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Growing up with hemophilia
Health related quality of life and psychosocial functioning
Limperg, P.F.
Publication date
2017
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Citation for published version (APA):
Limperg, P. F. (2017). Growing up with hemophilia: Health related quality of life and
psychosocial functioning.
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Chapter 6
Generic and disease-specific health related quality
of life in children and adolescents with bleeding
disorders
P.F. Limperg, M.M. H. Joosten, K. Fijnvandraat, M. Peters, M.A. Grootenhuis, L. Haverman
Abstract
Background: The use of health related quality of life (HRQOL) patient reported
outcomes (PROs) in daily clinical practice has received increased attention. This study assesses generic and disease-specifi c HRQOL of children and adolescents with bleeding disorders in the Netherlands in comparison to peers and between hemophilia severity groups.
Methods: All children with bleeding disorders (0-18 years) under treatment
at the Comprehensive Hemophilia Treatment Center AMC, Amsterdam were included. Participants completed online questionnaires as part of standard care in monitoring HRQOL in daily clinical practice. Generic HRQOL was measured using the TAPQOL (0-5 years) and the PedsQL (6-18 years). Disease-specifi c HRQOL was measured using the Haemo-QoL (4-18 years). Differences between children with bleeding disorders and norm groups, and between hemophilia severity groups, were tested using Mann Whitney U-tests.
Results: In total, 146 children with bleeding disorders participated. Children
(0-12 years) with bleeding disorders show no signifi cant impairments in generic HRQOL in comparison to their healthy and chronically ill peers. Boys (13-18 years) with bleeding disorders report higher generic HRQOL on the total and emotional functioning scales than their healthy and chronically ill peers. Girls (13-18 years) experience lower generic HRQOL on the total, social functioning and psychosocial health scales than their healthy peers. Boys (8-18 years) with severe hemophilia only report lower disease-specifi c HRQOL on the domain ‘family’ in comparison to boys with non-severe hemophilia.
Conclusion: Generic HRQOL of boys with bleeding disorders in the Netherlands
is comparable with healthy peers, while teenage girls with bleeding disorders show impaired generic HRQOL and boys with severe hemophilia show more problems in the family domain on disease-specifi c HRQOL. Despite positive results, continuing monitoring HRQOL in daily clinical practice for children with bleeding disorders is important, of girls especially, because possible infl uencing psychosocial factors can change over time.
121
Introduction
Health Related Quality of Life (HRQOL) as an outcome measure has received increased attention in pediatrics over the past years [1-3]. HRQOL is defi ned as a multidimensional concept that refers to the impact of health and illness on an individual’s quality of life, which encompasses not only physical aspects but also social and emotional aspects [4, 5]. Measuring HRQOL in children is challenging however and starts with making decisions regarding: generic versus disease-specifi c questionnaires, age-specifi c questionnaires with a narrow versus a wide age range, self-report versus proxy-report, and paper-pencil versus online questionnaires [3]. HRQOL is subjective by defi nition; an identical health condition in different patients may result in different ratings of HRQOL. Thus, the patient’s report is the best source of information when measuring HRQOL [6], and HRQOL assessment should be a form of a patient reported outcome (PRO).
Children growing up with bleeding disorders in the Netherlands nowadays experience the advances in medicine that have occurred over the past decades. Bleeding disorders are caused by a defi ciency of the blood clotting system, in which bleeding is prolonged and excessive. Hemophilia A and B and von Willebrand (VWD) are the most common bleeding disorders identifi ed [7]. Hemophilia is X-linked, which means that mothers are carriers and primarily boys are affected, which results in spontaneous and/or posttraumatic bleeds [8]. Other inherited bleeding disorders, such as VWD, affect both boys and girls. Since the introduction of home prophylactic treatment in the 1970’s, to prevent bleeding and disability with intensive factor replacement, the HRQOL of patients with bleeding disorders has increased tremendously [8]. Despite the advantages of being able to provide care at home (e.g. less hospital visits, more independence), the large responsibility for management of hemophilia, such as administration of treatment by intravenous infusion of clotting factor concentrate, is still burdensome [9]. Also, children and adolescents with hemophilia still endure diffi culties and impairments, such as hospital visits, frequent injections and limited participation in travel, educational- and sport activities [10, 11].
While the benefi ts of the advances in treatment are a privilege, children and adolescents with hemophilia can still suffer from pain, arthropathy and limitations which infl uences HRQOL [12-14]. So far, existing literature on the effect of hemophilia and its treatment on HRQOL in children and adolescents is confl icting. Some suggest that hemophilia does not affect HRQOL or psychosocial functioning during childhood negatively [15, 16], where other studies report that children with hemophilia do experience lower HRQOL compared to their healthy peers, particularly for those with more severe hemophilia [17-19]. Understanding what it is like to grow up in ‘the golden era’ of hemophilia care is valuable in accommodating the needs and possibilities of children with hemophilia.
