Barbara Polistena

Objective study was the quantification of controlled/inadequately controlled generalized myasthenia gravis (gMG) disease burden, health care resource utilization and costs in MG patients, followed-up at a reference center for MG in Italy. The study is a 2010 to 2020 retrospective analysis of gMG patients. Clinical and health economics variables were those observed during routine clinical care. Data were anonymized and treated in aggregated forms in compliance with GDPR. Only patients with gMG were included in the study. Out of 237 patients, 55.3% were males and 44.7% females with a median follow up duration of 4.7 years. Males were older, with a median age at onset of 58.3 years versus 45.7 years for females; an increased representation of late and very late onset patients was recorded. A shorter time from onset to diagnosis was observed in males. The incidence rate per year of exacerbations changed from 0.76 in the first year to 0.23 at the sixth year, with a similar trend for MG crisis; both exacerbations and crisis incidence were higher in inadequately controlled patients. Disease burden and health care resources utilizations were particularly evident in inadequately controlled patients, which showed a 138% increase of costs. Our data confirmed the observed epidemiological changes occurring in MG population and the high use of health care system resources in uncontrolled patients. The estimates obtained will provide a useful basis for assessing the impact of recently introduced targeted therapies on healthcare expenditure for MG.

Background: Gastroesophageal reflux disease (GERD) is a common reason for referral to pediatric and gastroenterology clinics. Still, uncertainty and variability exist in the evaluation, diagnostic approaches and management among different age groups and clinicians. This study aimed to report the results of a Guidelines process and an Italian expert Consensus focusing on the diagnosis of GERD in children to improve the clinical approach to these patients. Methods: A multidisciplinary board of 16 participants identified eight PICO (Population/Patient/Problem, Intervention, Comparator and Outcome) questions, including definition, signs and symptoms, risk factors, diagnostic tests, treatment and prognosis of gastroesophageal reflux (GER) and GERD in children: four PICO questions were related to the diagnosis of GERD. Four databases (PubMed/Medline, Embase, Web of Science and Google Scholar) were searched from their inception to May 11, 2024, limited to children (0–18 years) and English language. For each PICO question a specific search string was developed. Guidelines, systematic reviews and clinical studies on diagnosis and management in children were considered to formulate evidence-based recommendations. Agreement was defined based on a 9-point Likert scale. A two-round Delphi method was conducted and consensus was defined as ≥ 80% agreement or disagreement. This paper focused on clinical symptoms and diagnosis of GER and GERD in pediatric ages. Results: 123 studies were included that satisfied systematic research criteria. The panel provided 14 recommendations on diagnosis of GER and GERD and practice points for specific questions to clarify some clinical issues. Conclusion: Symptoms of GER(D) are common in the pediatric population while regurgitation is frequently reported in the first months of life. In infancy symptoms mostly disappear spontaneously or after dietary modification. In infants and children with esophageal or extresophageal persistent symptoms, esophageal pH-MII monitoring and endoscopy are indicated to detect and characterize reflux episodes, phenotypes of GERD and esophagitis. In older children and adolescents reporting typical heartburn or in those with severe neurological impairment, a time-limited empirical trial of PPI can be considered as an initial diagnostic approach, with further testing reserved for non-responders.

