Riluzole use in presence of contraindications in adults affected by amyotrophic lateral sclerosis and its off-label use in other motor neuron diseases: Findings from an Italian multicentre study (the {CAESAR} project)

Background: This analysis describes the use of riluzole in amyotrophic lateral sclerosis (ALS) individuals with contraindications and off-label use for subjects with other motor neuron diseases (o-MND) in the Italian regions of Latium, Tuscany and Umbria.Methods: A cohort of adults with ALS prescribed with riluzole during the years 2016–2019 was enrolled from administrative healthcare databases, excluding subjects with o-MND in the preceding 5 years. Being affected by ALS for more than 5 years, presence of tracheostomy, renal or hepatic failure were considered as contraindications to the use of riluzole. A cohort of adults with o-MND was enrolled in 2016–2019 for whom off-label use of riluzole was retrieved up to 4 years, analysing over the time differences related to sex.Results: Among 206 ALS individuals prescribed with riluzole in Latium, 336 in Tuscany and 60 in Umbria, less than 1% were diagnosed with ALS for more than 5 years. Less than 2% were tracheotomised or affected by hepatic failure. Renal failure was documented for 1.9%, 2.7%, and 5.0% of ALS individuals in Latium, Tuscany and Umbria. The o-MND cohort comprised 264 subjects in Latium, 222 in Tuscany, and 66 in Umbria. Non-negligible off-label riluzole use was observed: 8.5%, 33.0%, and 4.2% in females, and 19.9%, 26.5% and 2.4% in males in Latium, Tuscany and Umbria.Discussion: Riluzole use in ALS individuals in the presence of contraindications is rare, with slightly higher numbers in presence of renal failure. Off-label use in o-MND was found to be non-negligible, with variations between sexes

Arroyos, ambientes ribereños y sus servicios ecosistémicos

Este capítulo aborda el marco conceptual de los Servicios Ecosistémicos (SE) y su evolución desde su surgimiento. Asimismo, se enuncian y caracterizan los SE que proveen los arroyos en general, con especial énfasis en los ambientes ribereños. Finalmente se analiza a modo de caso de estudio el ambiente ribereño del arroyo de los Padres, afluente de la laguna homónima, en el partido de General Pueyrredon, un ambienteEEA BalcarceFil: Barral, María Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Oronoz, Sofia. Universidad FASTA "Santo Tomas de Aquino"; ArgentinaFil: Sirimarco, Marina Ximena. Universidad FASTA "Santo Tomas de Aquino"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Finocchietti, Cecilia. Universidad FASTA "Santo Tomas de Aquino"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Marco, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad FASTA "Santo Tomas de Aquino"; Argentin

Palivizumab reimbursement criteria and neonatal RSV hospitalisation: a regional retrospective review

In Italy, reimbursement restrictions regarding palivizumab prophylaxis approved in 2016 have been revoked in 2017, restoring use in infants with Gestational Age (GA) >29 weeks. Respiratory Syncytial Virus (RSV) hospitalisations and prevalence of palivizumab use in infants aged <6 months during five seasons (2014–2019), were considered according to different GA. Although RSV hospitalisations rate showed no significant changes, during different seasons in all GA, lower prevalence of palivizumab use in 2016 (0.8% vs 0.3%), returned to a higher level following the revoke of restrictions. Changes in reimbursement criteria were not associated with neonatal RSV hospitalisations rate but with a significant impact on palivizumab use

Evaluation of Statistical Treatment of Left-Censored Contamination Data: Example Involving Deoxynivalenol Occurrence in Pasta and Pasta Substitute Products

The handling of data on food contamination frequently represents a challenge because these are often left-censored, being composed of both positive and non-detected values. The latter observations are not quantified and provide only the information that they are below a laboratory-specific threshold value. Besides deterministic approaches, which simplify the treatment through the substitution of non-detected values with fixed threshold or null values, a growing interest has been shown in the application of stochastic approaches to the treatment of unquantified values. In this study, a multiple imputation procedure was applied in order to analyze contamination data on deoxynivalenol, a mycotoxin that may be present in pasta and pasta substitute products. An application of the proposed technique to censored deoxynivalenol occurrence data is presented. The results were compared to those attained using deterministic techniques (substitution methods). In this context, the stochastic approach seemed to provide a more accurate, unbiased and realistic solution to the problem of left-censored occurrence data. The complete sample of values could then be used to estimate the exposure of the general population to deoxynivalenol based on consumption data

