Our study showed a high burden of RVGE hospitalizations leading to significant health resource utilization and costs related to the management of these severe cases of RVGE.
Most of the hospitalized children with RVGE included in our study did not report previous medical conditions or chronic diseases [20, 21]. Moreover, among children hospitalized due to RVGE, similar to what has been observed for RVGE cases managed at primary care, attendance to daycare or school centers is not predominant [22, 23].
As described in other studies, dehydration is highly frequent among RVGE cases due to the occurrence and intensity of symptoms [24], with a not negligible proportion of cases suffering severe dehydration. However, our study was not designed to evaluate the rate of dehydration in RVGE, and the high rates of this complication could be biased, as dehydration was likely the cause of admission in many of the children. Seizures have been previously described as a complication related to RVGE. The frequency reported in our study (5%) is within the range of what has been observed in other studies [25–27]. Although RV-related seizures are usually benign and self-limited, they may lead to ER visits and hospitalizations and considerable stress for parents [28].
Regarding the use of health care resources, we found that almost half of the patients who were hospitalized due to an RVGE episode had previously attended the ER, and approximately 30% had visited a primary care pediatrician on more than one occasion before hospital admission. Moreover, approximately 15% of all RVGE cases were hospitalized despite having received pharmacological treatment, mainly oral rehydration solutions, prior to their hospital admission. Altogether, this suggests the significant impact of RVGE episodes on the disease burden at different health care levels.
It is important to highlight the long average length of the hospital stay (5.6 days) observed. This figure was somewhat higher than what has been reported in previous studies, ranging from 2.5 to 5 days [3, 4], but similar to those in others [19, 24]. The results from the study performed in the Autonomous Community of Valencia including a long period of time (2002–2015), showed the relationship of the average length of hospital stay with age, with children < 2 years having an approximately 50% longer average length of stay than the older groups, therefore, the age distributions in the different studies may explain these differences. Our study also took into consideration nosocomial infections, for whom length of hospital stay is difficult to estimate. We used the date of the microbiological diagnosis as a reference for its calculation, which may overestimate the prolongation of the stay related to RV infection in those cases. Other factors that may have contributed to longer hospital stays include the high percentage (almost 80%) of patients in our study who needed intravenous hydration. This figure is within the upper limit of the range of many European countries [3, 4].
Apart from the consequent high use of medical resources, we assume that this hospital stay must have had an important impact on the number of workdays lost by parents and caregivers, as well as other indirect costs, although the latter were not the objective of our study. In fact, it has been estimated that RVGE hospitalizations of children cause work absenteeism in nearly 70% of parents, with a mean number of days off from work of 4, negatively impacting their quality of life [12].
Regarding pharmacological treatment and other therapeutic interventions administered during hospitalization, surprisingly, antibiotic use was reported in ~ 25% of the RVGE cases in our study, despite the low frequency of detected bacterial coinfection. In line with this result, a study performed in 8 European countries including Spain, assessing the appropriateness of antibiotic prescription in febrile children, showed that one-third of all antibiotic prescriptions in ED were of inappropriate or inconclusive indication [29]. This suggest that certain vaccinations, including that against RV, may contribute to an improvement in rational use of antimicrobial and to the implementation of antimicrobial stewardship guidelines.
The mean medical cost of RVGE hospitalizations per episode was 3,940€, increasing to 4,100€ when out-of-hospital costs related to the episode were considered. It is important to note that these last costs may be underestimated due to the retrospective nature of our study, using the hospital medical records of patients in which not all medical visits and treatments occurring before hospitalization may be recorded. Our study only considered the most severe presentation of disease, representing the management of cases requiring hospitalizations. Although these costs represent a significant proportion of the economic burden of disease, the clinical burden of RV disease is much higher in primary care, and the indirect costs assumed by families are not negligible. The study by Bouzón-Alejandro et al. [30] prospectively assessed indirect costs related to RVGE in Spain, showing a mean cost per case of 192.7€ (SD 219.8€). Therefore, additional research contributing to the global economic impact of disease estimation is warranted.
More than 95% of the average total medical cost associated with hospital admission due to an RVGE episode was attributable to the hospital stay. This was expected, as there is no specific pharmacological treatment for RV infection, and case management is focused on fluid replacement and symptom mitigation [1].
Our estimated average cost per episode is higher than that reported in other studies performed previously in Spain [14, 15, 31]. Different factors may explain these differences. First, the increase in costs over time, as there were many years of differences between the periods analyzed in those previous studies and ours. Second, the cost in those studies was mainly estimated by using the Diagnosis Related Groups for Disease (DRG). According to the DRG reimbursement system, patients belong to a group of diagnostically homogeneous cases; therefore, patients within the same category are similar clinically and are expected to use the same level of hospital resources. There is no specific DRG for RV, and a DRG including AGE and other miscellaneous digestive disorders in age < 18 years was mainly used. RV is known to cause more severe AGE than other pathogens, probably leading to longer hospital stays [7]. Therefore, the lack of a specific GRD for RVGE may be responsible for an underestimation of RVGE hospitalization costs when using the DRG cost assignation. In our study, the use of different health resources related to hospitalization and unit costs calculated from hospital accounting information may have led to more precise estimations of the actual costs of RVGE-related hospitalizations. Finally, hospital length in our study seems to be longer than that obtained in other studies, as previously reported, with the cost per day of hospitalization being the major contributor to the total cost of episode management.
However, there is an important variability in the cost per RVGE hospitalization from one participating hospital to another, ranging from €3,000 to €5,800, probably due to differences in patient management protocols. Therefore, comparisons should be performed with caution.
This study has several strengths. This is the first nationwide study conducted in the post-licensure RV vaccine era evaluating the healthcare resources consumption and the direct medical costs associated to RV hospitalizations. Additionally, we included a large sample size from different hospitals and different regions and used hospital medical records as source of information, allowing us to obtain more detailed information on health care resource use and costs, unlike the use of administrative databases, which may have underestimated the actual burden of RVGE disease management at the hospital level [13, 16, 31, 32]. Furthermore, complementary information was retrieved from the microbiology department databases at each hospital.
Some study limitations must however be acknowledged. Due to its retrospective design, data availability was sometimes limited by the recorded information from study sources. A proportion of episodes in our sample were nosocomial and/or reported having previous medical conditions. It is known that RV infection may complicate the course of patients with previous conditions especially immunocompromising diseases [33]. This may have an impact on the severity and resource consumption analysis (including antibiotic use). While we cannot exclude the possibility of nosocomial transmission complicating the course of disease and resulting in cost overestimation due to RVGE, we have tried to minimize this bias by only including costs related to the treatment of RVGE in the estimations for nosocomial cases. Another limitation is the absence of an analysis of indirect costs, such as the absenteeism of parents and its economic consequences. Nonetheless, it has been confirmed that the greatest contribution to the disease burden comes from direct health care costs [3, 12].