Introduction Multiple sclerosis (MS) is a chronic autoimmune disease impacting the central nervous system. Individuals with highly active relapsing–remitting MS (HA-RRMS) frequently experience symptomatic episodes lasting more than 24 h, followed by a remission period completely or partially symptom free. This study aimed to assess the economic impact of cladribine tablets for the treatment of patients with HA-RRMS in the Italian context. Methods A Markov model developed by PRECISIONheor for simulating treatment outcomes in patients with HA-RRMS aged over 18 years over three treatment lines was adapted to the Italian National Health System organization. The model considers direct costs of treatment and relapse management, as well as costs related to adverse events and indirect costs. The model adopts the societal perspective and a 4-year time horizon. Uncertainty was addressed through deterministic sensitivity analysis. Results The analysis considered 16,691 out of 55,635 Italian patients with HA-RRMS (30%). Treatment with cladribine tablets extended the duration of patients’ responsive stage (relapse free) from 1.3 months (worst scenario) to 1.4 months (best scenario) when compared to oral disease-modifying therapies (DMTs) and from 2.4 to 5.7 months when compared to monoclonal antibody DMTs. cladribine tablets were associated with cost savings ranging from 69.9% to 10.9% compared to oral DMTs and from 74.3% to 33.0% compared to monoclonal antibody DMTs. The cost savings per additional month in responsive stage ranged from € 27,663.2 to € 4154.3 vs oral DMTs and from € 16,224.5 to € 3035.3 vs monoclonal antibody DMTs. Conclusion Cladribine tablets are associated with a benefit in terms of prolonging the non-relapsing phase in patients with HA-RRMS, as well as substantial direct cost savings in comparison with all other DMTs. Our analysis suggests that adopting cladribine tablets for HA-RRMS enables clinical benefits over a 4-year time horizon and savings for Italian society.

Purpose: The study aimed to present the results of a Delphi consensus involving Italian experts focusing on the management of hypophosphatemia in adults. Methods: A multidisciplinary advisory board of nine physicians, experts in hypophosphatemia management, was established. Next, a literature search was performed to identify international guidelines, consensus, and clinical pathways, which were later presented to the advisory board. Collaboratively, the advisory board and authoring team selected key statements for the consensus process and focused on areas of uncertainty related to the management of hypophosphatemia. The advisory board also indicated the experts to be invited to participate in the consensus process. The Delphi method was employed to reach a consensus. Results: The literature search yielded one guideline, five consensus documents, and one clinical pathway. While our search strategy aimed to identify documents on the management of all types of hypophosphatemia, most of the guidelines and consensus documents retrieved focused on X-linked hypophosphatemia. The consensus process focused on 11 key issues, achieving strong convergence (over 70% consensus) in the first Delphi round for 8 out of the 11 statements. Three statements proceeded to the second round, with strong agreement reached for two. Notably, consensus was not reached for the statement concerning the measurement of fibroblast growth factor 23 for diagnostic purposes. Conclusion: The study revealed that the community of clinical experts is well-informed and in agreement regarding hypophosphatemia management. It emphasized the importance of developing clear national guidance documents to support clinicians and multidisciplinary teams in patient management. These documents are crucial not only for healthcare professionals but also for those responsible for defining pathways and services, facilitating a more accurate management of hypophosphatemic patients.

Background: Respiratory syncytial virus (RSV) affects 60–80% of children below 1 year and it’s the first cause of acute bronchiolitis. The aim of this study was to assess the trend and characteristics of hospitalizations for RSV infections in Italy. Methods: This is a retrospective study based on the Italian Hospital Discharge Record (HDR) database. We analysed HDRs from June 2015 to May 2019, considering two groups of infants: Group 1 had a confirmed diagnosis of RSV; Group 2 had a diagnosis of acute bronchiolitis not RSV-coded. Results: There were 67,746 overall hospitalizations (40.1% Group 1, and 59.9% Group 2). Hospitalization rate increased for Group 1 from 125 to 178 per 10,000 infants (+ 42.4%), and for Group 2 from 210 to 234 per 10,000 (+ 11.4%). The mean hospitalization length was 6.3 days in Group 1, longer than Group 2 (+ 1.0 day). A further analysis revealed that infants with heart disease or born premature had longer mean hospital stay compared to infants without risk factors (10.7 days versus 6.1 days, p < 0.0001; 34.0 days versus 6.1 days, p < 0.0001, respectively). Group 1 required more critical care (oxygen therapy and/or mechanical ventilation) than Group 2. We found that, in proportion to hospital admissions in pediatric and general hospitals, RSV was more frequently diagnosed in the first ones. The mean hospitalization cost increased for Group 1 (from € 2,483 to € 2,617) and Group 2 (from € 2,007 to € 2,180). Conclusions: Our results confirmed that RSV pulmonary disease in infants is seasonal and often requires hospitalization. Our study suggested that RSV is responsible for an increasing hospitalization rate and related costs during the study period.

