Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p

Readout of a labr3:ce continuous crystal by an mppc array: First results

In this work preliminary results of single-photon measurements made with a LaBr3:Ce continuous scintillation crystal (BrilLanCe 380™, by Saint-Gobain Crystals, FR) coupled to an array of Multi-Pixel Photon Counters (MPPC™, by Hamamatsu Photonics, JP) are presented. The array of 7 MPPCs was realized as the innermost element of the hexagonal Anger-like structure suitable for growing to larger areas by adding peripheral elements. The design of MPPC electronic readout for position determination was based on Anger logic. Wide-band amplifiers (by MITEQ®, US) were used for signals conditioning. Digitized traces of background, 57Co and 133Ba collimated irradiation were captured, characterized and stored by using the data-logging capabilities of a WaveMaster Oscilloscope (by LeCroy, US). Results are presented in terms of energy response, position sensing and signals fall and rise times. © 2009 Elsevier B.V. All rights reserved

Assessing the status of amphibian breeding sites in Italy: a national survey

The ecological status of 203 amphibian aquatic breeding sites, selected from the national database of the Societas Herpetologica Italica (SHI), was surveyed in the period 2008-2009 to assess their ecological status. Sites were randomly extracted, after stratification by the three biogeographical regions present in Italy, besides Sardinia and Sicily. The field surveys, conducted by professionals, amateurs and volunteers, showed that since 1979 about 11% of the sites were destroyed or no more suitable for the reproduction of amphibians that bred in the same site in the past. The percentage of destroyed or altered sites was 8%, both in the Mediterranean and Alpine biogeographical regions, and 15% in the Continental one. However, there were no statistical significant differences among the regions, suggesting that the rate of amphibian site loss was similar in different parts of Italy. This nation-wide monitoring project demonstrated that in Italy, during the last thirty years, a relevant proportion of amphibian breeding habitats has been destroyed or altered. The main cause of site alteration were land reclamation and water extraction

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors