Cardiovascular Risk Management for All Older Patients?

Current guidelines on cardiovascular risk management are extrapolated to all older adults. It is, however, highly debatable whether recommendations also apply for patients with dementia since previous studies have not included this specific population. Time to benefit as well as higher risk of adverse events play a crucial role in the decision process of prescribing or deprescribing. Regular monitoring is needed in older patients with dementia, in order to make individual-based treatment strategies. Cardiovascular risk management in older patients with dementia should focus on quality of life, preventing cognitive and functional deterioration, and maintaining independence.

The reporting of neuropsychiatric symptoms in electronic health records of individuals with Alzheimer's disease: a natural language processing study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer's disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). METHODS: Two academic memory clinic cohorts were used: the Amsterdam UMC (n = 3001) and the Erasmus MC (n = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n = 500 EHRs from the Amsterdam UMC cohort and in a test set of n = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). RESULTS: Internal validation performance of the classifiers was excellent (AUC range: 0.81-0.91), but external validation performance decreased (AUC range: 0.51-0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients < 0.28), with substantially more reports of NPS in EHRs than on NPI assessments. CONCLUSIONS: NLP classifiers performed well in detecting a wide range of NPS in EHRs of patients with symptomatic AD visiting the memory clinic and showed that clinicians frequently reported NPS in these EHRs. Clinicians generally reported more NPS in EHRs than caregivers reported on the NPI.

Effects of the DICE Method to Improve Timely Recognition and Treatment of Neuropsychiatric Symptoms in Early Alzheimer's Disease at the Memory Clinic: The BEAT-IT Study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented. OBJECTIVE: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic. METHODS: We enrolled sixty community-dwelling people with mild cognitive impairment or AD dementia and NPS across six Dutch memory clinics with their caregivers. The first wave underwent care as usual (n = 36) and the second wave underwent the DICE method (n = 24). Outcomes were quality of life (QoL), caregiver burden, NPS severity, NPS-related distress, competence managing NPS, and psychotropic drug use. Reliable change index was calculated to identify responders to the intervention. A cost-effectiveness analysis was performed and semi-structured interviews with a subsample of the intervention group (n = 12). RESULTS: The DICE method did not improve any outcomes over time compared to care as usual. Half of the participants of the intervention group (52%) were identified as responders and showed more NPS and NPS-related distress at baseline compared to non-responders. Interviews revealed substantial heterogeneity among participants regarding NPS-related distress, caregiver burden, and availability of social support. The intervention did not lead to significant gains in quality-adjusted life years and well-being years nor clear savings in health care and societal costs. CONCLUSION: The DICE method showed no benefits at group-level, but individuals with high levels of NPS and NPS-related distress may benefit from this intervention.

The Multidimensional Prognostic Index Predicts Mortality in Older Outpatients with Cognitive Decline.

Since the heterogeneity of the growing group of older outpatients with cognitive decline, it is challenging to evaluate survival rates in clinical shared decision making. The primary outcome was to determine whether the Multidimensional Prognostic Index (MPI) predicts mortality, whilst assessing the MPI distribution was considered secondary. This retrospective chart review included 311 outpatients aged ≥65 years and diagnosed with dementia or mild cognitive impairment (MCI). The MPI includes several domains of the comprehensive geriatric assessment (CGA). All characteristics and data to calculate the risk score and mortality data were extracted from administrative information in the database of the Alzheimer's Center and medical records. The study population (mean age 76.8 years, men = 51.4%) was divided as follows: 34.1% belonged to MPI category 1, 52.1% to MPI category 2 and 13.8% to MPI category 3. Patients with dementia have a higher mean MPI risk score than patients with MCI (0.47 vs. 0.32; p < 0.001). The HRs and corresponding 95% CIs for mortality in patients in MPI categories 2 and 3 were 1.67 (0.81−3.45) and 3.80 (1.56−9.24) compared with MPI category 1, respectively. This study shows that the MPI predicts mortality in outpatients with cognitive decline.

Multidimensional Prognostic Index and Outcomes in Older Patients Undergoing Transcatheter Aortic Valve Implantation: Survival of the Fittest.

