Scientific literature debates on the economic affordability of transcatheter aortic valve implantation (TAVI) in order to give a useful support to decision makers aiming at establishing a ...reimbursement scheme for TAVI. For this reason, it is important to assess the quality and the generalizability of the existing economic evidences.
The first step was to run a literature search according to a predefined population, intervention, comparator, and outcome on the cost and effectiveness of the TAVI procedure in comparison to medical therapy and traditional surgery. Second, a manual search was carried out on the Web sites of the main HTA agencies. Third, the checklist developed by Augustovski et al. was applied in order to assess the quality and the generalizability of the articles resulting from the selection process.
Overall, 106 articles were obtained. Of these, sixty-five articles were excluded since the title was not consistent with the objective. Further selection took place after abstract and full-text reading. In the end, thirty-one documents were included for the review. According to the checklist, none of the articles was considered generalizable and only one was considered transferable which compares the TAVI procedure with Medical Management in inoperable patients.
Despite the overall quality of the selected studies was considered good, there is still a lack of evidence on whether evidences generated in different contexts can be considered generalizable. Further research on resource consumption and preferences is needed in order to provide decision makers with more robust evidences.
In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects ...entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions.
Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces.
From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up.
This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.
Clinical studies based on novel rationales and mechanisms of action of chemotherapy agents and cytokines can contribute to the development of new concepts and strategies of antitumor combination ...therapies. In previous studies, we investigated the paradoxical immunostimulating effects of some chemotherapeutics and the immunoadjuvant activity of interferon alpha (IFN-α) in preclinical and clinical models, thus unraveling novel rationales and mechanisms of action of chemotherapy agents and cytokines for cancer immunotherapy. Here, we carried out a randomized, phase II clinical trial, in which we analyzed the relapse-free (RFS) and overall survival (OS) of 34 completely resected stage III-IV melanoma patients, treated with peptide-based vaccination (Melan-A/MART-1 and NY-ESO-1) in combination with IFN-α2b, with (arm 2) or without (arm 1) dacarbazine preconditioning. All patients were included in the intention-to-treat analysis. At a median follow-up of 4.5 years (interquartile range, 15.4-81.0 months), the rates of RFS were 52.9 and 35.3% in arms 1 and 2, respectively. The 4.5-year OS rates were 68.8% in arm 1 and 62.7% in arm 2. No significant differences were observed between the two arms for both RFS and OS. Interestingly, the RFS and OS curves remained stable starting from 18 and 42 months, respectively. Grade 3 adverse events occurred in 5.9% of patients, whereas grade 4 events were not observed. Both treatments induced a significant expansion of vaccine-specific CD8
T cells, with no correlation with the clinical outcome. However, treatment-induced increase of polyfunctionality and of interleukin 2 production by Melan-A-specific CD8
T cells and expansion/activation of natural killer cells correlated with RFS, being observed only in nonrelapsing patients. Despite the recent availability of different therapeutic options, low-cost, low-toxic therapies with long-lasting clinical effects are still needed in patients with high-risk resected stage III/IV melanoma. The combination of peptide vaccination with IFN-α2b showed a minimal toxicity profile and resulted in encouraging RFS and OS rates, justifying further evaluation in clinical trials, which may include the use of checkpoint inhibitors to further expand the antitumor immune response and the clinical outcome.
https://www.clinicaltrialsregister.eu/ctr-search/search, identifier: 2008-008211-26.
In this article, we aim to present a tool for the early assessment of medical technologies. This evaluation system was designed and implemented by the National Centre for HTA and the National Centre ...for Innovative Technologies of the Istituto Superiore di Sanita, Italy, in order to respond to an institutional commitment within the "Health Technologies Assessment Team" that was established to face the huge demand for the evaluation of Health Technologies during the pandemic event caused by COVID-19, with a smart and easy-to-use framework.
Horizon scanning was conducted through a brief assessment carried out according to the multicriteria decision analysis methodology. Each HTA domain was attributed a score according to a pros/cons and opportunities/threats system, derived from evidence in the literature. Scores were weighted according to different perspectives. Scores were presented in a Cartesian graph showing the positioning according to the potential value and the perceived risk associated with the technology.
Two case studies regarding the early assessment were reported, concerning two specific technologies: an individual protection device and a contact tracking system.
