Vulnerability across the lifecourse

Vulnerability across the lifecourse

At both ends of the lifecourse, the course of health and disease is determined by vulnerability. This vulnerability (or frailty) has components of mental, physical and social functioning, which are part of routine pediatric and geriatric care. Identifying, measuring and defining vulnerability are important steps towards tailored and appropriate care. Increasingly, in contrast to measuring vulnerability, the concept of resilience is investigated and harnessed to aid in delivering appropriate care. This field of research includes biobank studies as well as (clinical) cohort and intervention studies on topics ranging from fetal development to end-of-life care, united by a focus on quality of life.

Ongoing projects

The Triage of Elderly Needing Treatment (TENT) Study

In the TENT study, we study the outcomes of older people who visit our out-patient clinic and receive a Geriatric Assessment prior to treatment for cancer (surgery, chemotherapy, radiation therapy, best supportive care). Patients are followed for 12 months for mortality, functional decline and quality of life. Recent work for the study has for instance illustrated that of the older patients with frailty who receive chemotherapy around 40% has died after 12 months and an additional 40% has worse functioning and quality of life compared to before the treatment. This knowledge sparks new research into prediction models to assist in decision making (such as in the PORTRET tool), more intense monitoring during treatment and rehabilitation (see also TOPFORM study below).

The COVID-19 in Older People (COOP) Study

Very early in the COVID-19 pandemic it became apparent that especially older people were very vulnerable and had high mortality rates of COVID-19. In decision making, the Clinical Frailty Scale was introduced in guidelines to aid in triage of referral to hospital and ICU. We initiated the national COOP study to study predictors of outcomes in older people. The most important findings were: 1) prediction of mortality using prediction models developed in the general population in older people was not accurate; 2) adding the Clinical Frailty Scale to the models did not improve prediction; 3) older people themselves did not have other treatment goals dependent on their level of frailty or vitality. These findings have implications for delivering care also in other diseases.

University Network for the Care Sector South-Holland (UNC-ZH)

In collaboration with 11 affiliated long-term care institutions in the province of Zuid-Holland, we conduct research to improve quality of life of vulnerable long-term care residents, such as:

  • Vitality garden: intervention study focusing on the effect of garden use on quality of life and behavioral and psychological symptoms in people living with dementia in nursing homes. This study resulted in an evidence-based practice toolkit on how to design a nursing home garden.
  • ENACT study: a co-creation study with healthcare professionals, family, and volunteers, aimed at developing a toolkit with ‘best practices’ to support caregivers when choosing and performing meaningful activities for people with severe dementia living in Dutch nursing homes.
  • Emotion Intelligent Care Robot: a co-creation study with residents, family, and professional caregivers, aimed at developing an emotion-intelligent robot that can help healthcare professionals provide person-oriented care.

Complex dynamic systems framework on aging

  • Leiden 85-plus study: The temporal dynamics between depressive symptoms and cognitive decline in individuals aged 85 and older was studied. The study found that depressive symptoms tended to precede cognitive impairment, with mood and apathy symptoms showing distinct clustering patterns. This suggests that early depressive symptoms may act as a precursor to cognitive decline, highlighting the importance of addressing mental health in older populations to potentially mitigate cognitive deterioration​.
  • Netherlands Study of Depression in Older People (NESDO): Dynamic time warping (DTW) analysis was used to understand depressive symptoms in older adults with major depression. By applying DTW to longitudinal data from NESDO, we identified symptom clusters that were stable across participants, with central symptoms identified that may inform personalized treatment approaches.
  • PointR within Longitudinal Aging Study Amsterdam (LASA): The temporal relationships are studied between perceived self-reliance and psychiatric symptoms in older adults, focusing on whether changes in self-reliance could predict the development or recovery from psychiatric conditions such as anxiety and depression. By applying DTW to LASA longitudinal data (aged 55+) we found that in asymptomatic individuals self-reliance indicators like mastery preceded improvements in psychiatric symptoms. However, in symptomatic individuals, psychiatric symptoms typically preceded declines in self-reliance.

