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Introduction: The road from usual care to fully implemented integrated care is long and bumpy. In 2018 we started the Zorgzaam Leuven project in the city of Leuven, which has a world class reputation when it comes to healthcare. The aim of this project is to develop, implement and evaluate the necessary steps, tools and changes to enable integrated care. Zorgzaam Leuven is growing and moves forward on the bumpy road, and the results of the past 4 years are very promising. Methods: Zorgzaam Leuven has developed a method to achieve integrated care through innovative collaborations. Essential building blocks were implemented: a large joint population oriented plan for the entire region, multidisciplinary primary care teams in the neighborhoods, care pathways and care programs, data driven population management, financial incentives. The change towards an integrated care system is supported by an integrator, consisting of an operational team and a group of ambassadors in primary care and specialized care. The integrator inspires caregivers, stimulates team spirit, facilitates change. Key findings: The results of the past four years show that working at different levels is essential to creating the right conditions to implement integrated care. The building blocks are the basis for: -A joint agenda with broad support in the region, based on a population approach. -Care givers and patients actively engaged in the integrator. They function as ambassadors who can convince others. -Care pathways implemented for large groups of patients with chronic diseases to make integrated care concrete for care providers. -Multidisciplinary primary care teams are an essential building block. As co-leaders, they allow for a certain degree of self-management within the regional population based approach. -small changes in financial support have a nudging-wise effect to motivate healthcare providers and organizations. -Caregivers are stimulated with data driven audits and feedback at the level of multidisciplinary teams. Conclusions: To sustain implementation, there is a need for a strong integrator and a plan with essential building blocks. Zorgzaam Leuven is on its way to becoming a truly integrated care system. In the next years, steps will be taken towards new partnerships also outside the city of Leuven, data-driven healthcare and financial innovation. Implications for transferability: This model is interesting for many world-wide projects, since it highlights the fundamentals of an implementation strategy in the complex healthcare system of Belgium. [ABSTRACT FROM AUTHOR]

Introduction The Belgian government needs to re-evaluate the current health care system and think about radical adaptations to the structure and payment of health care provision. Therefore, twelve local pilots (Integreo.be) started in Belgium to test different strategies for the implementation of integrated care. The Zorgzaam Leuven project is situated in the city of Leuven, which has a world class reputation when it comes to healthcare. Practice change implemented In Zorgzaam Leuven, a bottom up approach was used and a new care model was implemented in 9 vicinity networks of health care professionals. To fund the vicinity networks, flat rates are used as a surplus on top of the regular fee-for-service (FFS) system. This mixed financing model is based on the Cappuccino model. The vicinity networks are self-steering and free in allocating their budget within a general framework. Aim and theory of change The current, dominating FFS payment system (volume based) does not encourage health care providers to increase value for the patient. The mixed financing model in Zorgzaam Leuven, facilitates the provision of customized care that meets specific needs of the population and allows a more creative approach of the care needs. Targeted population and stakeholders All inhabitants of Leuven are targeted, 102.000 people. All relevant healthcare organizations participate in the project, which is financially supported by the federal government and by 60 local organizations. Timeline Pilot study (2018 - 2022). Highlights (innovation, Impact and outcomes) The model based on vicinity networks facilitates communication among professionals, improves coordination of the care process by coordinating the roles and sequencing the activities of the multidisciplinary care teams. Moreover, more attention is paid to preventive care and population management. To sustain implementation, there is a need for a strong integrator, motivated healthcare providers, policy factors, the availability of necessary resources and a long term vision. Conclusions (comprising key findings) The findings indicate that a new care model based on vicinity networks combined with a mixed financing model based on 'Cappucino', supports integrated care. It supports demand-driven and preventive care. Discussions and lessons learned Many hindrances will have to be overcome first in order to make a further implementation of new payment systems (e.g. bundled payment) possible in the future. The model implemented in Zorgzaam Leuven is very valuable, as it is a first and realistic step towards integrated care, in the complex health care system of Belgium. The main barrier to the implementation of bundled payments is the fragmentation of Belgium's political landscape and the separation of capital budgets (regional authority) and operational budget (federal government). Consequently, the current macro-policy is based on silos making changes difficult. To tackle this problem, the Federal Minister of Public Health states in his policy note that the Belgian government will build further on the federal plan for chronically ill people in order to arrive at an interfederal plan. Comments on sustainability and transferability This model is interesting for many world-wide projects, since it highlights the fundamentals of an implementation strategy in a complex healthcare system. [ABSTRACT FROM AUTHOR]

Background The prevalence of chronic kidney disease (CKD) increases with age, and new glomerular filtration rate-estimating equations have recently been validated. The epidemiology of CKD in older individuals and the relationship between a low estimated glomerular filtration rate as calculated by these equations and adverse outcomes remains unknown. Methods Data from the BELFRAIL study, a prospective, population-based cohort study of 539 individuals aged 80 years and older, were used. For every participant, five equations were used to calculate estimated glomerular filtration rate based on serum creatinine and/or cystatin C values: MDRD, CKD-EPIcreat, CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations. The outcomes analyzed included mortality combined with the necessity of new renal replacement therapy, severe cardiovascular events, and hospitalization. Results During the follow-up period, which was an average of 2.9 years, 124 participants died, 7 required renal replacement therapy, 271 were hospitalized, and 73 had a severe cardiovascular event. The prevalence of estimated glomerular filtration rate values <60 2 mL/min/1.73 m differed depending on the equation used as follows: 44% (MDRD), 45% (CKD-EPIcreat), 75% (CKD-EPIcyst), 65% (CKD-EPIcreatcyst), and 80% (BIS). All of the glomerular filtration rate-estimating equations revealed that higher cardiovascular mortality was associated with lower estimated glomerular filtration rates and that higher probabilities of hospitalization were associated with estimated glomerular filtration rates <30 mL/min/1.73 2 m . A lower estimated glomerular filtration rate did not predict a higher probability of severe cardiovascular events, except when using the CKD-EPIcyst equation. By calculating the net reclassification improvement, CKD-EPIcyst and CKD-EPIcreatcyst were shown to predict mortality (+25% and +18%) and severe cardiovascular events (+7% and +9%) with the highest accuracy. The BIS equation was less accurate in predicting mortality (-12%). Conclusion Higher prevalence of CKD were found using the CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations compared with the MDRD and CKD-EPIcreat equations. The new CKD- EPIcreatcyst and CKD-EPIcyst equations appear to be better predictors of mortality and severe cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: vitamin D deficiency is a well-known cause of bone loss and fractures but its association, especially among the oldest old, with muscle weakness is less obvious.Objective: to investigate the relationship between 25-hydroxyvitamin D (25-OHD) and muscle performance in persons aged 80 years and older.Methods: baseline results of the Belfrail study, a prospective, population-based cohort study were used to study balance, grip strength and gait speed in relation to 25-OHD serum levels in 367 subjects.Results: a sufficient 25-OHD serum level of 30 ng/ml or more was found in 12.8% of the population. The prevalence of vitamin deficiency (20–29 ng/ml), insufficiency (10–19 ng/ml) and severe insufficiency (<10 ng/ml) was 21.5, 33 and 32.7%, respectively. No significant relation between balance, gait speed and grip strength, and serum 25-OHD was detected neither in bivariate analysis nor after adjustment for age, gender, level of education, institutionalisation, smoking status, body mass index, co-morbidity, level of activity, season, CRP, renal function, serum calcium parathyroid hormone levels, vitamin D intake and use of loop or thiazide diuretics.Conclusion: in this cohort of octogenarians vitamin D deficiency was highly prevalent. We could not confirm the findings of previous studies showing an association between serum 25-OHD and physical performance in elderly. [ABSTRACT FROM PUBLISHER]

Background. The prevalence of chronic kidney disease (CKD) is high, especially among older patients. Methods. In order to identify risk factors for the evolution towards end-stage renal disease (ESRD), a cohort of patients ≥50 years of age for whom at least four serum creatinine measurements were available were selected from a primary care-based database. The slope of changes in estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease formula) was calculated, and ESRD was defined as eGFR <15 mL/min. Risk factors for ESRD were analysed using Cox regression analysis. Results. The cohort included 24 682 patients (13 305 women) with a mean age at first available measurement of 64 years. During follow-up (average 7.8 years), 212 patients (0.9%) developed ESRD. The incidence of ESRD per 10 000 person-years is low and depends on baseline eGFR (Stages 0–2: 3, Stage 3A: 13, Stage 3B: 121 and Stage 4: 765). Adjusted hazard ratios (HRs) for patients with baseline eGFR in Stage 3B or 4 depended on age (HR = 0.47 or 0.41 for patients 65–79 years and HR = 0.26 or 0.32 for patients ≥80 years compared with patients aged 50–64 years). Females (HR = 1.48) and patients with diabetes (HR = 1.20), hypertension (HR = 1.25), high total cholesterol (HR = 1.28) or high low-density lipoprotein (LDL) cholesterol (HR = 1.39) were at higher risk for ESRD. Conclusions. Baseline eGFR, diabetes, high cholesterol, high LDL, hypertension and female gender are independent risk factors for developing ESRD. Older age at baseline predicts a lower risk. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented regarding a study that aimed to identify differences in glomerular filtration rate (GFR).

Context: multiple studies of elderly patients show that the prevalence of chronic renal failure in people aged 65 years and older is dependent on the method used to calculate the glomerular filtration rate. We performed a systematic literature search with research question: What is the best method that could be applicable in clinical practice for evaluating renal function in the elderly? Studies using inulin, Cr-51-EDTA, Tc-DTPA or iohexol assays as the gold standard were included. Methods: we searched the PubMed and EMBASE databases. Articles found were screened first by title and abstract and then by five criteria. Retained articles were scored using an adapted version of QUADAS. Results: twelve articles had an identified population or subpopulation aged 65 years and older. The studies were heterogeneous with regard to the population investigated and the statistical procedures used to compare the methods and equations with the gold standard. The Cockcroft-Gault (CG) and MDRD equations and the serum cystatin C concentration produced the highest correlations with the gold standard. Conclusions: no accurate method to evaluate renal function in the elderly was found. Serum cystatin C concentration and the CG and MDRD formula might be valuable parameters, although there is insufficient evidence. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a study on the prevalence of chronic kidney disease in primary care patients aged 50 and older using data from Flemish general practice-based morbidity registry, called Intego.

In Flanders, the prevalence of chronic diseases is high and still increasing partially due to aging of the population and partially due to other reasons like surviving acute diseases or cancer. The aim of the Zorgzaam Leuven project is to test the impact of the implementation of a complex intervention based on the principles of integrated care for a well defined population of approximately 100.000 inhabitants in Belgium. To realize this aim an regional plan created based on integrated care principles and co-creation started in 2016. This plan results in a portfolio of actions for different types of patients with elements of disease management, case-management and proactive care. An integrator and open networks structure was created to make this happen within a learning network. The building blocks of this project are: 1. Gathering of data on the whole population. 2.Implementation of communications tools. 3 enhancing Teamwork by coaching and the use of PDCA cycli to increase quality. 4. Local care networks 5. Sharing of expertise. 6. Adaptation of different financial mechanism 7. Collaboration with research units to implement interventions with existing proof of concept 8. Scientific evaluation. [ABSTRACT FROM AUTHOR]

Background: The use of Electronic Health Records (EHR) data in clinical research is incredibly increasing, but the abundancy of data resources raises the challenge of data cleaning. It can save time if the data cleaning can be done automatically. In addition, the automated data cleaning tools for data in other domains often process all variables uniformly, meaning that they cannot serve well for clinical data, as there is variable-specific information that needs to be considered. This paper proposes an automated data cleaning method for EHR data with clinical knowledge taken into consideration.Methods: We used EHR data collected from primary care in Flanders, Belgium during 1994-2015. We constructed a Clinical Knowledge Database to store all the variable-specific information that is necessary for data cleaning. We applied Fuzzy search to automatically detect and replace the wrongly spelled units, and performed the unit conversion following the variable-specific conversion formula. Then the numeric values were corrected and outliers were detected considering the clinical knowledge. In total, 52 clinical variables were cleaned, and the percentage of missing values (completeness) and percentage of values within the normal range (correctness) before and after the cleaning process were compared.Results: All variables were 100% complete before data cleaning. 42 variables had a drop of less than 1% in the percentage of missing values and 9 variables declined by 1-10%. Only 1 variable experienced large decline in completeness (13.36%). All variables had more than 50% values within the normal range after cleaning, of which 43 variables had a percentage higher than 70%.Conclusions: We propose a general method for clinical variables, which achieves high automation and is capable to deal with large-scale data. This method largely improved the efficiency to clean the data and removed the technical barriers for non-technical people. [ABSTRACT FROM AUTHOR]

Objective: Self-management is a core theme within chronic care and several evidence-based interventions (EBIs) exist to promote self-management ability. However, these interventions cannot be adapted in a mere copy-paste manner. The current study describes and demonstrates a planned approach in adapting EBI's in order to promote self-management in community-dwelling people with chronic conditions.Methods: We used Intervention Mapping (IM) to increase the intervention's fit with a new context. IM helps researchers to take decisions about whether and what to adapt, while maintaining the working ingredients of existing EBI's.Results: We present a case study in which we used IM to adapt EBI's to the Flemish primary care context to promote self-management in people with one or more chronic disease. We present the reader with a contextual analysis, intervention aims, and content, sequence and scope of the resulting intervention.Conclusion: IM provides an excellent framework in providing detailed guidance on intervention adaption to a new context, while preserving the essential working ingredients of EBI's.Practice Implications: The case study is exemplary for public health researchers and practitioners as a planned approach to seek and find EBI's, and to make adaptations. [ABSTRACT FROM AUTHOR]

Background: Since 2014, Belgium's Superior Health Council has recommended pneumococcal vaccination for adults aged 19–85 years at increased risk for pneumococcal diseases with a specific vaccine administration sequence and timing. Currently, Belgium has no publicly funded adult pneumococcal vaccination program. This study investigated the seasonal pneumococcal vaccination trends, evolution of vaccination coverage and adherence to the 2014 recommendations. Methods: INTEGO is a general practice morbidity registry in Flanders (Belgium) that represents 102 general practice centres and comprised over 300.000 patients in 2021. A repeated cross-sectional study was performed for the period between 2017 and 2021. Using adjusted odds ratios computed via multiple logistic regression, the association between an individual's characteristics (gender, age, comorbidities, influenza vaccination status and socioeconomic status) and schedule-adherent pneumococcal vaccination status was assessed. Results: Pneumococcal vaccination coincided with seasonal flu vaccination. The vaccination coverage in the population at risk decreased from 21% in 2017 to 18.2% in 2018 and then started to increase to 23.6% in 2021. Coverage in 2021 was highest for high-risk adults (33.8%) followed by 50- to 85-year-olds with comorbidities (25.5%) and healthy 65- to 85-year-olds (18.7%). In 2021, 56.3% of the high-risk adults, 74.6% of the 50+ with comorbidities persons, and 74% of the 65+ healthy persons had an adherent vaccination schedule. Persons with a lower socioeconomic status had an adjusted odds ratio of 0.92 (95% Confidence Interval (CI) 0.87–0.97) for primary vaccination, 0.67 (95% CI 0.60–0.75) for adherence to the recommended second vaccination if the 13-valent pneumococcal conjugate vaccine was administered first and 0.86 (95% CI 0.76–0.97) if the 23-valent pneumococcal polysaccharide vaccine was administered first. Conclusion: Pneumococcal vaccine coverage is slowly increasing in Flanders, displaying seasonal peaks in sync with influenza vaccination campaigns. However, with less than one-fourth of the target population vaccinated, less than 60% high-risk and approximately 74% of 50 + with comorbidities and 65+ healthy persons with an adherent schedule, there is still much room for improvement. Furthermore, adults with poor socioeconomic status had lower odds of primary vaccination and schedule adherence, demonstrating the need for a publicly funded program in Belgium to ensure equitable access. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic kidney disease (CKD) increases with age, and new glomerular filtration rate-estimating equations have recently been validated. The epidemiology of CKD in older individuals and the relationship between a low estimated glomerular filtration rate as calculated by these equations and adverse outcomes remains unknown.Methods: Data from the BELFRAIL study, a prospective, population-based cohort study of 539 individuals aged 80 years and older, were used. For every participant, five equations were used to calculate estimated glomerular filtration rate based on serum creatinine and/or cystatin C values: MDRD, CKD-EPIcreat, CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations. The outcomes analyzed included mortality combined with the necessity of new renal replacement therapy, severe cardiovascular events, and hospitalization.Results: During the follow-up period, which was an average of 2.9 years, 124 participants died, 7 required renal replacement therapy, 271 were hospitalized, and 73 had a severe cardiovascular event. The prevalence of estimated glomerular filtration rate values <60 mL/min/1.73 m2 differed depending on the equation used as follows: 44% (MDRD), 45% (CKD-EPIcreat), 75% (CKD-EPIcyst), 65% (CKD-EPIcreatcyst), and 80% (BIS). All of the glomerular filtration rate-estimating equations revealed that higher cardiovascular mortality was associated with lower estimated glomerular filtration rates and that higher probabilities of hospitalization were associated with estimated glomerular filtration rates <30 mL/min/1.73 m2. A lower estimated glomerular filtration rate did not predict a higher probability of severe cardiovascular events, except when using the CKD-EPIcyst equation. By calculating the net reclassification improvement, CKD-EPIcyst and CKD-EPIcreatcyst were shown to predict mortality (+25% and +18%) and severe cardiovascular events (+7% and +9%) with the highest accuracy. The BIS equation was less accurate in predicting mortality (-12%).Conclusion: Higher prevalence of CKD were found using the CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations compared with the MDRD and CKD-EPIcreat equations. The new CKD-EPIcreatcyst and CKD-EPIcyst equations appear to be better predictors of mortality and severe cardiovascular events. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prevalence of CKD rises with age. The prevalence of CKD-related metabolic complications in the oldest old in relation to different GFR estimations is largely unknown. eGFR-based thresholds for the detection of these complications remain uncertain. Methods: A cross-sectional analysis embedded within the BELFRAIL study, a population-based prospective cohort study of the oldest old in Belgium, was performed. The prevalence of anemia, elevated serum parathyroid hormone (PTH), high serum phosphorus and low uncorrected serum calcium was analyzed in relation to GFR estimated by three serum creatinine-based equations and one cystatin C-based equation. Results: 567 patients aged 80 and over were included (63% women). The prevalence of anemia, elevated PTH and high phosphorus showed an inverse relationship with eGFR. This relationship remained after logistic regression analysis adjusting for demographics and co-morbidity. No such relationship between low calcium and eGFR was found. Using an eGFR of 60ml/min/1.73m2 modification of diet in renal disease equation (MDRD) as screening threshold for metabolic complications would result in a high incidence of missed complications: 29%, 28% and 40% for anemia, elevated PTH and high phosphorus, respectively. Conclusion: The presence of anemia, an elevated PTH or an elevated serum phosphorus level increased with lower eGFR but even among patients with an eGFR >60ml/min/1.73m2, these complications are common. Thus this eGFR cut-off appears inadequate for patients aged 80 and over. How the oldest old may be screened appropriately for these CKD-related complications requires further investigation. [Copyright &y& Elsevier]

Background: Early detection and treatment of chronic kidney disease (CKD) can prevent further deterioration and complications. Previous studies suggested that the diagnosis is often made when advanced renal failure occurs. The aims of this study were to describe the prevalence of unregistered CKD stages 3–5 in a Belgian General Practitioner population, to determine risk factors for under-registration and to investigate the diagnostic delay. Methods: The analyses were carried out in the INTEGO database, a Flanders general practice-based morbidity registration network. The study used INTEGO data from the year 2018 for all patients ≥18 years old. CKD was defined as two consecutive eGFR laboratory measurements (eGFR <60 mL/min/1.73m2) at least three months apart during the baseline period. Registered CKD was characterised by a documented diagnosis of CKD (ICPC2 U99) during the ≥12-month lookback period before the first eGFR measurement and up to six months after the second eGFR in the EHR. The prevalence of unregistered CKD and the median time of diagnostic delay were estimated. Baseline characteristics were described. A multivariate cross-sectional logistic regression analysis was conducted to identify determinants of unregistered CKD. We estimated the odds ratios and their 95% confidence interval. Results: Among included patients, there were 10 551 patients (5.5%) meeting the criteria of CKD. The prevalence of unregistered CKD was 68%. The mean diagnostic delay was 1.94 years (Standard deviation 0.93). Being a male, a concurrent diagnosis of diabetes, stroke, heart failure and hypertension, and more severe CKD (stages 3b, 4 and 5) independently increased the chance on registered CKD. Conclusion: The proportion of patients who had no registered CKD code in the EHR was substantial. The differences between registered and unregistered patients make thinking about solutions to facilitate registration in the EHR imperative. [ABSTRACT FROM AUTHOR]

Background: To improve the management of childhood urinary tract infections, it is essential to understand the incidence rates, testing and treatment strategy. Methods: A retrospective study using data from 45 to 104 general practices (2000 to 2020) in Flanders (Belgium). We calculated the incidence rates (per 1000 person-years) of cystitis, pyelonephritis, and lab-based urine tests per age (< 2, 2-4, 5-9 and 10-18 years)) and gender in children and performed an autoregressive time-series analysis and seasonality analysis. In children with UTI, we calculated the number of lab-based urine tests and antibiotic prescriptions per person-year and performed an autoregressive time-series analysis. Results: There was a statistically significant increase in the number of UTI episodes from 2000 to 2020 in each age group (p < 0.05), except in boys 2-4 years. Overall, the change in incidence rate was low. In 2020, the incidence rates of cystitis were highest in girls 2-4 years old (40.3 /1000 person-years 95%CI 34.5-46.7) and lowest in boys 10-18 (2.6 /1000 person-years 95%CI 1.8-3.6) The incidence rates of pyelonephritis were highest in girls 2-4 years (5.5, 95%CI 3.5-8.1 /1000 person-years) and children < 2 years of age (boys: 5.4, 95%CI 3.1-8.8 and girls: 4.9, 95%CI 2.7-8.8 /1000 person-years). In children 2-10 years, there was an increase in number of lab-based urine tests per cystitis episode per year and a decrease in total number of electronic antibiotic prescriptions per cystitis episode per year, from 2000 to 2020. In children with cystitis < 10 years in 2020, 51% (95%CI 47-56%) received an electronic antibiotic prescription, of which the majority were broad-spectrum agents. Conclusions: Over the last 21 years, there was a slight increase in the number of UTI episodes diagnosed in children in Flemish general practices, although the overall change was low. More targeted antibiotic therapy for cystitis in accordance with clinical guidelines is necessary to reduce the use of broad-spectrum agents in children below 10 years. [ABSTRACT FROM AUTHOR]

Introduction: The Covid-19 pandemic had a tremendous impact on healthcare but uncertainty remains about the extent to which primary care provision was affected. Therefore, this paper aims to assess the impact on primary care provision and the evolution of the incidence of disease during the first year of the Covid-19 pandemic in Flanders (Belgium). Methods: Care provision was defined as the number of new entries added to a patient's medical history. Pre-pandemic care provision (February 1, 2018–January 31, 2020) was compared with care provision during the pandemic (February 1, 2020-January 31, 2021). A large morbidity registry (Intego) was used. Regression models compared the effect of demographic characteristics on care provision and on acute and chronic diagnoses incidence both prior and during the pandemic. Results: During the first year of the Covid-19 pandemic, overall care provision increased with 9.1% (95%CI 8.5%;9.6%). There was an increase in acute diagnoses of 5.1% (95%CI 4.2%;6.0%) and a decrease in the selected chronic diagnoses of 12.8% (95% CI 7.0%;18.4%). Obesity was an exception with an overall incidence increase. The pandemic led to strong fluctuations in care provision that were not the same for all types of care and all demographic groups in Flanders. Relative to other groups in the population, the pandemic caused a reduction in care provision for children aged 0–17 year and patients from a lower socio-economic situation. Conclusion: This paper strengthened the claim that Covid-19 should be considered as a syndemic instead of a pandemic. During the first Covid-19 year, overall care provision and the incidence of acute diagnoses increased, whereas chronic diseases' incidence decreased, except for obesity diagnoses which increased. More granular, care provision and chronic diseases' incidence decreased during the lockdowns, especially for people with a lower socio-economic status. After the lockdowns they both returned to baseline. [ABSTRACT FROM AUTHOR]

Background: Depression is a common mental disorder in family practice with an impact on global health. The aim of this study is to provide insight in the trends of epidemiological measures as well as pharmacological treatments and comorbidities of depression. Methods: A study using data from INTEGO, a family practice registration network in Flanders, Belgium. Trends in age-standardized prevalence and incidence of depression from 2000 to 2019 as well as antidepressant prescriptions in prevalent depression cases were analyzed with join point regression. Comorbidity profiles were explored using the Cochran-Armitage test and the Jonckheere-Terpstra test. Results: We identified 538 299 patients older than 15 years during the study period. We found an increasing trend in the age-standardized prevalence of depression from 6.73 % in 2000 to 9.20 % in 2019. For the incidence of depression, a decreasing trend was observed from 2000 to 2015 with an incidence of 9.42/1000 in 2000 and 6.89/1000 in 2015, followed by an increasing trend from 2015 to 2019 (incidence of 13.64/1000 in 2019). The average number of chronic diseases per patient with depression increased significantly during the study period (from 1.2 to 1.8), and the proportion of patients relative to the whole study population that received at least one antidepressant prescription per year increased between 2000 and 2019 from 26.44% to 40.16%. Conclusions: The prevalence of depression increases while the incidence sharply rises, but only in recent years. Patients with depression tend to have more comorbidities, making a multi-faceted approach to these patients more important. [ABSTRACT FROM AUTHOR]

Objectives: To assess and compare the ability of two measures of multimorbidity and a simple disease count (DC) to predict health outcomes in a population of patients aged ≥80 years.Study Design and Setting: A prospective, observational, and population-based cohort study including 567 individuals [3.0 years (standard deviation ± 0.25) follow-up].Results: Of the patients, 37.6% were reported with five or more diseases. Multimorbidity was measured by means of a modified Charlson comorbidity index [mCCI; median score, 5 (range, 4-15)], Cumulative Illness Rating Scale [CIRS; median score, 4 (range, 1-11)], and a simple DC of 22 selected chronic conditions [median score, 4 (range, 0-13)]. All measures were independently related to mortality [adjusted hazard ratio (HR) mCCI, 2.5 (confidence interval {CI}: 1.5, 4.1); CIRS, 2.1 (CI: 1.4, 3.2); DC, 2.1 (CI: 1.4, 3.2)] and hospitalization [adjusted HR DC, 2.3 (CI: 1.7, 3.1); mCCI, 2.1 (CI: 1.5, 3.0), CIRS, 1.9 (CI: 1.5, 2.6)] but not to functional decline. Areas under the curve for mortality and hospitalization were all below 0.70. Net reclassification improvements did not indicate that any one measure provided a significant benefit over the others.Conclusion: In this population, the mCCI, CIRS, and unweighted DC predicted mortality and hospitalization but not functional decline. There is no clear advantage of using one measure over another. [ABSTRACT FROM AUTHOR]

Abstract: The hypothesis that natriuretic peptides could be used to identify ‘pancardiac’ damage has been proposed. However, multiple factors are known to influence circulating levels of natriuretic peptides, especially in the very old. Therefore, the impact of confounders on the association between natriuretic peptide levels and cardiac dysfunction was further explored in subjects aged 80 and older. A diagnostic cross-sectional study embedded within the BELFRAIL study (n =567) was performed. Baseline BNP and NT-proBNP levels were measured and echocardiograms were performed at the subject''s home. Cardiac dysfunction was defined as systolic dysfunction, valvular heart disease or isolated severe diastolic dysfunction. Several functional and structural echocardiographic parameters were independently related to circulating levels of natriuretic peptides. Cystatin C, BMI, β blockers, diabetes, heart frequency, usCRP, age and sex were identified as confounders. The prevalence of cardiac dysfunction was 17.1% in the subjects without and 30.8% in the subjects with chronic atrial fibrillation (CAF) or pacemaker (PM). Only in subjects with CAF or PM the C statistic for cardiac dysfunction improved after correcting for confounders. The post-test probability for a negative test (PTP−) ranged from 3.7% to 12.2% and the PTP+ ranged from 21.9% to 62.2% in different strata of confounders. According to these data adjusting for identified confounders does not improve the diagnostic accuracy of the natriuretic peptides for cardiac dysfunction, except in subjects with CAF or PM. Stratifying for individual confounders showed that different cut-off values could be used to optimize the diagnostic characteristics of natriuretic peptides. [Copyright &y& Elsevier]

Frailty has been related to inflammaging and certain immune parameters. In previous analyses of participants older than 80 years of age in the longitudinal BELFRAIL cohort study, the main focus was on T-cell phenotypes and the association with cytomegalovirus (CMV) serostatus and survival, finding that a CD4:CD8 ratio greater than 5 was associated with frailty, impaired activities of daily living (ADLs), and mortality (but only in women). Here, we phenotyped peripheral blood immune cells via multicolor flow cytometry and correlated these with the dynamics of changes in ADL, geriatric depression score, Mini-Mental State Examination, and Short Physical Performance Battery from baseline values over 18 months follow-up. We found that higher frequencies of B cells and late-differentiated CD8+ T cells at 18 months from baseline were associated with ADL impairment that had worsened over the preceding 18 months. There were no significant associations with monocyte, dendritic cell, or natural killer (NK) cell phenotypes. No associations with the Geriatric Depression Scale, the Mini-Mental State Examination, or the Short Physical Performance Battery were found. Thus, while these results do not establish causality, they suggest that certain adaptive immune, but not innate immune, parameters are associated with a worsened ADL in the very old. [ABSTRACT FROM AUTHOR]