Selecting patients with a high chance of endured benefit from transcatheter aortic valve implantation (TAVI) is becoming relevant with changing indications and increasing number of TAVI being performed. The aim of our study was to investigate the association of the multidimensional prognostic index (MPI) based on a comprehensive geriatric assessment (CGA) on survival. The TAVI Care & Cure program is a prospective, observational registry of patients referred for TAVI at the Erasmus MC University Medical Center. Consecutive patients who underwent a complete CGA and TAVI were included. CGA components were used to calculate the MPI score. The impact of the MPI score on survival was evaluated using Cox regression. Furthermore, 376 patients were included, 143 (38.0%) patients belonged to the MPI-1 group and 233 (61.9%) patients to the MPI-2-3 group. After 3 years, 14.9% of the patients in the MPI-1 group and 30.5% of the patients in the MPI-2-3 group died (p = 0.001). Patients in MPI-1 had increased chances of overall survival in comparison with patients in MPI group 2-3 Hazard Ratio (HR) 0.57, (95% Confidence Interval (CI) 0.33-0.98)). In this study we found that the MPI tool could be useful to assess frailty and to predict which patient will have a higher chance of enduring benefit from a TAVI procedure.

Impact of frailty on health-related quality of life 1 year after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) brings symptom relief and improvement in health-related quality of life (HRQoL) in the majority of patients treated for symptomatic, severe aortic stenosis. However, there is a substantial group of patients that do not benefit from TAVI. The aim of this study is to investigate the impact of frailty on HRQoL 1 year after TAVI. METHODS: The TAVI Care & Cure Program is an ongoing, prospective, observational study including patients referred for TAVI to our institution. A comprehensive geriatric assessment was performed to evaluate existence of frailty using the Erasmus Frailty Score (EFS). HRQoL was assessed using the EQ-5D-5 L at baseline and 1 year after TAVI. RESULTS: 239 patients underwent TAVI and completed HRQoL assessment 1 year after TAVI. Seventy (29.3%) patients were classified as frail (EFS ≥ 3). In non-frail patients, the EQ-5D-5 L index did not change (0.71(± 0.22) to 0.68(± 0.33) points, P = 0.22); in frail patients, the EQ-5D-5 L index decreased from 0.55(±0.26) to 0.44 points (±0.33) (P = 0.022). Frailty was an independent predictor of deteriorated HRQoL 1 year after TAVI (OR 2.24, 95% CI 1.07-4.70, P = 0.003). In frail patients, the absence of peripheral artery disease (OR 0.17, 95% 0.05-0.50, P = 0.001) and renal dysfunction (OR 0.13, 95% CI 0.04-0.41, P = <0.001) at baseline was associated with improved HRQoL 1 year after TAVI. CONCLUSION: Frailty is associated with deterioration of HRQoL 1 year after TAVI. Notably, HRQoL did improve in frail patients with no peripheral arterial disease or renal impairment at baseline.

Incidence, determinants and consequences of delirium in older patients after transcatheter aortic valve implantation.

BACKGROUND: delirium is an event leading to negative health outcomes and increased mortality in patients. The aim of this study is to investigate the incidence, determinants and consequences of post-operative delirium (POD) in older patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: The TAVI Care and Cure program is a prospective, observational registry in patients referred for TAVI at Erasmus University Medical Centre. The presence of delirium was evaluated by daily clinical assessment by a geriatrician pre- and up to 3 days post-TAVI. Mortality data were obtained from the Dutch Civil Registry. RESULTS: A total of 543 patients underwent TAVI between January 2014 and December 2017. Overall, the incidence of POD was 14% (75/543 patients) but declined from 18% in 2014 to 7% in 2017 (P = 0.009). Patients who developed POD were older (81.9 ± 5.8 versus 78.6 ± 8.3 years, P < 0.001), had higher prevalence of renal dysfunction and prior stroke (54% versus 40%, P = 0.02; 31% versus 18%, P = 0.01) and were more often frail (32% versus 25%, P = 0.02). From a procedural perspective, general anesthesia (odds ratios (OR), 2.31; 95% CI, 1.40-3.83; P = 0.001), non-transfemoral access (OR, 2.37; 95% CI, 1.20-4.70; P = 0.01) and longer procedural time (OR, 1.01; 95% CI, 1.01-1.02; P < 0.001) were significantly associated with POD. One-year survival rate was 68% among patients who had suffered a POD and was 85% in patients without a POD (hazard ratio's 1.8 (95% CI 1.01-3.10), P = 0.045). CONCLUSION: POD frequently occurs after TAVI and is associated with increased mortality. It might be speculated that patient selection and the minimalistic approach of TAVI may reduce the frequency of delirium.

Impact of Valvulo-Arterial Impedance on Long-Term Quality of Life and Exercise Performance After Transcatheter Aortic Valve Replacement.