VOILA and Medical Delta consortia

Data science in molecular biomarker studies (especially metabolomics, proteomics, DNA methylation, novel clinical markers and cellular senescence) is aimed at defining target groups of older adults based on increased vulnerability and resilience. These studies revealed the informativity of omics markers in the population at large on the risk of mortality, frailty, cognitive decline pneumonia and COVID hospitalization. These markers have shown to be less informative in the clinical setting for older patients when compared to traditional clinical variables as was tested for cancer and hip fractures, kidney failure, Other markers from the proteome (cytokines, GDF-15) are currently being investigated for their added value to metabolomics markers in the clinical setting. Lifestyle intervention studies in 60 + populations in VOILA form a background information source for those into prehabilitation.

BioClock Consortium

Within NWO-funded NWA project BioClock, we study the effect of timing of physical activity on clinically relevant outcomes in older persons (including sleep, cardiovascular disease, and mood and depression). We performed an intervention study (ON TIME) to assess the effect of timing of physical activity (morning activity versus evening activity) on insomnia severity in older persons with self-reported sleep problems (primary endpoint) as well as other physiological rhythms and parameters (secondary endpoints) using a cross-over design. We included 36 participants of whom 28 completed the intervention. Exercising together with peers was perceived by several study participants as beneficial. According to our latest information, to continue exercising on a regular basis in a group of peers, a new Vitality Club was started in Oegstgeest that comprises 10 of our previous study participants. In parallel to the intervention study, we aim to assess associations between timing of physical activity and risks of (i) cardiovascular disease, (ii) type 2 diabetes, (iii) depression, and (iv) osteoporosis in the large UK Biobank using multivariable-adjusted analyses. Published results indicated that being more active in the morning was associated with a lower risk of cardiovascular disease. These results warrant future research on the potential role of chrono-activity as a novel strategy to enhance resilience in old age.

Leiden TWIN studies

The Leiden University Medical Center is the national expertise center for complicated monochorionic twin pregnancies, fetal disease and therapy (ECZA, Ministry of Health, Welfare and Sport). Our extensive monochorionic twin biobank (from 2000 onwards) enables us to study the impact of adverse intrauterine circumstances on long-term health outcomes in a unique model of identical twins discordant for intrauterine adversity. The LUMC monochorionic twin biobank is the source of many (inter)national retro- and prospective studies and RCTs including the Solomon and TAPS trial, Twinlife, Contrast, LEMON, Well Bee, MELON and CITRUS. Monochorionic twins and parents with and without pregnancy complications are included from the onset of a monochorionic pregnancy (complication) to adolescence (17 years). The biobank is founded on >20 years collaboration between the LUMC departments of Obstetrics, Fetal Therapy, Pediatrics, Neonatology, Radiology, Pathology and Medical Psychology.

LEEF: Late effects and follow-up after high intensity treatment during fetal development, infancy and early childhood

The LUMC-WAKZ is an expertise center for rare diseases (ECZA) in pregnancy, infancy, and childhood including monochorionic pregnancy complications, fetal aortic stenosis, hypoplastic left heart syndrome, inborn errors of immunity and congenital blood disorders. The necessary innovative curative and complex treatments for these rare conditions are performed exclusively at the LUMC: fetal therapy, pediatric cardiac surgery (CAHAL), hematopoietic stem cell transplantation (HSCT) and cell therapy. The LEEF study, a collaboration between the departments of Obstetrics (fetal therapy), Cardiology (CAHAL), Hematology (SCT), Pediatrics (Neonatology) and Medical Psychology, determines 1. the late effects after high intensity treatment during fetal development, infancy and childhood and 2. identifies modifying factors, including: biological, pathophysiological, demographic, psychological and clinical determinants, which contribute to both lifelong vulnerability and resilience. LEEF aims to evaluate and improve aspects of patient-centered value based healthcare (PC-VBHC) organization and other (perceived) care aspects in infants, children, adolescents and adults after high intensity treatment by measurement of patient and treatment characteristics, patient-reported outcomes (PROMS), patient and healthcare providers reported experiences (PREMS), perceived patient-centeredness of care, health care use, costs, and the associations between these factors and health care outcome.

