Efficacy and Safety of Long-Term Treatment with Stiripentol in Children and Adults with Drug-Resistant Epilepsies: A Retrospective Cohort Study of 196 Patients

BACKGROUND: Stiripentol is an antiseizure medication with multiple potential mechanisms of action, indicated as adjunctive therapy in people with Dravet syndrome, whose seizures are not adequately controlled with clobazam and valproate. However, there are scattered data on its efficacy in other epilepsy aetiologies and types. We previously reported our single-centre experience on the efficacy of adjunctive stiripentol treatment in a cohort of 132 patients with different types of refractory epilepsies. OBJECTIVE: We aimed to expand our analysis to a larger cohort of 196 patients with a long-term follow-up. METHODS: We retrospectively evaluated long-term efficacy, tolerability and predictors of treatment response in 196 patients with a long-term follow-up (range 0.5-232.8 months). RESULTS: After an initial median follow-up of 3 months after stiripentol introduction, we observed a responder rate of 53% including seizure freedom in 9%. At subsequent follow-ups at 12 and 24 months, responder rates were 29% and 22%, respectively. Aetiology was associated with sustained response over time, with Dravet syndrome being the aetiology with the highest responder rate (64%) at 48 months compared with syndromes with other genetic causes (13%) or unknown aetiology (38%). A higher responder rate over time was also observed in patients with generalised (44%) and combined focal and generalised epilepsies (28%) than in patients with focal epilepsies (20%). The highest relapse free-survival was observed when stiripentol was initiated at the youngest age (0-4 years) or in adulthood. The retention rate (i.e. proportion of patients who continued stiripentol with no change in either pharmacological or non-pharmacological therapy) was 53% at 12 months and 33% at 24 months. CONCLUSIONS: Based on our findings, we suggest that stiripentol is an effective and well-tolerated therapeutic option not only in Dravet syndrome but also in other epilepsy syndromes with or without an established genetic aetiology. Response duration was influenced by age at stiripentol initiation across different aetiologies

Removal of diclofenac from aqueous solutions by adsorption on thermo‑plasma expanded graphite

The adsorption of diclofenac on thermo-plasma expanded graphite (a commercial product) from water solutions was investigated. The adsorbent material was characterized by SEM, TEM, BET, Raman and X-ray diffraction analyses. Typical diffractogram and Raman spectrum of graphitic material, dimension of 24.02 nm as crystallite dimension and a surface area of 47 m2 g−1 were obtained. The effect of pH on the adsorption capacity was evaluated in the range 1–7 and the adsorption mechanism was described by kinetic and isothermal studies. Pseudo-second order and Dubinin–Radushkevich models agreed with theoretical values of adsorption capacity (i.e. 400 and 433 mg g−1, respectively) and resulted to be the best fit for kinetics and isothermal experimental data. The thermodynamics of the process was evaluated by plotting the adsorption capacity/concentration ratio at the equilibrium as a function of different values of the multiplicative inverse of temperature. Moreover, the adsorbent regeneration was also investigated, comparing two different remediation techniques. Solvent washing performed with NaOH 0.2 M and thermo-treatment carried out by heating in an oven at 105 °C for 2 h and then at 200 °C for 4 h. The thermo-treatment was the best technique to regenerate the adsorbent, ensuring same performance after 4 cycles of use and regeneration

Central-line associated bloodstream infections in a tertiary care children's University hospital: a prospective study

BACKGROUND: The central-line associated bloodstream infections (CLABSI) are the most common healthcare-associated infections in childhood. Despite the international data available on healthcare-associated infections in selected groups of patients, there is a lack of large and good quality studies. The present survey is the first prospective study monitoring for 6 months the occurrence of central-line associated bloodstream infections in all departments of an Italian tertiary care children’s university hospital. METHODS: The study involved all children aged less than 18 years admitted to Meyer Children’s University Hospital, Florence, Italy who had a central line access between the October 15(th), 2014 and the April 14(th), 2015. CLABSI were defined according to the Center for Disease Control and Prevention criteria. CLABSI incidence rates with 95% confidence limits were calculated and stratified for the study variables. For each factor the relative risk and 95% confidence intervals were evaluated. Statistical analysis was performed using the statistical software SPSS for Windows, version 22.0 (SPSS Inc., Chicago, IL), p < 0.05 was considered statistically significant. RESULTS: CLABSI rate was 3.73/1000 (95% CI: 2.54–5.28) central line-days. A higher CLABSI incidence was seen with female gender (p = 0.045) and underlying medical conditions (excepting prematurity, surgical diseases and malignancy) (p = 0.06). In our study 5 infections, were caused by extended-spectrum β-lactamase producing organisms and in one case by carbapenem-resistant Klebsiella pneumoniae. CONCLUSIONS: Our study confirms the spreading of multi-resistant pathogens as causes of healthcare associated infections in children. An increased incidence rate of CLABSI in our study was related to underlying medical conditions. Pediatric studies focusing on healthcare infections in this type of patients should be done in order to deepen our understanding on associated risk factors and possible intervention areas

