The demanding environment that contemporary dance students are exposed to could result in high stress levels, which can influence injury susceptibility. Therefore, this study aims to investigate the association between stress and injuries. In the period between September 2016 and March 2020, four cohorts of first-year dance students (N = 186; mean age 19.21 ± 1.35 years) were followed for one academic year. Each month, general stress was assessed on a 0-100 visual analogous scale. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used on a monthly basis to monitor injuries. Injuries were defined as "all injuries" (i.e., any physical complaint irrespective of the need for medical attention or time-loss from dance) and "substantial injuries" (i.e., leading to moderate/severe/complete reductions in training volume or performance). Mann-Whitney tests were performed to measure differences in general stress levels between injured and injury-free students, while repeated-measures ANOVA were performed to investigate whether general stress scores increased before and during injury occurrence. The overall average monthly general stress score over all cohorts for all students was 39.81. The monthly general stress scores ranged from 31.75 to 49.16. Overall, injured and substantially injured students reported higher stress scores than injury-free students, with significant differences in 3 out of the 9 months for all injuries (September, October, March, p < 0.05), and in 5 months for substantial injuries (September, October, November, December, April, p < 0.05). Within the 3-month period before and during injury occurrence, a (marginally) significant linear effect of general stress across the time periods was found for all injuries [F(1.87,216.49) = 3.10, p = 0.051] and substantial injuries [F(2,138) = 4.16, p = 0.018]. The results indicate an association between general stress and injuries. Future research should focus on effects of varying stress levels on injury risk using higher sampling frequency, for instance by measuring weekly since stress levels are likely to fluctuate daily. Practically, strategies aiming at stress reduction might have the potential to reduce the burden of dance injuries and may have positive outcomes for dancers, teachers, schools, and companies.
The demanding environment that contemporary dance students are exposed to could result in high stress levels, which can influence injury susceptibility. Therefore, this study aims to investigate the association between stress and injuries. In the period between September 2016 and March 2020, four cohorts of first-year dance students (N = 186; mean age 19.21 ± 1.35 years) were followed for one academic year. Each month, general stress was assessed on a 0-100 visual analogous scale. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used on a monthly basis to monitor injuries. Injuries were defined as "all injuries" (i.e., any physical complaint irrespective of the need for medical attention or time-loss from dance) and "substantial injuries" (i.e., leading to moderate/severe/complete reductions in training volume or performance). Mann-Whitney tests were performed to measure differences in general stress levels between injured and injury-free students, while repeated-measures ANOVA were performed to investigate whether general stress scores increased before and during injury occurrence. The overall average monthly general stress score over all cohorts for all students was 39.81. The monthly general stress scores ranged from 31.75 to 49.16. Overall, injured and substantially injured students reported higher stress scores than injury-free students, with significant differences in 3 out of the 9 months for all injuries (September, October, March, p < 0.05), and in 5 months for substantial injuries (September, October, November, December, April, p < 0.05). Within the 3-month period before and during injury occurrence, a (marginally) significant linear effect of general stress across the time periods was found for all injuries [F(1.87,216.49) = 3.10, p = 0.051] and substantial injuries [F(2,138) = 4.16, p = 0.018]. The results indicate an association between general stress and injuries. Future research should focus on effects of varying stress levels on injury risk using higher sampling frequency, for instance by measuring weekly since stress levels are likely to fluctuate daily. Practically, strategies aiming at stress reduction might have the potential to reduce the burden of dance injuries and may have positive outcomes for dancers, teachers, schools, and companies.
BACKGROUND: We recently developed a model of stratified exercise therapy, consisting of (i) a stratification algorithm allocating patients with knee osteoarthritis (OA) into one of the three subgroups ('high muscle strength subgroup' representing a post-traumatic phenotype, 'low muscle strength subgroup' representing an age-induced phenotype, and 'obesity subgroup' representing a metabolic phenotype) and (ii) subgroup-specific exercise therapy. In the present study, we aimed to test the construct validity of this algorithm.METHODS: Data from five studies (four exercise therapy trial cohorts and one cross-sectional cohort) were used to test the construct validity of our algorithm by 63 a priori formulated hypotheses regarding three research questions: (i) are the proportions of patients in each subgroup similar across cohorts? (15 hypotheses); (ii) are the characteristics of each of the subgroups in line with their proposed underlying phenotypes? (30 hypotheses); (iii) are the effects of usual exercise therapy in the 3 subgroups in line with the proposed effect sizes? (18 hypotheses).RESULTS: Baseline data from a total of 1211 patients with knee OA were analyzed for the first and second research question, and follow-up data from 584 patients who were part of an exercise therapy arm within a trial for the third research question. In total, the vast majority (73%) of the hypotheses were confirmed. Regarding our first research question, we found similar proportions in each of the three subgroups across cohorts, especially for three cohorts. Regarding our second research question, subgroup characteristics were almost completely in line with the proposed underlying phenotypes. Regarding our third research question, usual exercise therapy resulted in similar, medium to large effect sizes for knee pain and physical function for all three subgroups.CONCLUSION: We found mixed results regarding the construct validity of our stratification algorithm. On the one hand, it is a valid instrument to consistently allocate patients into subgroups that aligned our hypotheses. On the other hand, in contrast to our hypotheses, subgroups did not differ substantially in effects of usual exercise therapy. An ongoing trial will assess whether this algorithm accompanied by subgroup-specific exercise therapy improves clinical and economic outcomes.
MULTIFILE
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.