Background: The prevalence of multimorbidity is increasing in recent years, and patients with multimorbidity often have a decrease in quality of life and require more health care. The aim of this study was to explore the evolution of multimorbidity taking the sequence of diseases into consideration.Methods: We used a Belgian database collected by extracting coded parameters and more than 100 chronic conditions from the Electronic Health Records of general practitioners to study patients older than 40 years with multiple diagnoses between 1991 and 2015 (N = 65 939). We applied Markov chains to estimate the probability of developing another condition in the next state after a diagnosis. The results of Weighted Association Rule Mining (WARM) allow us to show strong associations among multiple conditions.Results: About 66.9% of the selected patients had multimorbidity. Conditions with high prevalence, such as hypertension and depressive disorder, were likely to occur after the diagnosis of most conditions. Patterns in several disease groups were apparent based on the results of both Markov chain and WARM, such as musculoskeletal diseases and psychological diseases. Psychological diseases were frequently followed by irritable bowel syndrome.Conclusions: Our study used Markov chains and WARM for the first time to provide a comprehensive view of the relations among 103 chronic conditions, taking sequential chronology into consideration. Some strong associations among specific conditions were detected and the results were consistent with current knowledge in literature, meaning the approaches were valid to be used on larger data sets, such as National Health care Systems or private insurers. [ABSTRACT FROM AUTHOR]

Background: The electronic health record (EHR) of the general physician (GP) is an important tool that can be used to assess and improve the quality of healthcare. However, there are some problems when (re) using the data gathered in the EHR for quality assessments. One problem is the lack of data completeness in the EHR. Audit and feedback (A&F) is a well-known quality intervention that can improve the quality of healthcare. We hypothesize that an automated A&F intervention can be adapted to improve the data completeness of the EHR of the GP, more specifically, the number of correctly registered diagnoses of type 2 diabetes and chronic kidney disease.Methods: This study is a pragmatic cluster randomized controlled trial with an intervention at the level of GP practice. The intervention consists of an audit and extended electronically delivered feedback with multiple components that will be delivered 4 times electronically to general practices over 12 months. The data will be analyzed on an aggregated level (per GP practice). The primary outcome is the percentage of correctly registered diagnoses of type 2 diabetes. The key secondary outcome is the registration of chronic kidney disease. Exploratory secondary outcomes are the registration of heart failure, biometric data and lifestyle habits, and the evolution of 4 different EHR-extractable quality indicators.Discussion: This cluster randomized controlled trial intends to primarily improve the registration of type 2 diabetes in the EHR of the GP and to secondarily improve the registration of chronic kidney disease. In addition, the registration of heart failure, lifestyle parameters, and biometric data in the EHR of the GP are explored together with 4 EHR-extractable quality indicators. By doing so, this study aims to improve the data completeness of the EHR, paving the way for future quality assessments.Trial Registration: ClinicalTrials.gov NCT04388228 . Registered on May 14, 2020. [ABSTRACT FROM AUTHOR]

To compare the predictive performance of 3 frailty identification tools for mortality, hospitalization, and functional decline in adults aged ≥80 years using risk reclassification statistics and decision curve analysis. Population-based, prospective cohort. BELFRAIL study, Belgium. 560 community-dwelling adults aged ≥80 years. Frailty by Cardiovascular Health Study (CHS) phenotype, Longitudinal Aging Study Amsterdam (LASA) markers, and Groeningen Frailty Indicator (GFI); mortality until 5.1 ± 0.25 years from baseline and hospitalization until 3.0 ± 0.25 years; and functional status assessed by activities of daily living at baseline and after 1.7 ± 0.21 years. Frailty prevalence was 7.3% by CHS phenotype, 21.6% by LASA markers, and 22% by GFI. Participants determined to be frail by each tool had a significantly higher risk for all-cause mortality and first hospitalization. For functional decline, only frail by GFI had a higher adjusted odds ratio. Harrell 's C-statistic for mortality and hospitalization and area under receiver operating characteristic curve for functional decline were similar for all tools and <0.70. Reclassification statistics showed improvement only by LASA markers for hospitalization and mortality. In decision curve analysis, all tools had higher net benefit than the 2 default strategies of "treat all" and "treat none" for mortality risk ≥20%, hospitalization risk ≥35%, and functional decline probability ≥10%, but their curves overlapped across all relevant risk thresholds for these outcomes. In a cohort of adults aged ≥80 years, 3 frailty tools based on different conceptualizations and assessment sources had comparable but unsatisfactory discrimination for predicting mortality, hospitalization, and functional decline. All showed clinical utility for predicting these outcomes over relevant risk thresholds, but none was significantly superior. Future research on frailty tools should include a focus on the specific group of adults aged ≥80 years, and the predictive accuracy for adverse outcomes of different tools needs a comprehensive assessment that includes decision curve analysis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this paper was to describe the time trends in the prevalence of multimorbidity and polypharmacy in Flanders (Belgium) between 2000 and 2015, while controlling for age and sex. Methods: Data were available from Intego, a Flemish-Belgian general practice-based morbidity registration network. The practice population between 2000 and 2015 was used as the denominator, representing a mean of 159,946 people per year. Age and gender-standardised prevalence rates were used for the trends of multimorbidity and polypharmacy in the total population and for subgroups. Joinpoint regression analyses were used to analyse the time trends and breaks in trends, for the entire population as well as for specific age and sex groups. Results: Overall, in 2015, 22.7% of the population had multimorbidity, while the overall prevalence of polypharmacy was 20%. Throughout the study period the standardised prevalence rate of multimorbidity rose for both sexes and in all age groups. The largest relative increase in multimorbidity was observed in the younger age groups (up to the age of 50 years). The prevalence of polypharmacy showed a significant increase between 2000 and 2015 for all age groups except the youngest (0–25 years). Conclusion: For all adult age groups multimorbidity and polypharmacy are frequent, dynamic over time and increasing. This asks for both epidemiological and interventional studies to improve the management of the resulting complex care. [ABSTRACT FROM AUTHOR]

Background: Various methods exist to estimate disease prevalences. The aim of this study was to determine whether dispensed, self-reported and prescribed medication data could be used to estimate the prevalence of diabetes mellitus and thyroid disorders. Second, these pharmaco-epidemiological estimates were compared with prevalences based on self-reported diagnoses and doctor-registered diagnoses. Methods: Data on medication for diabetes and thyroid disorders were obtained from three different sources in Flanders (Belgium) for 2008: a purely administrative database containing data on dispensed medication, the Belgian National Health Interview Survey for self-reported medication and diagnoses, and a patient record database for prescribed medication and doctor- registered diagnoses. Prevalences were estimated based on medication data and compared with each other. Cross-tabulations of dispensed medication and self-reported diagnoses, and prescribed medication and doctor-registered diagnoses, were investigated. Results: Prevalences based on dispensed medication were the highest (4.39 and 2.98% for diabetes and thyroid disorders, respectively). The lowest prevalences were found using prescribed medication (2.39 and 1.72%, respectively). Cross-tabulating dispensed medication and self-reported diagnoses yielded a moderate to high sensitivity for diabetes (90.4%) and thyroid disorders (77.5%), while prescribed medication showed a low sensitivity for doctor-registered diagnoses (56.5 and 43.6%, respectively). The specificity remained above 99% in all cases. Conclusions: This study was the first to perform cross-tabulations for disease prevalence estimates between different databases and within (sub)populations. Purely administrative database was shown to be a reliable source to estimate disease prevalence based on dispensed medication. Prevalence estimates based on prescribed or self-reported medication were shown to have important limitations. [ABSTRACT FROM AUTHOR]

