirium from the 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, high-quality studies that compare different opioids are lacking. Further comparative research is needed.

Interaction between tramadol and selective serotonin reuptake inhibitors: are doctors aware of potential risks in their prescription practice?

OBJECTIVES: The combination of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) with tramadol can result in serotonin syndrome, characterised by neuromuscular and autonomic nervous system excitation and altered mental state. The incidence of serotonin syndrome with this combination of drugs is low, and the serotonin syndrome is generally mild or moderate in form, but can be life threatening and is more easily prevented than treated. We aimed to investigate whether prescribers in a general hospital were aware of this risk and if it influenced their prescriptions. METHODS: A questionnaire was sent to 194 physicians in a general teaching hospital with over 650 beds in The Netherlands. The questionnaire presented four cases, two of whom used an SSRI or SNRI among other medications, and asked the respondents to prescribe an opioid in each case. The respondents were not aware of the focus of our research. Actual prescription rates of tramadol in admitted patients who did or did not use an SSRI or SNRI were assessed using the hospital pharmacy database. RESULTS: Based on the questionnaire, respondents prescribed tramadol equally in patients with or without concomitant use of SSRIs/SNRIs. About one-third of respondents who prescribed tramadol indicated they were aware of the potential interaction with SSRIs/SNRIs. About one-fifth deliberately avoided tramadol because a potential interaction with SSRIs/SNRIs was identified. However, there was no difference in actual tramadol prescriptions, as recorded in the hospital pharmacy database: 23.8% of SSRI/SNRI users received tramadol versus 24.6% of non-SSRI/SNRI-users (calculated OR 0.96; 95% CI 0.78 to 1.17). CONCLUSIONS: In total, 20-30% of prescribers in a general hospital were aware of the potential interaction between tramadol and SSRIs or SNRIs, yet this did not translate to a difference in tramadol prescriptions between SSRI/SNRI users and non-users, as documented in the hospital pharmacy database. A physician's decision to prescribe tramadol to SSRI/SNRI users may be guided by a comprehensive individual benefit-risk assessment; expected benefits of tramadol may outweigh the small risk of serotonin syndrome. In order to increase awareness of the potential risk of a serotonin syndrome, hospital pharmacies may play an important role in signalling the potential interaction and providing information on the benefits and risks of tramadol and alternative analgesics in the presence of SSRIs or SNRIs.

Alzheimer biomarkers and clinical Alzheimer disease were not associated with increased cerebrovascular disease in a memory clinic population.

OBJECTIVE: Preclinical and post-mortem studies suggest that Alzheimer disease (AD) causes cerebrovascular dysfunction, and therefore may enhance susceptibility to cerebrovascular disease (CVD). The objective of this study was to investigate this association in a memory clinic population. METHODS: The AD biomarkers CSF amyloid ß42, amyloid ß40 and APOE-ε4 status have all been linked to increased CVD risk in AD, and therefore the first aim of this study was to analyze the association between these biomarkers and CVD. In 92 memory clinic patients the cross-sectional association between AD biomarkersand the severity of CVD was investigated with linear regression analysis. Additionally, we studied whether AD biomarkers modified the relation between vascular risk factors and CVD. CVD was assessed on MRI through a visual rating scale.Analyses were adjusted for age. The second aim of this study was to investigate the association between clinical AD and CVD, where 'clinical AD' was defined as follows: impairment in episodic memory, hippocampal atrophy and an aberrant concentration of cerebrospinal fluid (CSF) biomarkers. 47 of the 92 patients had AD. RESULTS: No association between CSF amyloid ß42, amyloid ß40 or APOE-ε4 status and CVD severity was found, nor did these AD biomarkers modify the relation between vascular risk factors and CVD. Clinical AD was not associated with CVD severity (p=0.83). Patients with more vascular risk factors had more CVD, but this relationship was not convincingly modified by AD (p=0.06). CONCLUSIONS: In this memory clinic population, CVD in patients with AD was related to vascular risk factors and age, comparable to patients without AD. Therefore, in our study, the preclinical and post-mortem evidence that AD would predispose to CVD could not be translated clinically. Further work, including replication of this work in a different and larger sample, is warranted.

