Aging and rare diseases: from epidemiology to a call to action

Aging and rare diseases: from epidemiology to a call to action | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Aging and rare diseases: from epidemiology to a call to action Monica Mazzucato, Giulia Fanton, Andrea Vianello, Cinzia Minichiello, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3875871/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The number of older people living with a rare disease (RD) is increasing worldwide due to the population aging and scientific progress. This phenomenon poses several challenges for both patients and healthcare providers, who need to be aware of the peculiarities of this twice-as-frail population. Methods In the present study, we used data from the Veneto region rare disease registry (VRRDR) to investigate the epidemiology of older people living with a RD in the Veneto region of Italy. We report the number of patients diagnosed in old age and the number of those transited from adulthood into old age, estimating the prevalence of older RD patients as of 31 December 2022. Finally, we analyzed the composition of their therapeutic plans. Results During the study period, 8,975 patients received an RD diagnosis after 65 years of age, while 4,214 diagnosed in their childhood or adulthood experienced the transition to old age. On 31 December 2022, there were 9,508 patients aged 65 years or more residing in the study area, 20.8% of all Veneto’s RD patients. The most common groups of RDs in elderly patients were systemic or rheumatologic, neurologic, and skin diseases, affecting 27%, 25%, and 9% of the monitored geriatric population, respectively. Among prevalent cases, 1,519 patients older than 65 years had a therapeutic plan related to their rare condition. Specifically, the most prescribed drugs were those affecting the nervous system (27.8%), the alimentary tract and metabolism (12.8%), and antineoplastic and immunomodulating agents (11.6%). Conclusions As older patients represent a growing number in the RD population, geriatricians and general practitioners should be involved in RD care and training programs. Further studies are needed to determine the unmet care needs of older RD patients in order to design health policies able to address the peculiar challenges posed by this group of patients emerging within the RD population. Aging rare disease registry epidemiology treatment transition prevalence Orphanet drugs public health Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Recent projections for 2050 indicate that, in the European Union (EU), the number of people over 65 will increase from 90.5 million to 129.8 million, while those aged 75–84 will increase by 56.1 million [ 1 ]. In Italy, where the birth rate has reached an all-time low and the number of centenarians has peaked (22,000 cases), the old-age group will represent more than a third of the entire population [ 2 ]. Old age is an arbitrary definition based on biological parameters, such as the multi-construct of frailty, and it is specific to a historical period and geographical context [ 3 , 4 ]. Major international organizations, such as the World Health Organization (WHO) and the United Nations (UN), consider a person to have entered old age after 60–65 years old [ 5 , 6 ]. Recently, the Italian Society of Gerontology and Geriatrics (SIGG) has advocated raising the threshold to 75 years, given better physical and cognitive conditions of the people compared to the past [ 7 ]. In this rapidly evolving scenario, the rare disease (RD) landscape is also undergoing epidemiological and social changes [ 8 ]. An RD is a complex health condition that affects a few people in the general population, with a cut-off threshold varying by country. In Europe, the prevalence should not exceed five cases per 10,000 individuals. [ 9 ]. According to recent estimates, the RD cumulative prevalence ranges from 3.5–5.9%, corresponding to 263 to 446 million people worldwide having one of the approximately 8,000 known RDs [ 10 ]. Thus, although RDs are individually uncommon, their global burden is far from negligible, making these medical conditions a public health priority [ 11 ]. Commonly, RDs are perceived as a pediatric issue as nearly 70% of them have a reported onset in childhood, with the remaining 12% and 18% emerging in adulthood and at all ages, respectively [ 10 ]. Nonetheless, the majority of patients fall within the adult demographic [ 11 ]. The number of people receiving a diagnosis of an RD in their old age is increasing due to the aging of the general population and the increase in diagnostic abilities [ 13 , 14 ]. At the same time, advancements in treatment options have elevated survival rates for conditions with unfavorable prognoses in the past, resulting in the transition of generations from adulthood into old age, as observed in paediatric patients [ 15 , 16 ]. It means a new group of patients is emerging, facing the challenges of living with an RD in their old age [ 17 ]. Some studies have provided insights into the epidemiology of RDs [ 10 , 18 , 19 ] but without focusing specifically on the elderly population. This study aims to describe the epidemiology of aging in RD patients in the Veneto region of Italy. We report the number of patients diagnosed in old age and the number of those transited from adulthood into old age, estimating the prevalence of older RD patients as of 31 December 2022. Finally, we described the drug use profile in RD geriatric patients, analyzing the composition of their therapeutic plans regarding the number and nature of treatments prescribed by RD Centres of expertise. Methods The present work is a registry-based retrospective cohort study. We used data from the Veneto region rare disease registry (VRRDR), ongoing since 2002. Veneto region is located in the north-east of Italy and has nearly 4.9 million inhabitants [ 20 ]. Based on the interaction between highly specialized hospitals and territorial services, the RD care network has been officially defined since 2002 and is monitored and periodically updated according to specific criteria. For the purpose of this study, we considered diseases included in the Italian list of RDs [ 21 ] and in the Orphanet nomenclature [ 22 ]. Patients affected by RDs indexed in the national list can benefit from an exemption from medical charges and other aids, such as drugs, visits, and medical devices. All medical prescriptions, designated by a Centre of expertise, define the patient’s therapeutic plan. The VRRDR, the RD care network, and the related activities have been previously described [ 15 , 18 ]. The RD care network is organized on three levels: 1) Centres of expertise: labelled on the basis of activity data derived from independent sources, in charge of performing the diagnostic and care activities for RD patients; 2) Centres of expertise part of the European Reference Network (ERN) for RDs, namely “Centres of excellence”; 3) Coordinating Centre: with the task of governing and monitoring the network and operating the RD registry. The VRRDR is interoperable with the regional administrative health database (AHD), which includes demographic information and the residential history of all the potential healthcare beneficiaries living in the region. For identifying patients diagnosed in old age and those transited from adulthood into old age, we considered all patients born until 1957 (i.e. all patients potentially 65 years old aged or above on 31 December 2022) and meeting the inclusion criteria. For calculating prevalent cases, we considered the number of patients aged above the cut-off threshold of 65 years old and residing in the study area on 31 December 2022 (point-prevalence); prevalence was calculated for the total sample and per province of residence. Diagnoses are recorded in the registry using the ICD-9-CM and ICD-10, OMIM and ORPHAcodes [ 23 ]. The information about the preferential parent, as derived from the Orphanet nomenclature pack, was used to group RDs diagnoses [ 22 ]. In the case of a double diagnosis, we considered the more recent one for the analyses. For the analysis of the therapeutic plans, we used the Anatomical Therapeutic Chemical (ATC) classification system for grouping prescribed drugs [ 24 ]. We conducted data management and analyses using SAS (version 9.4M6) and R software (version 4.2.1), through the RCommander graphical user interface (GUI), and the Microsoft Office suit and MapChart.net for graphs, tables, and figures. Patient consent was waived as the RD registry is established by law and respects the national data protection regulations. No individual data has been considered in the study analysis. Results Each patient included in the RD regional registry was followed from the date of first diagnosis up to 31 December 2022, date of death or emigration outside the study area. As of 31 December 2022, 13,718 individuals (47.7% males) residing in the Veneto region and born until 1957 received an RD diagnosis performed by an expert Centre of the RD care network. 8,975 patients were diagnosed in old age and 5,875 of them were alive at the end of the study period. Conversely, 4,743 patients received an RD diagnosis in adulthood. Overall, 4,214 patients experienced the transition into old age, and 9,508 patients aged 65 years old or over were living with an RD on 31 December 2022 (see Fig. 1 ) in the study area- None of the patients considered in the present study presented multiple RD diagnosis. Patients' characteristics are reported in Table 1. Table 1 Characteristics of all patients included in the study, overall and according to age of diagnosis. Diagnosis in Adulthood Old age Total N % N % N % Patients 4743 100 8975 100 13718 100 Age (years) at diagnosis, mean ± SD 58.8 ± 4.8 74.2 ± 6.25 68.9 ± 9.3 Age (years) at end of follow-up, mean ± SD 69.2 ± 5.19 78.4 ± 6.53 75.2 ± 7.5 Sex Female 2448 51.6 4733 52.7 7181 52.3 Male 2295 48.4 4242 47.3 6537 47.7 End of follow-up In adulthood 529 11.2 - - 529 3.9 In old age 4214 88.8 8975 100 13189 96.1 Patients in the registry on 31 Dec. 2022 Yes 3633 76.6 5875 65.5 9508 69.3 No 1110 23.4 3100 34.55 4210 30.7 Orphanet classification Rare neurologic diseases 1236 26.1 3293 36.7 4529 33.0 Rare systemic or rheumatologic diseases 1006 21.2 2255 25.1 3261 23.8 Rare skin diseases 336 7.1 1016 11.3 1352 9.9 Rare hematologic diseases 439 9.3 530 5.9 969 7.1 Rare inborn errors of metabolism 518 10.9 230 2.6 748 5.4 Rare ophthalmic disorders 321 6.8 423 4.7 744 5.4 Rare respiratory diseases 60 1.3 364 4.1 424 3.1 Rare gastroenterological diseases 206 4.3 211 2.3 417 3.1 Rare developmental defects during embryogenesis 187 3.9 153 1.7 340 2.5 Rare neoplastic diseases 190 4.0 91 1.0 281 2.0 Rare immune diseases 51 1.1 159 1.8 210 1.5 Rare urogenital diseases 85 1.8 111 1.2 196 1.4 Rare endocrine diseases 50 1.0 85 1.0 135 1.0 Other RDs 58 1.2 54 0.6 112 0.8 Abbreviations: SD standard deviation, RD rare disease. Patients diagnosed in old age A total of 8,975 patients (47.3% males, mean age of 74.2 years) received a diagnosis of an RD after reaching the age of 65 years. Among them, 3,076 (34.3%) died during the study period, with an average age at the time of death being 79.3 years (SD 7.10), and 24 moved outside the study area. Most of the patients (94.4%) received their diagnosis from RD Centres located in the Veneto region. Characteristics are shown in Table 1. The most represented disease groups in the geriatric RD population are neurologic (36.7%), systemic or rheumatologic (25.1%), and skin diseases (11.3%). In detail, the most common diagnoses are myasthenia gravis (976 cases, 10.9%), systemic sclerosis (939 cases, 10.5%), amyotrophic lateral sclerosis (ALS, 899cases, 10%) and bullous pemphigoid (658 cases, 7.3%). Patients transited from adulthood to old age During the study period, 4,743 patients (48.4% males) born up to 1957 were diagnosed in adulthood (i.e. before age 65) at a mean age of 58.8 years (SD 4.8). Approximately 4,214 patients (46.9% males) reached the age of 65 years; patients experiencing transition accounted for 31.9% of all older patients registered throughout the years (Table 2). As shown in Figure 2, over the years there has been an increase, in absolute terms, of RD patients reaching the age of 65. Table 2 Characteristics of RD patients experiencing the transition from adulthood to old age. N % Patients 4214 100 Age (years) at diagnosis, mean ± SD 59.1 ± 4.8 Age (years) at end of follow-up, mean ± SD 70.3 ± 4.3 Region where the RD Centre performing the diagnosis is located Veneto region 3381 94.5 Other regions 233 5.5 Orphanet classification Rare systemic or rheumatologic diseases 940 22.3 Rare neurologic diseases 904 21.5 Rare inborn errors of metabolism 488 11.6 Rare hematologic diseases 413 9.8 Rare skin diseases 319 7.6 Rare ophthalmic disorders 309 7.3 Rare developmental defects during embryogenesis 180 4.3 Rare gastroenterologic diseases 179 4.2 Other RDs 482 11.4 Abbreviations: SD standard deviation, RD rare disease. Prevalence As of 31 December 2022, there were 9,508 (45.7% males) patients aged 65 years or more residing in the study area, representing the 20.8% of all the RD patients monitored by the registry. Among those, 3,633 subjects (38.2%) were diagnosed before the age of 65, thus experiencing the transition from adulthood to old age. 8,987 (94.5%) patients received a diagnosis in an RD Center located in the Veneto region, and 521 (5.2%) in RD Centers located outside the region. The prevalence rates, reported in Table 3 , differ between provinces. Specifically, the highest registered prevalence rate was in the Province of Padua (Table 3 and Fig. 3 ). Table 3 Prevalence rates of older RD patients (≥ 65 years) by Province of residence (Veneto region) at 31.12.2022. Population ≥ 65 years old Total RD patients Prevalence rate per 10,000 95% CI Veneto region 1167759 9508 81.4 79.8–83.1 Provinces of Veneto Verona 211880 1772 83.6 79.8–87.5 Vicenza 196713 1398 71.1 67.4–74.8 Belluno 54934 411 74.8 67.6–82.0 Treviso 205214 1565 76.3 72.5–80.0 Venice 214764 1534 71.4 67.9–75.0 Padua 221344 2368 107.0 102.7-111.3 Rovigo 62910 460 73.1 66.5–79.8 Abbreviations: RD rare disease, CI confidence interval. Data from I. Stat. The most prevalent groups of RDs in the geriatric population under study are systemic or rheumatologic, neurological, and skin diseases (see Figure 4). In detail, RD with the highest incidence in the geriatric age group are: systemic sclerosis (994 cases, 10%), myasthenia gravis (914 cases, 9.6%), rare hereditary hemochromatosis (477, 5%), giant cell arteritis (339 cases, 3.6%), bullous pemphigoid (334 cases, 3.5%), chronic inflammatory demyelinating polyneuropathy (297 cases, 3.1%), retinitis pigmentosa (237 cases, 2.5%), idiopathic pulmonary fibrosis (228 cases, 2.4%) and idiopathic achalasia (213 cases, 2.2%). Treatment prescription profile Among 9,508 prevalent older patients, 1,519 had a therapeutic plan related to their RD issued in 2022. The total number of prescribed products amounted to 3,117, mainly drugs (66.9%) (see Table 4). Consistent with the RDs most commonly represented in the monitored geriatric population, drugs affecting the nervous system made up nearly 28% of all prescribed drugs. Table 4 Composition of the therapeutic plans of prevalent older patients (≥ 65 years) on 31.12.2022. N % Products 3117 100 Drugs 2084 66.9 Medical Foods 537 17.3 Medical Devices 286 9.2 Prosthetics 136 4.4 Galenic preparations 74 2.4 Drugs: ATC classification 2084 100 Nervous system 581 27.9 Alimentary tract and metabolism 268 12.9 Antineoplastic and immunomodulating agents 243 11.7 Blood and blood-forming organs 214 10.3 Anti-infective for systemic use 211 10.2 Cardiovascular system 155 7.5 Systemic hormonal preparations 1 104 5.0 Dermatologicals 98 4.7 Sensory organs 62 3.0 Others 148 7.1 1 excluding sex hormones and insulins. Abbreviations: ATC anatomical therapeutic chemical. Discussion Our study highlights that a considerable number of patients receive a RD diagnosis after the age of 65, with a significant portion transitioning from childhood or adulthood to old age. To our knowledge, this is the first attempt to provide epidemiologic and real-world drug prescription figures referred to older patients living with an RD using data from a population-based registry. Since the beginning of the Veneto region rare disease registry (VRRDR) activity, 8,975 patients were diagnosed when they were 65 years or older, and 4,214 experienced the transition from adulthood to old age living with an RD. According to our findings, patients aged over 65 years represent a significant proportion of all patients living with an RD in the monitored area at the end of the study period (20.8%). These findings are not directly comparable with other studies investigating the epidemiology and the healthcare utilization in patients diagnosed with RD as those data usually refer to two distinct age population subgroups, pediatric and non-pediatric, or are based on hospital-based data collection [25-28]. In general, data referring to older age classes are seldom available, with studies usually focusing on a limited number of RD [29]. A Chinese study analyzed the medical records of 78 tertiary and community hospitals providing data on the economic burden of 23 RDs. Patients older than 65 years were 10.9% of all the identified RD patients [30]. In our study, more than half of the RD geriatric patients who were still alive by the study's conclusion had a rare systemic or rheumatic disease or a rare neurological condition. Moreover, 40% of cases could be attributed to a limited number of RD entities, with systemic sclerosis and myasthenia gravis each accounting for 10% individually. This is in accordance with previous epidemiological studies on these two RDs showing higher prevalence values in older individuals and onset age progressively shifted to the elderly [31-38]. Data presented confirm that, despite the high number of monitored RDs, only a limited proportion of them constitute the majority of cases. These findings may have important implications in designing care pathways and tailored training programs for health professionals. According to the results from a national survey carried out in Italy in 2020, geriatrics had limited knowledge of RDs, even in the case of a condition such as cardiac amyloidosis, which typically affects older patients [39]. This can lead to misdiagnosis, and delay in diagnosis and treatment initiation [40]. Besides focusing on the changing demographic profile of the RD population over the years, we were further interested in describing the characteristics of the therapeutic plans of geriatric RD patients. In our study, only a limited proportion (16%) of the prevalent patients had a therapeutic plan active at the end of 2022. This finding is related to the fact that we considered mainly treatments prescribed for RDs, rather than an undertreatment phenomenon. In accordance with this interpretation are some previous studies. An Italian study investigating medication habits in people with amyotrophic lateral sclerosis (ALS) highlighted patients over 65 years old used more concomitant drugs and had more relevant drug-drug interactions than younger patients, with a worse quality of life [43]. Another population-based study carried out in the Tuscany region, Italy, showed that people aged 80–84 years with RDs had drug consumption three times higher than older people in the general population [44]. Further studies are needed in the monitored population to investigate the real impact of RD-related treatments vs treatments for common comorbidities, as polypharmacy can have peculiar consequences in the RD elderly population [45]. The present study is affected by the following limits. First, possible cases’ underestimation. During its initial years of activity, the registry had not yet reached full capacity, so correspondent data may not precisely reflect the true extent of the aging phenomenon during that time. Additionally, Walter et al. [41] showed a higher risk of being underdiagnosed or misdiagnosed for individuals with an RD living in more remote residential areas. This can apply also to our population, translating into an increased probability that older patients living far from RD Centres can be underrepresented. The impact of telemedicine in reducing the geographical barriers and expanding access to specialized care in geriatric RD patients should be further investigated [42]. Second, the list of monitored RDs, although it includes a broad range of entities and has been expanded over the years, does not fully cover all the RDs represented in the Orphanet nomenclature. To overcome this limit, the VRRRD has introduced the possibility of registering other RDs included in the Orphanet nomenclature, but not present in the Italian official RD list yet. Nevertheless, as this additional registering activity is not mandatory, the population coverage for these diseases may be reduced, and this is the reason why data referred to these RDs have not been considered in the present study. On the other hand, the main strengths of the present study are the long monitoring period and the size of the population under study, including patients of all ages. Furthermore, the adopted population-based approach prevents bias that can affect findings when based on data from disease-specific registries or derived from Centres caring for selected groups of patients. Conclusions To our knowledge, this is the first study describing the epidemiology of a consistent group of RD in older patients. Our results highlight an aging trend among RD patients, revealing a notable shift in the demographic profile of this population over the years. This emerging phenomenon poses several challenges for both patients and healthcare providers, who need to be aware of the peculiarities of this twice-as-frail population. Data provided by the present study can inform health services planning, highlighting not only the importance of identifying highly specialized Centres, but also of establishing connections between them and the local services, both hospital and territorial ones. In this scenario, the role of general practitioners and geriatricians should be better acknowledged, as they can represent the first and often the main point of access to care. Further studies are needed to determine the unmet needs of RD older patients to elaborate adequate health policies, including the use of telemedicine, accompanying carefully RD patients transitioning into old age and progressively becoming elderly. Abbreviations RD: Rare disease VRRDR: Veneto region rare disease registry EU: European Union WHO: World Health Organization UN: United Nations SIGG: Italian Society of Gerontology and Geriatrics ERN: European Reference Network ATC: Anatomical Therapeutic Chemical AHD: administrative health database GUI: graphical user interface SD: standard deviation CI: confidence interval ALS: amyotrophic lateral sclerosis Declarations Ethics approval and consent to participate The Veneto region RD registry - as the other Italian regional/interregional RD registries and the National RD Registry - is established and regulated by Law (Ministerial Decree 279/2001, DPCM 3.03.2017; Law n.175/2021). Consent for publication Patient consent was waived as the RD Registry is established by law and respects the national data protection regulations. No individual data has been considered in the study analysis. Availability of data and materials: The data that support the findings of this study are available from the corresponding authors [ to be completed ] upon reasonable request and with permission of the Veneto region. Competing interests: The authors declare no competing interests. Funding Università degli Studi di Padova provided Open access funding. The Veneto region RD registry is funded by the Veneto region. Authors' contributions Conceptualization: MM, GF, PF; Methodology and data analysis: MM, GF, AV, LVDP, PF; Data curation: MM, GF, LVDP, AV, ET; Writing draft preparation: MM, GF; Writing editing and reviewing: MM, GF, LVDP, CM; PF, AV, CC, AC, GS, ET. All authors have read and agreed to the published version of the manuscript. Acknowledgements We would like to thank all the clinicians and health professionals working in the regional Health Service who are dedicated to the care of RD patients. We are grateful to patients’ advocates, and particularly to Mr. Cees Smith, for bringing attention to the complex issue of aging with an RD. We are furthermore grateful to the Orphanet team for providing and maintaining the Orphanet RD nomenclature based on ORPHAcodes, a valuable resource to carry out epidemiologic studies to improve the visibility of RD and thus of RD patients. References Eurostat, Corselli-Nordblad L, Strandell H. Ageing Europe: looking at the lives of older people in the EU. 2020 ed. Luxemburg: Publications Office of the European Union; 2020. Istat, Indicatori demografici - Anno 2022. https://www.istat.it/it/archivio/283229 (2023). Accessed 7 Apr 2023. Covey HC. The definitions of the beginning of old age in history. Int J Aging Hum Dev. 1992,34(4):325-37. doi:10.2190/GBXB-BE1F-1BU1-7FKK. Gordon EH, Hubbard RE. Frailty: understanding the difference between age and ageing. Age Ageing. 