Because of the aforementioned reasons, it is important to monitor HRQOL in children and adolescents with hemophilia in daily clinical practice. One way to do this is, by using PROs systematically. This can be helpful in identifying and discussing HRQOL issues, such as emotional and psychosocial functioning, and provide tailored interventions if needed [20-22]. The current study is based on PROs, which were generated from routine assessment of HRQOL at the Hemophilia Comprehensive Care Center (HCCC) of the Emma Children’s Hospital/AMC in Amsterdam. To monitor and discuss HRQOL as part of standard care, the HCCC uses the KLIK system [23]. KLIK (in Dutch: Kwaliteit Leven In Kaart, in English: quality of life in clinical practice) is a web-based tool developed for the use of PROs in daily clinical practice [24]. It is mainly designed to monitor HRQOL and improve the communication about HRQOL and psychosocial problems between the doctor and patient [20]. While monitoring HRQOL in daily clinical practice as standard part of care, data on HRQOL is collected and can be used for research. This study compares the generic HRQOL of children with bleeding disorders to healthy and chronically ill Dutch peers, and disease-specifi c HRQOL as well as severity in boys with hemophilia.
123
Methods
Participants
Eligible participants included all patients (0-18 years) with hemophilia (severe and non-severe) and other severe congenital bleeding disorders and their parents, under treatment at the HCCC.
KLIK procedure
Patients received a letter in which KLIK was introduced as part of standard care and parents and the children were asked to register on the KLIK website (www.hetklikt.nu). Prior to consultation, children and/or parents completed online questionnaires at home. Before completing any questionnaires, parents and/or children (>12 years) had to give pro-active informed consent for their data to be used for research purposes. Without this consent, children and parents could still complete the questionnaires, but limited for use in daily clinical practice. In total, four children and parents (3%) did not give consent for research purposes. Children 8-18 years old completed the questions themselves. For younger patients (≤7 years old), parents completed the questionnaires. During consultation, the results of completed questionnaires (KLIK PROfi les) are discussed by the pediatric hematologist or other member of the multidisciplinary team.
Study design
Data used in this study was retrieved from the KLIK website. We used a cross-sectional design: data was used and analyzed from patients who were under treatment at the HCCC between September 2011 and November 2016. Data from the fi rst time patients completed the questionnaire via KLIK were used. For those participants with hemophilia A or B, a disease-specifi c HRQOL questionnaire was added to the set of questionnaires in 2014. The current study was approved by Medical Ethics Committee of the Academic Medical Center Amsterdam.
Measures
Socio-demographics
Information on socio-demographic characteristics regarding age, gender, ethnicity, education, employment and marital status was collected by a self-composed questionnaire. Educational level of the parents was divided into three categories according to the classifi cation of Statistics Netherlands; low (primary education, lower vocational education, lower and middle general secondary education), intermediate (middle vocational education, higher secondary education, pre-university education), high (higher vocational education, university). In addition, medical information regarding the type and severity of the bleeding disorder and treatment was obtained from medical records.
Generic Health Related Quality of Life: TAPQOL (0-5 years)
The TNO-AZL Preschool Children Quality of Life (TAPQOL) was used to assess the generic HRQOL of young children (0-5 years old) by proxy-report [25]. The TAPQOL contains 32 or 43 items (when the child is aged ≥1.5 years 11 additional questions are asked) in 12 scales: stomach problems (3 items), skin problems (3 items), lung problems (3 items), sleeping problems (4 items), appetite (3 items), problem behavior (7 items), positive mood (3 items), anxiety (3 items), liveliness (3 items), social functioning (3 items), motor functioning (4 items), and communication (4 items). Each item states a problem and refers to the past three months. On a 3-point Likert scale, ranging from 1 (never) to 3 (often), parents indicate whether his/her child had problems with that item. A higher score (0-100) represents a better HRQOL. Good validity and reliability for this instrument have been shown [25]. The reliability (Cronbach’s α) of the TAPQOL scales in the present study ranged from .48 (stomach) to .88 (communication). A comparison group of Dutch peers of 0-1 years and of 2-5 years was available.
125 Generic Health Related Quality of Life: PedsQL 4.0 Generic Core Scales (6-18
years)
The Pediatric Quality of Life Inventory (PedsQL) was used to assess the generic HRQOL of children 6-18 years old, by proxy-report (6-7 years) or self-report (8-18 years) [26]. The PedsQL contains 23 items in four scales; physical health (8 items), emotional functioning (5 items), social functioning (5 items) and school functioning (5 items). Each of the 23 items states a problem and refers to the past week (acute version). On a 5-point Likert scale, ranging from 0 (never) to 4 (almost always), the child or parent indicates whether he/she had problems with that item. Each answer is reversed scored and rescaled to a 0-100 scale. A psychosocial health scale score (sum of the emotional, social and work/school functioning scales) and a total scale score can be computed. Higher scores on the PedsQL indicate better HRQOL. Good validity and reliability for this instrument have been shown, also in a Dutch population [26, 27]. The reliability (Cronbach’s α) of the PedsQL scales in the present study range from .68 (school functioning) to .93 (total scale). A comparison group of healthy and chronically ill peers (6-18 years) was available [27].
