Results

In total, 94 patients met the inclusion criteria and were enrolled in the study as shown in Fig. 1. The total follow-up duration was 451 patient-years with a median follow-up time of 4.0 years (IQR 2.0 - 6.0). The included patients completed the PedsQL 455 times in the period January 2012 through September 2021. This is 237 times by patients in the non-hospitalized group, and 218 times by patients in the hospitalized group (Supplemental Fig. S1). The median number of PedsQL completions per patient was 4 (IQR 3 - 6).
Table 1 shows the baseline characteristics of the study population. The median age of first completion of the PedsQL was 11.8 years (IQR 9.3 - 14.1) and 64% of the patients was male. There were 37 patients who had at least one hospitalization for a VOC, while the remaining 57 patients had no hospitalization for a VOC prior to measurement of the HRQoL. Patients with HbSS/HbSβ0were more prevalent in the hospitalized group compared to the non-hospitalized group (89% vs 42%, p<0.01) and a larger proportion of patients used hydroxyurea (78%) compared to the non-hospitalized group (32%).
There were 37 patients with a total of 122 hospitalizations for VOC. Out of these 37 children, 22 children (59.5%) had been admitted more than once during follow-up. The median admission rate of these children was 4 times (IQR 2 - 6). Intravenous morphine was administered in 62% of the hospitalized patients for the median period of 3.0 days (IQR 0.0 - 5.0). About one-third of the cases (36%) required oxygen support, while blood transfusion was administered in 16% of the cases, mainly because of a decrease in Hb level to below 5.6 g/dL. During four hospitalizations (3%), three patients developed an acute chest syndrome. Admission to the pediatric intensive care unit occurred in three hospitalizations (3%).
In this study, the Cronbach’s α for the total HRQoL score was for all versions greater than 0.8, and therefore good. For the subscales, Cronbach’s α scores for the version 8-12 years version were moderate/good ranging from 0.64-0.74, except for school functioning (α = 0.49). For the 13-18 years version, Cronbach’s α scores were moderate/good ranging from 0.62-0.78. The mean total HRQoL score from the completed PedsQLs was significantly lower in the group with hospitalization (75 points, SD ± 1.5) compared to the total HRQoL score from the group without hospitalization (80 points, SD ± 1.3) (Table 2) .

Impact of occurrence of hospitalization for VOC

The impact of occurrence of hospitalizations in the last 3, 6, 9 and 12 months on HRQoL is shown in Table 3 . There is a trend showing that the negative effect of hospitalization for VOC diminishes over time for all subscales (Fig. 2) . The decrease of the total HRQoL and all subscales scores were most pronounced 3 months after hospitalization with decreases between 3.3 and 5.8 points, except for physical functioning. The impact on physical functioning was most pronounced 6 months after hospitalization with a decrease of 6.1 points. Most affected were the total HRQoL and the subscale physical functioning.

Impact of frequency of hospitalization for VOC

The results for the impact of frequency of hospitalization in the last 12 months are shown in Table 4 . There was a significant decrease in total HRQoL of 2.3 points for every additional hospitalization over a period of 12 months. The most affected subscales were physical functioning and school functioning. For every hospitalization, a decrease of 2.7 points in physical functioning and 2.6 points in school functioning was observed.

Impact of severity of hospitalization

Out of 37 children who had been admitted at least once for a VOC during follow-up, 15 children (41%) experienced a hospitalization classified as severe. Approximately one third of the patients had a hospitalization classified as mild (32%). Although not significant, the severity of the hospitalization had a little negative effect on HRQoL at 3 months, which disappeared after 3 months. (Supplemental Table S2) .