2022;51(8). doi:10.1093/ageing/afac185. United Nations Department of Economic and Social Affairs, Population Division. World Population Prospects 2022: Summary of Results. New York: United Nations; 2022. UN DESA/POP/2022/TR/NO. 3 World Health Organization. Ageing and health. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. Accessed 7 Apr 2023. Società Italiana di Gerontologia e Geriatria. Quando si diventa “anziani”? https://www.sigg.it/news-geriatria/quando-si-diventa-anziani/. Accessed 7 Apr 2023. Tambuyzer E, Vandendriessche B, Austin CP, Brooks PJ, Larsson K, Miller Needleman KI, Valentine J, Davies K, Groft SC, Preti R, Oprea TI, Prunotto M. Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov. 2020;(2):93-111. doi:10.1038/s41573-019-0049-9. Montserrat A, Taruscio, D. Policies and actions to tackle rare diseases at European level. Annali dell’Istituto Superiore di Sanità. 2014;55(3):296–304. https://annali.iss.it/index.php/anna/article/view/953 Nguengang Wakap S, Lambert DM, Olry A, Rodwell C, Gueydan C, Lanneau V, Murphy D, Le Cam Y, Rath A. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28(2):165–73. doi:10.1038/s41431-019-0508-0 Chung CCY, Chu ATW, Chung BHY, Hong Kong Genome Project. Rare disease emerging as a global public health priority. Front Public Health. 2022;10. doi:10.3389/fpubh.2022.1028545. Adachi T, El-Hattab AW, Jain R, Nogales Crespo KA, Quirland Lazo CI, Scarpa M, Summar M, Wattanasirichaigoon D. Enhancing equitable access to rare disease diagnosis and treatment around the world: A review of evidence, policies, and challenges. Int J Environ Res Public Health. 2023;20(6):4732. doi:10.3390/ijerph20064732. Ambrosio MR, Gagliardi I, Chiloiro S, Ferreira AG, Bondanelli M, Giampietro A, Bianchi A, Marinis LD, Fleseriu M, Zatelli MC. Acromegaly in the elderly patients. Endocrine. 2020;68(1):16–31. doi.org/10.1007/s12020-020-02206-7. Gilstrap LG, Dominici F, Wang Y, El-Sady MS, Singh A, Di Carli MF, Falk RH, Dorbala S. Epidemiology of cardiac amyloidosis–associated heart failure hospitalizations among fee-for-service Medicare beneficiaries in the United States. Circ Heart Fail. 2019;12(6). doi:10.1161/circheartfailure.118.005407. Mazzucato M, Visonà Dalla Pozza L, Minichiello C, Manea S, Barbieri S, Toto E, Vianello A, Facchin P. The epidemiology of transition into adulthood of rare diseases patients: Results from a population-based registry. Int J Environ Res Public Health. 2018;15(10):2212. doi:10.3390/ijerph15102212 Sabbà C, Lenato GM, Custodero C, Suppressa P. Rare diseases in the elderly: a new perspective for the specialist in geriatrics: Rare Diseases in the elderly. Geriatr Care. 2019;5(3). doi:10.4081/gc.2019.8769. Smit C. Ageing in rare, chronic diseases. Orphanet J Rare Dis. 2010;5(S1). doi:10.1186/1750-1172-5-s1-o23. Mazzucato M, Visonà Dalla Pozza L, Manea S, Minichiello C, Facchin P. A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region’s rare diseases registry. Orphanet J Rare Dis. 2014;9(1). doi:10.1186/1750-1172-9-37. Mazzucato M, Visonà Dalla Pozza L, Minichiello C, Toto E, Vianello A, Facchin P. Estimating mortality in rare diseases using a population-based registry, 2002 through 2019. Orphanet J Rare Dis. 2023;18(1). doi:10.1186/s13023-023-02944-7. Istat, Popolazione residente al 1° gennaio: Veneto. http://dati.istat.it/Index.aspx?QueryId=18549. Accessed 7 Apr 2023. Decreto del Presidente del Consiglio dei Ministri 12 Gennaio 2017. Definizione e aggiornamento dei livelli essenziali di assistenza, di cui all’articolo 1, comma 7, del decreto legislativo 30 dicembre 1992, n. 502 (17A02015). G.U. Serie Generale, n. 65 del 18 Marzo 2017. https://www.gazzettaufficiale.it/eli/id/2017/03/18/17A02015/sg. Accessed: 30 Jun 2023. Orphanet. Orphanet Nomenclaure Pack 2023. https://www.orphadata.com/pack-nomenclature/. Accessed 30 Jun 2023. Mazzucato M, Pozza LVD, Facchin P, Angin C, Agius F, Cavero-Carbonell C, Corrochano V, Hanusova K, Kirch K, Lambert D, Lucano C, Maiella S, Panzaru M, Rusu C, Weber S, Zurriaga O, Zvolsky M, Rath A. ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability. Orphanet J Rare Dis. 2023;18(1). doi:10.1186/s13023-023-02864-6. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2023. 26th ed. Oslo: Norwegian Institute of Public Health; 2022. Gunne E, Lambert DM, Ward AJ, Murphy DN, Treacy EP, Lynch SA. An estimate of the cumulative paediatric prevalence of rare diseases in Ireland and comment on the literature. Eur J Hum Genet. 2022;30(11):1211–5. doi:10.1038/s41431-022-01144-4. Walker CE, Mahede T, Davis G, Miller LJ, Girschik J, Brameld K, Sun W, Rath A, Aymé S, Zubrick SR, Baynam GS, Molster C, Dawkins HJS, Weeramanthri TS. The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort. Genet Med. 2017;19(5):546–52. doi:10.1038/gim.2016.143 17. Dye DE, Brameld KJ, Maxwell S, Goldblatt J, Bower C, Leonard H, Bourke J, Glasson EJ, O’Leary P. The impact of single gene and chromosomal disorders on hospital admissions of children and adolescents: A population-based study. Public Health Genomics. 2011;14(3):153–61. doi:10.1159/000321767 Dye DE, Brameld KJ, Maxwell S, Goldblatt J, O’Leary P. The impact of single gene and chromosomal disorders on hospital admissions in an adult population. J Community Genet. 2011;2(2):81–90. doi:10.1007/s12687-011-0043-3. Cai X, Genchev GZ, He P, Lu H, Yu G. Demographics, in-hospital analysis, and prevalence of 33 rare diseases with effective treatment in Shanghai. Orphanet J Rare Dis. 2021;16(1). doi:10.1186/s13023-021-01830-4. Cai X, Yang H, Genchev GZ, Lu H, Yu G. Analysis of economic burden and its associated factors of twenty-three rare diseases in Shanghai. Orphanet J Rare Dis. 2019;14(1). doi:10.1186/s13023-019-1168-4. Yoshikawa H, Adachi Y, Nakamura Y, Kuriyama N, Murai H, Nomura Y, Sakai Y, Iwasa K, Furukawa Y, Kuwabara S, Matsui M, Taskforce of Validation of Evidence-based Diagnosis and Guidelines, and Impact on Quality of Life (QOL) in Patients with Neuroimmunological Diseases. Two-step nationwide epidemiological survey of myasthenia gravis in Japan 2018. PLoS One. 2022;17(9):e0274161. doi:10.1371/journal.pone.0274161. Hsu JC, Wu H-C, Feng W-C, Chou C-H, Lai EC-C, Lu CY. Disease and economic burden for rare diseases in Taiwan: A longitudinal study using Taiwan’s National Health Insurance Research Database. PLoS One. 2018;13(9):e0204206. doi:10.1371/journal.pone.0204206. Gianferrari G, Martinelli I, Simonini C, Zucchi E, Fini N, Caputo M, Ghezzi A, Gessani A, Canali E, Casmiro M, et al. Insight into elderly ALS patients in the Emilia Romagna Region: Epidemiological and clinical features of late-onset ALS in a prospective, population-based study. Life (Basel). 2023;13(4):942. doi:10.3390/life13040942. Marin B, Hamidou B, Couratier P, Nicol M, Delzor A, Raymondeau M, Druet-Cabanac M, Lautrette G, Boumediene F, Preux PM, et al. Population‐based epidemiology of amyotrophic lateral sclerosis (ALS) in an ageing Europe – the French register of ALS in Limousin (FRALim register). Eur J Neurol. 2014;21(10):1292. doi:10.1111/ene.12474. Bernatsky S, Joseph L, Pineau CA, Belisle P, Hudson M, Clarke AE. Scleroderma prevalence: Demographic variations in a population‐based sample. Arthritis Care Res. 2009;61(3):400–4. doi:10.1002/art.24339. Ingegnoli F, Ughi N, Mihai C. Update on the epidemiology, risk factors, and disease outcomes of systemic sclerosis. Best Pract Res Clin Rheumatol. 2018;32(2):223–40. doi:10.1016/j.berh.2018.08.005. Bergamasco A, Hartmann N, Wallace L, Verpillat P. Epidemiology of systemic sclerosis and systemic sclerosis-associated interstitial lung disease. Clin Epidemiol. 2019; 11:257–73.doi: 10.2147/CLEP.S191418. Broussalis E, Grinzinger S, Kunz AB, Killer-Oberpfalzer M, Haschke-Becher E, Hartung HP, Kraus J, et al. Late age onset of amyotrophic lateral sclerosis is often not considered in elderly people. Acta Neurol Scand. 2018;137(3):329–34. doi:10.1111/ane.12869. Lelli D, Pedone C, Leosco D, Antonelli Incalzi R, for the Società Italiana di Gerontologia e Geriatria. Cardiac amyloidosis awareness among residents/specialists in Geriatrics: an Italian national survey. J Gerontol Geriatr. 2021;69(3):177–187. doi.10.36150/2499-6564-n374 Paganoni S, Macklin EA, Lee A, Murphy A, Chang J, Zipf A, et al. Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5–6):453–6. doi:10.3109/21678421.2014.903974. Walter A-L, Baty F, Rassouli F, Bilz S, Brutsche MH. Diagnostic precision and identification of rare diseases is dependent on distance of residence relative to tertiary medical facilities. Orphanet J Rare Dis. 2021;16(1). doi:10.1186/s13023-021-01769-6. Gao H, Yous ML, Connelly D, Hung L, Garnett A, Hay M, Snobelen N. Implementation and impacts of virtual team-based care planning for older persons in formal care settings: A scoping review. Digit Health. 2023;9:20552076231151567. doi:10.1177/2055207623115156. Diamanti L, Bianchi E, Mucaj K, Cereda C, Garattini S, Beghi E, Pupillo E. Drug treatments and interactions, disease progression and quality of life in ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2022;23(5–6):415–23. doi:10.1080/21678421.2021.2019279. Gorini F, Santoro M, Pierini A, Mezzasalma L, Baldacci S, Coi A. Profile of drug utilization in patients with Rare Diseases in Tuscany, Italy: A population-based study. Int J Environ Res Public Health. 2023;20(2):937. doi:10.3390/ijerph20020937. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1). doi:10.1186/s12877-017-0621-2. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3875871","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270280356,"identity":"7a2f0333-1d95-45da-9d69-a9c4b6739df6","order_by":0,"name":"Monica Mazzucato","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABQ0lEQVRIie2QMUvDQBTHXzm4LodZUwLpJxCuBA6FfBOXC8K5mL1DwYAQl2tdO+lXqAjOCQfpcrRrQYeKUBzbJWQoxVQRejaKo2B+w3Hv8X78Hw+gpuaPkhiVtX34bgf/rFBoRYZS/nCFYyjUDOV7MYdX/TQpenBiXY8XdtFbu96jUq/z7pML9mk2XxU+HLSjXYXpCU9lBuEwSURLZtRjEyGOuF54YIuzzpCLr4ux2TlVZXIYpVHmAKbBgyaMBrEKIqKZQ7iqVjYQ3qpG7MCGBvfSyrfKRUSmubP+RmnEEI4yhJ1GTIMRIWheKhyaEjtQoWhN0/7ADu80Rsf9gefZGjPgWnXiZsxaUgiCMTeUsfSWRe6HN9Px86zIXdeS6GVVdFXbQqi8oe+77Uvz7h/YRoXfy891SMX8Hmj5m6mampqaf8Mb0MJ10L76fekAAAAASUVORK5CYII=","orcid":"","institution":"Padua University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Monica","middleName":"","lastName":"Mazzucato","suffix":""},{"id":270280357,"identity":"8ae213c7-82ee-4171-a988-f7c49d4b48fb","order_by":1,"name":"Giulia Fanton","email":"","orcid":"","institution":"Padua University 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Dalla","lastName":"Pozza","suffix":""},{"id":270280361,"identity":"ca0d5d67-fc4a-4895-9690-7661aff5e76d","order_by":5,"name":"Ema Toto","email":"","orcid":"","institution":"Padua University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ema","middleName":"","lastName":"Toto","suffix":""},{"id":270280362,"identity":"5d900c55-6043-4203-9ce7-bb23cf014480","order_by":6,"name":"Chiara Ceolin","email":"","orcid":"","institution":"Padua University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chiara","middleName":"","lastName":"Ceolin","suffix":""},{"id":270280363,"identity":"bc7d4723-9b58-44e9-be99-d89900c37602","order_by":7,"name":"Alessandra Coin","email":"","orcid":"","institution":"Padua University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alessandra","middleName":"","lastName":"Coin","suffix":""},{"id":270280364,"identity":"dc032aee-d77a-48ae-8771-885d89c032a5","order_by":8,"name":"Giuseppe Sergi","email":"","orcid":"","institution":"University of Padua","correspondingAuthor":false,"prefix":"","firstName":"Giuseppe","middleName":"","lastName":"Sergi","suffix":""},{"id":270280365,"identity":"9eb7fea0-207d-458a-9638-52c102b64e43","order_by":9,"name":"Paola Facchin","email":"","orcid":"","institution":"University of Padua","correspondingAuthor":false,"prefix":"","firstName":"Paola","middleName":"","lastName":"Facchin","suffix":""}],"badges":[],"createdAt":"2024-01-18 13:14:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3875871/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3875871/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50567240,"identity":"682710da-cca6-498a-b71f-45556f753fda","added_by":"auto","created_at":"2024-02-02 15:18:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":721146,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of the selection process of the patients included in the analyses.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3875871/v1/7157583ffb9efbe3bb4f9c11.jpg"},{"id":50567237,"identity":"c2714c6c-b9f8-4cf5-a72f-77fd8a18d6f2","added_by":"auto","created_at":"2024-02-02 15:18:47","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":412322,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOlder RD patients experiencing the transition from adulthood to old age (2016-2022).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3875871/v1/23fb3fcbac6b6863a0c3c00b.jpg"},{"id":50568725,"identity":"96a5db9b-0c90-4a80-93a1-5ce2f64b823a","added_by":"auto","created_at":"2024-02-02 15:26:47","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":539551,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence map of older RD patients (≥ 65 years) residing in the Veneto region (per 10,000 inhabitants).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3875871/v1/3bbd8b3501a3a24df0117206.jpg"},{"id":50567238,"identity":"5dac183c-02d7-4d35-8e48-d11226730994","added_by":"auto","created_at":"2024-02-02 15:18:47","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1015940,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of RDs in the older patients (≥ 65 years) by Orphanet classification.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3875871/v1/618577916ba37c6e07ae6026.jpg"},{"id":86647895,"identity":"92dd36f6-9a20-4bbc-9ed4-a36f53088fc4","added_by":"auto","created_at":"2025-07-14 09:09:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3828746,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3875871/v1/4f7eec5b-cc8a-4ec6-a309-8648c4c84a59.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Aging and rare diseases: from epidemiology to a call to action","fulltext":[{"header":"Background","content":"\u003cp\u003eRecent projections for 2050 indicate that, in the European Union (EU), the number of people over 65 will increase from 90.5\u0026nbsp;million to 129.8\u0026nbsp;million, while those aged 75\u0026ndash;84 will increase by 56.1\u0026nbsp;million [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In Italy, where the birth rate has reached an all-time low and the number of centenarians has peaked (22,000 cases), the old-age group will represent more than a third of the entire population [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Old age is an arbitrary definition based on biological parameters, such as the multi-construct of frailty, and it is specific to a historical period and geographical context [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Major international organizations, such as the World Health Organization (WHO) and the United Nations (UN), consider a person to have entered old age after 60\u0026ndash;65 years old [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Recently, the Italian Society of Gerontology and Geriatrics (SIGG) has advocated raising the threshold to 75 years, given better physical and cognitive conditions of the people compared to the past [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this rapidly evolving scenario, the rare disease (RD) landscape is also undergoing epidemiological and social changes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. An RD is a complex health condition that affects a few people in the general population, with a cut-off threshold varying by country. In Europe, the prevalence should not exceed five cases per 10,000 individuals. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. According to recent estimates, the RD cumulative prevalence ranges from 3.5\u0026ndash;5.9%, corresponding to 263 to 446\u0026nbsp;million people worldwide having one of the approximately 8,000 known RDs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Thus, although RDs are individually uncommon, their global burden is far from negligible, making these medical conditions a public health priority [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCommonly, RDs are perceived as a pediatric issue as nearly 70% of them have a reported onset in childhood, with the remaining 12% and 18% emerging in adulthood and at all ages, respectively [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Nonetheless, the majority of patients fall within the adult demographic [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The number of people receiving a diagnosis of an RD in their old age is increasing due to the aging of the general population and the increase in diagnostic abilities [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. At the same time, advancements in treatment options have elevated survival rates for conditions with unfavorable prognoses in the past, resulting in the transition of generations from adulthood into old age, as observed in paediatric patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It means a new group of patients is emerging, facing the challenges of living with an RD in their old age [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome studies have provided insights into the epidemiology of RDs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] but without focusing specifically on the elderly population.\u003c/p\u003e \u003cp\u003eThis study aims to describe the epidemiology of aging in RD patients in the Veneto region of Italy. We report the number of patients diagnosed in old age and the number of those transited from adulthood into old age, estimating the prevalence of older RD patients as of 31 December 2022. Finally, we described the drug use profile in RD geriatric patients, analyzing the composition of their therapeutic plans regarding the number and nature of treatments prescribed by RD Centres of expertise.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe present work is a registry-based retrospective cohort study. We used data from the Veneto region rare disease registry (VRRDR), ongoing since 2002. Veneto region is located in the north-east of Italy and has nearly 4.9\u0026nbsp;million inhabitants [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Based on the interaction between highly specialized hospitals and territorial services, the RD care network has been officially defined since 2002 and is monitored and periodically updated according to specific criteria. For the purpose of this study, we considered diseases included in the Italian list of RDs [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and in the Orphanet nomenclature [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Patients affected by RDs indexed in the national list can benefit from an exemption from medical charges and other aids, such as drugs, visits, and medical devices. All medical prescriptions, designated by a Centre of expertise, define the patient\u0026rsquo;s therapeutic plan. The VRRDR, the RD care network, and the related activities have been previously described [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe RD care network is organized on three levels:\u003c/p\u003e \u003cp\u003e1) Centres of expertise: labelled on the basis of activity data derived from independent sources, in charge of performing the diagnostic and care activities for RD patients;\u003c/p\u003e \u003cp\u003e2) Centres of expertise part of the European Reference Network (ERN) for RDs, namely \u0026ldquo;Centres of excellence\u0026rdquo;;\u003c/p\u003e \u003cp\u003e3) Coordinating Centre: with the task of governing and monitoring the network and operating the RD registry.\u003c/p\u003e \u003cp\u003eThe VRRDR is interoperable with the regional administrative health database (AHD), which includes demographic information and the residential history of all the potential healthcare beneficiaries living in the region. For identifying patients diagnosed in old age and those transited from adulthood into old age, we considered all patients born until 1957 (i.e. all patients potentially 65 years old aged or above on 31 December 2022) and meeting the inclusion criteria. For calculating prevalent cases, we considered the number of patients aged above the cut-off threshold of 65 years old and residing in the study area on 31 December 2022 (point-prevalence); prevalence was calculated for the total sample and per province of residence. Diagnoses are recorded in the registry using the ICD-9-CM and ICD-10, OMIM and ORPHAcodes [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The information about the preferential parent, as derived from the Orphanet nomenclature pack, was used to group RDs diagnoses [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In the case of a double diagnosis, we considered the more recent one for the analyses.\u003c/p\u003e \u003cp\u003eFor the analysis of the therapeutic plans, we used the Anatomical Therapeutic Chemical (ATC) classification system for grouping prescribed drugs [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe conducted data management and analyses using SAS (version 9.4M6) and R software (version 4.2.1), through the RCommander graphical user interface (GUI), and the Microsoft Office suit and MapChart.net for graphs, tables, and figures.\u003c/p\u003e \u003cp\u003e Patient consent was waived as the RD registry is established by law and respects the national data protection regulations. No individual data has been considered in the study analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eEach patient included in the RD regional registry was followed from the date of first diagnosis up to 31 December 2022, date of death or emigration outside the study area. As of 31 December 2022, 13,718 individuals (47.7% males) residing in the Veneto region and born until 1957 received an RD diagnosis performed by an expert Centre of the RD care network. 8,975 patients were diagnosed in old age and 5,875 of them were alive at the end of the study period. Conversely, 4,743 patients received an RD diagnosis in adulthood. Overall, 4,214 patients experienced the transition into old age, and 9,508 patients aged 65 years old or over were living with an RD on 31 December 2022 (see Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) in the study area- None of the patients considered in the present study presented multiple RD diagnosis. Patients' characteristics are reported in Table\u0026nbsp;1.