Papers by Peter Engelfriet
Additional file of In-depth immune cellular profiling reveals sex-specific associations with frailty
Additional file 1 upplementary Figures S1-S5 and Tables S1-S8.
Clinical & Translational Immunology, 2022
The aim of this exploratory study was to investigate the development of low‐grade inflammation du... more The aim of this exploratory study was to investigate the development of low‐grade inflammation during ageing and its relationship with frailty.
Little is known about the development of low-grade inflammation with age and its relationship wit... more Little is known about the development of low-grade inflammation with age and its relationship with the onset of frailty. In this exploratory study, we investigated 18 inflammatory markers measured in blood of 144 individuals aged 65-75 years at study endpoint, collected over 20 years at five-year intervals. IFNγ-induced markers and platelet activation markers changed in synchrony over time. Chronically elevated levels of IL-6-related markers, such as CRP and sIL-6R, were associated with frailty and becoming frail over time, poorer lung function, or less physical strength. Overweight was a possible driver of these associations. More and stronger associations were detected in women, such as between increasing sCD14 levels and frailty, indicating possible monocyte overactivation. Multivariate prediction of frailty showed low accuracy but confirmed the main results. In summary, we documented 20-year temporal changes of inflammatory markers in an aging population, and related these to cl...
Little is known about the development of low-grade inflammation with age and its relationship wit... more Little is known about the development of low-grade inflammation with age and its relationship with the onset of frailty. In this exploratory study, we investigated 18 inflammatory markers measured in blood of 144 individuals aged 65-75 years at study endpoint, collected over 20 years at five-year intervals. IFNγ-induced markers and platelet activation markers changed in synchrony over time. Chronically elevated levels of IL-6-related markers, such as CRP and sIL-6R, were associated with frailty and becoming frail over time, poorer lung function, or less physical strength. Overweight was a possible driver of these associations. More and stronger associations were detected in women, such as between increasing sCD14 levels and frailty, indicating possible monocyte overactivation. Multivariate prediction of frailty showed low accuracy but confirmed the main results. In summary, we documented 20-year temporal changes of inflammatory markers in an aging population, and related these to cl...
Aims To investigate the role of guidelines in structuring the clinical care for adult patients wi... more Aims To investigate the role of guidelines in structuring the clinical care for adult patients with conge-nital heart disease (CHD), and to assess adherence to the guidelines in Europe. Methods and results A selected number of current guidelines were chosen pertaining to operative pro-cedures, investigations, and the use of medication (‘interventions’). The source for this analysis was the database of the Euro Heart Survey on adult CHD, which contains retrospectively collected data on 4110 patients followed-up for a median of 5.1 years. For each guideline investigated, patients were selected from the database for whom the particular guideline was relevant. The selected cases were classified according to two criteria: was there an indication for the particular intervention and did the interven-
The spectrum of adult congenital heart disease
Aims The increasing number of adults with congenital heart disease (CHD) has prompted the develop... more Aims The increasing number of adults with congenital heart disease (CHD) has prompted the development of recommendations for the management of these patients and for the organization of their healthcare. The aim of this report is to describe the delivery of care in Europe for adults with congenital cardiac anomalies. Methods and results As part of the Euro Heart Survey on Adult Congenital Heart Disease,we obtained data from 71 voluntarily participating centres that detailed their care practices for these patients. Forty-eight of these centres were specialist centres and 23 were non-specialist centres. We found that only 19 % of the specialist centres complied with defined standards for optimal care structure. The criteria that appeared to be most difficult for all centres to achieve were performing 50 congenital heart operations or more per year and involving nurse specialists in the care of these patients. Conclusion This survey indicated that the provision of care in Europe for ad...
Nederlands Tijdschrift voor Geneeskunde, 2018
Over recent years there has been renewed focus on medicalisation. Amongst other things, this is t... more Over recent years there has been renewed focus on medicalisation. Amongst other things, this is the result of the realisation that expansion of the medical domain can also have undesirable effects. However, the line between justified medical interventions and overdiagnosis is difficult to draw. The first step in regaining control of undesirable medicalisation is to identify and quantify the processes behind it and the situations in clinical practice in which it may occur. In this article we discuss different types of medicalisation and, on the basis of this, we give an indication of the frequency with which medicalisation occurs. Finally, we discuss the mechanisms that facilitate medicalisation.
Blood, 2021
Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL pr... more Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis o...
Background: Elderly often show reduced immune functioning and develop chronic low-grade inflammat... more Background: Elderly often show reduced immune functioning and develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with differences in cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65-77 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Plasma inflammatory markers had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results: We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and ...
Metabolites, 2021
Pooling metabolomics data across studies is often desirable to increase the statistical power of ... more Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples’ originating stu...
