Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale >= 6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients

Ice core record of dust sources in the western United States over the last 300 years

Over the past ~ 5000 years, amplified dust generation and deposition in the American West has been linked to human activity. In recent decades, intensified rates of agriculture and livestock grazing have been correlated with greater dust production detected on seasonal to annual timescales. The combination of land use intensification and climate change (i.e. increased drought frequency) in North America highlights the importance of characterizing the sources of dust both before and after the influence of anthropogenic activity. We apply high-precision geochemical and isotopic (Sr and Nd isotopes) techniques to an ice core from the Upper Fremont Glacier (Wyoming, USA) to produce the first glacial dataset from the American West. Our Sr-Nd isotopic composition data indicates the evolving dust provenance to the Upper Fremont Glacier (UFG) from a long-range transport of mineral dust to a local source. This increasing input of dust from a local source is supported by a rise in average dust particle diameter combined with greater average dust concentration throughout the record. The greater presence of dust particles smaller than 2.5 μm in the most recent samples from UFG ice core record support existing satellite and sediment core data regarding the effects of anthropogenic activity upon dust sources and pathways in the American West. Although the Sr-Nd isotope database in North America needs be expanded, our results provide a survey of windborne dust through the past 270 years

Once-a-Day (QD) <i>vs</i> Twice-Daily (BID) Nevirapine as simplification in PITreated patients after 2 mos. of BID induction

To assess the efficacy and the tolerability of once-daily (QD) versus twice-daily (BID) nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in virologically suppressed, HIV-positive patients switched from protease inhibitor (PI)-based HAART. Eligible patients were enrolled in the multicenter trial if HIV RNA levels were &lt; 50 copies/mL for ≥6 months prior. Patients were switched from a PI to NVP 200 mg BID for 2 months, and then randomized to continue with that regimen (group A) or NVP 400 mg QD (group B) for a further 10 months. Virological efficacy (primary endpoint) and tolerability/toxicity were evaluated according to an intention-to-treat analysis. A total of 126 patients (63 per group) were enrolled. Withdrawals from the study (any reason) numbered 15 in group A and 14 in B, virological failures numbered 5 and 2, respectively, and there were 4 cases of adverse events in each group (all p = NS). Mean alanine aminotransaminase (ALT) and gamma-glutamyl transpeptidase (γ-GT) level increases were significant for the whole cohort (33.2±22.9 to 43.3±29.1, p &lt; 0.001; 57.3±72 to 109±131 U/L, p &lt; 0.0002, respectively), but there were no differences between the two groups. Apparently, no significant differences between the QD and BID NVP groups were found, in terms of virological failures or tolerability/toxicity. The switch to NVP may be safely pursued with a QD schedule

Cost-effectiveness of bedaquiline in MDR and XDR tuberculosis in Italy

Objective: To evaluate the cost-effectiveness of bedaquiline plus background drug regimens (BR) for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in Italy. Methods: A Markov model was adapted to the Italian setting to estimate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR in the treatment of MDR-TB and XDR-TB over 10 years, from both the National Health Service (NHS) and societal perspective. Cost-effectiveness was evaluated in terms of life-years gained (LYG). Clinical data were sourced from trials; resource consumption for compared treatments was modelled according to advice from an expert clinicians panel. NHS tariffs for inpatient and outpatient resource consumption were retrieved from published Italian sources. Drug costs were provided by reference centres for disease treatment in Italy. A 3% annual discount was applied to both cost and effectiveness. Deterministic and probabilistic sensitivity analyses were conducted. Results: Over 10 years, BBR vs. BR alone is cost-effective, with ICERs of €16,639/LYG and €4081/LYG for the NHS and society, respectively. The sensitivity analyses confirmed the robustness of the results from both considered perspectives. Conclusion: In Italy, BBR vs. BR alone has proven to be cost-effective in the treatment of MDR-TB and XDR-TB under a range of scenarios

RACCOMANDAZIONI PER L\u2019ASSISTENZA ALLA DONNA VITTIMA DI VIOLENZA SESSUALE

Di fronte ad una vittima di violenza sessuale la priorit\ue0 assistenziale dovr\ue0 essere la tutela della sua salute e del suo benessere. \uc8 importante restituire alla donna il suo valore di persona in ogni fase del percorso clinico. Trattare la donna con rispetto ed empatia pu\uf2 essere di aiuto nella successiva elaborazione del trauma. \u2022 L\u2019esame fisico e la raccolta delle prove dovrebbero avvenire nello stesso tempo per evitare visite ripetute e lo stress a queste correlato. La completezza dell\u2019esame comporta un inevitabile impegno di tempo e di risorse da parte del personale sanitario. \u2022 Sar\ue0 importante riservare una stanza predisposta per accogliere la vittima per tutto il tempo che rimane nella struttura (in caso di Ospedale la stanza dovr\ue0 essere preferibilmente nel punto di ac\u2011 cesso e cio\ue8 il Pronto Soccorso). Il personale dovr\ue0 rivolgersi alla vittima con voce calma, senza esprimere sorpresa o incredulit\ue0, con parole e atteggiamento assolutamente non giudicante. \u2022 Per aiutare il sanitario ad applicare correttamente le procedure diagnostiche e terapeutiche validate, \ue8 suggerito l\u2019impiego di una SCHEDA CLINICA GUIDATA che si applica alle ragazze di et\ue0 superiore ai 13 anni e alle donne adulte. \u2022 La scheda costituisce documentazione clinica da archiviare e da consegnare eventualmente alla donna in copia per gli usi che ritiene opportuni (per es. la denuncia) oltre al verbale di Pronto Soc\u2011 corso che viene abitualmente compilato. \uc8 inoltre uno strumento che favorisce la raccolta di dati epidemiologici per lo studio del fenomeno. \u2022 Si dovr\ue0 ottenere il consenso per tutta la procedura e per la comunicazione delle informazioni a terzi. Le domande e le scelte della donna saranno assecondate in ogni fase. Nel caso in cui il personale sanitario debba procedere con la denuncia d\u2019ufficio all\u2019Autorit\ue0 Giudiziaria, la donna deve esserne informata ma non \ue8 richiesto consenso. \u2022 La scheda clinica guidata dovr\ue0 inserirsi in una PROCEDURA di accoglienza pi\uf9 ampia sviluppata in modo MULTIDISCIPLINARE che preveda un iter specifico fin dal momento in cui la donna incontra la struttura (generalmente il pronto soccorso) per la risposta standardizzata a ogni problematica presente in caso di violenza sessuale. In particolare si dovr\ue0 definire un protocollo per il metodo di raccolta e conservazione delle prove forensi, un protocollo per la profilassi dell\u2019HIV, un protocollo per i test tossi\u2011 cologici dato che spesso la violenza \ue8 facilitata dall\u2019uso di sostanze, infine un protocollo per la presa in carico successiva della vittima che non pu\uf2 essere abbandonata dopo la prima valutazione. \u2022 La costituzione di una RETE multidisciplinare composta dalle varie competenze e risorse presenti nello specifico ambito territoriale garantir\ue0 la coerenza della presa in carico in fase iniziale e di quella nei tempi successivi, per una tutela della vittima non solo sanitaria ma anche psicologica e sociale nonch\ue9 legale. La legge prevede la denuncia a querela di parte entro dodici mesi, quando non sono presenti le condizioni per denuncia d\u2019ufficio