Design and pilot results of a single blind randomized controlled trial of systematic demand-led home visits by nurses to frail elderly persons in primary care [ISRCTN05358495]

BACKGROUND: The objective of this article is to describe the design of an evaluation of the cost-effectiveness of systematic home visits by nurses to frail elderly primary care patients. Pilot objectives were: 1. To determine the feasibility of postal multidimensional frailty screening instruments; 2. to identify the need for home visits to elderly. METHODS: Main study: The main study concerns a randomized controlled in primary care practices (PCP) with 18 months follow-up and blinded PCPs. Frail persons aged 75 years or older and living at home but neither terminally ill nor demented from 33 PCPs were eligible. Trained community nurses (1) visit patients at home and assess the care needs with the Resident Assessment Instrument-Home Care, a multidimensional computerized geriatric assessment instrument, enabling direct identification of problem areas; (2) determine the care priorities together with the patient; (3) design and execute interventions according to protocols; (4) and visit patients at least five times during a year in order to execute and monitor the care-plan. Controls receive usual care. Outcome measures are Quality of life, and Quality Adjusted Life Years; time to nursing home admission; mortality; hospital admissions; health care utilization. Pilot 1: Three brief postal multidimensional screening measures to identify frail health among elderly persons were tested on percentage complete item response (selected after a literature search): 1) Vulnerable Elders Screen, 2) Strawbridge's frailty screen, and 3) COOP-WONCA charts. Pilot 2: Three nurses visited elderly frail patients as identified by PCPs in a health center of 5400 patients and used an assessment protocol to identify psychosocial and medical problems. The needs and experiences of all participants were gathered by semi-structured interviews. DISCUSSION: The design holds several unique elements such as early identification of frail persons combined with case-management by nurses. From two pilots we learned that of three potential postal frailty measures, the COOP-WONCA charts were completed best by elderly and that preventive home visits by nurses were positively evaluated to have potential for quality of care improvement

The association of glucose metabolism measures and diabetes status with Alzheimer's disease biomarkers of amyloid and tau: A systematic review and meta-analysis

Conflicting evidence exists on the relationship between diabetes mellitus (DM) and Alzheimer's disease (AD) biomarkers. Therefore, we conducted a random-effects meta-analysis to evaluate the correlation of glucose metabolism measures (glycated hemoglobin, fasting blood glucose, insulin resistance indices) and DM status with AD biomarkers of amyloid-β and tau measured by positron emission tomography or cerebrospinal fluid. We selected 37 studies from PubMed and Embase, including 11,694 individuals. More impaired glucose metabolism and DM status were associated with higher tau biomarkers (r=0.11[0.03-0.18], p=0.008; I2=68%), but were not associated with amyloid-β biomarkers (r=-0.06[-0.13-0.01], p=0.08; I2=81%). Meta-regression revealed that glucose metabolism and DM were specifically associated with tau biomarkers in population settings (p=0.001). Furthermore, more impaired glucose metabolism and DM status were associated with lower amyloid-β biomarkers in memory clinic settings (p=0.004), and in studies with a higher prevalence of dementia (p<0.001) or lower cognitive scores (p=0.04). These findings indicate that DM is associated with biomarkers of tau but not with amyloid-β. This knowledge is valuable for improving dementia and DM diagnostics and treatment

Data harmonization and federated learning for multi-cohort dementia research using the OMOP common data model:A Netherlands consortium of dementia cohorts case study

Background: Establishing collaborations between cohort studies has been fundamental for progress in health research. However, such collaborations are hampered by heterogeneous data representations across cohorts and legal constraints to data sharing. The first arises from a lack of consensus in standards of data collection and representation across cohort studies and is usually tackled by applying data harmonization processes. The second is increasingly important due to raised awareness for privacy protection and stricter regulations, such as the GDPR. Federated learning has emerged as a privacy-preserving alternative to transferring data between institutions through analyzing data in a decentralized manner. Methods: In this study, we set up a federated learning infrastructure for a consortium of nine Dutch cohorts with appropriate data available to the etiology of dementia, including an extract, transform, and load (ETL) pipeline for data harmonization. Additionally, we assessed the challenges of transforming and standardizing cohort data using the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) and evaluated our tool in one of the cohorts employing federated algorithms. Results: We successfully applied our ETL tool and observed a complete coverage of the cohorts’ data by the OMOP CDM. The OMOP CDM facilitated the data representation and standardization, but we identified limitations for cohort-specific data fields and in the scope of the vocabularies available. Specific challenges arise in a multi-cohort federated collaboration due to technical constraints in local environments, data heterogeneity, and lack of direct access to the data. Conclusion: In this article, we describe the solutions to these challenges and limitations encountered in our study. Our study shows the potential of federated learning as a privacy-preserving solution for multi-cohort studies that enhance reproducibility and reuse of both data and analyses.</p