\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\u003ccaption\u003e\n\u003cp\u003eTable 1\u003c/p\u003e\n\u003cp\u003eCharacteristics of all patients included in the study, overall and according to age of diagnosis.\u003c/p\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis in\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"116\"\u003e\n\u003cp\u003e\u003cstrong\u003eAdulthood\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"116\"\u003e\n\u003cp\u003e\u003cstrong\u003eOld age\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e%\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e%\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e%\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003ePatients \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u003cstrong\u003e4743\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e100\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u003cstrong\u003e8975\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e100\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e\u003cstrong\u003e13718\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e100\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years) at diagnosis, mean \u003c/strong\u003e\u0026plusmn;\u003cstrong\u003e SD\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e58.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u0026plusmn;\u003cem\u003e4.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e74.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u0026plusmn;\u003cem\u003e6.25\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e68.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u0026plusmn;\u003cem\u003e9.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years) at end of follow-up, mean \u003c/strong\u003e\u0026plusmn;\u003cstrong\u003e SD\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e69.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u0026plusmn;\u003cem\u003e5.19\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e78.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u0026plusmn;\u003cem\u003e6.53\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e75.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u0026plusmn;\u003cem\u003e7.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e2448\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e51.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e4733\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e52.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e7181\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e52.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e2295\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e48.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e4242\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e47.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e6537\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e47.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003eEnd of follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eIn adulthood\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e529\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e11.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e529\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e3.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eIn old age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e4214\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e88.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e8975\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e100\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e13189\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e96.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003ePatients in the registry on 31 Dec. 2022\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e3633\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e76.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e5875\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e65.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e9508\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e69.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e1110\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e23.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e3100\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e34.55\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e4210\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e30.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003e\u003cstrong\u003eOrphanet classification\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare neurologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e1236\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e26.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e3293\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e36.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e4529\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e33.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare systemic or rheumatologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e1006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e21.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e2255\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e25.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e3261\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e23.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare skin diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e336\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e7.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e1016\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e11.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e1352\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e9.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare hematologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e439\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e9.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e530\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e5.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e969\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e7.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare inborn errors of metabolism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e518\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e10.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e230\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e2.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e748\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e5.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare ophthalmic disorders\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e321\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e6.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e423\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e4.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e744\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e5.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare respiratory diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e364\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e4.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e424\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e3.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare gastroenterological diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e206\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e4.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e211\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e2.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e417\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e3.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare developmental defects during embryogenesis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e3.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e153\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e340\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e2.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare neoplastic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e190\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e4.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e281\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e2.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare immune diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e51\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e159\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e210\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e1.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare urogenital diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e111\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e196\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e1.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eRare endocrine diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e135\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e1.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"274\"\u003e\n\u003cp\u003eOther RDs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e1.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"57\"\u003e\n\u003cp\u003e54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"58\"\u003e\n\u003cp\u003e\u003cem\u003e0.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"52\"\u003e\n\u003cp\u003e112\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"48\"\u003e\n\u003cp\u003e\u003cem\u003e0.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eRD\u003c/em\u003e rare disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients diagnosed in old age\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 8,975 patients (47.3% males, mean age of 74.2 years) received a diagnosis of an RD after reaching the age of 65 years. Among them, 3,076 (34.3%) died during the study period, with an average age at the time of death being 79.3 years (SD 7.10), and 24 moved outside the study area. Most of the patients (94.4%) received their diagnosis from RD Centres located in the Veneto region. Characteristics are shown in Table 1.\u003c/p\u003e\n\u003cp\u003eThe most represented disease groups in the geriatric RD population are neurologic (36.7%), systemic or rheumatologic (25.1%), and skin diseases (11.3%). In detail, the most common diagnoses are myasthenia gravis (976 cases, 10.9%), systemic sclerosis (939 cases, 10.5%), amyotrophic lateral sclerosis (ALS, 899cases, 10%) and bullous pemphigoid (658 cases, 7.3%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatients transited from adulthood to old age\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the study period, 4,743 patients (48.4% males) born up to 1957 were diagnosed in adulthood (i.e. before age 65) at a mean age of 58.8 years (SD 4.8). Approximately 4,214 patients (46.9% males) reached the age of 65 years; patients experiencing transition accounted for 31.9% of all older patients registered throughout the years (Table 2). As shown in Figure 2, over the years there has been an increase, in absolute terms, of RD patients reaching the age of 65.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCharacteristics of RD patients experiencing the transition from adulthood to old age.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e%\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePatients\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e4214\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e100\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years) at diagnosis, mean\u003c/strong\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026plusmn;\u0026thinsp;\u003cem\u003e4.