Discussion
In the first decade of life, VOCs are the most common complication of
SCD,38 and associated with an impaired
HRQoL.39,40 Generally, SCD is associated with a high
health care utilization including emergency room visits and
hospitalizations due to VOCs.41 With age, the
frequency of hospitalization for VOC increases.39,42This study shows that occurrence of hospitalization for VOC has a
negative effect on total HRQoL, evident up to 12 months after
hospitalization in children with SCD. This effect was most pronounced if
HRQoL was measured closely after hospitalization and decreased over time
independently of the frequency of hospitalization. As the number of
hospitalization increases, the negative effect on total HRQoL
significantly increases as well.
Our study is in line with previous research involving the impact of
hospitalization for VOC on HRQoL in children with
SCD.43 Brandow et al. prospectively found a decrease
in HRQoL after hospitalization for VOC, but this effect seemed to
disappear after one week.43 The authors compared HRQoL
during hospitalization for VOC with control patients in steady state.
The discrepancy with our study could be attributed to the
cross-sectional design of their study and the comparison with a separate
control group. Instead, we used repeated measures over time to compare
HRQoL between patients and within patients with and without
hospitalization for VOC. Using repeated measures in the same patients
allows us to monitor changes of HRQoL over time, while controlling for
factors that cause variability. In our longitudinal analyses, although
the effect of occurrence of hospitalization on HRQoL was greatest after
3 months, this effect was not significant most probably due to lack of
power. Nevertheless, the trend up to 12 months is evidently present, and
decreasing over time.
In addition, previous studies have showed an inverse correlation between
self-reported HRQoL and the frequency of hospitalizations and emergency
department visits, comparable to our study.44-48 As
the effect of frequency of hospitalization on HRQoL in our study does
not look clinically relevant, it will become relevant as healthcare
utilization increases with age. Accordingly, Campball et al. reported
the higher the frequency of VOCs, the lower the self-reported total
HRQoL in children with SCD.42
Dampier et al. found in regression models that mainly occurrence of
pain-related acute care visits was responsible for negatively affected
HRQoL subscales.17 All HRQoL subscales are found to be
affected in patients with SCD compared to healthy
norms,24,44,49 but the subscale physical functioning
seems to be the most affected across previous
studies.25,39 This is line with our study, reinforcing
the fact that hospitalization has a negative impact mainly on the
physical functioning lasting for months. School functioning was only
significantly affected after 12 months, so it seems that the effect of
hospitalization on school functioning only manifests over time. Even
though the reliability of the PedsQL for school functioning was poor in
our study, hospitalization for VOC does result in school absenteeism,
which in turn can lead to poor school performance or academic
functioning.50-53 As a matter of fact, the frequency
of hospitalization has been reported to be a predictor of poor HRQoL
with regard to school functioning in children with
SCD.50
In several studies, SCD severity and complications were associated with
worse HRQoL.54 In the association between
hospitalization for VOC and HRQoL, the severity of hospitalization has
not been taken into account before. According to our subanalysis,
severity of hospitalization could have affected total HRQoL, but only
until 3 months after hospitalization. After this time, severity does not
seem to affect the total HRQoL score. However, these results were not
significant, as this analysis was conducted within a subgroup of
patients with 45 completed PedsQLs.
Strengths and limitations
An important strength of this study is its longitudinal nature with data
covering the last 10 years with at least two measurements of HRQoL per
patient. Also, our study population with SCD is closely monitored at our
SCD comprehensive care center, as each patient is requested to annually
fill out PROMs before a regular visit as part of standard care.
There are also limitations that should be taken into account when
interpreting the data. First of all, patients with SCD who have mainly
VOCs managed at home, are not taken into account in the analyses, while
these VOCs burden patients as well. This also applies to patients with
other SCD-related complications such as chronic pain, that may have a
harmful effect on aspects of HRQoL. We did exclude patients on a chronic
transfusion therapy as they were more likely to have less
hospitalizations for VOC, while carrying the burden of frequent blood
transfusions. Second, the PedsQL was found to have moderate/good
reliability for all subscales, except for school functioning. Therefore,
the PedsQL results for school functioning should be interpreted with
caution. Third, patients without hospitalization completed the PedsQL
more often than the hospitalized patients. Hospitalized patients may
experience a higher disease burden or stress causing them to have less
time for completion of PedsQLs. Another explanation is, when a patient
is hospitalized, while having a visit scheduled at the outpatient
clinic, this visit is not automatically rescheduled to after
hospitalization.
Half of the eligible patients (or caregivers) did not give consent to
use the HRQoL data for scientific research. Moreover, not all children
were able to fill out the PedsQL regularly. For instance, children
and/or caregiver(s) who lack digital literacy, did not complete the
PedsQL via the online platform. However, we are facilitating and
offering technical support at the outpatient clinic for these patients
and their caregivers to overcome this problem. All of the above could
have caused selection bias of the study population affecting the
generalizability. In addition, our dataset was too limited to include
socio-economic status in our analyses. Considering that socio-economic
status is a well-known potential confounder of HRQoL, this may have
caused a bias as well.
Based on findings of this study, there are some implications for
clinical practice and recommendations for future research. Because of
the negative impact of both the occurrence and frequency of
hospitalizations for VOC on HRQoL, it is important to focus on the
prevention of VOCs and the usage of disease-modifying drugs. In case of
hospitalization, close monitoring and psychosocial support aimed at all
aspects of HRQoL, but in particular physical functioning (e.g. by
offering physiotherapy), should be considered. After frequent
hospitalizations, there should be sufficient attention for school
functioning as well. Furthermore, the KLIK PROM portal is an important
tool in clinical practice to assess the need for extra psychosocial
support in patients with SCD. SCD-specific symptom list in addition to
the generic PROMs evaluating aspects of HRQoL could increase the
reliability making research more replicable and easily comparable in
this patients with SCD. Ultimately, a mixed-methods study should be
performed to provide in-depth insights into how HRQoL is affected by
hospitalization for VOC. This could allow healthcare providers to
identify and better respond to the needs of children with SCD, who have
been hospitalized for VOC, and customize their care.