Budget impact analysis of the use of paricalcitol for the treatment of secondary hyperparathyroidism in chronic kidney disease

OBJECTIVE: Evaluation of the budget impact of the use of paricalcitol (compared to alternative treatment) for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) when used at two different timing of therapy.METHODS: Two Markov models related to a different timing of treatment have been developed: the intermediate stage of chronic kidney disease (CKD3) and the dialysis stage. The analysis was conducted with the perspective of the Italian National Health System and over a 5-year time horizon. The clinical and economic data used in the model were derived from the literature and other assumptions were made based on the opinion of clinical experts. Univariate sensitivity analysis was conducted to test the robustness of the results.RESULTS: The base case shows that starting paricalcitol treatment from the dialysis stage (considering 13,311 possible candidates) is associated with a reduction in direct costs from € 1,782,921,351 to € 1,622,357,209 over 5 years. Furthermore, considering a collective of 1,000 subjects eligible and starting treatment with paricalcitol since the intermediate stages of the CKD, is associated with an overall cost saving of € 1,197,500.DISCUSSION AND CONCLUSIONS: Paricalcitol is expected to be cost-saving in patients with SHPT in Italy considering both the therapeutic indications of the drug. Moreover, despite the higher cost of using paricalcitol in pre-dialysis stage, an early treatment of SHPT determine an overall decrease in direct medical costs

New Perspective to Improve Care of Patients with Infected Diabetic Foot Ulcer: Early Economic Impact of the Use of Photodynamic Therapy with RLP068 (Based) System

Objective: To perform an early economic evaluation of a system based on photodynamic advanced adjuvant therapy with photosensitizer RLP068/CI to facilitate the healing process of foot/leg skin lesions/ulcers with an excellent safety profile.Design: An early short-term (10 weeks) cost-effectiveness and a budget impact analysis (over 5 years) comparing photodynamic therapy with photosensitizer RLP068/CI based (PDT-RLP068) system added to Standard of Care (SoC) vs SoC alone.Setting: The Italian National Healthcare System perspective considering both the outpatient and the day-hospital regimen.Participants: Hypothetical patients with diabetic foot infection (DFI) grades I/IIB.Interventions: The PDT-RLP068 system as an add-on to Standard of Care (SoC) vs SoC alone as the first-line treatment for the management of DFIs.Main Outcomes: Days within which the clinical target was achieved and direct health costs for patients' management.Results: Additional costs generated by the use of the PDT-RLP068 system progressively decreased as time to reach the target induced by the novel system decreased. In the outpatient regimen, when time to reach clinical target decreased in the range 7-28 days, ICERs varied from about 1 to 70 for each additional day gained with clinical target achieved. The system was dominant when halving time to reach the target in the outpatient regimen and even for modest reduction of time in day-hospital regimen. In terms of budget impact, when considering day-hospital regimen, if the PDT-RLP068 based system allowed a shortened duration to reach the clinical target of between 7-28 days, BI was 8,100,000 to 700,000, with saving less than 2,000,000 with 50% reduction of time. Considering the inpatient setting, the use of the PDT-RLP068 system would result in saving even with the modest impact on the time needed to activate the healing process.Conclusion: The early economic evaluation performed suggested that, if the claimed effectiveness of the technology demonstrated in case reports and in preliminary clinical studies can be confirmed in larger population studies, and allowing for shortening of the time needed to activate the healing process, the PDT-RLP068 system could offer the chance to improve care for DFI patients without compromising the sustainability of the system

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of C9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS. // Methods: We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR). // Results: In total, 62 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%). C9orf72 repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia. // Conclusions: Our results indicate that C9orf72 hexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population

Differential activity and clinical utility of latanoprost in glaucoma and ocular hypertension

Background: The purpose of this study was to demonstrate the hypotensive efficacy and tolerability of latanoprost when used as monotherapy and as polytherapy associated with antiglaucomatous medication proven to be ineffective in keeping intraocular pressure under control. Methods: Three hundred and thirty-seven patients (672 eyes) affected by primary open-angle glaucoma and intraocular hypertension were recruited over a period of 10 years from the Glaucoma Centre, Department of Ophthalmological Sciences, University of Rome "Sapienza", and treated, subject to informed consent, with latanoprost 0.005% alone or in combination with other ocular hypotensive drugs. The patients were followed during this period at regular intervals, with determination of visual field, fundus oculi, visual acuity, and eventual onset of local and systemic side effects. Results: Latanoprost used as monotherapy and as polytherapy renders possible optimal and durable control of intraocular pressure in the form of one antiglaucomatous drug because it can substitute for one or more drugs and obtain the same hypotensive effect. Conclusion: Latanoprost can be described as the ideal hypotensive drug, not only because of its ideal compliance profile (only one daily dose in the evening), excellent hypotensive effect, and, above all, few systemic side effects. © 2012 Pacella et al, publisher and licensee Dove Medical Press Ltd

RarERN Path: a methodology towards the optimisation of patients’ care pathways in rare and complex diseases developed within the European Reference Networks