Disease-specifi c Health Related Quality of Life: Haemo-QoL
Disease-specifi c HRQOL of children with hemophilia was assessed with the Haemophilia Quality of Life Questionnaire (Haemo-QoL), proxy-report (4-7 years) or self-report (8-18 years) [28]. In this study, the short form measures were used. The version for children 4-7 years contains 16 items in eight domains: physical health (2 items), feeling (2 items), view of yourself (2 items), family (2 items), friends (2 items), other persons (2 items), sports and school (2 items) and treatment (2 items). The version for children 8-18 years contains 35 items in nine domains: physical health (4 items), feeling (4 items), view of yourself (4 items), family (4 items), friends (3 items), other persons (4 items), sports and school (4 items), dealing with hemophilia (4 items) and treatment (4 items) [28, 29]. On a 5-point Likert scale, ranging from 0 (never) to 4 (always), the child or parent indicates whether he/she had problems with that item and refers to the past 4 weeks. Each answer is scored and scaled from 0-100, where high
values indicate low HRQOL scores. Good validity and acceptable reliability for this measurement have been shown [28, 29]. In our sample, Cronbach’s alphas ranged from .48 (deal) to .92 (feel) for the child version and from .34 (friends) to .89 (feel) for the parent version.
Statistical Analyses
The Statistical Package for Social Sciences (SPSS) version 23.0 was used for all statistical analyses [30]. First, preparatory analyses were performed: computing of scale scores and calculation of the internal consistencies (Cronbach’s alphas), and the distributions of the scale scores were considered.
Next, descriptive analyses were performed to describe the sample. Demographic characteristics of our sample, non-respondents and the norm groups were compared using χ2-tests for categorical data and t-tests for
continuous data. The sample did not differ from non-respondents on gender, age or type of bleeding disorder.
Since hemophilia affects primarily boys, the sample of children with bleeding disorders had a signifi cantly higher percentage (p<.05, 77%) of boys than the norm groups (56%). In addition, bleeding disorders have a different impact on boys than girls, and therefore we analyzed the outcomes for gender separately. Since bleeding disorders other than hemophilia have a less clear distinction in severity, differences between YA boys with severe and non-severe hemophilia only were analyzed on generic and disease-specifi c HRQOL. Differences in the TAPQOL and PedsQL scale scores between the present sample and children in the norm population, and differences between severe and non-severe hemophilia on the PedsQL and Haemo-QoL were analyzed with Mann Whitney U-tests. Haemo-QoL scales with a low internal consistency (Cronbach’s alpha ≤.60) were eliminated from analyses (4-7 years: friends; 8-17 years: other persons, dealing with hemophilia). To adjust for multiple testing, we used a Bonferroni correction for the TAPQOL (.05/12=.004), PedsQL (.05/6=0.008) and Haemo-QoL (.05/8=.006 and .05/9=.006) scale scores. Effect sizes were calculated by dividing the Z-scores by the square root of the sample size. Effect sizes up to 0.1, 0.3, and 0.5 were considered to be small,
127 Table 1. Socio-demographic and disease characteristics of the sample.
† Highest level completed: Low: primary education, lower vocational education, lower and middle general secondary education; Intermediate:middle vocational education, higher secondary education, pre-university education; High: higher vocational education, university.
* not all parents completed the socio-demographic questionnaire (n=116). Of those, six parents completed an incorrect date of birth Boys with bleeding
disorders Girls with bleeding disorders Non-participants - boys Non-participants - girls N M SD N M SD N M SD p N M SD p Age 112 9.63 5.06 34 9.91 6.02 20 11.33 5.81 .23 12 10.78 5.22 .64
N % N % N % N %
Type of bleeding disorder
Hemophilia A 71 63.4 5 14.7 11 55.0 .77 3 25.0 .59 Hemophilia B 9 8.1 2 5.9 3 15.0 0 0.0
Von Willebrand type 2/3 22 19.6 19 55.9 4 20.0 5 41.7 Other congenital bleeding disorder 10 8.9 8 23.5 2 10.0 4 33.3 Severity of hemophilia A/B
Severe (<1%) 30 37.5 0 0.0 Moderate (1-5%) 8 10.0 0 0.0 Mild (>5%) 42 52.5 7 100.0 Type of treatment
On prophylaxis 33 29.5 1 3.0 On demand - in case of bleed 79 70.5 33 97.0
Parent* N M SD N M SD Age 83 39.56 7.31 27 40.44 6.97 N % N % Ethnicity (Dutch) 75 85.2 22 78.6 Education† High 41 46.5 12 42.9 Middle 40 45.5 14 50.0 Low 7 8.0 2 7.1
Paid employment (yes) 67 76.1 21 75.0
moderate, and large respectively [31].
Results
Socio-demographics
During the period 2011-2016, 178 children were under treatment at the HCCC. They were all invited to participate for the administration of questionnaires. In total, 146 children with bleeding disorders or their parents participated (response rate 84% from eligible children under treatment at time of data collection; see Figure 1). The mean age of the 112 boys (76%) was 9.63 years (SD 5.06) and of the 34 girls 9.91 years (SD 6.02). Table 1 represents the socio-demographic and disease characteristics of the cohort.
Generic HRQOL scores - TAPQOL 0-5 years
Boys and girls with bleeding disorders age 0-1 and 2-5 years did not differ from their peers in HRQOL (see Table 2) according to the assessment by their parents.
Generic HRQOL scores – PedsQL 6-18 years
Boys and girls with bleeding disorders age 6-12 years did not differ from their healthy or chronically ill peers in generic HRQOL.
