The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher... Show moreThe genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development. Show less
Looman, N.; Graaf, J. de; Thoonen, B.; Asselt, D. van; Groot, E. de; Kramer, A.; ... ; Fluit, C. 2022
Background: To preserve quality and continuity of care, collaboration between primary-care and secondary-care physicians is becoming increasingly important. Therefore, learning intraprofessional... Show moreBackground: To preserve quality and continuity of care, collaboration between primary-care and secondary-care physicians is becoming increasingly important. Therefore, learning intraprofessional collaboration (intraPC) requires explicit attention during postgraduate training. Hospital placements provide opportunities for intraPC learning, but these opportunities require interventions to support and enhance such learning. Design-Principles guide the design and development of educational activities when theory-driven Design-Principles are tailored into context-sensitive Design-Principles. The aim of this study was to develop and substantiate a set of theory-driven and context-sensitive Design-Principles for intraPC learning during hospital placements. Methods: Based on our earlier research, we formulated nine theory-driven Design-Principles. To enrich, refine and consolidate these principles, three focus group sessions with stakeholders were conducted using a Modified Nominal Group Technique. Next, two work conferences were conducted to test the feasibility and applicability of the Design-Principles for developing intraPC educational activities and to sharpen the principles into a final set of Design-Principles. Results: The theoretical Design-Principles were discussed and modified iteratively. Two new Design-Principles were added during focus group 1, and one more Design-Principle was added during focus group 2. The Design-Principles were categorised into three clusters: (i) Culture: building collaborative relations in a psychologically safe context where patterns or feelings of power dynamics between primary and secondary care physicians can be discussed; (ii) Connecting Contexts: making residents and supervisors mutually understand each other's work contexts and activities; and (iii) Making the Implicit Explicit: having supervising teams act as role models demonstrating intraPC and continuously pursuing improvement in intraPC to make intraPC explicit. Participants were unanimous in their view that the Design-Principles in the Culture cluster were prerequisites to facilitate intraPC learning. Conclusion: This study led to the development of 12 theory-driven and context-sensitive Design-Principles that may guide the design of educational activities to support intraPC learning during hospital placements. Show less
Rietbergen, T.; Marang-van de Mheen, P.J.; Graaf, J. de; Diercks, R.L.; Janssen, R.P.A.; Linden-van der Zwaag, H.M.J. van der; ... ; SMART Study Grp 2022
Purpose: To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients >= 50 years with degenerative knee disease in 13 Dutch orthopaedic... Show morePurpose: To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients >= 50 years with degenerative knee disease in 13 Dutch orthopaedic centers (intervention group) compared with all other Dutch orthopaedic centers (control group). Methods: All patients with degenerative knee disease >= 50 years admitted to Dutch orthopaedic centers from January 2016 to December 2018 were included. The tailored intervention included participation of clinical champions, education on the Dutch Choosing Wisely recommendation for MRI's and arthroscopies in degenerative knee disease, training of orthopaedic surgeons to manage patient expectations, performance feedback, and provision of a patient brochure. A difference-in-difference analysis was used to compare the time trend before (admitted January 2016-June 2017) and after introduction of the intervention (July 2017-December 2018) between intervention and control hospitals. Primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy, weighted by type of hospital. Results: 136,446 patients were included, of whom 32,163 were treated in the intervention hospitals. The weighted percentage of patients receiving a MRI on average declined by 0.15% per month (beta = - 0.15, P < 0.001) and by 0.19% per month for arthroscopy (beta = - 0.19, P < 0.001). However, these changes over time did not differ between intervention and control hospitals, neither for MRI (beta = - 0.74, P = 0.228) nor arthroscopy (beta = 0.13, P = 0.688). Conclusions: The extent to which patients >= 50 years with degenerative knee disease received a MRI or arthroscopy declined significantly over time, but could not be attributed to the tailored intervention. This secular downward time trend may reflect anoverall focus of reducing low value care in The Netherlands. Show less
Ketzetzi, S.; Rinaldin, M.; Droge, P.; Graaf, J. de; Kraft, D.J. 2022
Biological microswimmers such as bacteria show collective motion that is made possible by an intricate interplay of sensing and signaling. Ketzetzi et al. reproduce this phenomenon in a catalytic... Show moreBiological microswimmers such as bacteria show collective motion that is made possible by an intricate interplay of sensing and signaling. Ketzetzi et al. reproduce this phenomenon in a catalytic system undergoing, for instance, cooperative speed-ups and dynamic reconfiguration of microswimmer chains.Cooperative motion in biological microswimmers is crucial for their survival as it facilitates adhesion to surfaces, formation of hierarchical colonies, efficient motion, and enhanced access to nutrients. Here, we confine synthetic, catalytic microswimmers along one-dimensional paths and demonstrate that they too show a variety of cooperative behaviours. We find that their speed increases with the number of swimmers, and that the activity induces a preferred distance between swimmers. Using a minimal model, we ascribe this behavior to an effective activity-induced potential that stems from a competition between chemical and hydrodynamic coupling. These interactions further induce active self-assembly into trains where swimmers move at a well-separated, stable distance with respect to each other, as well as compact chains that can elongate, break-up, become immobilized and remobilized. We identify the crucial role that environment morphology and swimmer directionality play on these highly dynamic chain behaviors. These activity-induced interactions open the door toward exploiting cooperation for increasing the efficiency of microswimmer motion, with temporal and spatial control, thereby enabling them to perform intricate tasks inside complex environments. Show less
Purpose Shared decision making calls for clinician communication strategies that aim to foster choice awareness and to present treatment options neutrally, such as by not showing a preference.... Show morePurpose Shared decision making calls for clinician communication strategies that aim to foster choice awareness and to present treatment options neutrally, such as by not showing a preference. Evidence for the effectiveness of these communication strategies to enhance patient involvement in treatment decision making is lacking. We tested the effects of 2 strategies in an online randomized video-vignettes experiment. Methods We developed disease-specific video vignettes for rheumatic disease, cancer, and kidney disease showcasing a physician presenting 2 treatment options. We tested the strategies in a 2 (choice awareness communication present/absent) by 2 (physician preference communication present/absent) randomized between-subjects design. We asked patients and disease-naive participants to view 1 video vignette while imagining being the patient and to report perceived room for involvement (primary outcome), understanding of treatment information, treatment preference, satisfaction with the consultation, and trust in the physician (secondary outcomes). Differences across experimental conditions were assessed using 2-way analyses of variance. Results A total of 324 patients and 360 disease-naive respondents participated (mean age, 52 +/- 14.7 y, 54% female, 56% lower educated, mean health literacy, 12 +/- 2.1 on a 3-15 scale). The results showed that choice awareness communication had a positive (M-present = 5.2 v. M-absent = 5.0, P = 0.042, eta(2)(partial) = 0.006) and physician preference communication had no (M-present = 5.0 v. M-absent = 5.1, P = 0.144, eta(2)(partial) = 0.003) significant effect on perceived room for involvement in decision making. Physician preference communication steered patients toward preferring that treatment option (M-present = 4.7 v. M-absent = 5.3, P = 0.006, eta(2)(partial) = 0.011). The strategies had no significant effect on understanding, satisfaction, or trust. Conclusions This is the first experimental evidence for a small effect of fostering choice awareness and no effect of physician preference on perceived room to participate in decision making. Physician preference steered patients toward preferring that option. Show less
Iotova, V.; Schalin-Jantti, C.; Bruegmann, P.; Broesamle, M.; Graaf, J. de; Bratina, N.; ... ; Hiort, O. 2021
Aim To perform a baseline survey on condition-specific information access among patients/parents/caregivers with rare endocrine disorders (RD) in Europe. Methods Electronic invitation to... Show moreAim To perform a baseline survey on condition-specific information access among patients/parents/caregivers with rare endocrine disorders (RD) in Europe. Methods Electronic invitation to participate in a survey (19 questions) was sent to 120 patient advocacy groups (PAGs), and further distributed to 32 European countries. Results A total of 1138 respondents from 22 countries (74% women), aged between 1 year (parents) and 70 years, participated. The Netherlands, France, Germany, Italy and France had highest participation rates. All Main Thematic Groups (MTGs) were represented; the adrenal (32%), pituitary (26%) and thyroid (22%) were the most common. The majority of the respondents got information from their endocrinologist (75%), PAGs (37%) and expert reference centre (22%); 95% received information in their mother tongue. Leaflets (70%), infographics (65%), webinars (60%) and Internet films (55%) were preferred ways of learning. Respondents relied mostly on materials by PAGs and alliances (79%), rather than from specific international RD sites (15%). Fifty-six percent used Facebook, and 37% other social media, with a significant age difference (40 years) among non-users, 19% vs. 36%, p < 0.0001. Of all, 685 answered questions on informational materials for children-79% wanted materials that can be used by the children themselves. There was significant age difference (40 years) in the willingness to help create new educational materials; 49% vs. 34%, p < 0.001. Conclusions Our current patient information access survey provides a sound basis for further planning and execution of educational and teaching activities by Endo-ERN. Show less
Verweij, R.W.; Ketzetzi, S.; Graaf, J. de; Kraft, D.J. 2020
