According to our study a longer travel time between residence and the next tertiary medical center is associated with less diagnostic diversity, i.e. precision, and a lower chance of being diagnosed with a rare disease, most likely due to varying accessibility to suitable health care resources even in a well-economized country like Switzerland. The effect is particularly pronounced in patients with rare diseases, where standardized incidence rates for several orphan disease groups fell below 50% at travel times of >60 minutes to the next tertiary health center. Although 20-60 minutes travel time seems to be irrelevant in comparison to other countries. But the 39 centers are accompanied by 242 other inpatient facilities(18).
Standardized incidence rates of all different groups of rare diseases were affected except for teratologic diseases and rare allergic diseases. Teratologic diseases include embryofetopathies, especially malformation syndromes, which are rather obvious to detect. Rare allergic diseases primarily refer to many different reasons of angioedema and urticaria, which as well are visual, and, thus, less missed diagnoses regardless of the cause(19). The term “rare diseases” is misleading as rare diseases are listed as main or co-diagnoses in more than 1 in 4 hospitalizations in our study. Of the 6’172 rare diseases listed by Orphanet, 84.5% have a prevalence of <1/1’000’000. Nguengang et al. assume that the prevalence of rare diseases is at least 3.5-5.9%, meaning 18-30 million persons in the EU, 263-446 million persons worldwide(20). Thus, our findings point to a relevant as well as prevalent structural issue of health care accessibility in relation to geographical dispersion and might indicate a higher risk of being mis-, under- or late diagnosed in more remote residential areas. This is especially important for those rare diseases which appear accentuated in rural areas of residence as sarcoidosis(21). Underdiagnoses or diagnostic delay has been shown to have a negative impact on the course of the disease in many rare diseases(6). In idiopathic pulmonary fibrosis early treatment can slow down disease progression and therefore the decline in lung function(22). Those low prevalent diseases with nonspecific symptoms as interstitial lung diseases (cough, dyspnea) are explicitly in danger to have a diagnostic delay(3,23). In Glucose transporter-1 deficiency syndrome ketogenic diet reduces the frequency of seizures and severity of motoric impairment(24). Early treatment in patients with Hurler Syndrome (mucopolysaccharidosis type 1) prevents cognitive and physical disability(25). So an early and precise diagnosis is crucial. Of course this fact is also well known in acute cardiovascular and neurological situations, but also in oncological diseases with negative impact due to therapeutic delay(26–28).
There are different possible strategies to overcome the “distance-to-center” challenge. The obvious option is to optimize health care location planning using geographic information systems, average travel distance to the next clinic site and electronic health records, as Soares et al. investigated in the United States of America (USA)(29). Such an approach allows for a proactive planning of health care infrastructure optimizing for accessibility as well as sufficient caseload. The importance of the latter is well known for complex surgical interventions, as well as for some emergency conditions and low-risk procedures in Germany(30). But also diagnostic performance is strongly associated with caseload(17). In contrast to a high number of smaller hospitals with limited diagnostic capabilities, a smaller number of high-volume inpatient facilities can offer a comprehensive access to subspecialties. Tele-health care will also probably gain even more importance in the future. Tele-health care is defined as a complex intervention, with information from patients being electronically transferred over a distance to health care professionals, who analyze this information and give immediate and personalized feedback and advice to the patient(31) via telephone or internet. Electronic consultations (e-consults) “offer a rapid, direct, and documented communication pathway for consultation between primary care and specialist”(32). Muse et al. provided an interactive platform for physicians to discuss complex cases on an international base, which found favor especially with younger medical practitioners. 37’706 physicians from 171 countries on every continent used the platform during the 2 years duration of this study(33). As tele-health care promises to be available anywhere and anytime, it could optimize health care access independent of the geographic and socio-cultural dispersion. Furthermore there are diagnostic decision support systems (DDSSs) available to assess “case data based on incorporated medical knowledge, compiling lists of differential diagnoses appropriate for a given sample of evidence”(34). McGowan et al. used a just-in-time librarian consultation system with a highly positive impact in decision making in primary care(35). Electronic online-services developed by Orphanet and by other EU-funded projects are claimed to contribute to put patients in contact with other patients and develop patient communities, to share databases between research groups, to collect data for clinical research, to register patients willing to participate in clinical research, and to submit cases to experts which improves the quality of diagnoses and treatment(6). European registries are thought to be an important column of quality of care in rare diseases. Collaborative networks between centers and smaller institutions could be another option to handle the distance-to-center problem.
The quality of medical coding – although professionalized in all institutions – might be limited and varying between institutions. The ICD-10 coding doesn’t represent the majority of rare diseases adequately, so there will be an expansion of the number of specific codes in ICD-11(36). The latter is going to come into force on 1st of January 2022(37). The database does not allow accounting for differences in socio-economic status between cases or regions. Another limitation is that only inpatient cases are documented in the available data. Also, we concentrated on individual motorized transport times and didn’t include transfer times by public means of transport. Ambulances might transport patients more likely within cantonal borders than to the actual nearest hospital. As Switzerland is a rather small country with a total area of 41’285 square kilometers(38), the longest distance to cover in our cohort was approximately 250 km. The regional differences in health care quality in larger countries are likely even more relevant depending on the distances to the next center. Of course, besides geographic disparities there are other factors influencing access to healthcare, e.g. socio-economic status. Last, pediatric hospitals are not included in the list of tertiary centers as they are not considered as general care institutions and represent an own group of 3 hospitals in Switzerland(18).