Protontherapy is hadrontherapy’s fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy’s superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy’s ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts.The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines.After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Low measles, mumps and rubella (MMR) immunization levels in European children highlight the importance of identifying determinants of parental vaccine uptake to implement policies for increasing vaccine compliance. The aim of this paper is to identify the main factors associated with partial and full MMR vaccination uptake in European parents, and combine the different studies to obtain overall quantitative measures. This activity is included within the ESCULAPIO project, funded by the Italian Ministry of Health. ORs and CIs were extracted, sources of heterogeneity explored and publication bias assessed. Forty-five papers were retrieved for the qualitative study, 26 of which were included in the meta-analysis. The following factors were associated with lower MMR vaccine uptake: misleading knowledge, beliefs and perceptions on vaccines (OR 0.57, CI 0.37-0.87); negative attitudes and behaviors toward vaccination (OR 0.71, CI 0.52-0.98); demographic characteristics, such as different ethnicity in Southern populations (OR 0.44, CI 0.31-0.61), higher child's age (OR 0.80, CI 0.76-0.85); low socio-economic status (OR 0.64, CI 0.51-0.80), especially low income (OR 0.39, CI 0.25-0.60) and education (OR 0.64, CI 0.48-0.84), high number of children (OR 0.54, CI 0.42-0.69), irregular marital status (OR 0.80, CI 0.66-0.96). The factors explaining heterogeneity were country location, administration modality, collection setting and responses reported on MMR alone or in combination. Findings from this study suggest policy makers to focus communication strategies on providing better knowledge, correct beliefs and perceptions on vaccines, and improving attitudes and behaviors in parents; and to target policies to people of ethnic minority from Southern Europe, low educated and deprived, with higher number of children and non-married marital status.