Teenage boys 13-18 years report a higher generic HROQL than their healthy peers on the total scale and emotional functioning with small to moderate effect sizes (p<.008). Boys 13-18 years also report better generic total HRQOL, emotional functioning and psychosocial health than their peers with chronic illness, with moderate effect sizes (p<.008).
Teenage girls (13-18 years) report a lower generic HRQOL than their healthy peers on the total scale, school functioning and psychosocial health, with moderate effect sizes (p<.008). No differences were found between girls 13-18 years and their chronically ill peers (see Table 3).
Figure 1. Flowchart of patient inclusion and questionnaires administrated.
All children under treatment at the HCCC
2011 2016
New patients added to the cohort
Haemo-Qol added to the set of questionnaires (2014) Socio-demographic questionnaire 0-18 yrs (n=116) Generic HRQOL (n=146) - TapQol 0-5 yrs (n=43) - PedsQL 6-7 yrs (n=15) - PedsQL 8-18 yrs (n=88) Disease-specifi c HRQOL (n=48) - Haemo-QoL 4-7 yrs (n=19) - Haemo-QoL 8-18 yrs (n=29)
6
129 Disease-specifi c HRQOL scores
The Haemo-QoL was completed by 48 parents/boys with hemophilia. The Haemo-QoL scores for the boys 4-7 years old as reported by parents ranged from 0 to 78 with a mean of 18.20 (SD 10.41). The Haemo-QoL scores for the boys 8-18 years old ranged from 0 to 100 with a mean of 19.85 (SD 11.05; Table 4).
HRQOL between severity groups
On the generic HRQOL, parents of boys with severe hemophilia (0-5 years; Mean 68.57, SD 11.27) report more ‘problem behavior’ than boys with non-severe hemophilia (Mean 87.36, SD 12.43; p=.002), with a moderate effect size (data not shown). No differences were found for the other age groups in generic HRQOL. Parents reported no differences on disease-specifi c HRQOL between boys with severe and non-severe hemophilia 4-7 years old. Boys with severe hemophilia (Mean 24.55, SD 17.07) 8-18 years only report worse ‘family functioning’ on the Haemo-QoL than their peers with non-severe hemophilia (Mean 9.17, SD 8.47; p=.004), with a moderate effect size.
Table 2.
Differ
ences between the sample and the T
APQOL nor
m gr
oup ages 0-1 and 2-5.
Bleeding disor der s Nor m gr oup Bleeding disor der s vs nor m gr oup TAPQOL (sub)scale N Median (Range) Mean (SD) N Median (range) Mean (SD) p value Effect size Boys 0-1 Stomach 13 100.00 (58.00-100.00) 87.82 (15.07) 114 91.67 (33.00-100.00) 87.57 (15.21) .98 .0.01 Skin 13 91.67 (50.00-100.00) 85.26 (13.67) 114 91.67 (50.00-100.00) 90.35 (12.42) .08 0.12 Lungs 13 100.00 (83.00-100.00) 98.08 (4.99) 114 100.00 (42.00-100.00) 92.54 (14.93) .40 0.12 Sleep 13 75.00 (50.00-100.00) 72.60 (17.41) 114 75.00 (19.00-100.00) 73.68 (20.70) .75 0.02 Appetite 13 100.00 (75.00-100.00) 92.31 (10.47) 114 100.00 (33.00-100.00) 89.69 (16.01) .83 0.05 Liveliness 13 100.00 (67.00-100.00) 96.15 (9.99) 114 100.00 (0.00-100.00) 97.95 (11.12) .16 0.05 Positive mood 13 100.00 (83.00-100.00) 97.44 (6.26) 114 100.00 (0.00-100.00) 98.54 (10.05) .06 0.04 Pr oblem behavior 13 85.71 (57.00-100.00) 82.42 (16.40) 