BACKGROUND: In aortic stenosis, valvulo-arterial impedance (Zva) estimates the overall left ventricular afterload (valve and arterial component). We investigated the association of Zva (≥5 versus <5 mm Hg mL-1 m-2) on quality of life (QOL) and exercise performance (EP) ≥1 year after transcatheter aortic valve replacement (TAVR). METHODS: The study population consists of 250 TAVR patients in whom baseline Zva and follow-up QOL was prospectively assessed using EuroQOL-5-dimensions instruments; EP was assessed in 192 patients who survived ≥1 year after TAVR using questionnaires related to daily activities. In 124 patients, Zva at 1-year was also available and was used to study the change in Zva (baseline to 1 year) on QOL/EP. RESULTS: Elevated baseline Zva was present in 125 patients (50%). At a median of 28 (IQR, 17-40) months, patients with elevated baseline Zva were more limited in mobility (88% versus 71%; P=0.004), self-care (40% versus 25%; P=0.019), and independent daily activities (taking a shower: 53% versus 38%, P=0.030; walking 100 meter: 76% versus 54%, P=0.001; and walking stairs: 74% versus 54%, P=0.011). By multivariable analysis, elevated Zva predicted unfavorable QOL (lower EuroQOL-5-dimensions-Utility Index, odds ratio, 1.98; CI, 1.15-3.41) and unfavorable EP (any limitation in ≥3 daily activities, odds ratio, 2.55; CI, 1.41-4.62). After TAVR, the proportion of patients with elevated Zva fell from 50% to 21% and remained 21% at 1 year and was found to be associated with more limitations in mobility, self-care, and daily activities compared with patients with Zva <5 mm Hg mL-1 m-2. CONCLUSIONS: Elevated Zva was seen in half of patients and predicted unfavorable long-term QOL and EP. At 1 year after TAVR, the prevalence of elevated Zva was 21% but remained associated with poor QOL/EP.

TAVI Care and Cure, the Rotterdam multidisciplinary program for patients undergoing transcatheter aortic valve implantation: Design and rationale.

BACKGROUND: The capacity of TAVI-programs and numbers of sites performing TAVI has rapidly increased. This necessitated the initiation of the Rotterdam TAVI Care & Cure Program, aiming to improve patient-centered care during the TAVI pathway. METHODS: Consenting patients with severe aortic stenosis and an indication for TAVI will be included. The TAVI Care & Cure program will facilitate prognostic contributions to improve outcomes, patient satisfaction and quality of life in patients with valvular heart disease who are treated with a transcatheter aortic valve implantation in collaboration with the departments of cardiology, cardio-thoracic surgery, anesthesiology and geriatrics. CONCLUSION: With a single center observational registry, we aim to assess the TAVI patient clinical pathway, focusing on pre, peri and post interventional variables including functional status and HRQoL. We will evaluate the patient's complexity by applying an extended multidisciplinary approach, which includes a systematic application of geriatric assessments of frailty and cognitive function.

Short-term changes of blood pressure and aortic stiffness in older patients after transcatheter aortic valve implantation.

BACKGROUND: Both aortic valve stenosis and aortic stiffness are moderators of arterio ventricular coupling and independent predictors of cardiovascular morbidity and mortality. Studies on the effect of transcatheter aortic valve implantation (TAVI) on aortic functional properties are limited. We performed a study to investigate the possible short-term changes in aortic stiffness and other aortic functional properties after TAVI in older patients. METHODS: TAVI Care&Cure is an observational ongoing study including consecutive patients undergoing a TAVI procedure. Central and peripheral hemodynamic measurements were measured non invasively 1 day before (T-1) and 1 day after (T+1) TAVI using a validated oscillometric method using a brachial cuff (Mobil-O-Graph). RESULTS: 40 patients were included. Mean aortic valve area at baseline was 0.76±0.24 cm2. Indices of severity of aortic valve stenosis improved significantly. Systolic blood pressure (SBP) dropped by 8.5%, from 130.3±22.9 mmHg to 119.5±15.8 mmHg (p=0.005). Diastolic blood pressure (DBP) dropped by 13.1% from 74.8±14.5 mmHg to 65.0±11.3 mmHg (p<0.001). The arterial pulse wave velocity (aPWV) decreased from 12.05±1.99 m/s to 11.6±1.56 m/s (p=0.006). Patients with high aPWV at baseline showed a significantly larger reduction in SBP in comparison to patients with low aPWV: - 20.3 mmHg (-14.1%) vs - 3.1 mmHg (-2.6%), respectively (p=0.033). The same trend was found for the DBP: -16.2 (-20.4%) vs -4.5 mmHg (-6.3%) for high vs low aPWV at baseline (p=0.037). CONCLUSION: We found short-term changes in blood pressure and aortic stiffness after TAVI. The amplitude of the changes was the largest in patients with elevated aortic stiffness at baseline.