The international scientific literature reports no data on the prevalence and effectiveness of back protector devices (BPD). In Italy, no data have been collected on BPD because their use is not ...mandatory. To fill this gap, the National Institute of Health implemented a cross-sectional study in collaboration with the National Traffic Police.Accident cases were collected from 1 December 2011 to 25 October 2013. Overall, data from 2104 accidents involving 2319 injured subjects were analysed: 1821 (78.5%) of these were motorcyclists and 498 (21.5%) mopedists. The use of Hard-shell BPD or jackets with airbags in motorcyclists is higher then in moped drivers (16.2% vs 1.3%,P¼0.000). Concerning level of protection, there are no differences between drivers and passengers. In most severely injured motorcyclists (i.e. hospitalized or deceased), the percentage of injuries to the spine was lower (13.6%) among those who used a high level safety device (hard-shell BPD and/or airbags) and rose to 27.3% among those who used only protective clothing (P¼0.022). When the variables potentially affecting the results of not using a high-safety device were controlled, a bivariate analysis showed that the odds of serious spinal injury were 2.72 times greater (P¼0.049) and a multivariate analysis showed that they were 2.81 times greater (P¼0.012). This study points out that greater use of BPD could reduce the number of injuries to the spinal column resulting from road traffic accidents involving motorized two-wheeled vehicles.
This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum ...25-hydroxyvitamin D 25(OH)D (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (
n
= 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (
n
= 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (
n
= 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42,
p
< 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36–0.84,
p
= 0.01) and was inversely associated with ADHD symptom severity (
β
= − 2.52, 95% CI − 4.16–0.88,
p
< 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD.
Aim
To investigate the association between circulating anti‐dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs).
Method
One hundred ...and thirty‐seven children with CTDs (108 males, 29 females; mean age SD 10y 0mo 2y 7mo, range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti‐D2R antibodies were evaluated using a cell‐based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti‐D2R antibodies was measured with McNemar’s test and repeated‐measure logistic regression models, adjusting for potential demographic and clinical confounders.
Results
At exacerbation, 11 (8%) participants became anti‐D2R‐positive (‘early peri‐exacerbation seroconverters’), and nine (6.6%) became anti‐D2R‐positive at post‐exacerbation (‘late peri‐exacerbation seroconverters’). The anti‐D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar’s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs.
Interpretation
There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.
This original article is commented on by Conceição on pages 1118–1119 of this issue.
Genetic predisposition, autoimmunity and environmental factors e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events might interact to create ...a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive–compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3–10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3–16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host’s immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders.
•Using IHC only 12% of the cohort showed mild evidence of neuronal antibodies.•8% of the preclinical and onset samples showed hippocampus and/or cerebellum bindings.•Using CBAs two patients had ...antibodies against the NMDAR and none against LGI1/CASPR2.
In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease.
Sera from children with Tourette Syndrome or another chronic tic disorder (TS/TD), collected as part of the longitudinal European Multicenter Tics in Children Study, were investigated. Participants included 30 siblings of patients with TS/TD prior to developing tics (preclinical stage) and the same children after the first tic onset (onset), and 158 patients in the chronic phase undergoing an acute relapse (exacerbation). Presence of antibodies binding to rodent brain tissue was assessed by immunohistology on rat brain sections and by immunofluorescent staining of live hippocampal neurons. Live cell-based assays were used to screen for antibodies to NMDAR, CASPR2, LGI1, AMPAR and GABAAR.
Immunohistology indicated evidence of antibodies reactive with brain tissue, binding mainly to the hippocampus, the basal ganglia or the cerebellum in 26/218 (12%), with 8% of the preclinical or onset sera binding to the dentate gyrus/CA3 region or cerebellum. Only two individuals (one pre-clinical, one chronic) had antibodies binding the NMDAR and the binding was only weakly positive. No other specific antibodies were detected.
Despite some immunoreactivity towards neuronal antigens on brain tissue, this was not mirrored by antibodies binding to live neurons, suggesting the presence of non-specific antibodies or those that bind non-pathogenic intracellular epitopes. NMDAR or the other neuronal surface antibodies tested were very infrequent in these patients. The evidence for pathogenic antibodies that could be causative of TS is weak.
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