114 85.71 (29.00-100.00) 82.77 (15.49) .90 0.01 Anxiety 13 83.33 (50.00-100.00) 87.18 (15.45) 114 83.33 (50.00-100.00) 85.09 (17.23) .79 0.04 Social^ 4 100.00 (100.00-100.00) 100.00 (0.00) 28 100.00 (50.00-100.00) 92.86 (15.33) .32 0.17 Motor^ 4 96.88 (81.00-100.00) 93.75 (8.84) 28 100.00 (44.00-100.00) 92.63 (14.93) .64 0.03 Communication^ 4 78.13 (75.00-88.00) 79.69 (5.98) 28 87.50 (38.00-100.00) 85.49 (17.76) .20 0.12 Boys 2-5 Stomach 16 87.50 (67.00-100.00) 88.54 (12.12) 126 100.00 (42.00-100.00) 90.81 (14.02) .27 0.05 Skin 16 95.83 (58.00-100.00) 90.10 (14.02) 125 91.67 (50.00-100.00) 92.53 (9.97) .82 0.07 Lungs 16 100.00 (50.00-100.00) 86.98 (19.48) 126 100.00 (8.00-100.00) 94.38 (15.16) .05 0.15 Sleep 16 87.50 (50.00-100.00) 83.98 (14.06) 126 87.50 (31.00-100.00) 84.13 (15.90) .76 0.00 Appetite 16 91.67 (67.00-100.00) 87.50 (12.91) 125 83.33 (25.00-100.00) 83.27 (12.37) .20 0.11 Liveliness 16 100.00 (83.00-100.00) 98.96 (4.17) 126 100.00 (50.00-100.00) 97.75 (9.03) .87 0.04 Positive mood 16 100.00 (50.00-100.00) 94.79 (14.55) 126 100.00 (50.00-100.00) 98.02 (8.33) .34 0.11 Pr oblem behavior 16 75.00 (43.00-93.00) 73.21 (14.17) 126 64.29 (7.00-100.00) 64.74 (15.88) .03 0.17 Anxiety 16 83.33 (33.00-100.00) 80.21 (20.38) 126 83.33 (33.00-100.00) 77.78 (18.14) .51 0.04 Social 16 100.00 (67.00-100.00) 95.83 (11.39) 124 100.00 (17.00-100.00) 89.65 (18.48) .13 0.11 Motor 16 100.00 (63.00-100.00) 94.92 (11.00) 123 100.00 (81.00-100.00) 99.24 (2.95) .02 0.29 Communication 16 100.00 (56.00-100.00) 92.58 (12.95) 124 93.75 (50.00-100.00) 91.13 (10.84) .29 0.04
6
131 Girls 2-5 Stomach 11 83.33 (67.00-100.00) 84.09 (10.84) 95 100.00 (50.00-100.00) 90.26 (14.11) .02 0.14 Skin 11 91.67 (50.00-100.00) 84.85 (17.80) 96 91.67 (42.00-100.00) 90.54 (13.11) .30 0.13 Lungs 11 100.00 (75.00-100.00) 97.73 (7.54) 95 100.00 (17.00-100.00) 93.60 (16.60) .46 0.08 Sleep 11 75.00 (50.00-94.00) 75.57 (16.88) 95 87.50 (6.00-100.00) 83.03 (17.67) .09 0.13 Appetite 11 83.33 (25.00-100.00) 79.55 (21.20) 96 83.33 (33.00-100.00) 81.60 (13.41) .95 0.04 Liveliness 11 100.00 (83.00-100.00) 98.48 (5.03) 96 100.00 (50.00-100.00) 97.74 (7.88) .95 0.03 Positive mood 11 100.00 (100.00-100.00) 100.00 (0.00) 96 100.00 (67.00-100.00) 99.31 (4.13) .55 0.05 Pr oblem Behavior 11 64.29 (57.00-86.00) 65.58 (10.01) 96 65.48 (29.00-100.00) 66.25 (15.00) .64 0.01 Anxiety 11 66.67 (50.00-100.00) 72.72 (18.67) 96 66.67 (33.00-100.00) 73.09 (17.83) .95 0.01 Social 11 100.00 (83.00-100.00) 96.97 (6.74) 95 100.00 (40.00-100.00) 93.33 (12.73) .48 0.09 Motor 11 100.00 (94.00-100.00) 99.43 (1.88) 93 100.00 (75.00-100.00) 99.33 (1.88) .76 0.01 Communication 11 100.00 (81.00-100.00) 96.59 (6.47) 94 100.00 (69.00-100.00) 93.55 (8.12) .20 0.12 Higher scor
es indicate better HRQOL.
Age gr
oup 0-1 contained 3 girls, which wer
e eliminated fr
om this table
^
TAPQOL domain only contains items for childr
en aged ≥ 1,5 year
s
*
Diffe
rence at p<.004, ad
justed for multiple testing
Table 2.
Differ
ences between the sample and the T
APQOL nor
m gr
oup ages 0-1 and 2-5.
(Continued)
Table 3.