Early recognition and treatment of neuropsychiatric symptoms to improve quality of life in early Alzheimer's disease: protocol of the BEAT-IT study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are very common in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and are associated with various disadvantageous clinical outcomes including a negative impact on quality of life, caregiver burden, and accelerated disease progression. Despite growing evidence of the efficacy of (non)pharmacological interventions to reduce these symptoms, NPS remain underrecognized and undertreated in memory clinics. The BEhavioural symptoms in Alzheimer's disease Towards early Identification and Treatment (BEAT-IT) study is developed to (1) investigate the neurobiological etiology of NPS in AD and (2) study the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) approach to structure and standardize the current care of NPS in AD. By means of the DICE method, we aim to improve the quality of life of AD patients with NPS and their caregivers who visit the memory clinic. This paper describes the protocol for the intervention study that incorporates the latter aim. METHODS: We aim to enroll a total of 150 community-dwelling patients with MCI or AD and their caregivers in two waves. First, we will recruit a control group who will receive care as usual. Next, the second wave of participants will undergo the DICE method. This approach consists of the following steps: (1) describe the context in which NPS occur, (2) investigate the possible causes, (3) create and implement a treatment plan, and (4) evaluate whether these interventions are effective. Primary outcomes are the quality of life of patients and their caregivers. Secondary outcomes include NPS change, caregiver burden, caregivers' confidence managing NPS, psychotropic medication use, the experiences of patients and caregivers who underwent the DICE method, and the cost-effectiveness of the intervention. CONCLUSIONS: This paper describes the protocol of an intervention study that is part of the BEAT-IT study and aims to improve current recognition and treatment of NPS in AD by structuring and standardizing the detection and treatment of NPS in AD using the DICE approach. TRIAL REGISTRATION: The trial was registered on the Netherlands Trial Registry ( NTR7459 ); registered 6 September 2018.

Mannose binding lectin and prediction of risk for chemotherapy induced febrile neutropenia in patients with a solid tumor.

Mannose-binding lectin (MBL) - deficient patients who undergo chemotherapy for a solid tumor might have an increased risk developing febrile neutropenia (FN). We investigated in a prospective cohort study relations between MBL-serum levels and polymorphisms in MBL promotor genotypes (-550H/L and -221X/Y) on incidence and severity of FN. Risk of FN was 17.9% in MBL-deficient and 22.5% in MBL-sufficient patients (RR = 0.796, p = 0.45). Median MBL serum levels at baseline were respectively 1.39 µg/mL and 1.09 µg/mL (p = 0.92) in patients with and without FN. In conclusion, serum MBL and MBL genotypes (-550H/L and -221X/Y) do not determine the risk for developing FN.

The Erasmus Frailty Score is associated with delirium and 1-year mortality after Transcatheter Aortic Valve Implantation in older patients. The TAVI Care & Cure program.

BACKGROUND: Frailty in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) has been associated with an increased 1-year mortality rate but the relation of frailty and short term outcomes yields conflicting results. This study investigated the association of a novel and self-developed Erasmus Frailty Score with both short and long term outcomes after TAVI. METHODS: TAVI Care & Cure is an observational ongoing study, which includes consecutive patients undergoing TAVI at the Erasmus University Medical Centre. Prior to the TAVI, frailty status was assessed. The Erasmus Frailty Score (EFS) was defined as follows: 1 point assigned if: MMSE was <27 points, MUST ≥2 points, grip strength <20 kg for females, <30 kg for males, KATZ index ≥1 limited activity, Lawton and Brody index ≥2 limited activity. The maximum score was 5. Patients were classified as frail when the score was ≥3. Presence of delirium was evaluated by daily clinical assessment by a geriatrician pre- and post-TAVI. Mortality data were obtained from the Dutch Civil Registry. The impact of frailty on short and long term outcomes was evaluated. RESULTS: 213 patients were included for analysis. Frailty was present in 28.6% (n = 61), (EFS ≥ 3). Baseline frailty was associated with patients developing a delirium [OR 3.3 (95% CI 1,55-7,10), p = 0.002] and with increased risk of 1-year mortality [HR 2.1 (95% CI 1.01-4.52), p = 0.047]. CONCLUSION: The Erasmus Frailty Score is associated with delirium and 1 year mortality in older patients after TAVI and can be used as a complement to traditional risk factors.

Validation of the Rotterdam Elderly Pain Observation Scale in the Hospital Setting.