Background: adults aged 80 and over, a fast growing age-group, with increased co-morbidity and frailty have not been the focus of previous research on dyspnoea. We investigate the correlates of dyspnoea and its association with adverse outcomes in a cohort of adults aged 80 and over. Methods: about 565 community-dwelling adults aged 80 and over of the BELFRAIL prospective cohort had assessment of Medical Research Council dyspnoea scale (MRC), forced expiratory volume in 1 s (FEVi), N-terminal pro-brain natriuretic peptide (NT-proBNP), physical performance tests, grip strength, 15 items geriatric depression scale, activities of daily living (ADL), body mass index (BMI) and demographics data. Kaplan--Meier survival curves, Cox and logistic multivariable regression, classification and regression tree (CART) analysis assessed association of dyspnoea (MRC 3-5) with time-to-cardiovascular and all- cause death (5 years), time to first hospitalisation (3 years), new/worsened ADL disability (2 years), and its correlates. Results: participants with dyspnoea MRC 3-5 (29.9%) had increased hazard ratios for cardiovascular mortality 2.85 (95% confidence interval 1.93-4.20), all-cause mortality 2.04 (1.58-2.64), first hospitalisation 1.72 (1.35-2.19); and increased odds ratio for new/worsened disability 2.49 (1.54-4.04), independent of age, sex and smoking status. Only FEV1, physical performance, BMI and NT-proBNP (in order of importance) were selected in the tree-based classification model for dyspnoea. Conclusions: in a cohort of adults aged 80 and over, dyspnoea was common and an independent predictor of adverse outcomes, with cardio-respiratory and physical performance impairments as key independent correlates. Its routine and comprehensive evaluation in primary care could be very valuable in caring for this age-group. [ABSTRACT FROM AUTHOR]

The occurrence and general applicability of the CD4:8 ratio as a surrogate predictor of mortality among the oldest old have only been tested in a few longitudinal studies. Here, the predictive value of CD4:8 ratio for mortality with respect to the role of cytomegalovirus (CMV) infection was investigated. Using polychromatic flow cytometry, the CD4:8 ratio and T-cell subsets of 235 individuals aged 81.5 years or older were analyzed, and mortality data were collected after a mean period of 3.3 years. The hazard for all-cause mortality adjusted for age, comorbidity, and CMV serostatus increased 1.53-fold (95% CI: 0.94-2.51) with every increment in the CD4:8 ratio from R < 1, to 1 < R < 5 and R > 5 among women. A negative hazard ratio of 0.50 for CMV seropositivity in women indicated an apparently protective effect of this virus. In men, no associations with survival were observed. No mediation effect could be found for the CD4:8 ratio with respect to the relationship between CMV serostatus and mortality. Very elderly CMV-negative women with a R > 5 experienced the highest mortality rates, independent of age and comorbidity. The associations of CMV serostatus and CD4:8 ratio with mortality seem to reflect distinct pathways mediating life span in very old humans. [ABSTRACT FROM AUTHOR]

Objectives Forced expiratory volume in 1 second (FEV 1 ) is proposed as a marker of healthy ageing and FEV 1 expressions that are independent of reference values have been reported to be better at predicting mortality in older adults. We assess and compare the predictive value of different FEV 1 expressions for mortality, hospitalization, and physical and mental decline in adults aged 80 and older. Design Population-based, prospective, cohort study. Setting The BELFRAIL study, Belgium. Participants A total of 501 community-dwelling adults aged 80 and older (mean age 84.7 years). Measurements Baseline FEV 1 expressed as percent predicted (FEV 1 PP) and z -score (FEV 1 Z) using the Global Lung Function Initiative 2012 reference values; over lowest sex-specific percentile (FEV 1 Q), and height squared (FEV 1 /Ht 2 ) and cubed (FEV 1 /Ht 3 ). Mortality data until 5.1 ± 0.2 years from baseline; hospitalization data until 3.0 ± 0.25 years. Activities of daily living, battery of physical performance tests, Mini-Mental State Examination, and 15-item Geriatric Depression Scale at baseline and after 1.7 ± 0.2 years. Results Individuals in the lowest quartile of FEV 1 expressions had higher adjusted risk than the rest of study population for all-cause mortality (highest hazard ratio 2.05 [95% Confidence Interval 1.50–2.80] for FEV 1 Q and 2.01 [1.47–2.76] for FEV 1 /Ht 3 ), first hospitalization (highest hazard ratio 1.63 [1.21–2.16] for FEV 1 /Ht 2 and 1.61[1.20–2.16] for FEV 1 /Ht 3 ), mental decline (highest odds ratio 2.80 [1.61–4.89] for FEV 1 Q) and physical decline (only FEV 1 /Ht 3 with odds ratio 1.93 [1.13–3.30]). Based on risk classification improvement measures, FEV 1 /Ht 3 and FEV 1 Q performed better than FEV 1 PP. Conclusion In a cohort of adults aged 80 and older, FEV 1 expressions that are independent of reference values (FEV 1 /Ht 3 and FEV 1 Q) were better at predicting adverse health outcomes than traditional expressions that depend on reference values, and should be used in further research on FEV 1 and aging. [ABSTRACT FROM AUTHOR]

Purpose: We set out to assess whether a high sense of coherence (SOC) protects from adverse health outcomes in patients aged 80 years and older who have multiple chronic diseases.Methods: A population-based prospective cohort study in 29 primary care practices throughout Belgium included 567 individuals aged 80 years and older. We plotted the highest tertile of SOC scores in Kaplan-Meier curves representing 3-year mortality and time to first hospitalization. Using Cox proportional hazard regression analyses and multiple logistic regression analyses adjusted for sociodemographic characteristics, depression, cognition, disability, and multimorbidity we examined the relationship between SOC and mortality, hospitalization, and decline in performance of activities of daily living (ADL).Results: Subjects with high SOC scores showed a higher cumulative survival than others (Log rank = 0.004) independent of other prognostic characteristics (adjusted hazard ratio 0.62 (95% CI, 0.38-1.00), P = .049). For ADL decline, a high SOC was shown to be protective, and this effect tended to be independent from the covariates under study (adjusted odds ratio 0.56 (95% CI, 0.31-1.0), P = .05).Conclusion: Even very elderly persons with high SOC scores were shown to have lower mortality rates and less functional decline. These effects were independent of multimorbidity, depression, cognition, disability, and sociodemographic characteristics. [ABSTRACT FROM AUTHOR]

Although degenerative aortic valve stenosis (AS) is common with increasing age, limited data exist regarding the prevalence and prognostic impact of its various valve area-gradient patterns in patients ?80 years. To test this, echocardiograms were obtained in 542 randomly selected subjects aged ?80 years recruited in the Belgium Cohort Study of the Very Elderly study (BFC80+). Subjects were divided into 3 groups: no or mild AS, moderate AS, and severe AS. Patients with severe AS were further stratified into those with high mean gradients (HG-AS) and those with paradoxically low mean gradients (LG-AS). Prevalence of moderate-to-severe AS was 14.7% and that of severe AS was 5.9%. In patients with severe AS, most (72%) exhibited paradoxical LG-AS. All patients with severe HG-AS were asymptomatic at the time of inclusion, whereas 48% of those with severe paradoxical LG-AS had significant symptoms. During follow-up, there were 2 aortic valve replacements and 230 deaths, of which 100 (43%) were of cardiovascular origin. Five-year overall survival rate was significantly worse in severe HG-AS than in any of the other groups (22 ± 14% vs 62 ± 2% in no or mild AS, 48 ± 7% in moderate AS, and 43 ± 10% in severe paradoxical LG-AS, p <0.01). Survival rate was similar among severe paradoxical LG-AS with and without low flow. In conclusion, in this large population-based sample of subjects ?80 years, the prevalence of severe AS was 5.9%. Most of these subjects presented with the severe paradoxical LG-AS and a third of them were symptomatic. In this elderly community, severe HG-AS is a major determinant of prognosis, even in the absence of symptoms, whereas severe paradoxical LG-AS seems to behave similarly to moderate AS. [ABSTRACT FROM AUTHOR]