Differ
ences between the sample and the P
edsQL nor
m gr
oup per age gr
oup and gender
. Bleeding disor der s Healthy sample Chr
onically ill sample
Bleeding disorder
s vs
healthy
Bleeding disorder
s vs chr onic ill PedsQL (sub)scale N Median (range) Mean (SD) N Median (range) Mean (SD) N Median (range) Mean (SD) p value Effect size r p value Effect size r Boys 6-7 year s Ŧ Total scor e 15 94.57 (59.00-100.00) 85.65 (14.98) 83 88.04 (46.00-100.00) 86.21 (11.04) 11 79.35 (48.00-100.00) 77.08 (16.80) .55 .02 .18 0.27 Physical health 15 96.88 (50.00-100.00) 89.79 (15.19) 83 96.88 (66.00-100.00) 93.45 (8.22) 11 93.75 (31.00-100.00) 84.38 (19.81) .69 .14 .24 0.10 Emotional functioning 15 85.00 (30.00-100.00) 82.33 (18.79) 83 80.00 (35.00-100.00) 77.71 (15.09) 11 75.00 (25.00-100.00) 69.09 (22.23) .16 .11 .08 0.32 Social functioning 15 100.00 (35.00-100.00) 85.33 (24.81) 83 90.00 (25.00-100.00) 84.94 (19.02) 11 80.00 (50.00-100.00) 77.27 (17.52) .19 .01 .13 0.19 School functioning 15 90.00 (30.00-100.00) 82.67 (20.25) 83 90.00 (45.00-100.00) 84.40 (15.29) 11 75.00 (45.00-100.00) 73.18 (24.73) .98 .04 .41 0.21 Psychosocial health 15 91.67 (43.00-100.00) 83.44 (18.66) 83 85.00 (35.00-100.00) 82.35 (13.91) 11 70.00 (43.00-100.00) 73.18 (18.88) .33 .03 .16 0.27
Boys 8-12 year s Total scor e 33 86.96 (65.00-99.00) 84.65 (9.21) 93 83.70 (58.00-98.00) 83.37 (8.33) 11 79.35 (67.00-92.00) 79.64 (8.03) .38 .07 .10 0.24 Physical health 33 90.63 (50.00-100.00) 87.78 (12.41) 93 87.50 (63.00-100.00) 85.74 (9.10) 11 81.25 (59.00-94.00) 79.55 (9.92) .11 .09 .03 0.29 Emotional functioning 33 85.00 (50.00-100.00) 81.06 (15.04) 93 80.00 (50.00-100.00) 79.5 (12.58) 11 80.00 (60.00-95.00) 78.18 (12.70) .42 .05 .45 0.09 Social functioning 33 95.00 (60.00-100.00) 90.76 (10.16) 93 90.00 (50.00-100.00) 87.13 (10.61) 11 85.00 (65.00-100.00) 82.73 (11.04) .03 .15 .02 0.32 School functioning 33 80.00 (50.00-95.00) 77.12 (11.93) 93 80.00 (50.00-100.00) 79.61 (11.46) 11 80.00 (60.00-100.00) 78.18 (11.89) .38 .10 .98 0.04 Psychosocial health 33 86.67 (58.00-98.00) 82.98 (10.22) 93 83.33 (53.00-98.00) 82.10 (9.31) 11 78.33 (65.00-97.00) 79.70 (9.06) .48 .04 .23 0.15 Girls 8-12 year s Total scor e 7 82.61 (66.00-86.00) 80.28 (6.63) 99 82.61 (57.00-99.00) 81.52 (9.21) 15 80.43 (66.00-99.00) 81.44 (10.76) .71 .34 .91 0.06 Physical health 7 87.50 (63.00-100.00) 87.05 (11.75) 99 87.50 (63.00-100.00) 85.14 (8.49) 15 84.38 (47.00-100.00) 83.93 (14.02) .34 .06 .49 0.12 Emotional functioning 7 70.00 (55.00-80.00) 67.14 (8.09) 99 75.00 (45.00-100.00) 74.64 (14.31) 15 77.50 (50.00-100.00) 79.64 (14.47) .12 .13 .04 0.44 Social functioning 7 95.00 (80.00-100.00) 90.71 (7.89) 99 90.00 (40.00-100.00) 85.87 (13.74) 15 85.00 (45.00-100.00) 83.93 (14.83) .49 .09 .32 0.25 School functioning 7 70.00 (55.00-90.00) 72.14 (14.39) 99 80.00 (40.00-100.00) 78.27 (12.29) 15 75.00 (40.00-100.00) 76.79 (14.86) .26 .12 .44 0.15 Psychosocial health 7 76.67 (68.00-83.00) 76.67 (5.53) 99 80.83 (47.00-100.00) 79.59 (11.07) 15 83.33 (62.00-98.00) 80.12 (12.05) .27 .07 .54 0.16 Boys 13-18 year s Total scor e 35 90.22 (49.00-100.00) 87.30 (12.22) 69 83.70 (59.00-100.00) 83.01 (9.55) 11 78.26 (61.00-92.00) 77.08 (10.68) .01* .19 .00* 0.35 Physical health 35 96.88 (47.00-100.00) 90.80 (13.04) 69 90.63 (63.00-100.00) 87.02 (9.70) 11 84.38 (56.00-100.00) 83.52 (12.89) .01* .16 .03 0.24 Emotional functioning 35 95.00 (40.00-100.00) 90.57 (13.97) 69 85.00 (40.00-100.00) 79.46 (14.69) 11 75.00 (50.00-100.00) 74.55 (15.08) .00* .35 .00* 0.44 Social functioning 35 95.00 (25.00-100.00) 89.86 (15.68) 69 95.00 (45.00-100.00) 88.23 (12.85) 11 85.00 (55.00-100.00) 80.45 (15.08) .30 .06 .03 0.26 School functioning 35 75.00 (25.00-100.00) 75.86 (16.96) 69 75.00 (45.00-100.00) 74.92 (13.04) 11 65.00 (45.00-85.00) 65.91 (10.45) .47 .03 .02 0.27 Psychosocial health 35 88.33 (47.00-100.00) 85.43 (13.05) 69 83.33 (57.00-100.00) 80.87 (11.15) 11 73.33 (58.00-88.00) 73.64 (10.32) .02 .18 .00* 0.38 Girls 13-18 year s Total scor e 13 73.91 (41.00-96.00) 70.40 (16.21) 91 82.07 (62.00-100.00) 83.00 (8.63) 14 76.09 (62.00-91.00) 77.32 (8.42) .01* .38 .27 0.27 Physical health 13 81.25 (44.00-100.00) 76.20 (18.73) 91 87.50 (63.00-100.00) 86.12 (9.08) 14 81.25 (59.00-91.00) 79.58 (11.13) .12 .30 .86 0.12 Emotional functioning 13 70.00 (0.00-100.00) 63.46 (28.46) 91 75.00 (45.00-100.00) 75.80 (15.20) 14 75.00 (35.00-100.00) 69.33 (17.31) .17 .23 .75 0.13 Social functioning 13 85.00 (55.00-100.00) 81.15 (15.96) 91 95.00 (40.00-100.00) 91.42 (9.83) 14 90.00 (65.00-100.00) 85.33 (10.77) .02 .31 .62 0.16 School functioning 13 60.00 (25.00-90.00) 57.31 (20.37) 91 75.00 (50.00-100.00) 76.82 (12.39) 14 70.00 (45.00-100.00) 73.67 (17.06) .00* .44 .03 0.41 Psychosocial health 13 68.33 (37.00-97.00) 67.31 (18.67) 91 81.67 (58.00-100.00) 81.34 (9.59) 14 76.67 (63.00-92.00) 76.11 (8.83) .01* .39 .19 0.31
es indicate better HRQOL
No girls 6-7 year
s in the bleeding disor
der
s sample
Diffe
rence at p<.008, ad
justed for multiple testing
Table 3.
