The purpose of the research we undertook for this Conference Paper was to investigate whether marketing campaigns for specific types of drinks could be directed towards age cohorts rather than towards intercultural differences between countries. We developed consumer profiles based on drinking motives and drinking behavior by age cohorts. We hypothesized that differences between countries in the youngest age groups are smaller than in the older age groups, where country specific tradition and culture still plays a more prominent role. We, therefore tested, from the data obtained by the COnsumer BEhaviouR Erasmus Network (COBEREN), the hypothesis that the extent to which the age specific profiles differ between countries increases with age. The results confirm our hypothesis that the extent to which drinking motives differ between countries increases with age. Our results suggest that marketing campaigns which are directed towards drinking motives, could best be tailored by age cohort, in particular when it concerns age group 18-37 and more particular for beer, spirits and especially premix drinks. Marketing campaigns for non-alcoholic beverages should be made specific for the British countries and the Western countries, but even more effectively be made specific for the age cohort 18-37.
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INTRODUCTION: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.METHODS: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.FINDINGS: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2).INTERPRETATION: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality.
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Purpose: There is growing international interest in the implementation of structured osteoarthritis management programs (OAMPs) to deliver best evidence osteoarthritis (OA) care. A consortium of researchers, clinicians and consumers concerned with optimising implementation of OAMPs have established the ‘Joint Effort’ Initiative (the Initiative), endorsed by the Osteoarthritis Research Society International (OARSI) in 2018. A priority action of the Initiative is to evaluate the outcomes and implementation of existing OAMPs.Marked differences between existing international OAMP models include treatments offered, settings and mode of delivery, intensity, duration and health disciplines involved. There is some evidence of effectiveness from randomised controlled trials (RCTs) and longitudinal cohort studies reporting outcomes from OAMPS in different real-world settings, however, this research is still in its infancy. The effects of different OAMP models have not been compared head-to-head and given the prohibitive costs and logistics associated with comparing OAMP models in RCTs, it is unlikely that these trials will take place. Instead, we will leverage research efforts and costs that have already been spent by combining data from existing cohort studies to compare the outcomes of different OAMP models.We aim to combine Individual Patient Data (IPD) from the existing international OAMP cohorts and use meta-analytic techniques to address the following objectives: 1) Compare the short-, medium- and long-term changes in pain, physical function, body weight, Quality of Life, fear of movement and goal achievement between different OAMPs. 2) Determine the short-, medium- and long-term overall effects of OAMPs on pain and physical function for people with knee and hip OA. 3) Examine the characteristics of OAMP participants who achieved/ did not achieve the Patient Acceptable Symptom State (PASS), OMERACT-OARSI responder criteria, and completers vs dropouts. 4) Describe the implementation evaluation outcomes of OAMPsMethods: We will use de-identified IPD from nine existing OAMP clinical cohorts from Australia, Norway, Sweden, Netherlands, UK, New Zealand and USA. Clinical cohorts will be eligible if they are derived from a hip/knee OAMP in a real-world setting with the following components: i) personalised OA care; ii) package of care with reassessment and progression; iii) minimum of two core treatments of education, exercise, and/or weight-loss, and; iv) optional adjunctive treatments. We will include both published and unpublished data.Based on scoping work on the outcomes measures and time points currently collected by each OAMP, our primary outcomes will be the difference in pain (numerical rating scale 0-10) and function (Western Ontario and McMasters Osteoarthritis Index function score (WOMAC)), at 12-weeks. Secondary outcomes will be changes in pain and function at 26- and 52-weeks. Other secondary outcomes at 12-, 26- and 52- weeks will be changes in: body weight; quality of life (EuroQol, Short Form 12); disease specific measures (Knee Injury and Osteoarthritis Outcome score, Hip Disability and Osteoarthritis Outcome score, WOMAC); functional performance (30-second chair stand test, six-minute walk test); fear of movement; and patient satisfaction. We will report against the PASS, OMERACT-OARSI definition of responders/non-responders and examine implementation outcomes where available including the Osteoarthritis Quality Indicator Questionnaire, uptake, reach and fidelity.The IPD will be harmonised and aggregated to create one large dataset. We will use descriptive statistics to compare the characteristics of participants across OAMPs. We will take a two-step approach to IPD meta-analytic techniques. First, we will estimate the change in outcomes for each OAMP (pain, function and other outcomes) with multivariable regression modelling. Second, we will weight and pool estimates using random-effects methods to determine the overall effects on pain and function, account for differences in effects across studies and examine prognostic effects and interactions of characteristics (e.g. baseline symptomatic severity, functional performance) of participants who achieved/did not achieve the PASS, OMERACT OARSI responder criteria and those who completed/dropped out of the OAMPs.Results: This study has received ethical approval from the NSLHD Human Research Ethics Committee (Australia). Ethical approval for use of other cohort data is being sought by researchers in their respective countries. We have performed extensive work with the stakeholders involved to identify appropriate co-collected outcomes and will collaborate with the OA Trial Bank to store and collate the cohort data, the first database of its kind.Conclusions: This project will be the first to compare patient and implementation outcomes across international OAMPs. It will address a priority of the Initiative and make recommendations on the “optimal” OAMP model/s to use.