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years) at end of follow-up, mean\u003c/strong\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026plusmn;\u0026thinsp;\u003cem\u003e4.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRegion where the RD Centre performing the diagnosis is located\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVeneto region\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3381\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e94.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOther regions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e233\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e5.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eOrphanet classification\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare systemic or rheumatologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e940\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e22.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare neurologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e904\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e21.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare inborn errors of metabolism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e488\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e11.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare hematologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e413\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e9.8\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare skin diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e319\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e7.6\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare ophthalmic disorders\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e309\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e7.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare developmental defects during embryogenesis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e180\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e4.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRare gastroenterologic diseases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e179\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e4.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOther RDs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e482\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cem\u003e11.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\"\u003eAbbreviations: \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eRD\u003c/em\u003e rare disease.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePrevalence\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs of 31 December 2022, there were 9,508 (45.7% males) patients aged 65 years or more residing in the study area, representing the 20.8% of all the RD patients monitored by the registry.\u003c/p\u003e\n\u003cp\u003eAmong those, 3,633 subjects (38.2%) were diagnosed before the age of 65, thus experiencing the transition from adulthood to old age. 8,987 (94.5%) patients received a diagnosis in an RD Center located in the Veneto region, and 521 (5.2%) in RD Centers located outside the region. The prevalence rates, reported in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, differ between provinces. Specifically, the highest registered prevalence rate was in the Province of Padua (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026nbsp;and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePrevalence rates of older RD patients (\u0026ge;\u0026thinsp;65 years) by Province of residence (Veneto region) at 31.12.2022.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePopulation\u0026thinsp;\u0026ge;\u0026thinsp;65 years old\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRD patients\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePrevalence rate per 10,000\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95% CI\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eVeneto region\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1167759\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9508\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e81.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e79.8\u0026ndash;83.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eProvinces of Veneto\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVerona\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e211880\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1772\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e83.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e79.8\u0026ndash;87.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVicenza\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e196713\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1398\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e71.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e67.4\u0026ndash;74.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBelluno\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e54934\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e411\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e74.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e67.6\u0026ndash;82.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTreviso\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e205214\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1565\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e76.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e72.5\u0026ndash;80.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVenice\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e214764\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1534\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e71.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e67.9\u0026ndash;75.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePadua\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e221344\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2368\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e107.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e102.7-111.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRovigo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e62910\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e460\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e73.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e66.5\u0026ndash;79.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eAbbreviations: \u003cem\u003eRD\u003c/em\u003e rare disease, \u003cem\u003eCI\u003c/em\u003e confidence interval. Data from I. Stat.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003eThe most prevalent groups of RDs in the geriatric population under study are systemic or rheumatologic, neurological, and skin diseases (see Figure 4). In detail, RD with the highest incidence in the geriatric age group are: systemic sclerosis (994 cases, 10%), myasthenia gravis (914 cases, 9.6%), rare hereditary hemochromatosis (477, 5%), giant cell arteritis (339 cases, 3.6%), bullous pemphigoid (334 cases, 3.5%), chronic inflammatory demyelinating polyneuropathy (297 cases, 3.1%), retinitis pigmentosa (237 cases, 2.5%), idiopathic pulmonary fibrosis (228 cases, 2.4%) and idiopathic achalasia (213 cases, 2.2%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTreatment prescription profile\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 9,508 prevalent older patients, 1,519 had a therapeutic plan related to their RD issued in 2022.\u003c/p\u003e\n\u003cp\u003eThe total number of prescribed products amounted to 3,117, mainly drugs (66.9%) (see Table 4). Consistent with the RDs most commonly represented in the monitored geriatric population, drugs affecting the\u0026nbsp;nervous system made up nearly 28% of all prescribed drugs.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComposition of the therapeutic plans of prevalent older patients (\u0026ge;\u0026thinsp;65 years) on 31.12.2022.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eProducts\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e3117\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e100\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDrugs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2084\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e66.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedical Foods\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e537\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e17.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedical Devices\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e286\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e9.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProsthetics\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e136\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e4.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGalenic preparations\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e2.4\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDrugs: ATC classification\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e2084\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNervous system\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e581\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e27.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlimentary tract and metabolism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e268\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e12.9\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAntineoplastic and immunomodulating agents\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e243\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e11.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlood and blood-forming organs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e214\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e10.3\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnti-infective for systemic use\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e211\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e10.2\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCardiovascular system\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e155\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e7.5\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSystemic hormonal preparations\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e104\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e5.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDermatologicals\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e4.7\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSensory organs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e3.0\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOthers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e148\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e7.1\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\"\u003e\u003csup\u003e1\u003c/sup\u003e excluding sex hormones and insulins. Abbreviations: ATC anatomical therapeutic chemical.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study highlights that a considerable number of patients receive a RD diagnosis after the age of 65, with a significant portion transitioning from childhood or adulthood to old age. To our knowledge, this is the first attempt to provide epidemiologic and real-world drug prescription figures referred to older patients living with an RD using data from a population-based registry.