Differ
ences between the sample and the P
edsQL nor
m gr
oup per age gr
oup and gender
. (Continued)
133
Table 4.
Scor
es on the Haemo-QoL in boys with hemophilia A/B (4-18 year
s).
Lower scor
es indicate better HRQOL
Due to low inter
nal consistency
, the subscale ‘friends’ was eliminated (4-7 year
s), and ‘
other per
sons’ and ‘
dealing with hemophilia’ (8-18 year
s).
*
Diffe
rence at p<.006, ad
justed for multiple testing
Total gr
oup hemophilia
Boys with sever
e hemophilia
Boys with non-sever
e hemophilia Sever e vs non-sever e Haemo-QoL (sub)scale N Median (range) Mean (SD) N Median (range) Mean (SD) N Median (range) Mean (SD) p value Effect size r Par ent (4-7) Physical health 19 0.00 (0.00-50.00) 15.26 (18.10) 8 13.00 (0.00-50.00) 16.14 (18.69) 11 0.00 (0.00-38.00) 16.09 (18.85) 1.00 0.00 Feeling 19 0.00 (0.00-63.00) 11.89 (20.68) 8 0.00 (0.00-50.00) 14.29 (19.67) 11 0.00 (0.00-63.00) 11.45 (22.79) .66 0.07 View o f your self 19 0.00 (0.00-75.00) 7.89 (20.50) 8 0.00 (0.00-50.00) 10.71 (19.67) 11 0.00 (0.00-75.00) 6.82 (22.61) .60 0.09 Family 19 0.00 (0.00-78.00) 16.37 (24.67) 8 11.11 (0.00-78.00) 22.22 (27.22) 11 0.00 (0.00-56.00) 14.14 (24.39) .29 0.16 Other P er sons 19 0.00 (0.00-38.00) 7.37 (12.89) 8 0.00 (0.00-38.00) 7.29 (14.38) 11 0.00 (0.00-38.00) 8.09 (13.00) .86 0.03 Spor ts and school 19 50.00 (0.00-50.00) 30.95 (22.17) 8 50.00 (0.00-50.00) 42.86 (18.90) 11 25.00 (0.00-50.00) 25.00 (22.36) .13 0.40 Tr eatment 19 50.00 (0.00-75.00) 40.21 (24.79) 8 25.00 (25.00-50.00) 35.71 (13.36) 11 50.00 (0.00-75.00) 45.55 (29.66) .38 0.20 Haemo-QoL total 19 16.00 (0.00-38.00) 17.89 (10.17) 8 16.00 (11.00-38.00) 20.14 (9.81) 11 17.00 (0.00-34.00) 17.27 (10.80) .60 0.14 Child (8-18) Physical health 29 6.25 (0.00-50.00) 16.59 (18.01) 14 0.00 (0.00-56.00) 26.34 (17.71) 15 0.00 (0.00-44.00) 7.50 (13.20) .01 0.53 Feeling 29 0.00 (0.00-56.00) 7.11 (13.85) 14 0.00 (0.00-56.00) 11.16 (18.04) 15 0.00 (0.00-25.00) 3.33 (7.03) .26 0.29 View o f your self 29 6.25 (0.00-63.00) 15.95 (18.79) 14 9.38 (0.00-63.00) 17.86 (20.49) 15 6.25 (0.00-50.00) 14.17 (17.60) .69 0.10 Family 29 12.50 (0.00-69.00) 16.59 (15.24) 14 21.88 (0.00-69.00) 24.55 (17.07) 15 6.25 (0.00-25.00) 9.17 (8.47) .01* 0.51 Friends 29 41.67 (0.00-100.00) 48.85 (26.89) 14 45.83 (0.00-83.00) 43.45 (25.57) 15 41.67 (8.00-100.00) 53.89 (27.97) .39 0.20 Spor ts and school 29 25.00 (0.00-94.00) 25.43 (28.43) 14 37.50 (0.00-94.00) 38.39 (34.40) 15 18.75 (0.00-31.00) 13.33 (13.12) .02 0.45 Tr eatment 29 25.00 (0.00-69.00) 26.51 (16.17) 14 18.75 (0.00-44.00) 21.88 (13.81) 15 25.00 (6.00-69.00) 30.83 (17.43) .11 0.28 Haemo-QoL total 29 17.14 (4.00-53.00) 19.85 (11.05) 14 20.36 (9.00-53.00) 23.11 (13.40) 15 15.00 (4.00-30.00) 16.81 (7.53) .33 0.29
Discussion
This study demonstrates that children, boys and girls (0-12 years), with bleeding disorders in the Netherlands show no signifi cant impairments in HRQOL in comparison to their healthy and chronically ill peers. Older boys with bleeding disorders even (13-18 years) report higher total HRQOL and emotional functioning than their healthy and chronically ill peers. On the other hand, girls (13-18 years) experience lower HRQOL than their healthy peers.