Background: In 2017, the European Commission has launched the European Reference Networks (ERNs), virtual networks involving healthcare providers across Europe. The aim of the ERNs is to tackle complex and rare diseases and conditions that require highly specialized treatment and a concentration of knowledge and resources. The ERN on rare and complex connective tissue and musculoskeletal diseases (ERN ReCONNET) is one of the 24 ERNs approved that aims to improve the management of Rare and Complex Connective Tissue and Musculoskeletal Diseases. Objective: The RarERN Path methodology aims to create a single reference organisational model for patients’ care pathways which, if applied in different contexts, helps to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases. Methods: Starting from existing standard methods for the creation and elaboration of patients’ care pathways, a specific methodology was created in order to take advantage of the distinctive and peculiar characteristics of the ERNs. Specifically, the development of the RarERN Path methodology involved different stakeholders: health economists, clinicians and researchers expert in rare and complex diseases, communication experts, experts in patients’ involvement and narrative medicine and policy-makers. Results: The RarERN Path methodology foresees six consecutive phases, each with different and specific aims. Specifically, the six phases are represented by: Phase 1—mapping of existing patients’ care pathways and patients’ stories; Phase 2—design of an optimised common patients’ care pathway; Phase 3—consensus on an optimised common patients’ care pathway; Phase 4—key performance indicators definition; Phase 5—refinement; Phase 6—pilot phase (optional). Conclusion: The application of RarERN Path to the different disease-specific and geographical contexts would help to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases across Europe as well as a possible tangible action towards the integration of ERNs into the different European healthcare systems

TABLET TOSCANA to Develop Innovative Organizational Models for Tele-Rehabilitation in Subjects with Congenital and Acquired Developmental Disabilities: A Wait-List Control Group Trial Protocol

Background/Objectives: In recent years, the advent of new technologies has fostered their application in neuro-psychomotor and language rehabilitation, particularly since the COVID-19 pandemic. Tele-rehabilitation has emerged as an innovative and timely solution, enabling personalized interventions monitored by clinicians. TABLET TOSCANA project aims to develop innovative tele-rehabilitation organizational models in children, adolescents and young adults with congenital and acquired developmental disabilities, using the Virtual Reality Rehabilitation System (VRRS) Home Kit and the MedicoAmico APP. Methods: The trial is designed according to the CONSORT statement guidelines. The project encompasses three phases: adapting the technologies for pediatric use, validating them through a wait-list study, and analyzing feasibility and effectiveness data to define new organizational models. A randomized wait-list-control study with 100 subjects aged 6 to 30 years will compare tele-rehabilitation versus prosecution of standard care. Discussion: Although literature highlights tele-rehabilitation benefits such as improved access, cost savings, and enhanced treatment adherence, practical implementation remains limited (i.e., the definition of standardized procedures). TABLET TOSCANA project seeks to address these gaps by focusing on multi-domain treatments for neurodevelopmental disabilities and emphasizing the integration of tele-rehabilitation into local health services. Conclusion: The project aims to improve the continuity and intensity of care through innovative models that integrate tele-rehabilitation into local health services. The results could inform healthcare policies and promote the development of innovative and collaborative models of care, paving the way for more effective and widespread tele-rehabilitation solutions and fostering collaborative networks among professionals

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in VPS13D-Related Disorder

VPS13D is one of four human homologs of the vacuolar sorting protein 13 gene (VPS13). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237−1G > A) and a non-canonical (NM_018156.4: c.941+3G>A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved significantly by bilateral deep brain stimulation (DBS) in the ventralis intermedius (VIM) nucleus of the thalamus. We also conducted a literature review and summarized the phenotypical spectrum of reported VPS13D-related disorders. Our study underscores that looking for mutations outside the canonical splice sites is important not to miss a genetic diagnosis, especially in disorders with a highly heterogeneous presentation without specific red flags

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS) [version 2; peer review: 2 approved]

Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of C9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS. Methods We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR). Results In total, 62 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%). C9orf72 repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia. Conclusions Our results indicate that C9orf72 hexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population

The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: A multicenter study in Italy.

Background: The aim of this study is to determine the 99th upper-reference limit (URL) for cardiac troponin T (cTnT) in Italian apparently healthy subjects. Methods: The reference population was selected from 5 cities: Bolzano (n = 290), Milano (CAMELIA-Study, n = 287), Montignoso (MEHLP-Study, n = 306), Pisa (n = 182), and Reggio Calabria (MAREA-Study, n = 535). Subjects having cardiac/systemic acute/chronic diseases were excluded. Participants to MEHLP project underwent cardiac imaging investigation. High-sensitive cTnT was measured with Cobas-e411 (Roche Diagnostics). Results: We enrolled 1600 healthy subjects [54.6%males; age range 10–90 years; mean (SD): 36.4 (21.2) years], including 34.6% aged b20 years, 54.5% between 20 and 64 years, and 10.9% over 65 years. In the youngest the 99th URL was 10.9 ng/L in males and 6.8 ng/L in females; in adults 23.2 ng/L and 10.2 ng/L; and in elderly 36.8 ng/L and 28.6 ng/L. After the exclusion of outliers the 99th URL values were significantly decreased (P b 0.05) in particular those of the oldest (13.8 ng/L and 14 ng/L). MEHLP participants were divided in healthy and asymptomatic, according to known cardiovascular risk factors (HDL, LDL, glucose, C-reactive protein): the 99th URL of cTnT values of these subgroups was significantly different (19.5 vs. 22.7, P b 0.05). Conclusions: 99th URL of cTnT valueswas strongly affected by age, gender, selection of subjects and the statistical evaluation of outliers

Pure cerebellar ataxia due to bi-allelic PRDX3 variants including recurring p.Asp202Asn

Bi-allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent-onset pure and complex cerebellar ataxia