Objective: Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is one of the main causes of short stature in children and adolescents. The aim of this study is to evaluate the epidemiology of pediatric GHD worldwide, since no other systematic review has been published so far. Methods: We searched PubMed, Embase, and Web of Science up to July 2023 to find epidemiological studies involving children with GHD. Two review authors independently screened articles, extracted data and performed the quality assessment. Results: We selected 9 epidemiological studies published from 1974 to 2022. The range of prevalence was 1/1107–1/8,646. A study based on a registry of GH users in the Piedmont region (Italy) reported the highest mean prevalence. In the included studies, the mean incidence ranged from 1/28,800 to 1/46,700 cases per year. One study reported a 20-year cumulative incidence of 127/100,000 for boys and 93/100,000 for girls. Studies were heterogeneous in terms of population (age and GHD etiology) and diagnostic criteria. As for the methodological quality of included studies, all but one study satisfied the majority of the checklist items. Conclusions: The included studies are mostly European, so the provided estimates cannot be considered global. International multicentre studies are needed to compare epidemiological estimates of GHD among different ethnical groups. Considering the considerable cost of human recombinant GH, the only available therapy to treat GHD, understanding accurate epidemiological estimates of GHD in each country is fundamental for resource allocation.

The Health Technology Assessment (HTA) Working Group of the Emerging Technology Division of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) aims to develop a methodological approach for producing structured HTA information for laboratory medicine technologies. This approach seeks to support decision-making processes at the country, regional, and/or hospital levels regarding the introduction of specific technologies. The focus of this model will primarily be on defining assessment elements within the domains of ‘organizational aspects’ and ‘costs and economic evaluations’, potentially differentiated by the type of diagnostic technology (e.g., genetic tests, molecular tests). To achieve this project’s goal, a literature review and examination of websites of international HTA agencies have been conducted. The research aims to identify multidisciplinary methodological approaches used to assess laboratory diagnostic technologies and to pinpoint the domains and assessment elements utilized. We found 7 methodological articles describing methodological approaches adopted to assess laboratory diagnostic technologies. Among the HTA organizations considered, 23 reports were found, of which 7 were produced by the European Network of HTA (EUnetHTA), 4 by the National Institute for Health and Care Excellence Diagnostic Assessment Program (NICE DAP), and 12 by other HTA agencies. The EUnetHTA reports were rapid collaborative assessments covering various domains, while the NICE DAP reports focused on diagnostic guidances, including descriptions of technologies, clinical need and practice, diagnostic tests, accuracy, effectiveness, and cost-effectiveness. Finally, a survey targeting laboratory professionals will be conducted to introduce assessment elements, differentiated by the type of diagnostic technology, primarily for organizational and economic domains.

Purpose: Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy. Methods: A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents. Results: 143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708–8,354) was estimated in € 48.5–71.0 million, corresponding to 0.04–0.06% of the total Italian public health expense in the year 2020. Conclusions: The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.

Introduction: There are an estimated 26 million rare disease patients in Europe, about 2 million in Italy. Access to orphan drugs has been evaluated nationally and internationally, and delays have been observed due to evaluation of price and therapeutic value. The objectives of this study are: to assess the availability of EMA-authorized orphan drugs at national and regional level; to study time trends and regional variability in consumption and spending, and to estimate the time to access in Italian regions. Methods: We evaluate the availability of EMA authorized orphan drugs in Italy. Based on data from the Traceability of medicines dataflow for period 2016-2021 we evaluate the expenditure, consumption and availability of orphan drugs in each region. To estimate the time to access we consider the days between the end of negotiation procedure and the first purchase by regions. Results: In 2021 in Italy are available 94% of EMA authorized orphan drugs. The expenditure and consumption have grown during the last decade. The availability is higher in bigger regions, that also take care of patients from smaller regions. The pro capite expenditure and consumption in DDD/1,000 ab die is similar in all the geographic area. Time to regional access is on average 123 days, that grows to 224 excluding the orphan drugs dispensed before the end of reimbursement procedure.