The sample used in this study was drawn from the population under treatment at the Emma Children’s Hospital who completed PROs on the KLIK website (www.hetklikt.nu) for use in daily clinical practice. Most of these patients have been using prophylaxis since a young age, so the number of bleeds in patients in this group is quite low and a high HRQOL can be expected [15, 32, 33]. Thus, these results are consistent with what one would expect based on clinical experience and which has been previously reported by literature in Europe [28, 34]. However, a higher generic HRQOL in boys with bleeding disorders than their peers was not expected (in age group 13-18 years). A possible explanation may be that boys with bleeding disorders have received adequate treatment and psychosocial care from an extensive multidisciplinary team their whole life. For example, the psychosocial care contains support for parents by a social worker, and a psychologist for children when necessary; many different psycho-educational and peer-related activities are organized throughout the year, and interventions related to coping are offered [23], leading to good emotional functioning and overall HRQOL [23]. Another explanation could be that boys with bleeding disorders do not like to be confronted with their disease and have the desire to be as others, which could lead to favorable reporting of HRQOL [35, 36].
Teenage girls (13-18 years) with bleeding disorders however experience lower HRQOL than their healthy peers on total HRQOL, school functioning and psychosocial health. A possible explanation could be that the effect of bleeding disorders is different for boys and girls. One of the most important infl uences on HRQOL for girls are heavy menstruations. Girls start to menstruate during early adolescence, the mean age is around 13 years old [37]. Heavy
135 menstrual bleeding is common in girls with bleeding disorders, and this has
a substantial impact on HRQOL [38, 39]. For all teenage girls, the adolescent phase is characterized by insecurities. Having a bleeding disorder seems to increase these feelings, which in turn may affect social activities and academic achievements [38]. This fi nding underlines the importance of monitoring these girls with bleeding disorders in clinical practice, and to discuss these, perhaps, uncomfortable topics.
Parents of young boys (0-5 years) with severe hemophilia report slightly more problem behavior than boys with non-severe hemophilia on the generic HRQOL questionnaire. Although studies on psychological issues in boys with hemophilia are scarce, some suggest that boys may have diffi culties in behavioral functioning [40]. For families, dealing with the diagnosis of hemophilia and intravenous treatment is stressful, while also learning to take on a child’s treatment [41]. For boys, having to undergo burdensome and painful treatment may lead to diffi culties in behavior. On the disease-specifi c HRQOL, boys severe hemophilia report lower HRQOL on the domain ‘family’ than their peers with non-severe hemophilia. Items in this domain are related to concepts such as overprotection by parents, or being a burden on the family. Given the nature of the home treatment that boys with severe hemophilia receive in contrast to their peers with non-severe hemophilia, one can imagine this treatment can be related to such feelings [9].
We encountered some limitations of our study as well. First, despite the high inclusion rate and relatively large sample size, the number of patients per age group was still low for some subgroups (e.g. 0-1 and 2-5 years). Second, the internal consistency of some scales of the Haemo-QoL was insuffi cient, and had to be eliminated from the results. Low internal consistency for some subscales of the Haemo-QoL has been shown previously [28, 42]. Third, at time of inclusion, the preschool version (2-4 years) of the PedsQL had not yet been validated and translated into Dutch [43]. Therefore, we were forced to use the TAPQOL questionnaire for young children. Finally, we did not have information regarding the number of bleeds for these patients. Because we used data that was collected during a period of fi ve years, we were not able to retrace this
information for all patients that were included.
In this study, a cross-sectional design was used. While this is highly informative with regard to current functioning, it makes it impossible to examine HRQOL and psychosocial functioning over time. However, it would be very interesting to look at the longitudinal data from the KLIK system as well, since this provides insight into the causality of outcomes over time. With this information, children and adolescents can be identifi ed who are most likely to develop problems in daily life.
In conclusion, HRQOL of boys with bleeding disorders in the Netherlands is comparable with healthy peers, while teenage girls with bleeding disorders show impaired generic HRQOL and boys with severe hemophilia show more impaired HRQOL compared to non-severe hemophilia on some domains. This emphasizes the importance of continuing monitoring HRQOL in daily clinical practice for children with bleeding disorders, especially girls, because possible infl uencing psychosocial factors can change over time.
Acknowledgements
We would like to thank all participating children and parents in this study.
137
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