Arroyos, ambientes ribereños y sus servicios ecosistémicos

Este capítulo aborda el marco conceptual de los Servicios Ecosistémicos (SE) y su evolución desde su surgimiento. Asimismo, se enuncian y caracterizan los SE que proveen los arroyos en general, con especial énfasis en los ambientes ribereños. Finalmente se analiza a modo de caso de estudio el ambiente ribereño del arroyo de los Padres, afluente de la laguna homónima, en el partido de General Pueyrredon, un ambiente de gran atractivo turístico, recreativo y de gran importancia socioecológica.Fil: Barral, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Oronoz, Sofia. Universidad FASTA "Santo Tomas de Aquino"; ArgentinaFil: Sirimarco, Marina Ximena. Universidad FASTA "Santo Tomas de Aquino"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Finocchietti, Cecilia. Universidad FASTA "Santo Tomas de Aquino"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Marco, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad FASTA "Santo Tomas de Aquino"; Argentin

Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study.

Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16-2.46) and a higher incidence of severe infections (1.25;1.00-1.55), but a lower risk of diabetes (0.66;0.47-0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68-1.62), reject/graft loss (0.61;0.36-1.04) and severe infections (0.76;0.56-1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project)

Abstract Background Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation. Methods An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009–2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Confidence intervals. Factors with statistically significance were identified as characteristics associated with treatment regimens: cyclosporin-CsA vs tacrolimus-Tac and, within the latter group, mTOR inhibitors vs mycophenolate-MMF. Results We identified 3,622 kidney patients undergoing transplantation in 17 hospitals located in 4 Italian regions, 78.3% was treated with TAC-based therapy, of which 78% and 22% in combination with MMF and mTOR, respectively. For both comparison groups, the choice of immunosuppressive regimens was mostly guided by standard hospital practices. Only few recipient and donor characteristics were found associated with specific regimen (donor/receipt age, immunological risk and diabetes). Conclusions The choice of post-renal transplant immunosuppressive therapy seems to be mostly driven by standard Centre practices, while only partially based on patient’s characteristics and recognized international guidelines

Table1_An Italian multicentre distributed data research network to study the use, effectiveness, and safety of immunosuppressive drugs in transplant patients: Framework and perspectives of the CESIT project.docx

The goal of post-transplant immunosuppressive drug therapy is to prevent organ rejection while minimizing drug toxicities. In clinical practice, a multidrug approach is commonly used and involves drugs with different mechanisms of action, including calcineurin inhibitors (CNI) (tacrolimus or cyclosporine), antimetabolite (antimet) (mycophenolate or azathioprine), inhibitors of mechanistic target of rapamycin (mTOR) (sirolimus or everolimus), and/or steroids. Although evidence based on several randomized clinical trials is available, the optimal immunosuppressive therapy has not been established and may vary among organ transplant settings. To improve the knowledge on this topic, a multiregional research network to Compare the Effectiveness and Safety of Immunosuppressive drugs in Transplant patients (CESIT) has been created with the financial support of the Italian Medicines Agency. In this article, we describe the development of this network, the framework that was designed to perform observational studies, and we also give an overview of the preliminary results that we have obtained. A multi-database transplant cohort was enrolled using a common data model based on healthcare claims data of four Italian regions (Lombardy, Veneto, Lazio, and Sardinia). Analytical datasets were created using an open-source tool for distributed analysis. To link the National Transplant Information System to the regional transplant cohorts, a semi-deterministic record linkage procedure was performed. Overall, 6,914 transplant patients from 2009–19 were identified: 4,029 (58.3%) for kidney, 2,219 (32.1%) for liver, 434 (6.3%) for heart, and 215 (3.1%) for lung. As expected, demographic and clinical characteristics showed considerable variability among organ settings. Although the triple therapy in terms of CNI + antimet/mTOR + steroids was widely dispensed for all settings (63.7% for kidney, 33.5% for liver, 53.3% for heart, and 63.7% for lung), differences in the active agents involved were detected. The CESIT network represents a great opportunity to study several aspects related to the use, safety, and effectiveness of post-transplant maintenance immunosuppressive therapy in real practice.</p