\u003c/p\u003e\n\u003cp\u003eSince the beginning of the Veneto region rare disease registry (VRRDR) activity, 8,975 patients were diagnosed when they were 65 years or older, and 4,214 experienced the transition from adulthood to old age living with an RD. According to our findings, patients aged over 65 years represent a significant proportion of all patients living with an RD in the monitored area at the end of the study period (20.8%).\u003c/p\u003e\n\u003cp\u003eThese findings are not directly comparable with other studies investigating the epidemiology and the healthcare utilization in patients diagnosed with RD as those data usually refer to two distinct age population subgroups, pediatric and non-pediatric, or are based on hospital-based data collection [25-28].\u003c/p\u003e\n\u003cp\u003eIn general, data referring to older age classes are seldom available, with studies usually focusing on a limited number of RD [29].\u003c/p\u003e\n\u003cp\u003eA Chinese study analyzed the medical records of 78 tertiary and community hospitals providing data on the economic burden of 23 RDs. Patients older than 65 years were 10.9% of all the identified RD patients [30].\u003c/p\u003e\n\u003cp\u003eIn our study, more than half of the RD geriatric patients who were still alive by the study\u0026apos;s conclusion had a rare systemic or rheumatic disease or a rare neurological condition. Moreover, 40% of cases could be attributed to a limited number of RD entities, with systemic sclerosis and myasthenia gravis each accounting for 10% individually. This is in accordance with previous epidemiological studies on these two RDs showing higher prevalence values in older individuals and onset age progressively shifted to the elderly [31-38].\u003c/p\u003e\n\u003cp\u003eData presented confirm that, despite the high number of monitored RDs, only a limited proportion of them constitute the majority of cases. These findings may have important implications in designing care pathways and tailored training programs for health professionals. According to the results from a national survey carried out in Italy in 2020, geriatrics had limited knowledge of RDs, even in the case of a condition such as cardiac amyloidosis, which typically affects older patients [39]. This can lead to misdiagnosis, and delay in diagnosis and treatment initiation [40].\u003c/p\u003e\n\u003cp\u003eBesides focusing on the changing demographic profile of the RD population over the years, we were further interested in describing the characteristics of the therapeutic plans of geriatric RD patients. In our study, only a limited proportion (16%) of the prevalent patients had a therapeutic plan active at the end of 2022. This finding is related to the fact that we considered mainly treatments prescribed for RDs, rather than an undertreatment phenomenon. In accordance with this interpretation are some previous studies.\u003c/p\u003e\n\u003cp\u003eAn Italian study investigating medication habits in people with amyotrophic lateral sclerosis (ALS) highlighted patients over 65 years old used more concomitant drugs and had more relevant drug-drug interactions than younger patients, with a worse quality of life [43]. Another population-based study carried out in the Tuscany region, Italy, showed that people aged 80\u0026ndash;84 years with RDs had drug consumption three times higher than older people in the general population [44]. Further studies are needed in the monitored population to investigate the real impact of RD-related treatments vs treatments for common comorbidities, as polypharmacy can have peculiar consequences in the RD elderly population [45].\u003c/p\u003e\n\u003cp\u003eThe present study is affected by the following limits. First, possible cases\u0026rsquo; underestimation. During its initial years of activity, the registry had not yet reached full capacity, so correspondent data may not precisely reflect the true extent of the aging phenomenon during that time. Additionally, Walter et al. [41] showed a higher risk of being underdiagnosed or misdiagnosed for individuals with an RD living in more remote residential areas. This can apply also to our population, translating into an increased probability that older patients living far from RD Centres can be underrepresented. The impact of telemedicine in reducing the geographical barriers and expanding access to specialized care in geriatric RD patients should be further investigated [42]. Second, the list of monitored RDs, although it includes a broad range of entities and has been expanded over the years, does not fully cover all the RDs represented in the Orphanet nomenclature. To overcome this limit, the VRRRD has introduced the possibility of registering other RDs included in the Orphanet nomenclature, but not present in the Italian official RD list yet. Nevertheless, as this additional registering activity is not mandatory, the population coverage for these diseases may be reduced, and this is the reason why data referred to these RDs have not been considered in the present study. On the other hand, the main strengths of the present study are the long monitoring period and the size of the population under study, including patients of all ages. Furthermore, the adopted population-based approach prevents bias that can affect findings when based on data from disease-specific registries or derived from Centres caring for selected groups of patients.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTo our knowledge, this is the first study describing the epidemiology of a consistent group of RD in older patients. Our results highlight an aging trend among RD patients, revealing a notable shift in the demographic profile of this population over the years. This emerging phenomenon poses several challenges for both patients and healthcare providers, who need to be aware of the peculiarities of this twice-as-frail population. Data provided by the present study can inform health services planning, highlighting not only the importance of identifying highly specialized Centres, but also of establishing connections between them and the local services, both hospital and territorial ones. In this scenario, the role of general practitioners and geriatricians should be better acknowledged, as they can represent the first and often the main point of access to care.\u003c/p\u003e\n\u003cp\u003eFurther studies are needed to determine the unmet needs of RD older patients to elaborate adequate health policies, including the use of telemedicine, accompanying carefully RD patients transitioning into old age and progressively becoming elderly.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRD: Rare disease\u003c/p\u003e\n\u003cp\u003eVRRDR: Veneto region rare disease registry\u003c/p\u003e\n\u003cp\u003eEU: European Union\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization\u003c/p\u003e\n\u003cp\u003eUN: United Nations\u003c/p\u003e\n\u003cp\u003eSIGG: Italian Society of Gerontology and Geriatrics\u003c/p\u003e\n\u003cp\u003eERN: European Reference Network\u003c/p\u003e\n\u003cp\u003eATC: Anatomical Therapeutic Chemical\u003c/p\u003e\n\u003cp\u003eAHD: administrative health database\u003c/p\u003e\n\u003cp\u003eGUI: graphical user interface\u003c/p\u003e\n\u003cp\u003eSD: standard deviation\u003c/p\u003e\n\u003cp\u003eCI: confidence interval\u003c/p\u003e\n\u003cp\u003eALS: amyotrophic lateral sclerosis\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e The Veneto region RD registry - as the other Italian regional/interregional RD registries and the National RD Registry - is established and regulated by Law (Ministerial Decree 279/2001, DPCM 3.03.2017; Law n.175/2021).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e Patient consent was waived as the RD Registry is established by law and respects the national data protection regulations. No individual data has been considered in the study analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The data that support the findings of this study are available from the corresponding authors [\u003cem\u003eto be completed\u003c/em\u003e] upon reasonable request and with permission of the Veneto region.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e Universit\u0026agrave; degli Studi di Padova provided Open access funding. The Veneto region RD registry is funded by the Veneto region.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003eConceptualization: MM, GF, PF; Methodology and data analysis: MM, GF, AV, LVDP, PF; Data curation: MM, GF, LVDP, AV, ET; Writing draft preparation: MM, GF; Writing editing and reviewing: MM, GF, LVDP, CM; PF, AV, CC, AC, GS, ET. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eWe would like to thank all the clinicians and health professionals working in the regional Health Service who are dedicated to the care of RD patients. We are grateful to patients\u0026rsquo; advocates, and particularly to Mr. Cees Smith, for bringing attention to the complex issue of aging with an RD. We are furthermore grateful to the Orphanet team for providing and maintaining the Orphanet RD nomenclature based on ORPHAcodes, a valuable resource to carry out epidemiologic studies to improve the visibility of RD and thus of RD patients.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n\u003cli\u003eEurostat, Corselli-Nordblad L, Strandell H. Ageing Europe: looking at the lives of older people in the EU. 2020 ed. Luxemburg: Publications Office of the European Union; 2020. \u003c/li\u003e\n\u003cli\u003eIstat, Indicatori demografici - Anno 2022. https://www.istat.it/it/archivio/283229 (2023). Accessed 7 Apr 2023.\u003c/li\u003e\n\u003cli\u003eCovey HC. The definitions of the beginning of old age in history. Int J Aging Hum Dev. 1992,34(4):325-37. doi:10.2190/GBXB-BE1F-1BU1-7FKK.\u003c/li\u003e\n\u003cli\u003eGordon EH, Hubbard RE. Frailty: understanding the difference between age and ageing. Age Ageing. 2022;51(8). doi:10.1093/ageing/afac185.\u003c/li\u003e\n\u003cli\u003eUnited Nations Department of Economic and Social Affairs, Population Division. World Population Prospects 2022: Summary of Results. New York: United Nations; 2022. UN DESA/POP/2022/TR/NO. 3\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Ageing and health. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. Accessed 7 Apr 2023.\u003c/li\u003e\n\u003cli\u003eSociet\u0026agrave; Italiana di Gerontologia e Geriatria. Quando si diventa \u0026ldquo;anziani\u0026rdquo;? https://www.sigg.it/news-geriatria/quando-si-diventa-anziani/. Accessed 7 Apr 2023.\u003c/li\u003e\n\u003cli\u003eTambuyzer E, Vandendriessche B, Austin CP, Brooks PJ, Larsson K, Miller Needleman KI, Valentine J, Davies K, Groft SC, Preti R, Oprea TI, Prunotto M. Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov. 2020;(2):93-111. doi:10.1038/s41573-019-0049-9.\u003c/li\u003e\n\u003cli\u003eMontserrat A, Taruscio, D. Policies and actions to tackle rare diseases at European level. Annali dell\u0026rsquo;Istituto Superiore di Sanit\u0026agrave;. 2014;55(3):296\u0026ndash;304. https://annali.iss.it/index.php/anna/article/view/953\u003c/li\u003e\n\u003cli\u003eNguengang Wakap S, Lambert DM, Olry A, Rodwell C, Gueydan C, Lanneau V, Murphy D, Le Cam Y, Rath A. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28(2):165\u0026ndash;73. doi:10.1038/s41431-019-0508-0\u003c/li\u003e\n\u003cli\u003eChung CCY, Chu ATW, Chung BHY, Hong Kong Genome Project. Rare disease emerging as a global public health priority. Front Public Health. 2022;10. doi:10.3389/fpubh.2022.1028545.\u003c/li\u003e\n\u003cli\u003eAdachi T, El-Hattab AW, Jain R, Nogales Crespo KA, Quirland Lazo CI, Scarpa M, Summar M, Wattanasirichaigoon D. Enhancing equitable access to rare disease diagnosis and treatment around the world: A review of evidence, policies, and challenges. Int J Environ Res Public Health. 2023;20(6):4732. doi:10.3390/ijerph20064732.\u003c/li\u003e\n\u003cli\u003eAmbrosio MR, Gagliardi I, Chiloiro S, Ferreira AG, Bondanelli M, Giampietro A, Bianchi A, Marinis LD, Fleseriu M, Zatelli MC. Acromegaly in the elderly patients. Endocrine. 2020;68(1):16\u0026ndash;31. doi.org/10.1007/s12020-020-02206-7.