Although degenerative aortic valve stenosis (AS) is common with increasing age, limited data exist regarding the prevalence and prognostic impact of its various valve area--gradient patterns in patients =80 years. To test this, echocardiograms were obtained in 542 randomly selected subjects aged ≥80 years recruited in the Belgium Cohort Study of the Very Elderly study (BFC80+). Subjects were divided into 3 groups: no or mild AS, moderate AS, and severe AS. Patients with severe AS were further stratified into those with high mean gradients (HG-AS) and those with paradoxically low mean gradients (LG-AS). Prevalence of moderate-to-severe AS was 14.7% and that of severe AS was 5.9%. In patients with severe AS, most (72%) exhibited paradoxical LG-AS. All patients with severe HG-AS were asymptomatic at the time of inclusion, whereas 48% of those with severe paradoxical LG-AS had significant symptoms. During follow-up, there were 2 aortic valve replacements and 230 deaths, of which 100 (43%) were of cardiovascular origin. Five-year overall survival rate was significantly worse in severe HG-AS than in any of the other groups (22 ± 14% vs 62 ± 2% in no or mild AS, 48 ± 7% in moderate AS, and 43 ± 10% in severe paradoxical LG-AS, p <0.01). Survival rate was similar among severe paradoxical LG-AS with and without low flow. In conclusion, in this large population-based sample of subjects =80 years, the prevalence of severe AS was 5.9%. Most of these subjects presented with the severe paradoxical LG-AS and a third of them were symptomatic. In this elderly community, severe HG-AS is a major determinant of prognosis, even in the absence of symptoms, whereas severe paradoxical LG-AS seems to behave similarly to moderate AS. [ABSTRACT FROM AUTHOR]

Background Certain inflammatory biomarkers increase with age, provide information about general burden of illness and could cause or reflect any collateral damage to healthy cells and organs. However, comparative studies to predict adverse outcomes are missing. Therefore, our study validated and identified the principal prognostic marker to predict important adverse outcomes in the oldest old from an extensive battery of serum inflammatory markers. Methods A large battery of potential 'inflammaging' markers (IL-1a, IL1-ß, IL-4, IL-6, IL-8, IL-10, TNF-a, IFN-?, EGF, VEGF, MCP-1, usCRP, prealbumin) was assessed in a representative sample of 415 heterogenic individuals 80 years of age or older in the BELFRAIL study. Kaplan-Meier, Cox proportional hazards and CART analyses determined the overall prognostic value of these markers for predicting all-cause, cardiovascular and non-cardiovascular mortality as well as hospitalization. Results Serum IL-6 and usCRP levels were strongly associated with time of survival, independent of cause of death. Serum IL-6 levels had the most robust dose-response relationship with mortality. To a lesser extent, IL-10 and IL-1ß were associated with all-cause mortality but were restricted to non-cardiovascular or cardiovascular mortality, respectively. Having a low IL-6 at baseline (< 1.77 pg/ml) could predict 90% of those who were not at risk for all-cause mortality after 3 years, even after adjusting for confounders. Similarly, we observed an 83.6% chance of identifying those cases with 0 or 1 hospitalization using low IL-6 serum levels. Conclusion The results suggest that a single measurement of low IL-6 serum levels is the first choice to guide clinical practice in the oldest old and could summarize the short-term risk of death and hospitalization. [ABSTRACT FROM AUTHOR]

We retrospectively compared the long-term evolution of IgG anti-spike (S) and anti-nucleocapsid (N) levels (Abbott immunoassays) in 116 non-severe and 115 severe SARS-CoV-2 infected patients from 2 university hospitals up to 365 days post positive RT-PCR. IgG anti-S and anti-N antibody levels decayed exponentially up to 365 days after a peak 0 to 59 days after positive RT-PCR. Peak antibody level/cut-off ratio 0 to 59 days after positive RT-PCR was more than 70 for anti-S compared to less than 6 for anti-N (P < 0.01). Anti-S and anti-N were significantly higher in severe compared to non-severe patients up to 180 to 239 days and 300 to 365 days, respectively (P < 0.05). Despite similar half-lives, the estimated time to 50% seronegativity was more than 2 years for anti-S compared to less than 1 year for anti-N in non-severe and severe COVID-19 patients, due to the significantly higher peak antibody level/cut-off ratio for anti-S compared to anti-N. [ABSTRACT FROM AUTHOR]

Background and objectives Conflicting evidence exists about the value of general practitioners' (GPs') diagnoses of chronic heart failure (CHF), especially in older persons. Therefore, the relationship between GPs' judgement of CHF and objective cardiac abnormalities and their respective prognostic value for 5-year mortality in patients aged 80 and older was studied. Methods and results These analyses were embedded within the prospective, population-based BELFRAIL study. At baseline, 525 patients (mean age 85 ± 3.7 years, 37% men) were clinically assessed by their GPs, had NT-proBNP levels determined and received a detailed echocardiography at home. GPs were asked to judge the presence of CHF and to list their arguments in favour or against CHF. Cause-specific mortality was collected until 5.2 ± 0.25 years after baseline. GPs suspected CHF in 154 patients (29%). The prevalence of objective cardiac abnormalities was 35% (n = 183). GPs' judgement predicted objective cardiac abnormalities inaccurately (sensitivity 45% (95% CI 38-53), specificity 79% (95% CI 75-83)). However, both objective cardiac abnormalities and GPs' diagnoses of CHF were good predictors of 5-year mortality (HR 2.1 (95% CI 1.6-2.7) vs 1.7 (95% CI 1.3-2.3), respectively). Furthermore, the presence of objective cardiac abnormalities was not significantly better than GPs' judgement in identifying patients at risk for mortality, although a trend for better cardiovascular mortality risk classification was noted (NRI 10% (95% CI - 2 to 21%), P = 0.13). Conclusions Although GPs' judgement of CHF and objective cardiac abnormalities correlated poorly, the validity of GPs' clinical judgement for mortality risk stratification was demonstrated. [ABSTRACT FROM AUTHOR]

A subset of older people is at increased risk of hospitalization and dependency. Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8 ratio and cytomegalovirus (CMV) seropositivity plays an important role in the pathophysiology of functional decline. Nevertheless, the relation between CD4:8 ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and T-cell phenotypes of 235 community-dwelling persons aged >=81.5 years in the BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8 ratio, which was associated with CMV seropositivity, less naive, and more late-differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a phenotype associated with a higher proportion of naive T cells and absent in young donors. In CMV seropositives, this subgroup had lower proportions of late-differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G reactivity. This novel naive T-cell-dominated phenotype was counterintuitively associated with a higher proportion of those with impaired physical functioning in the very elderly people infected with CMV. This underscores the notion that in very elderly people, not merely CMV infection but also the state of its accompanying immune dysregulation is of crucial importance with regard to physical impairment. [ABSTRACT FROM AUTHOR]

A subset of older people is at increased risk of hospitalization and dependency. Emerging evidence suggests that immunosenescence reflected by an inverted CD4:8 ratio and cytomegalovirus (CMV) seropositivity plays an important role in the pathophysiology of functional decline. Nevertheless, the relation between CD4:8 ratio and functional outcome has rarely been investigated. Here, CD4:8 ratio and T-cell phenotypes of 235 community-dwelling persons aged ≥81.5 years in the BELFRAIL study and 25 younger persons (mean age 28.5 years) were analyzed using polychromatic flow cytometry. In the elderly persons, 7.2% had an inverted CD4:8 ratio, which was associated with CMV seropositivity, less naive, and more late-differentiated CD4+ and CD8+ T cells. However, 32.8% had a CD4:8 ratio >5, a phenotype associated with a higher proportion of naive T cells and absent in young donors. In CMV seropositives, this subgroup had lower proportions of late-differentiated CD4+ and CD8+ T cells and weaker anti-CMV immunoglobulin G reactivity. This novel naive T-cell-dominated phenotype was counterintuitively associated with a higher proportion of those with impaired physical functioning in the very elderly people infected with CMV. This underscores the notion that in very elderly people, not merely CMV infection but also the state of its accompanying immune dysregulation is of crucial importance with regard to physical impairment. [ABSTRACT FROM PUBLISHER]