Re-use of wastewater for a sustainable forest production and climate change mitigation under arid environments

Over the last decades biotic and abiotic constrains together with human actions are determining a substantial environmental pressure, particularly in dry lands as the south of the Mediterranean region. From very long time, indeed, simultaneous drivers such as demographic growth, climate change and socio-economic factors are weakening the previous homeostasis between human needs and natural resources on the regional scale.Resulting pressures are determining environmental degradation and increase of desertification risk for the arid and semiarid lands. Water quality and availability are both crucial points limiting people well-being and livelihoods in the same context. Scarcity of fresh water and heavy and mismanaged production of wastewater are the main factors affecting water resources. Increasing pollution of soil and ground waters reduces the possibility of sustainable development of local communities with relevant social consequences. The FAO's supporting program in north Africa aims to: a) develop new and cheaper phytotechnologies (e.g. constructed wetland system; innovative treatment system for reuse of waste water for fertigation); b) treat wastewater for water quality protection; c) promote land recovery by means of sustainable multipurpose forestry; d) adopt bioengineering interventions to stop slopes erosion and protect urban, and semi-urban infrastructures; e) create pilot demonstrative areas to test multi-purpose sustainable agroforestry systems. Within this frame, an integrated approach was designed to promote innovative sustainable water management and multipurpose forestry, in order to mitigate the effects of climate change, promote land recovery, and improve the livelihoods of local population. The present paper aims to provide an overview of the FAO project GCP/RAB/013/ITA. Particularly, two pilot studies are shown and discussed

The colorectal cancer screening program in the Local Health Unit n. 6 of Livorno: evaluation of the screening activity in the period 2000-2011

Introduction. The colorectal cancer screening program in the Local Health Unit n. 6 of Livorno is running since July 2000 and is meant to residents, aged between 50 and 70, who are invited to perform the test for faecal occult blood every 2 years. The aim of this work is an evaluation of the screening activity in the period 2000-2011. Methods. The evaluation is based on the analysis of the main quality indicators formulated by GISCoR (Italian Group for Colorectal screening). Results. The screening activity extension reached 93% in 2006 and 100% in 2009. The compliance level was maintained above the acceptable GISCoR value (&gt; 45%) with a maximum of 54.9%. Values around 80% were recorded for the compliance to colonosopy. The detection rate (DR) for cancer and advanced adenoma showed, as expected, the highest values in the early years and then move on values consistently lower than the regional average. In 2011, the raw DR for cancer was 0.9 x 1000 and the raw DR for advanced adenoma 5.3 x 1000. The distribution by stage at diagnosis of screen-detected carcinomas shows that 58.1% of these were identified at stage I while the proportion of cases in stage III+ is 19.5%. Conclusions. The overall analysis shows a good performance of the program. The proportion of colonoscopies performed on the total number of positive subjects remains a critical point of the system. The distribution by stage of screen-detected cancers shows an excellent diagnostic anticipation of the screening program

Location of primary tumor and benefit from anti-epidermal growth factorreceptor monoclonalantibodies in patients with RAS and BRAF wild-typemetastatic colorectal cancer

Introduction. Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients and Methods. Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. Results. Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p 5 .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p, .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97;95%confidence interval: 2.09–7.53; p,.0001). Conclusion. Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti- EGFRs

Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC

A registry for Dravet syndrome: The Italian experience

Objectives: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. / Methods: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. / Results: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0–9) while at last follow-up was 11 years (IQR 5–18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). / Significance: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes