Transition readiness among adolescents and young adults with haemophilia in the Netherlands: Nationwide questionnaire study.

INTRODUCTION: Care for adolescents with haemophilia is transferred from paediatric to adult care around the age of 18 years. Transition programs help to prepare adolescents for this transfer and prevent declining treatment adherence. Evaluating transition readiness may identify areas for improvement. OBJECTIVE: Assess transition readiness among Dutch adolescents and young adults with haemophilia, determine factors associated with transition readiness, and identify areas of improvement in transition programs. METHODS: All Dutch adolescents and young adults aged 12-25 years with haemophilia were invited to participate in a nationwide questionnaire study. Transition readiness was assessed using multiple-choice questions and was defined as being ready or almost ready for transition. Potential factors associated with transition readiness were investigated, including: socio-demographic and disease-related factors, treatment adherence, health-related quality of life, and self-efficacy. RESULTS: Data of 45 adolescents and 84 young adults with haemophilia (47% with severe haemophilia) were analyzed. Transition readiness increased with age, from 39% in 12-14 year-olds to 63% in 15-17 year-olds. Nearly all post-transition young adults (92%, 77/84) reported they were ready for transition. Transition readiness was associated with treatment adherence, as median VERITAS-Pro treatment adherence scores were worse in patients who were not ready (17, IQR 9-29), compared to those ready for transition (11, IQR 9-16). Potential improvements were identified: getting better acquainted with the adult treatment team prior to transition and information on managing healthcare costs. CONCLUSIONS: Nearly all post-transition young adults reported they were ready for transition. Improvements were identified regarding team acquaintance and preparation for managing healthcare costs.

The legacy of haemophilia: Memories and reflections from three survivors.

Following the publication of a book of personal memories by one of us (CS1,2 ), we have attempted to synthesis our joint memories of three ageing men, born in the era preceding universal access to treatment, in an attempt to describe our experience, our challenges and our reflections on the development of therapies, which have ensured that our experience of growing up with haemophilia in the 1950s and 1960s has not been mirrored by the current generation of patients. We describe our upbringing in different parts of Europe in health care systems which, while of varying standards, were all unable to offer the kind of care which developed after the development of specific therapies. We assess the effect of the contamination of these therapies by blood-borne pathogens on our own development, and the development of our communities around us. In addition, we reflect on the lessons learnt, sometimes painfully, by our generation of people with haemophilia and how some of these enabled us to overcome substantial hurdles, survive and build productive lives. Finally, we survey the development of therapies in the past 20 years, and offer some reflections on how our experience can be integrated in a realistic expectation of what the future holds for our community, in our own affluent societies and in countries less advantaged economically. We hope that our thoughts may contribute to continued progress in the field of haemophilia care.

Adherence to prophylaxis and its association with activation of self-management and treatment satisfaction.

INTRODUCTION: Prophylactic replacement therapy (prophylaxis) in patients with haemophilia (PWH) requires lifelong, frequent (self)infusions. Prophylaxis effectiveness depends on adherence, and the drivers of treatment adherence among PWH are unclear. AIM: To quantify prophylaxis adherence and associations between adherence and patients' treatment attitudes and satisfaction in a large cohort of children and adults with haemophilia. METHODS: In a nationwide, cross-sectional, questionnaire-based study, PWH with complete information currently using prophylaxis were selected. Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis (VERITAS-Pro; normalised score range: 0-100, optimum 0) measured treatment adherence; the Patient Activation Measure (PAM-13; total score range 0-100, optimum 100) measured activation of self-management; Hemophilia Patient Satisfaction Scale (Hemo-Sat; range 0-100, optimum 0) measured treatment satisfaction. Groups were compared according to age (children: <12 years; adolescents: 12-18 years; adults >18 years) and adherence levels using non-parametric tests, and correlations were assessed using Spearman's rho. RESULTS: Among 321 participants (median age 33 years, interquartile range [IQR]:15-54 years), adherence was high (median VERITAS-Pro total score 17, 89% adherent) but worsened with age, with median scores of 5, 14 and 20 in children, adolescents, adults, respectively (p < .001). Attitudes towards treatment (median 66 vs. 68) participants and treatment satisfaction (12 vs. 10) were similar between adherent and non-adherent patients. The VERITAS-Pro total score was moderately correlated with PAM-13 (r = .41) but not with Hemo-Sat (r = -.11). DISCUSSION: Prophylaxis adherence was high (89%) but decreased significantly with age and was not correlated with treatment attitude or treatment satisfaction.

Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study.

INTRODUCTION: Although sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking. AIM: to assess sports participation in Dutch PWH (6-65 years) compared to the Dutch general population (GP). METHODS: Data from a nationwide, cross-sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high-risk sports. Groups were compared using Chi-square testing. RESULTS: A total of 524 Adult PWH (median age: 45 (IQR: 30-55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8-14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High-risk sports participation decreased with age in PWH: from 65% (6-12 years) to 17% (50-65 years), which was also observed in the GP. Sports participation in children was independent of severity (non-severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non-severe: 75%, severe: 62%; P < 0.01). Non-severe PWH played more high-risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07). DISCUSSION: These results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high-risk sports than adults. More studies on sports-related injury-risk are needed for adequate counselling.

The impact of non-response bias due to sampling in public health studies: A comparison of voluntary versus mandatory recruitment in a Dutch national survey on adolescent health.

BACKGROUND: In public health monitoring of young people it is critical to understand the effects of selective non-response, in particular when a controversial topic is involved like substance abuse or sexual behaviour. Research that is dependent upon voluntary subject participation is particularly vulnerable to sampling bias. As respondents whose participation is hardest to elicit on a voluntary basis are also more likely to report risk behaviour, this potentially leads to underestimation of risk factor prevalence. Inviting adolescents to participate in a home-sent postal survey is a typical voluntary recruitment strategy with high non-response, as opposed to mandatory participation during school time. This study examines the extent to which prevalence estimates of adolescent health-related characteristics are biased due to different sampling methods, and whether this also biases within-subject analyses. METHODS: Cross-sectional datasets collected in 2011 in Twente and IJsselland, two similar and adjacent regions in the Netherlands, were used. In total, 9360 youngsters in a mandatory sample (Twente) and 1952 youngsters in a voluntary sample (IJsselland) participated in the study. To test whether the samples differed on health-related variables, we conducted both univariate and multivariable logistic regression analyses controlling for any demographic difference between the samples. Additional multivariable logistic regressions were conducted to examine moderating effects of sampling method on associations between health-related variables. RESULTS: As expected, females, older individuals, as well as individuals with higher education levels, were over-represented in the voluntary sample, compared to the mandatory sample. Respondents in the voluntary sample tended to smoke less, consume less alcohol (ever, lifetime, and past four weeks), have better mental health, have better subjective health status, have more positive school experiences and have less sexual intercourse than respondents in the mandatory sample. No moderating effects were found for sampling method on associations between variables. CONCLUSIONS: This is one of first studies to provide strong evidence that voluntary recruitment may lead to a strong non-response bias in health-related prevalence estimates in adolescents, as compared to mandatory recruitment. The resulting underestimation in prevalence of health behaviours and well-being measures appeared large, up to a four-fold lower proportion for self-reported alcohol consumption. Correlations between variables, though, appeared to be insensitive to sampling bias.

The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia A.

Objectives: Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities. Methods: All persons with hemophilia A (mild (FVIII > 5-40 IU/dL)/moderate [FVIII 1-5 IU/dL)/severe (FVIII < 1 IU/dL)] with an available plasma sample who participated in the sixth Hemophilia in the Netherlands study between 2018 and 2019 were included. The presence of anti-FVIII antibodies of the immunoglobulin A, M, and G isotypes and IgG subclasses, along with antibody titer levels, were assessed using direct-binding ELISAs. FVIII specificity was assessed using a competition-based ELISA approach. The inhibitor status was determined using the Nijmegen ultra-sensitive Bethesda assay (NusBA) and the Nijmegen Bethesda assay (NBA). Results: In total, 788 persons with hemophilia A (336 (42.6%) mild, 123 (15.6%) moderate, 329 (41.8%) severe hemophilia) were included. The median age was 45 years (IQR 24-60), and the majority (50.9%) had over 150 exposure days to FVIII concentrates. Within our population, 144 (18.3%) individuals had non-neutralizing FVIII-specific antibodies, 10 (1.3%) had very low-titer inhibitors (NusBA positive; NBA negative), and 13 (1.6%) had inhibitors (both NusBA and NBA positive). IgG1 was the most abundant FVIII-specific antibody subclass, and the highest titer levels were found for IgG4. In individuals without a reported history of inhibitor development, no clear differences were observed in antibody patterns between those who were minimally or highly exposed to FVIII concentrates. IgG4 subclass antibodies were only observed in persons with a reported history of FVIII inhibitor or in those with a currently detected (very low-titer) inhibitor. Conclusion: In this cross-sectional study, we identified non-neutralizing antibodies in a relatively large proportion of persons with hemophilia A. In contrast, in our population, consisting of persons highly exposed to FVIII concentrates, (very low-titer) inhibitors were detected only in a small proportion of persons, reflecting a well-tolerized population. Hence, our findings suggest that only a small subpopulation of non-neutralizing FVIII-specific antibodies is associated with clinically relevant inhibitors.

Desmopressin in nonsevere hemophilia A: patient perspectives on use and efficacy.

Background: Desmopressin increases plasma factor VIII and von Willebrand factor levels in persons with nonsevere hemophilia A. Patients' perspectives on desmopressin are relevant to increase and optimize its suboptimal use. However, patients' views on desmopressin are not reported. Objectives: To evaluate the perspectives of persons with nonsevere hemophilia A on desmopressin use, barriers for its use, side effects, and their knowledge about desmopressin's efficacy and side effects. Methods: Persons with nonsevere hemophilia A were included in a cross-sectional, national, multicenter study. Questionnaires were filled out by adult patients and children aged ≥12 years themselves. Caretakers filled out questionnaires for children aged <12 years. Results: In total, 706 persons with nonsevere hemophilia A were included (544 mild, 162 moderate, [age range, 0-88 years]). Of 508 patients, 234 (50%) patients reported previous desmopressin use. Desmopressin was considered as at least moderately effective in 171 of 187 (90%) patients. Intranasal administration was the modality of choice for 138 of 182 (76%) patients. Flushing was the most reported side effect in 54 of 206 (26%) adults and 7 of 22 (32%) children. The most frequently reported advantage and disadvantage were the convenience of intranasal, out-of-hospital administration by 56% (126/227) and side effects in 18% (41/227), respectively. Patients' self-perceived knowledge was unsatisfactory or unknown in 28% (63/225). Conclusion: Overall, desmopressin was most often used intranasally and considered effective, with flushing as the most common side effect. The most mentioned advantage was the convenience of intranasal administration and disadvantage was side effects. More information and education on desmopressin could answer unmet needs in patients with current or future desmopressin treatment.

Socioeconomic participation of persons with hemophilia: Results from the sixth hemophilia in the Netherlands study.

Background and objectives: Treatment availability and comprehensive care have resulted in improved clinical outcomes for persons with hemophilia. Recent data on socioeconomic participation in the Netherlands are lacking. This study assessed participation in education, in the labor market, and social participation for persons with hemophilia compared with the general male population. Methods: Dutch adults and children (5-75 years) of all hemophilia severities (n = 1009) participated in a questionnaire study that included sociodemographic, occupational, and educational variables. Clinical characteristics were extracted from electronic medical records. General population data were extracted from Statistics Netherlands. Social participation was assessed with the PROMIS Ability to Participate in Social Roles and Activities short form, with a minimal important difference set at 1.0. Results: Data from 906 adults and children were analyzed. Participation in education of 20 to 24 year olds was 68% (general male population: 53%). Educational attainment was higher compared with Dutch males, especially for severe hemophilia. Absenteeism from school was more common than in the general population. The employment-to-population ratio and occupational disability were worse for severe hemophilia than in the general population (64.3% vs. 73.2% and 14.7% vs. 4.8%, respectively), but similar for nonsevere hemophilia. Unemployment was 5.4% (general male population: 3.4%). Absenteeism from work was less common (38% vs. 45.2%). Mean PROMIS score was similar to or higher than in the general population (54.2; SD 8.9 vs. 50; SD 10). Conclusion: Socioeconomic participation of persons with nonsevere hemophilia was similar to the general male population. Some participation outcomes for persons with severe hemophilia were reduced.

Hepatitis C virus in hemophilia: Health-related quality of life after successful treatment in the sixth Hemophilia in the Netherlands study.

INTRODUCTION: Persons with hemophilia and hepatitis C virus (HCV) infection have a lower health-related quality of life (HRQoL) than those never HCV infected. However, it is unknown whether HRQoL after HCV eradication is comparable to individuals never HCV infected. We aimed to compare HRQoL between HCV-cured and never chronically HCV-infected persons with hemophilia. METHODS: All persons with hemophilia in the Netherlands were invited for a nationwide study conducted in 2018-2019. For the current analysis, participants born before 1992 with data on HRQoL and HCV status were included. HCV status was collected from medical records. HRQoL was measured by RAND-36 questionnaire, with a minimally important difference set at 4.0 points. Multivariable linear regression was used to adjust for age, hemophilia severity, HIV status, and self-reported joint impairment. RESULTS: In total, 486 persons were eligible; 180 were HCV cured and 306 never chronically HCV infected. Compared with those never HCV infected, HCV-cured individuals were older (57 vs. 53 years), more often had severe hemophilia (67% vs. 21%), and reported more impaired joints (median 3 vs. 0). Compared with those never HCV infected, adjusted RAND-36 domain scores of HCV-cured individuals cured were lower on all RAND-36 domains except Pain, ranging from a difference of 4.5 (95% CI, -8.8 to -0.3) for Physical functioning to 11.3 (95% CI, -19.4 to -3.1) for Role limitations due to physical problems. CONCLUSION: Despite effective HCV treatment, HRQoL of HCV-cured persons with hemophilia is still lower than HRQoL of those never chronically HCV-infected on all RAND-36 domains. This implies that careful psychosocial follow-up and support are indicated.

Health and treatment outcomes of patients with hemophilia in the Netherlands, 1972-2019.

INTRODUCTION: We conducted six cross-sectional nationwide questionnaire studies among all patients with hemophilia in the Netherlands from 1972 until 2019 to assess how health outcomes have changed, with a special focus on patients >50 years of age. METHODS: Data were collected on patient characteristics, treatment, (joint) bleeding, joint impairment, hospitalizations, human immunodeficiency virus and hepatitis C infections, and general health status (RAND-36). RESULTS: In 2019, 1009 patients participated, of whom 48% had mild, 15% moderate, and 37% severe hemophilia. From 1972 to 2019, the use of prophylaxis among patients with severe hemophilia increased from 30% to 89%. Their median annual bleeding rate decreased from 25 to 2 bleeds. Patients with severe hemophilia aged <16 years reported joint impairment less often over time, but in those aged >40 years joint status did not improve. In 2019, 5% of all 1009 patients were positive for the human immunodeficiency virus. The proportion of patients with an active hepatitis C infection drastically decreased from 45% in 2001 to 2% in 2019 due to new anti-hepatitis C treatment options. Twenty-five percent had significant liver fibrosis even after successful therapy. Compared to the general male population, patients aged >50 years reported much lower scores on the RAND-36, especially on physical functioning. DISCUSSION/CONCLUSION: Our study shows that increased use of prophylactic treatment and effective hepatitis C treatment have improved joint health and nearly eradicated hepatitis C infection in patients with hemophilia in the Netherlands. However, patients still suffer from hemophilia-related complications, especially patients aged >50 years.

Validation of PROMIS Profile-29 in adults with hemophilia in the Netherlands.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) Profile-29 questionnaire is widely used worldwide, but it has not yet been validated in the Netherlands, nor in persons with hemophilia. OBJECTIVE: To validate the Dutch-Flemish version of the PROMIS-29 Profile v2.01 in adults with hemophilia. METHODS: Dutch males with hemophilia (all severities) completed questionnaires that contained sociodemographic and clinical characteristics, the PROMIS-29, RAND-36, and the Hemophilia Activities List (HAL). Structural validity of each subscale was assessed with confirmatory factor analysis (CFA). Internal consistency was calculated for each subscale with sufficient model fit in CFA. Construct validity was assessed by testing hypotheses about (1) correlations of each PROMIS-29 subscale with corresponding scales of RAND-36 and domains of HAL, and (2) mean differences in T-scores between subgroups with different hemophilia severities, self-reported joint impairment, and HIV infection status. We considered ≥75% of data in accordance with the hypotheses evidence for construct validity. RESULTS: In total, 770 persons with hemophilia participated in this cross-sectional study. CFA revealed sufficient structural validity for five subscales: Physical Function, Depression, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Internal consistency was high and Cronbach's alpha ranged from 0.79 for Sleep Disturbance to 0.96 for Pain Interference. Differences between clinical subgroups were in the expected direction. Construct validity was confirmed for Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, and Pain Intensity. CONCLUSION: This study revealed sufficient evidence for structural validity, internal consistency, and construct validity for most PROMIS Profile-29 subscales among people with hemophilia in the Netherlands.

Patient-relevant health outcomes for hemophilia care: Development of an international standard outcomes set.

BACKGROUND: Patient-relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia. METHODS: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables. Persons with hemophilia and multidisciplinary health care providers were involved in an iterative nominal consensus process to select the most important health outcomes and risk adjustment variables for persons with hemophilia. Recommendations were made for outcome measurement instruments. RESULTS: Persons with hemophilia were defined as all men and women with an X-linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII or IX with plasma activity levels <40 IU/dL. We recommend collecting the following 10 health outcomes at least annually, if applicable: (i) cure, (ii) impact of disease on life expectancy, (iii) ability to engage in normal daily activities, (iv) severe bleeding episodes, (v) number of days lost from school or work, (vi) chronic pain, (vii) disease and treatment complications, (viii) sustainability of physical functioning, (ix) social functioning, and (x) mental health. Validated clinical as well as patient-reported outcome measurement instruments were endorsed. Demographic factors, baseline clinical factors, and treatment factors were identified as risk-adjustment variables. CONCLUSION: A consensus-based international set of health outcomes relevant to all persons with hemophilia, and corresponding measurement instruments, was identified for use in clinical care to facilitate harmonized longitudinal monitoring and comparison of outcomes.

Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001-2018.

BACKGROUND: Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands. OBJECTIVE: This observational cohort study aimed to assess all-cause and cause-specific mortality in patients with hemophilia in the Netherlands between 2001 and 2018 and to compare mortality and life expectancy with previous survival assessments from 1973 onward. PATIENTS/METHODS: All 1066 patients with hemophilia who participated in a nationwide survey in 2001 were followed until July 2018. RESULTS: Information on 1031 individuals (97%) was available, of whom 142 (14%) deceased during follow-up. Compared with the general Dutch male population, mortality of patients with hemophilia was still increased (standardized mortality ratio: 1.4, 95% confidence interval: 1.2-1.7). Intracranial bleeding and malignancies were the most common causes of death. Estimated median life expectancy of patients with hemophilia was 77 years, 6 years lower than the median life expectancy of the general Dutch male population (83 years). Over the past 45 years, death rates of patients with hemophilia have consistently decreased, approaching the survival experience of the general population. Over the past decades, mortality due to human immunodeficiency virus and hepatitis C virus infections has decreased, death due to intracranial hemorrhages has increased, and death due to ischemic heart disease has remained consistently low over time. CONCLUSIONS: Survival in patients with hemophilia in the Netherlands has improved over time but is still lower than that of the general population.

Patient Perspectives on Novel Treatments in Haemophilia: A Qualitative Study.

BACKGROUND AND OBJECTIVE: New treatments for haemophilia are under development or entering the market, including extended half-life products, designer drugs and gene therapy, thereby increasing treatment options for haemophilia. It is currently unknown how people with haemophilia decide whether to switch to a new treatment. Therefore, the objective of this study was to explore what factors may play a role when Dutch patients and parents of boys with moderate or severe haemophilia make decisions about whether to switch to a different treatment, and how disease and treatment characteristics may affect these decisions. This may aid clinical teams in tailored information provision and shared decision making. METHODS: We conducted interviews among adults with moderately severe or severe haemophilia and parents of young boys with severe haemophilia. We aimed to include participants from a variety of backgrounds in terms of involvement in the haemophilia community, age, treatment centre and treatments. Participants were recruited through the Netherlands Haemophilia Society and a haemophilia treatment centre. Semi-structured interviews were recorded and transcribed verbatim. Thematic content analysis was used to analyse the data. RESULTS: Twelve people with haemophilia and two mothers of boys with haemophilia were included. In general, participants reported to be satisfied with their current treatment. However, they considered ease of use of the medication (fewer injections, easier handling, alternative administration) an added value of new treatments. Participants were aware of the high cost of coagulation factor products and some expressed their concern about the Netherlands Haemophilia Society's long-term willingness to pay for current and novel treatments, especially for increased usage due to high-risk activities. Participants also expressed their concerns about the short- and long-term safety of new treatments and believed the effects of gene therapy were not yet fully understood. Participants expected their treatment team to inform them when a particular new treatment would be suitable for them. CONCLUSIONS: With the number of treatment options set to increase, it is important for healthcare providers to be aware of how patient experiences shape patients' decisions about new therapies.

Impact of a technological disaster on young children: a five-year postdisaster multiinformant study.

Children exposed to a technological disaster during an understudied part of the lifespan, preschool age and early middle childhood, were assessed in a 5-year follow-up regarding mental health problems, anxiety disorder symptoms, depressive symptoms, physical symptoms, and posttraumatic stress symptoms. Exposed children and their parents (n = 264) reported significantly more problems than controls (n = 515). The differences were greater for conduct problems (including hyperactivity) and physical symptoms, than for anxiety and depression. The long-term effects of a technological disaster on children of pre-school age at exposure appear to differ from those in children, who were victimized at a later age. This may reflect interference with completion of specific developmental tasks.

Patients to learn from: on the need for systematic integration of research and care in academic health care.

Patients suffering from rare, extreme or extremely complex sets of symptoms have something to expect from efforts to improve care through research. Biomedical research and care have often been approached as distinct worlds which are and should be only loosely connected. For observational research focusing on data drawn from real-world settings, however, that approach is found wanting. Integrating research and care responsibly is the main challenge instead. Integrated IT infrastructures facilitating Personalized medicine and Big Data are crucial components of a learning health care system, in which patients regularly play a double role: as individuals to be treated and as cases to learn from. Drawing on the example of the Dutch Parelsnoer Institute (PSI), a national biobanking and IT infrastructure integrated with clinical care procedures, this article outlines the reforms that are needed. Systematic integration of research and care offers a promising avenue, provided that a number of conditions are met: data and IT infrastructures will require overhauls in order to facilitate secure, high-quality data integration between research and care; institutional focus is needed to bring patient populations and expertise together; ethical frameworks and approaches for integrating research and care responsibly require further elaboration; clinical procedures and professional responsibilities may need to be adapted in order to accommodate research requirements in clinical processes; and involvement of patients and other stakeholders in design and research priority setting is needed to further the goals of real-world and patient relevance. RELEVANCE FOR PATIENTS: Integrating research and care in academic medicine in a more systematic fashion offers a promising perspective to current and future patients. In order to live up to these promises, research and care should be integrated more systematically in academic health science, with patients being included as research participants by default. Data and tissue infrastructures and facilities can provide a platform for doing so. At the same time, many issues remain to be settled. New ethical ways and means for protecting and respecting patient-participants in such a double role are also needed in this respect. In this way a deeper transformation is at stake as well: a change towards a setting in which patients fully take center stage in debate and action on the future of biomedicine.