Clinical & Translational Immunology, 2020
Objectives. Cytomegalovirus infection is thought to affect the immune system and to impact genera... more Objectives. Cytomegalovirus infection is thought to affect the immune system and to impact general health during ageing. Higher CMV-specific antibody levels in the elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally differentiated and CMVspecific T cells are hallmarks of CMV infection, which are thought to expand over time, a process also referred to as memory inflation. Methods. We studied CMV-specific antibody levels over 27 years in 268 individuals (aged 60-89 years at study endpoint), and to link duration of CMV infection to T-cell numbers, CMVspecific T-cell functions, frailty and cardiovascular disease at study endpoint. Results. In our study, 136/268 individuals were longterm CMV seropositive and 19 seroconverted during follow-up (seroconversion rate: 0.56%/year). CMV-specific antibody levels increased slightly over time. However, we did not find an association between duration of CMV infection and CMV-specific antibody levels at study endpoint. No clear association between duration of CMV infection and the size and function of the memory T-cell pool was observed. Elevated CMV-specific antibody levels were associated with the prevalence of cardiovascular disease but not with frailty. Age at CMV seroconversion was positively associated with CMV-specific antibody levels, memory CD4 + T-cell numbers and frailty. Conclusion. Cytomegalovirusspecific memory T cells develop shortly after CMV seroconversion but do not seem to further increase over time. Age-related effects other than duration of CMV infection seem to contribute to CMVinduced changes in the immune system. Although CMV-specific
Experimental Gerontology, 2019
Take-down policy If you believe that this document breaches copyright please contact us providing... more Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
PLOS ONE, 2018
The objective of this study was to explore trajectories of lung function decline with age in the ... more The objective of this study was to explore trajectories of lung function decline with age in the general population, and to study the effect of sociodemographic and life style related risk factors, in particular smoking and BMI. For this purpose, we used data from the Doetinchem Cohort Study (DCS) of men and women, selected randomly from the general population and aged 20-59 years at inclusion in 1987-1991, and followed until the present. Participants in the DCS are assessed every five years. Spirometry has been performed as part of this assessment from 1994 onwards. Participants were included in this study if spirometric measurement of FEV 1 , which in this study was the main parameter of interest, was acceptable and reproducible on at least one measurement round, leading to the inclusion of 5727 individuals (3008 females). Statistical analysis revealed three typical trajectories. The majority of participants followed a trajectory that closely adhered to the Global Lung Initiative Reference values (94.9% of men and 96.4% of women). Two other trajectories showed a more pronounced decline. Smoking and the presence of respiratory complaints were the best predictors of a trajectory with stronger decline. A greater BMI over the follow-up period was associated with a more unfavorable FEV 1 course both in men (β =-0.027 (SD = 0.002); P < 0.001) and in women (β =-0.008 (SD = 0.001); P < 0.001). Smokers at baseline who quit the habit during follow-up, showed smaller decline in FEV 1 in comparison to persistent smokers, independent of BMI change (In men β =-0.074 (SD = 0.020); P < 0.001. In women β =-0.277 (SD = 0.068); P < 0.001). In conclusion, three typical trajectories of age-related FEV1 decline could be distinguished. Change in the lifestyle related risk factors, BMI and smoking, significantly impact aging-related decline of lung function. Identifying deviant trajectories may help in early recognition of those at risk of a diagnosis of lung disease later in life.
Medical decision making : an international journal of the Society for Medical Decision Making, Jan 12, 2016
Mortality rates in Markov models, as used in health economic studies, are often estimated from su... more Mortality rates in Markov models, as used in health economic studies, are often estimated from summary statistics that allow limited adjustment for confounders. If interventions are targeted at multiple diseases and/or risk factors, these mortality rates need to be combined in a single model. This requires them to be mutually adjusted to avoid 'double counting' of mortality. We present a mathematical modeling approach to describe the joint effect of mutually dependent risk factors and chronic diseases on mortality in a consistent manner. Most importantly, this approach explicitly allows the use of readily available external data sources. An additional advantage is that existing models can be smoothly expanded to encompass more diseases/risk factors. To illustrate the usefulness of this method and how it should be implemented, we present a health economic model that links risk factors for diseases to mortality from these diseases, and describe the causal chain running from th...
Health economics, 2015
The aim of EuroHOPE was to provide new evidence on the performance of healthcare systems, using a... more The aim of EuroHOPE was to provide new evidence on the performance of healthcare systems, using a disease-based approach, linkable patient-level data and internationally standardized methods. This paper summarizes its main results. In the seven EuroHOPE countries, the Acute Myocardial Infarction (AMI), stroke and hip fracture patient populations were similar with regard to age, sex and comorbidity. However, non-negligible geographic variation in mortality and resource use was found to exist. Survival rates varied to similar extents between countries and regions for AMI, stroke, hip fracture and very low birth weight. Geographic variation in length of stay differed according to type of disease. Regression analyses showed that only a small part of geographic variation could be explained by demand and supply side factors. Furthermore, the impact of these factors varied between countries. The findings show that there is room for improvement in performance at all levels of analysis and c...
Opportunities for preventing diabetes and its cardiovascular complications: a modelling approach ... more Opportunities for preventing diabetes and its cardiovascular complications: a modelling approach If interventions aimed to reduce overweight and promote physical activity would be implemented on a national scale in the Netherlands, between 1% and 2% of new cases of diabetes would be prevented over a 20-year period. More intensive treatment of persons with diabetes would prevent 5% to 10% of new cases of macrovascular complications. In order to prevent the burden of disease due to diabetes, prevention is crucial. In this study the long-term efficacy of various interventions in preventing diabetes and its complications was investigated. In addition the costs and cost-effectiveness of these interventions were evaluated. This was done with the help of a computer model that was designed to track the evolution of the Dutch population over time, with regard to risk factors, chronic diseases and mortality. Reducing the prevalence of overweight is the most powerful tool in preventing diabetes. As the interventions currently available allow the realisation of not more than a small part of the potential health gains, it is mandatory to continue to invest in identifying and developing effective measures to loose weight in a sustainable manner. Smoking cessation does not contribute to preventing diabetes. But, of course, it does prevent other diseases. In treating indivuals with diabetes, interventions aimed at lowering cholesterol and blood pressure result in greater health gains than intensifying blood sugar control. Succesful prevention of diabetes and its complications leads to higher overall costs of care due to the fact that people live longer and as a consequence incur healthcare costs in life years gained. However, in all interventions evaluated, health gains justify the extra costs.
The Journal of Asian Studies, 2013
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Papers by Peter Engelfriet