\u003c/li\u003e\n\u003cli\u003eGilstrap LG, Dominici F, Wang Y, El-Sady MS, Singh A, Di Carli MF, Falk RH, Dorbala S. Epidemiology of cardiac amyloidosis\u0026ndash;associated heart failure hospitalizations among fee-for-service Medicare beneficiaries in the United States. Circ Heart Fail. 2019;12(6). doi:10.1161/circheartfailure.118.005407.\u003c/li\u003e\n\u003cli\u003eMazzucato M, Vison\u0026agrave; Dalla Pozza L, Minichiello C, Manea S, Barbieri S, Toto E, Vianello A, Facchin P. The epidemiology of transition into adulthood of rare diseases patients: Results from a population-based registry. Int J Environ Res Public Health. 2018;15(10):2212. doi:10.3390/ijerph15102212\u003c/li\u003e\n\u003cli\u003eSabb\u0026agrave; C, Lenato GM, Custodero C, Suppressa P. Rare diseases in the elderly: a new perspective for the specialist in geriatrics: Rare Diseases in the elderly. Geriatr Care. 2019;5(3). doi:10.4081/gc.2019.8769.\u003c/li\u003e\n\u003cli\u003eSmit C. Ageing in rare, chronic diseases. Orphanet J Rare Dis. 2010;5(S1). doi:10.1186/1750-1172-5-s1-o23.\u003c/li\u003e\n\u003cli\u003eMazzucato M, Vison\u0026agrave; Dalla Pozza L, Manea S, Minichiello C, Facchin P. A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region\u0026rsquo;s rare diseases registry. Orphanet J Rare Dis. 2014;9(1). doi:10.1186/1750-1172-9-37.\u003c/li\u003e\n\u003cli\u003eMazzucato M, Vison\u0026agrave; Dalla Pozza L, Minichiello C, Toto E, Vianello A, Facchin P. Estimating mortality in rare diseases using a population-based registry, 2002 through 2019. Orphanet J Rare Dis. 2023;18(1). doi:10.1186/s13023-023-02944-7.\u003c/li\u003e\n\u003cli\u003eIstat, Popolazione residente al 1\u0026deg; gennaio: Veneto. http://dati.istat.it/Index.aspx?QueryId=18549. Accessed 7 Apr 2023.\u003c/li\u003e\n\u003cli\u003eDecreto del Presidente del Consiglio dei Ministri 12 Gennaio 2017. Definizione e aggiornamento dei livelli essenziali di assistenza, di cui all\u0026rsquo;articolo 1, comma 7, del decreto legislativo 30 dicembre 1992, n. 502 (17A02015). G.U. Serie Generale, n. 65 del 18 Marzo 2017. https://www.gazzettaufficiale.it/eli/id/2017/03/18/17A02015/sg. Accessed: 30 Jun 2023.\u003c/li\u003e\n\u003cli\u003eOrphanet. Orphanet Nomenclaure Pack 2023. https://www.orphadata.com/pack-nomenclature/. Accessed 30 Jun 2023.\u003c/li\u003e\n\u003cli\u003eMazzucato M, Pozza LVD, Facchin P, Angin C, Agius F, Cavero-Carbonell C, Corrochano V, Hanusova K, Kirch K, Lambert D, Lucano C, Maiella S, Panzaru M, Rusu C, Weber S, Zurriaga O, Zvolsky M, Rath A. ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability. Orphanet J Rare Dis. 2023;18(1). doi:10.1186/s13023-023-02864-6.\u003c/li\u003e\n\u003cli\u003eWHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2023. 26th ed. Oslo: Norwegian Institute of Public Health; 2022.\u003c/li\u003e\n\u003cli\u003eGunne E, Lambert DM, Ward AJ, Murphy DN, Treacy EP, Lynch SA. An estimate of the cumulative paediatric prevalence of rare diseases in Ireland and comment on the literature. Eur J Hum Genet. 2022;30(11):1211\u0026ndash;5. doi:10.1038/s41431-022-01144-4.\u003c/li\u003e\n\u003cli\u003eWalker CE, Mahede T, Davis G, Miller LJ, Girschik J, Brameld K, Sun W, Rath A, Aym\u0026eacute; S, Zubrick SR, Baynam GS, Molster C, Dawkins HJS, Weeramanthri TS. The collective impact of rare diseases in Western Australia: an estimate using a population-based cohort. Genet Med. 2017;19(5):546\u0026ndash;52. doi:10.1038/gim.2016.143 17.\u003c/li\u003e\n\u003cli\u003eDye DE, Brameld KJ, Maxwell S, Goldblatt J, Bower C, Leonard H, Bourke J, Glasson EJ, O\u0026rsquo;Leary P. The impact of single gene and chromosomal disorders on hospital admissions of children and adolescents: A population-based study. Public Health Genomics. 2011;14(3):153\u0026ndash;61. doi:10.1159/000321767\u003c/li\u003e\n\u003cli\u003eDye DE, Brameld KJ, Maxwell S, Goldblatt J, O\u0026rsquo;Leary P. The impact of single gene and chromosomal disorders on hospital admissions in an adult population. J Community Genet. 2011;2(2):81\u0026ndash;90. doi:10.1007/s12687-011-0043-3.\u003c/li\u003e\n\u003cli\u003eCai X, Genchev GZ, He P, Lu H, Yu G. Demographics, in-hospital analysis, and prevalence of 33 rare diseases with effective treatment in Shanghai. Orphanet J Rare Dis. 2021;16(1). doi:10.1186/s13023-021-01830-4.\u003c/li\u003e\n\u003cli\u003eCai X, Yang H, Genchev GZ, Lu H, Yu G. Analysis of economic burden and its associated factors of twenty-three rare diseases in Shanghai. Orphanet J Rare Dis. 2019;14(1). doi:10.1186/s13023-019-1168-4.\u003c/li\u003e\n\u003cli\u003eYoshikawa H, Adachi Y, Nakamura Y, Kuriyama N, Murai H, Nomura Y, Sakai Y, Iwasa K, Furukawa Y, Kuwabara S, Matsui M, Taskforce of Validation of Evidence-based Diagnosis and Guidelines, and Impact on Quality of Life (QOL) in Patients with Neuroimmunological Diseases. Two-step nationwide epidemiological survey of myasthenia gravis in Japan 2018. PLoS One. 2022;17(9):e0274161. doi:10.1371/journal.pone.0274161.\u003c/li\u003e\n\u003cli\u003eHsu JC, Wu H-C, Feng W-C, Chou C-H, Lai EC-C, Lu CY. Disease and economic burden for rare diseases in Taiwan: A longitudinal study using Taiwan\u0026rsquo;s National Health Insurance Research Database. PLoS One. 2018;13(9):e0204206. doi:10.1371/journal.pone.0204206.\u003c/li\u003e\n\u003cli\u003eGianferrari G, Martinelli I, Simonini C, Zucchi E, Fini N, Caputo M, Ghezzi A, Gessani A, Canali E, Casmiro M, et al. Insight into elderly ALS patients in the Emilia Romagna Region: Epidemiological and clinical features of late-onset ALS in a prospective, population-based study. Life (Basel). 2023;13(4):942. doi:10.3390/life13040942.\u003c/li\u003e\n\u003cli\u003eMarin B, Hamidou B, Couratier P, Nicol M, Delzor A, Raymondeau M, Druet-Cabanac M, Lautrette G, Boumediene F, Preux PM, et al. Population‐based epidemiology of amyotrophic lateral sclerosis (ALS) in an ageing Europe \u0026ndash; the French register of ALS in Limousin (FRALim register). Eur J Neurol. 2014;21(10):1292. doi:10.1111/ene.12474.\u003c/li\u003e\n\u003cli\u003eBernatsky S, Joseph L, Pineau CA, Belisle P, Hudson M, Clarke AE. Scleroderma prevalence: Demographic variations in a population‐based sample. Arthritis Care Res. 2009;61(3):400\u0026ndash;4. doi:10.1002/art.24339.\u003c/li\u003e\n\u003cli\u003eIngegnoli F, Ughi N, Mihai C. Update on the epidemiology, risk factors, and disease outcomes of systemic sclerosis. Best Pract Res Clin Rheumatol. 2018;32(2):223\u0026ndash;40. doi:10.1016/j.berh.2018.08.005.\u003c/li\u003e\n\u003cli\u003eBergamasco A, Hartmann N, Wallace L, Verpillat P. Epidemiology of systemic sclerosis and systemic sclerosis-associated interstitial lung disease. Clin Epidemiol. 2019; 11:257\u0026ndash;73.doi: 10.2147/CLEP.S191418.\u003c/li\u003e\n\u003cli\u003eBroussalis E, Grinzinger S, Kunz AB, Killer-Oberpfalzer M, Haschke-Becher E, Hartung HP, Kraus J, et al. Late age onset of amyotrophic lateral sclerosis is often not considered in elderly people. Acta Neurol Scand. 2018;137(3):329\u0026ndash;34. doi:10.1111/ane.12869.\u003c/li\u003e\n\u003cli\u003eLelli D, Pedone C, Leosco D, Antonelli Incalzi R, for the Societ\u0026agrave; Italiana di Gerontologia e Geriatria. Cardiac amyloidosis awareness among residents/specialists in Geriatrics: an Italian national survey. J Gerontol Geriatr. 2021;69(3):177\u0026ndash;187. doi.10.36150/2499-6564-n374\u003c/li\u003e\n\u003cli\u003ePaganoni S, Macklin EA, Lee A, Murphy A, Chang J, Zipf A, et al. Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5\u0026ndash;6):453\u0026ndash;6. doi:10.3109/21678421.2014.903974. \u003c/li\u003e\n\u003cli\u003eWalter A-L, Baty F, Rassouli F, Bilz S, Brutsche MH. Diagnostic precision and identification of rare diseases is dependent on distance of residence relative to tertiary medical facilities. Orphanet J Rare Dis. 2021;16(1). doi:10.1186/s13023-021-01769-6.\u003c/li\u003e\n\u003cli\u003eGao H, Yous ML, Connelly D, Hung L, Garnett A, Hay M, Snobelen N. Implementation and impacts of virtual team-based care planning for older persons in formal care settings: A scoping review. Digit Health. 2023;9:20552076231151567. doi:10.1177/2055207623115156.\u003c/li\u003e\n\u003cli\u003eDiamanti L, Bianchi E, Mucaj K, Cereda C, Garattini S, Beghi E, Pupillo E. Drug treatments and interactions, disease progression and quality of life in ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2022;23(5\u0026ndash;6):415\u0026ndash;23. doi:10.1080/21678421.2021.2019279.\u003c/li\u003e\n\u003cli\u003eGorini F, Santoro M, Pierini A, Mezzasalma L, Baldacci S, Coi A. Profile of drug utilization in patients with Rare Diseases in Tuscany, Italy: A population-based study. Int J Environ Res Public Health. 2023;20(2):937. doi:10.3390/ijerph20020937.\u003c/li\u003e\n\u003cli\u003eMasnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1). doi:10.1186/s12877-017-0621-2.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Aging, rare disease, registry, epidemiology, treatment, transition, prevalence, Orphanet, drugs, public health","lastPublishedDoi":"10.21203/rs.3.rs-3875871/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3875871/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe number of older people living with a rare disease (RD) is increasing worldwide due to the population aging and scientific progress. This phenomenon poses several challenges for both patients and healthcare providers, who need to be aware of the peculiarities of this twice-as-frail population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn the present study, we used data from the Veneto region rare disease registry (VRRDR) to investigate the epidemiology of older people living with a RD in the Veneto region of Italy. We report the number of patients diagnosed in old age and the number of those transited from adulthood into old age, estimating the prevalence of older RD patients as of 31 December 2022. Finally, we analyzed the composition of their therapeutic plans.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDuring the study period, 8,975 patients received an RD diagnosis after 65 years of age, while 4,214 diagnosed in their childhood or adulthood experienced the transition to old age. On 31 December 2022, there were 9,508 patients aged 65 years or more residing in the study area, 20.8% of all Veneto\u0026rsquo;s RD patients. The most common groups of RDs in elderly patients were systemic or rheumatologic, neurologic, and skin diseases, affecting 27%, 25%, and 9% of the monitored geriatric population, respectively. Among prevalent cases, 1,519 patients older than 65 years had a therapeutic plan related to their rare condition. Specifically, the most prescribed drugs were those affecting the nervous system (27.8%), the alimentary tract and metabolism (12.8%), and antineoplastic and immunomodulating agents (11.6%).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAs older patients represent a growing number in the RD population, geriatricians and general practitioners should be involved in RD care and training programs. Further studies are needed to determine the unmet care needs of older RD patients in order to design health policies able to address the peculiar challenges posed by this group of patients emerging within the RD population.\u003c/p\u003e","manuscriptTitle":"Aging and rare diseases: from epidemiology to a call to action","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-02 15:18:42","doi":"10.21203/rs.3.rs-3875871/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"21590969-f901-4bf9-b55e-c3807b8a31fa","owner":[],"postedDate":"February 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-13T09:33:33+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-02 15:18:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3875871","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3875871","identity":"rs-3875871","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}