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Huntington’s disease (HD) and various spinocerebellar ataxias (SCA) are autosomal dominantly inherited neurodegenerative disorders caused by a CAG repeat expansion in the disease-related gene1. The impact of HD and SCA on families and individuals is enormous and far reaching, as patients typically display first symptoms during midlife. HD is characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. SCAs are mainly characterized by ataxia but also other symptoms including cognitive deficits, similarly affecting quality of life and leading to disability. These problems worsen as the disease progresses and affected individuals are no longer able to work, drive, or care for themselves. It places an enormous burden on their family and caregivers, and patients will require intensive nursing home care when disease progresses, and lifespan is reduced. Although the clinical and pathological phenotypes are distinct for each CAG repeat expansion disorder, it is thought that similar molecular mechanisms underlie the effect of expanded CAG repeats in different genes. The predicted Age of Onset (AO) for both HD, SCA1 and SCA3 (and 5 other CAG-repeat diseases) is based on the polyQ expansion, but the CAG/polyQ determines the AO only for 50% (see figure below). A large variety on AO is observed, especially for the most common range between 40 and 50 repeats11,12. Large differences in onset, especially in the range 40-50 CAGs not only imply that current individual predictions for AO are imprecise (affecting important life decisions that patients need to make and also hampering assessment of potential onset-delaying intervention) but also do offer optimism that (patient-related) factors exist that can delay the onset of disease.To address both items, we need to generate a better model, based on patient-derived cells that generates parameters that not only mirror the CAG-repeat length dependency of these diseases, but that also better predicts inter-patient variations in disease susceptibility and effectiveness of interventions. Hereto, we will use a staggered project design as explained in 5.1, in which we first will determine which cellular and molecular determinants (referred to as landscapes) in isogenic iPSC models are associated with increased CAG repeat lengths using deep-learning algorithms (DLA) (WP1). Hereto, we will use a well characterized control cell line in which we modify the CAG repeat length in the endogenous ataxin-1, Ataxin-3 and Huntingtin gene from wildtype Q repeats to intermediate to adult onset and juvenile polyQ repeats. We will next expand the model with cells from the 3 (SCA1, SCA3, and HD) existing and new cohorts of early-onset, adult-onset and late-onset/intermediate repeat patients for which, besides accurate AO information, also clinical parameters (MRI scans, liquor markers etc) will be (made) available. This will be used for validation and to fine-tune the molecular landscapes (again using DLA) towards the best prediction of individual patient related clinical markers and AO (WP3). The same models and (most relevant) landscapes will also be used for evaluations of novel mutant protein lowering strategies as will emerge from WP4.This overall development process of landscape prediction is an iterative process that involves (a) data processing (WP5) (b) unsupervised data exploration and dimensionality reduction to find patterns in data and create “labels” for similarity and (c) development of data supervised Deep Learning (DL) models for landscape prediction based on the labels from previous step. Each iteration starts with data that is generated and deployed according to FAIR principles, and the developed deep learning system will be instrumental to connect these WPs. Insights in algorithm sensitivity from the predictive models will form the basis for discussion with field experts on the distinction and phenotypic consequences. While full development of accurate diagnostics might go beyond the timespan of the 5 year project, ideally our final landscapes can be used for new genetic counselling: when somebody is positive for the gene, can we use his/her cells, feed it into the generated cell-based model and better predict the AO and severity? While this will answer questions from clinicians and patient communities, it will also generate new ones, which is why we will study the ethical implications of such improved diagnostics in advance (WP6).