Data harmonization and federated learning for multi-cohort dementia research using the OMOP common data model:A Netherlands consortium of dementia cohorts case study

Background: Establishing collaborations between cohort studies has been fundamental for progress in health research. However, such collaborations are hampered by heterogeneous data representations across cohorts and legal constraints to data sharing. The first arises from a lack of consensus in standards of data collection and representation across cohort studies and is usually tackled by applying data harmonization processes. The second is increasingly important due to raised awareness for privacy protection and stricter regulations, such as the GDPR. Federated learning has emerged as a privacy-preserving alternative to transferring data between institutions through analyzing data in a decentralized manner. Methods: In this study, we set up a federated learning infrastructure for a consortium of nine Dutch cohorts with appropriate data available to the etiology of dementia, including an extract, transform, and load (ETL) pipeline for data harmonization. Additionally, we assessed the challenges of transforming and standardizing cohort data using the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) and evaluated our tool in one of the cohorts employing federated algorithms. Results: We successfully applied our ETL tool and observed a complete coverage of the cohorts’ data by the OMOP CDM. The OMOP CDM facilitated the data representation and standardization, but we identified limitations for cohort-specific data fields and in the scope of the vocabularies available. Specific challenges arise in a multi-cohort federated collaboration due to technical constraints in local environments, data heterogeneity, and lack of direct access to the data. Conclusion: In this article, we describe the solutions to these challenges and limitations encountered in our study. Our study shows the potential of federated learning as a privacy-preserving solution for multi-cohort studies that enhance reproducibility and reuse of both data and analyses.</p

Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study

Background: Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD). Aims: To evaluate the association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD. Methods: IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid-free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders. Results: We included 203 vedolizumab- and 207 ustekinumab-treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9-104.0) and 48.4 (IQR 24.4-55.1) weeks, median follow-up time 104.0 (IQR 103.1-104.0) and 52.0 weeks (IQR 49.3-100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022-1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127-2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034-2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes. Conclusions: Comorbidity - but not age - is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients

Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis

IMPORTANCE: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes. DATA SOURCES: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies. STUDY SELECTION: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data. DATA EXTRACTION AND SYNTHESIS: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy). MAIN OUTCOMES AND MEASURES: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method. RESULTS: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years. CONCLUSIONS AND RELEVANCE: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years

Effectiveness and cost-effectiveness of proactive and multidisciplinary integrated care for older people with complex problems in general practice: An individual participant data meta-analysis

Purpose: to support older people with several healthcare needs in sustaining adequate functioning and independence, more proactive approaches are needed. This purpose of this study is to summarise the (cost-) effectiveness of proactive, multidisciplinary, integrated care programmes for older people in Dutch primary care. Methods design: individual patient data (IPD) meta-analysis of eight clinically controlled trials. Setting: primary care sector. Interventions: combination of (i) identification of older people with complex problems by means of screening, followed by (ii) a multidisciplinary integrated care programme for those identified. Main outcome: activities of daily living, i.e. a change on modified Katz-15 scale between baseline and 1-year follow-up. Secondary outcomes: quality of life (visual analogue scale 0-10), psychological (mental well-being scale Short Form Health Survey (SF)-36) and social well-being (single item, SF-36), quality-adjusted life years (Euroqol-5dimensions-3level (EQ-5D-3L)), healthcare utilisation and cost-effectiveness. Analysis: intention-to-treat analysis, two-stage IPD and subgroup analysis based on patient and intervention characteristics. Results: included were 8,678 participants: median age of 80.5 (interquartile range 75.3; 85.7) years; 5,496 (63.3%) women. On the modified Katz-15 scale, the pooled difference in change between the intervention and control group was -0.01 (95% confidence interval -0.10 to 0.08). No significant differences were found in the other patient outcomes or subgroup analyses. Compared to usual care, the probability of the intervention group to be cost-effective was less than 5%. Conclusion: compared to usual care at 1-year follow-up, strategies for identification of frail older people in primary care combined with a proactive integrated care intervention are probably not (cost-) effective

Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data

We investigated whether amyloid-β (Aβ) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had Aβ status and neuropsychological data available. Linear mixed models were used to assess the associations of Aβ and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with Aβ status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without Aβ pathology (Aβ- norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the Aβ- norms rightfully identified an additional group of individuals at risk of dementia. For non-memory test we found no difference. We confirmed the relationship between Aβ and cognition in cognitively normal individuals. The Aβ- norms for memory tests in combination with published norms improve prognostic accuracy of dementia