Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

The impact of a remote monitoring system of healthcare resource consumption in patients on automated peritoneal dialysis (APD): A simulation study
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AIMS: Remote monitoring (RM) can improve management of chronic diseases. We evaluated the impact of RM in automated peritoneal dialysis (APD) in a simulation study. MATERIALS AND METHODS: We simulated 12 patient scenarios with common clinical problems and estimated the likely healthcare resource consumption with and without the availability of RM (RM+ and RM- groups, respectively). Scenarios were evaluated 4 times by randomly allocated nephrologist-nurse teams or nephrologist-alone assessors. RESULTS: The RM+ group was assessed as having significantly lower total healthcare resource consumption compared with the RM- group (36.8 vs. 107.5 total episodes of resource consumption, p = 0.002). The RM+ group showed significantly lower "unplanned hospital visits" (2.3 vs. 11.3, p = 0.005), "emergency room visits" (0.5 vs. 5.3, p = 0.003), "home visits" (0.5 vs. 5.8, p = 0.016), "exchanges over the telephone" (18.5 vs. 57.8, p = 0.002), and "change to hemodialysis" (0.5 vs. 2.5, p = 0.003). Evaluations did not differ between nephrologist-nurse teams vs. nephrologist-alone assessors. CONCLUSION: RM can be expected to reduce healthcare resource consumption in APD patients.
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A significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage.

Although most of the radiation damage to genomic DNA could be rendered harmless using repair enzymes in a living cell, a certain fraction of the damage is persistent resulting in serious genetic effects, such as mutation induction. In order to understand the mechanisms of the deleterious DNA damage formation in terms of its earliest physical stage at the radiation track end, dynamics of low energy electrons and their thermalization processes around DNA molecules were investigated using a dynamic Monte Carlo code. The primary incident (1 keV) electrons multiply collide within 1 nm (equivalent to three DNA-base-pairs, 3bp) and generate secondary electrons which show non-Gaussian and non-thermal equilibrium distributions within 300 fs. On the other hand, the secondary electrons are mainly distributed within approximately 10 nm from their parent cations although approximately 5% of the electrons are localized within 1 nm of the cations owing to the interaction of their Coulombic fields. The mean electron energy is 0.7 eV; however, more than 10% of the electrons fall into a much lower-energy region than 0.1 eV at 300 fs. These results indicate that pre-hydrated electrons are formed from the extremely decelerated electrons over a few nm from the cations. DNA damage sites comprising multiple nucleobase lesions or single strand breaks can therefore be formed by multiple collisions of these electrons within 3bp. This multiple damage site is hardly processed by base excision repair enzymes. However, pre-hydrated electrons can also be produced resulting in an additional base lesion (or a strand break) more than 3bp away from the multi-damage site. These damage sites may be finally converted into a double strand break (DSB) when base excision enzymes process the additional base lesions. This DSB includes another base lesion(s) at their termini, and may introduce miss-rejoining by DSB repair enzymes, and hence may result in biological effects such as mutation in surviving cells.

Deceleration processes of secondary electrons produced by a high-energy Auger electron in a biological context.

PURPOSE: To simulate the deceleration processes of secondary electrons produced by a high-energy Auger electron in water, and particularly to focus on the spatial and temporal distributions of the secondary electron and the collision events (e.g. ionization, electronic excitation, and dissociative electron attachment) that are involved in the multiplication of lesions at sites of DNA damage. MATERIALS AND METHODS: We developed a dynamic Monte Carlo code that considers the Coulombic force between an ejected electron and its parent cation produced by the Auger electron in water. Thus our code can simulate some return electrons to the parent cations. Using the code, we calculated to within the order of femtoseconds the temporal evolution of collision events, the mean energy, and the mean traveling distance (including its spatial probability distribution) of the electron at an ejected energy of 20 eV. RESULTS: Some of the decelerating electrons in water in the Coulombic field were attracted to the ionized atoms (cations) by the Coulombic force within hundreds of femtoseconds, although the force did not significantly enhance the number of ionization, electronic excitation, and dissociative electron attachment collision events leading to water radiolysis. CONCLUSIONS: The secondary electrons are decelerated in water by the Coulombic force and recombined to the ionized atoms (cations). Furthermore, the some return electrons might be prehydrated in water layer near the parent cation in DNA if the electrons might be emitted from the DNA. The prehydrated electron originated from the return electron might play a significant role in inducing DNA damage.