Addition of MHPG to Alzheimer's disease biomarkers improves differentiation of dementia with Lewy bodies from Alzheimer's disease but not other dementias.

BACKGROUND: Overlapping clinical features make it difficult to distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and other dementia types. In this study we aimed to determine whether the combination of cerebrospinal fluid (CSF) biomarkers, amyloid-ß42 (Aß42), total tau protein (t-tau), and phosphorylated tau protein (p-tau), in combination with 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), could be useful in discriminating DLB from vascular dementia (VaD) and frontotemporal dementia (FTD), as we previously demonstrated for differentiation of DLB from AD. METHODS: We retrospectively analyzed concentrations of MHPG, Aß42, t-tau, and p-tau in CSF in patients with DLB, AD, VaD, and FTD. Using previously developed multivariate logistic regression models we assessed the diagnostic value of these CSF parameters. RESULTS: The currently used combination of Aß42, t-tau, and p-tau yielded a sensitivity of 61.9% and a specificity of 91.7% for the discrimination between DLB and AD, but could not discriminate between DLB and VaD or FTD. The addition of MHPG to Aß42, t-tau, and p-tau improves the discrimination of DLB from AD, yielding a sensitivity of 65.1% and specificity of 100%, but could not distinguish DLB from other forms of dementia. CONCLUSIONS: Our results confirm in a separate patient cohort that addition of MHPG to Aß42, t-tau, and p-tau improves the discrimination of DLB from AD but not the differentiation of DLB from VaD or FTD.

A prediction model to calculate probability of Alzheimer's disease using cerebrospinal fluid biomarkers.

BACKGROUND: We aimed to develop a prediction model based on cerebrospinal fluid (CSF) biomarkers, that would yield a single estimate representing the probability that dementia in a memory clinic patient is due to Alzheimer's disease (AD). METHODS: All patients suspected of dementia in whom the CSF biomarkers had been analyzed were selected from a memory clinic database. Clinical diagnosis was AD (n = 272) or non-AD (n = 289). The prediction model was developed with logistic regression analysis and included CSF amyloid ß42, CSF phosphorylated tau181, and sex. Validation was performed on an independent data set from another memory clinic, containing 334 AD and 157 non-AD patients. RESULTS: The prediction model estimated the probability that AD is present as follows: p(AD) = 1/(1 + e (- [-0.3315 + score])), where score is calculated from -1.9486 × ln(amyloid ß42) + 2.7915 × ln(phosphorylated tau181) + 0.9178 × sex (male = 0, female = 1). When applied to the validation data set, the discriminative ability of the model was very good (area under the receiver operating characteristic curve: 0.85). The agreement between the probability of AD predicted by the model and the observed frequency of AD diagnoses was very good after taking into account the difference in AD prevalence between the two memory clinics. CONCLUSIONS: We developed a prediction model that can accurately predict the probability of AD in a memory clinic population suspected of dementia based on CSF amyloid ß42, CSF phosphorylated tau181, and sex.

Reviewing reasons for the decreased CSF Abeta42 concentration in Alzheimer disease.