Jongeren met chronische aandoeningen worden vaak geconfronteerd met problemen in het dagelijks functioneren, waarbij vermoeidheid wordt genoemd als het meest invaliderend. De prevalentie van vermoeidheid onder jongeren met chronische aandoeningen varieert tussen de 51-75%. Vermoeidheid kan onafhankelijk ontstaan van het onderliggende pathologisch mechanisme; uit literatuur blijkt dat ziekte-specifieke benaderingen weinig of nauwelijks effect hebben op vermoeidheid. Vermoeidheid wordt bovendien te laat opgemerkt of blijft onbehandeld. Inzicht in de ziekte-overstijgende mechanismen van vermoeidheid is van belang om vroegtijdig opsporen en de ontwikkeling van passende interventies te faciliteren. Dit postdoc onderzoek richt zich op het ontrafelen van ziekte-overstijgende mechanismen van vermoeidheid vanuit het perspectief van jongeren, het gezin en de fysieke en sociale leefomgeving. Binnen een longitudinale cohortstudie gedurende 12 maanden worden 208 jongeren met verschillende chronische aandoeningen gemonitord. Naast traditionele onderzoeksmethodieken zoals vragenlijsten en fysieke testen, wordt gebruik gemaakt van remote sensoring, linked data en context mapping (=kwalitatieve methode). Studenten die participeren in het onderzoek zullen de mogelijkheden en beperkingen van zulke methoden ervaren. Dit kan o.a. bijdragen aan het integreren van zorgtechnologie in het dagelijks (kinder)fysiotherapeutisch handelen. We ontwikkelen een theoretisch raamwerk dat de basis legt voor betere vroegdetectie (op afstand en non-invasief) van vermoeidheid en voor het identificeren van mogelijke aangrijpingspunten voor behandeling (doelstelling 1 en 2). Verder draagt het postdoc onderzoek bij aan een beter inzicht in de rol van de sociale en fysieke leefomgeving bij de maatschappelijke participatie van jongeren met chronische aandoeningen (doelstelling 3). Studenten zullen in veldwerk ter plaatse metingen doen, de leefsituatie verkennen en samen met zorgprofessionals en docenten hun klinische blik verrijken. Doordat zij daadwerkelijk in de leefomgeving van jongeren zelf aanwezig zijn kan dit bijdragen aan bewustzijn over de rol van verschillende sociale en fysieke factoren op vermoeidheid en op de maatschappelijke participatie van jongeren met uiteenlopende chronische aandoeningen.
Reumatoïde artritis (RA) is een chronische auto-immuunziekte die veelal leidt tot beperkingen in dagelijkse activiteiten en maatschappelijke participatie bij een relatief jonge doelgroep (ca. 258.600 RA-patiënten in Nederland). Momenteel staat de medicamenteuze behandeling van RA op de poli van VieCuri Medisch Centrum centraal, maar er is steeds meer aandacht voor leefstijlinterventies als aanvullende behandeling, die mogelijk op den duur een deel van de medicatie kan vervangen. Voor een duurzame leefstijlgedragsverandering zijn programma’s nodig die advies en praktische ondersteuning op maat kunnen bieden. Recentelijk onderzoek uit de systeembiologie laat zien dat mensen met RA andere onderliggende oorzaken kunnen hebben, zogenaamde subtypes. Deze subtypes kunnen als vliegwiel dienen om sneller tot gepersonaliseerde leefstijlinterventies te komen. Subtypes voor RA worden onder andere valide bepaald door onderzoek naar biomarkers in bloed en urine en uitgebreide vragenlijsten (>100 vragen). Het multidisciplinaire team van de reumatologie van VieCuri Medische Centrum/Human Cristal Research bv vraagt zich af of het bepalen van het subtype nog eenvoudiger kan en wil dit in een cohortstudie onderzoeken (n=50). Volgende vraagstellingen zijn hierbij leidend: Kan de reeds ontwikkelde symptoomvragenlijst valide ingekort en gedigitaliseerd worden zodat deze hanteerbaarder is in de praktijk? Welke subtypes RA komen er in deze steekproef voor en welke globale leefstijladviezen passen daar het beste bij? Deze KIEM-aanvraag draagt bij aan een innovatief praktijkmodel waarbij (meer) gepersonaliseerde behandeling op basis van subtyperingen van mensen met RA centraal staat. Er wordt een bestaand samenwerkingsverband in Zuid-Limburg tussen Zuyd Hogeschool, VieCuri Medisch Centrum/Human Cristal Research bv, Struqt, Bool Studios en het Louis Bolk Instituut vernieuwd en verstevigd, om de gezondheidsachterstanden in de regio mee aan te pakken. Zowel zorgprofessionals als ook de betrokkenen kennisinstellingen en bedrijven zullen dan ook belangrijke gebruikers van het resultaat zijn.