Innovative transmural care pathways and resilience pipeline

Pipelines

Patients are getting older while at the same time undergoing increasingly intensive treatments. This brings up the concept of physical resilience – the ability to recover and adapt after health-related stressors such as surgery or chemotherapy. Identifying physical resilience in older patients may enable more personalized treatment plans, ultimately allowing for better recovery and improved functional outcomes. The first step, however, is being able to measure physical resilience.

  • In the TOPFORM study, which is a sub study of the TENT study, wearable devices are used to monitor recovery trajectories in patients undergoing surgical oncological treatment. Specific research questions are:
    1. Can we identify distinct trajectories of physical resilience (operationalized as step count recovery) in patients 70 years and older in the first 3 months after undergoing major oncologic surgery.
    2. What is the feasibility of measuring physical resilience using wearable technology post-operatively in older patients in both in-hospital and at-home setting
    3. What baseline characteristics are potential determinants of physical resilience.
  • CLEOPATRA study: To help care teams objectively detect older patients’ recovery potential to adverse outcomes of systemic oncology treatment, this project develops and validates an easy-to-use smart digital resilience self-monitoring solution. The resilience solution consists of a set of measurements in multiple domains (i.e. cognition, mobility) using a patients’ smartphone. Home monitoring of resilience, through longitudinal measurements, enables the detection of delayed recovery or even an early functional positive response to therapy. Thereby facilitating timely interventions within specific domains. Additionally, early prediction of recovery potential permits refined prognostication, shared decision making and optimization of care. The overall aim of this study is to develop, evaluate, validate and test in a real world setting the innovative digital resilience assessment tool (Orion).
  • Recovery box: The overall objective of this project is to develop, implement and test an innovative transmural blended solution for optimal recovery of geriatric patients who have been admitted to the hospital to improve outcomes.
  • HOME project: Emergency department (ED) visits and hospitalizations of frail older patients are highly associated with the occurrence of complications, functional decline and mortality. For older patients with dyspnea health care providers often face diagnostic dilemmas and experience difficulties in providing treatment and care in the home setting. Accordingly, patients are often sent to the ED after which a hospital admission frequently follows. To prevent these ED visits and hospitalizations in older patients with dyspnea, we developed a regional care path the ‘HOME project’. This study will evaluate the implementation of the care path, our ultimate goal is to evaluate these patients in their home environment to prevent ED visits.
  • DOSAGE trial: Colorectal cancer is one of the most frequently occurring cancers in older adults. Yet, generally very fit. This strongly limits the evidence base for the treatment of the majority of older adults with an average vitality and cancer. Due to this lack of evidence, there are no guidelines on how to tailor treatment for older adults with metastasized colorectal cancer, leading to high toxicity rates, unplanned hospitalizations and reduced quality of life. Prior research showed that upfront dose reduction of chemotherapy in older adults with metastasized colorectal cancer strongly reduced toxicity rates of up to 20-30%, while efficacy is maintained.

    The objective of the DOSAGE trial is to demonstrate that upfront dose-reduced chemotherapy in patients with metastasized colorectal cancer is non-inferior to full-dose treatment with regard to progression-free survival (PFS), will lead to lower toxicity rates, better QoL and physical functioning, lower hospital admissions and health care costs, with a stratification for monochemotherapy versus polychemotherapy depending on individual risk of toxicity. Trial design: Phase III open-label non-inferiority randomized controlled clinical trial

Nefrogeriatrics

In a joint working group with 5 PhD students and representatives of the departments of Nephrology of LUMC, Haga- and St Antonius-hospitals, UMCU and the department of Geriatrics of LUMC, we investigate treatment strategies for old, frail, kidney patients. We did so using various methodologies: retrospective analyses showing decreasing value of dialysis treatment in elderly (eg Verberne, and COPE cohort), developing and implementing a “nephro-geriatric” assessment (POLDER study) and a large prospective study to evaluate both the nephro-geriatric assessment and its effect on treatment choice and subsequent treatment outcome in frail and non-frail elderly (DIALOGICA study).

Most important references