Cerebrospinal fluid (CSF) amyloid beta42 (Abeta42) concentrations are decreased in patients with Alzheimer disease (AD). Consequently, low Abeta42 is considered a positive biomarker for AD. Surprisingly, the mechanisms that underlie the decrease in CSF Abeta42 remain speculative. Better understanding of this biomarker is an essential step to unravel AD pathophysiology and to develop and evaluate treatment. Therefore, we systematically examined the possible reasons for the decreased CSF Abeta42 concentration in AD. Under normal conditions, Abeta42 can be degraded by proteases, taken up by microglia, or cleared from the brain interstitial fluid across the blood brain barrier. Alternatively, it can be transported to the CSF and be cleared from there. Aggregation of Abeta42 appears the most likely cause for the decreased CSF Abeta42 concentration in AD: the aggregated state inhibits Abeta42 from being transported from the ISF to the CSF. Evidence for other possibilities such as a decreased production of Abeta42, an increased proteolytic breakdown or microglial uptake of Abeta42, or an increased clearance of Abeta42 to the blood, is - at best - scarce or even absent.

Hourly variability of cerebrospinal fluid biomarkers in Alzheimer's disease subjects and healthy older volunteers.

Large hour-to-hour variability has previously been demonstrated in the cerebrospinal fluid (CSF) concentrations of Alzheimer's disease (AD) biomarkers amyloid ß(42) (Aß(42)) and Aß(40) in healthy younger subjects. We investigated the within-subject variability over 36 hours in CSF Aß and tau proteins, in older subjects and AD patients. Six patients with mild stage AD (59-85 years, Mini Mental State Examination (MMSE) 16-26) and 6 healthy older volunteers (64-77 years) received an intrathecal catheter from which, during 36 hours, each hour 6 mL of CSF was drawn. Concentrations of Aß(42), Aß(40), total tau, and phosphorylated tau were determined and the variability was analyzed. Within-subject variability within 3-hour periods was assessed as the coefficient of variation, which was comparable for these 4 biomarkers in controls (4.2%-4.6%) and AD (3.1%-5.8%). Variability over 12 hour periods was 5.3% to 9.5%. These findings suggest that CSF biomarker variability is relatively low in healthy older controls and AD patients. Furthermore, continuous sampling of CSF proved to be a useful and robust method, which may also be used to investigate AD pathogenesis and to evaluate pharmacotherapeutic interventions.

CSF α-synuclein concentrations do not fluctuate over hours and are not correlated to amyloid ß in humans.

Reports on the value of cerebrospinal fluid (CSF) α-synuclein as a biomarker for dementia with Lewy bodies and Parkinson disease are contradicting. This may be explained by fluctuating CSF α-synuclein concentrations over time. Such fluctuations have been suggested for CSF amyloid ß concentrations. Furthermore, a physiological relationship between α-synuclein and amyloid ß has been suggested based on in vitro research. We performed repeated CSF sampling in healthy elderly and AD patients and showed that sinusoidal fluctuations in CSF α-synuclein concentrations were not present. Furthermore, we did not find evidence for an interaction between amyloid ß and α-synuclein concentrations in CSF.

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

Analysis of the brain specific biomarkers amyloid beta(42) (Abeta(42)) 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.

Cerebrospinal fluid alpha-synuclein does not discriminate between dementia disorders.

Alpha-synuclein is the major constituent of Lewy bodies found in neurons in dementia with Lewy bodies (DLB) and might be of diagnostic value as a biomarker for DLB. We hypothesized that, as a consequence of increased accumulation of alpha-synuclein intraneuronally in DLB, the levels of alpha-synuclein in cerebrospinal fluid (CSF) of DLB patients would be lower than in other dementias. Our objective was to investigate the CSF levels of alpha-synuclein in several dementia disorders compared to control levels and to investigate the diagnostic value of CSF alpha-synuclein as a marker to discriminate between DLB and other types of dementia. We analyzed the levels of alpha-synuclein in CSF of 40 DLB patients, 131 patients with Alzheimer's disease, 28 patients with vascular dementia, and 39 patients with frontotemporal dementia. We did not find any significant differences in CSF alpha-synuclein levels between DLB patients and patients with Alzheimer's disease, vascular dementia or frontotemporal dementia. We conclude that in clinically diagnosed patients, alpha-synuclein does not appear to be a useful biomarker for the differentiation between DLB and other types of dementia.