Objective: previous studies have demonstrated an association between cytomegalovirus (CMV) infection and mortality in adults. In this prospective study, it was investigated whether these findings could be confirmed in the oldest old.Methodology: data obtained from a prospective observational cohort study (2008–2012) of 549 community-dwelling persons in Belgium aged 80 and older.Results: seventy-six percent were anti-CMV seropositive of whom 37.5% had an anti-CMV IgG titre in the highest tertile (>250 IU/ml). After a median time of follow-up of 1,049 days, 127 deaths occurred. Cox proportional hazard models failed to show an association between CMV serostatus and all-cause mortality. Among persons seropositive for CMV, after adjusting for multiple confounders an anti-CMV in the highest tertile was statistically significantly associated with all-cause mortality (hazard ratio: 1.64, 95% confidence interval: 1.08, 2.48).Conclusion: in contrast to previous findings, a positive CMV serostatus was not associated with an increased risk for all-cause mortality in this cohort of very old people. This is probably the result of a survival effect. CMV seropositive subjects with high anti-CMV titres were at higher risk for all-cause mortality compared with other individuals. This may reflect CMV infection reactivation to be more common in the end stages of life. [ABSTRACT FROM AUTHOR]

Objective: previous studies have demonstrated an association between cytomegalovirus (CMV) infection and mortality in adults. In this prospective study, it was investigated whether these findings could be confirmed in the oldest old.Methodology: data obtained from a prospective observational cohort study (2008–2012) of 549 community-dwelling persons in Belgium aged 80 and older.Results: seventy-six percent were anti-CMV seropositive of whom 37.5% had an anti-CMV IgG titre in the highest tertile (>250 IU/ml). After a median time of follow-up of 1,049 days, 127 deaths occurred. Cox proportional hazard models failed to show an association between CMV serostatus and all-cause mortality. Among persons seropositive for CMV, after adjusting for multiple confounders an anti-CMV in the highest tertile was statistically significantly associated with all-cause mortality (hazard ratio: 1.64, 95% confidence interval: 1.08, 2.48).Conclusion: in contrast to previous findings, a positive CMV serostatus was not associated with an increased risk for all-cause mortality in this cohort of very old people. This is probably the result of a survival effect. CMV seropositive subjects with high anti-CMV titres were at higher risk for all-cause mortality compared with other individuals. This may reflect CMV infection reactivation to be more common in the end stages of life. [ABSTRACT FROM PUBLISHER]

The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose–response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old. [ABSTRACT FROM AUTHOR]

• Antibody response was stronger after vaccination compared to mild natural infection. • Antibody response after vaccination was stronger in previously infected individuals. • Only 32% of uninfected vaccinated individuals had a high titer of anti-S antibodies at three months. We report IgG anti-spike levels up to 3 months after vaccination with 2 doses of BNT162b2 mRNA vaccine in healthcare workers (HCW). The antibody response was significantly stronger in previously infected vaccinated HCW compared to uninfected HCW, and stronger after vaccination compared to (mostly) mild natural infection. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the predictive value of muscle strength and physical performance in the oldest old for all-cause mortality; hospitalization; and the onset of disability, defined as a decline in activities of daily living ( ADLs), independent of muscle mass, inflammatory markers, and comorbidities. Design A prospective, observational, population-based follow-up study. Setting Three well-circumscribed areas of Belgium. Participants Five hundred sixty participants aged 80 and older were followed for 33.5 months (interquartile range 31.1-35.6 months). Measurements Grip strength, Short Physical Performance Battery ( SPPB) score, and muscle mass were measured at baseline; ADLs at baseline and after 20 months; and all-cause mortality and time to first hospitalization from inclusion onward. Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization. Logistic regression analysis was used to determine predictors of decline in ADLs. Results Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score. The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization, independent of muscle mass, inflammatory markers, and comorbidity. A relationship was found between SPPB score and decline in ADLs, independent of muscle mass, inflammation, and comorbidity. Conclusion In people aged 80 and older, physical performance is a strong predictor of mortality, hospitalization, and disability, and muscle strength is a strong predictor of mortality and hospitalization. All of these relationships were independent of muscle mass, inflammatory markers, and comorbidity. [ABSTRACT FROM AUTHOR]

Studies estimating the added value of natriuretic peptide levels and electrocardiographic findings beyond all relevant clinical information to identify cardiac dysfunction remain scarce. The aim of this study was to assess the presence of clinically relevant cardiac dysfunction in an unselected population of subjects aged 80 years. A cross-sectional analysis using an "intention-to-diagnose" strategy was performed within the BELFRAIL study (n = 567). Baseline B-type natriuretic peptide and N-terminal pro--B-type natri-uretic peptide levels were determined and echocardiography was performed at subjects' homes. Logistic regression analysis and classification and regression tree analysis were used as complementary analytic tools. Cardiac dysfunction was present in 17% of subjects without and 31% of subjects with chronic atrial fibrillation (AF) or pacemaker. In subjects without chronic AF or pacemaker, the clinical model showed a C-statistic of 0.79 (95% confidence interval 0.74 to 0.85). The combination of natriuretic peptides with normal results on electrocardiography increased, only marginally, the C-statistic. In subjects with chronic AF or pacemaker, the clinical model showed a very high C-statistic of 0.90 (95% confidence interval 0.82 to 0.98). Classification and regression tree analysis showed that an additional 58 subjects (13%) were correctly classified using natriuretic peptides and elec-trocardiographic findings among those without chronic AF or pacemaker. Of participants with chronic AF or pacemaker, ≥90% were correctly classified. In conclusion, in a large population-based sample of patients aged à80 years, the clinical model possessed high accuracy to identify cardiac dysfunction in daily practice. Among subjects without chronic AF or pacemaker, a larger number were correctly classified by integrating natriuretic peptides and electrocardiographic findings in the strategy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about the relationship between cardiac dysfunction and poor functioning in the elderly. This study sought to describe the prevalence of cardiac dysfunction in the very elderly and to investigate the correlation between echocardiographic abnormalities and indicators of poor functioning. Methods: A cross-sectional analysis within the BELFRAIL (BFC80+) study of 567 subjects aged 80years and older. The clinical research assistant performed an examination including performance testing, questionnaires and technical examinations. Echocardiography was performed at the subject''s home by a cardiologist using a portable system. Results: The mean age of the participants was 84.7years and 62.9% were women. Severe cardiac dysfunction was found in 19.3% and was defined as systolic dysfunction (5.8%), valvular heart disease (10.4%) or isolated severe diastolic dysfunction (3.1%). Severe cardiac dysfunction showed to be an independent identifier of poor performance (OR 1.8 (95% CI 1.1–3.2)), a low LAPAQ (LASA Physical Activity Questionnaire) score (OR 1.9 (95% CI 1.2–3.3)) and a high GDS-15 (Geriatric Depression Scale) score (OR 1.7 (95% CI 1.0–2.9)). This relationship was mainly explained by the independent correlation between aortic stenosis and poor functioning. Classic indicators of systolic and diastolic dysfunction were not able to identify participants with poor functioning. Conclusion: This study shows the very elderly represent a heterogeneous group of subjects with a high prevalence of comorbidities, among whom poor functioning might be triggered by multiple causes. Severe cardiac dysfunction, and more specifically aortic stenosis, showed an independent relationship with poor functioning. [Copyright &y& Elsevier]