BACKGROUND: The Rotterdam Elderly Pain Observation Scale (REPOS) has been proven useful to assess pain in noncommunicative and cognitively impaired nursing home residents. We evaluated whether the REPOS is also reliable and valid for pain assessment in the hospital setting. METHODS: In this prospective multicenter observational study, surgical patients were observed perioperatively at bedside and internal medicine patients were filmed during a possible painful moment and at rest. Pain behavior was assessed from the video recordings with the REPOS and the Pain Assessment Checklist for seniors with Severe Dementia-Dutch language (PACSLAC-D). Longitudinal associations between REPOS score and numeric rating scale pain ratings from observers and nurses (NRSobs and NRSproxy ) corrected for patients' gender were assessed with linear mixed models. RESULTS: In total, 72 patients were included; 118 observations of surgical and 68 observations of internal medicine patients were analyzed. Interobserver reliability between the researcher and 2 other observers was good, with Cohen's kappa values of 0.71 (confidence interval [CI] 0.59 to 0.83) and 0.84 (CI 0.74 to 0.94), respectively. The intraobserver reliability of the principal investigator was good, with Cohen's kappa 0.82 (CI 0.67 to 0.91). Linear mixed modeling revealed correlation values between the REPOS and NRSobs of 0.67 and the REPOS and NRSproxy of 0.73. Optimal sensitivity (78%) and specificity (90%) for the detection of pain were found with a REPOS cutoff score of ≥3, using an NRS score of ≥4 as the reference value. CONCLUSIONS: The REPOS is reliable and valid for the assessment of postoperative and chronic pain in hospital patients who cannot self-report pain.

Long-term follow-up of quality of life in high-risk patients undergoing transcatheter aortic valve implantation for symptomatic aortic valve stenosis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe symptomatic aortic stenosis (AS) considered at very high risk for surgical aortic valve replacement. The purpose of this sub-study was to evaluate long-term (> 4 years) health-related quality of life (QoL) in octogenarians who underwent TAVI. METHODS: A single center observational registry in twenty patients who underwent frame analysis assessment ≥ 4 years after TAVI. Health-related QoL was evaluated, using the Short Form-36 (SF-36), the EuroQoL-5D (EQ-5D) and the visual analogue score (EQ-VAS) questionnaires. RESULTS: The mean SF-36 subscale scores at follow-up were physical functioning 40.8 ± 26.3, role physical functioning 67.7 ± 34.9, vitality 54.6 ± 21.6, general health 52.1 ± 20.4, social functioning 63.8 ± 37.7, role emotional functioning 70.2 ± 36.0, mental health 73.2 ± 23.3 and bodily pain 80.9 ± 22.9. The mean EQ-VAS score > 4 years after TAVI was 64.7 ± 15.1. With respect to functional class, 80% of the patients were in NYHA class I/II at follow-up compared to 15% prior to TAVI. CONCLUSIONS: This sub-study reports a significant improvement in functional class (NYHA) in a selected group of very elderly patients > 4 years after TAVI. Furthermore, all patients showed a satisfactory QoL despite their age and multiple comorbidities. In addition, our study reveals a lower QoL when compared with the general age matched Dutch population.

Circulating insulin-like growth factors may contribute substantially to insulin receptor isoform A and insulin receptor isoform B signalling.

BACKGROUND: Only a fraction of circulating insulin-like activity is due to insulin itself. The aim of this study was to determine total serum insulin-like activity mediated via the insulin receptor isoform A (IR-A) and isoform B (IR-B) by using kinase receptor activation (KIRA) assays specific for the IR-A and IR-B. METHODS: The IR-A and IR-B KIRA assays use human embryonic kidney cells which have been transfected with the human IR-A or IR-B gene and quantify serum-mediated phosphorylation of the IR. RESULTS: Both IR KIRA assays were sensitive (detection limit 32 pmol/L) and precise (intra- and inter assay CV: <12% and <15%). The EC50s of insulin, IGF-I and IGF-II were 1.4, 11.2 and 6.7 nmol/L for the IR-A KIRA assay, and 1.3, 31.0 and 15.7 nmol/L for the IR-B KIRA assay. The operational range of both assays allowed for determination of total insulin-like activity in human serum. Analysis of serum samples showed that there was a significant positive correlation between serum insulin-like and immunoreactive insulin concentrations (IR-A: r = 0.56, p = 0.01, IR-B: r = 0.68, p = 0.001). Importantly, addition of IGF-I or IGF-II antibodies to human serum samples could substantially decrease the endpoint signal in both KIRA assays. CONCLUSIONS: We showed that serum IGF-I and IGF-II may substantially contribute to IR signalling. Since IR isoform specific KIRA assays also take into account the contribution of IGFs present in serum on IR signalling, they may help to gain more insight into the roles of IGF mediated IR-A and IR-B activation in health and disease.