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Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (−) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach. Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed. Results: First-line treatment options in HR+/HER2− MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53–0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53–0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47–0.86 for abemaciclib + AI) and patient’s characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors. Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics.

Agenzia Italiana del Farmaco-Observational Study Register (RSO). Registration code: PIERRE/1 What is Known: • Pain is frequent in children presented to emergency department. • International recommendations on pain management are often not implemented. What is New: • Acetaminophen and ibuprofen were frequently underdosed in children prescribed for pain in the Italian emergency departments. • Under-dosage may be related to the habit of using acetaminophen and ibuprofen in the recommended range for fever treatment.

IntroductionPain is a common symptom presented in the emergency department (ED) although it is often underestimated, poorly evaluated and treated. The application of a protocol for timely pain management ensured by the nurse can avoid the delays in the analgesic treatment and improve the patient’s quality of waiting.AimsTo check the effectiveness and efficiency of the protocol aimed at early pain management in triage, active in our ED. In particular, the response to analgesic treatment was evaluated 60 minutes after the administration and at discharge. Patient satisfaction was also evaluated using two anonymous questionnaires both at discharge and 48 hours later via telephone.MethodsA single-center, observational study was conducted on a prospective cohort of patients (aged ≥4 years) with a pain symptom at admission in ED with no surgical picture.ResultsIn the observation period (June 2015–May 2016), 382 patients were enrolled, and of these, 312 (84.8%) accepted pain therapy during triage stage in the ED. In 97.4% of the cases, orosoluble paracetamol 1000 mg was administered. In the re-evaluation done 60 minutes later, 65.9% of the patients showed a reduction of at least 2 points on Numeric Rating Scale (NRS), equal to a mean reduction of 2.24 points (95% CI: 2.03–2.45). The mean time of analgesia intake was equal to 5.9 minutes (95% CI: 3.8–8.1). In the re-evaluation done at discharge, 33.2% of the patients showed a reduction of NRS score >50%, leading to a mean reduction of 39% (95% CI: 35.3%−41.9%). The level of patient satisfaction was high with a mean value >9 points (maximum satisfaction =10).ConclusionThis protocol shows that optimal pain management was achieved by patients rapidly receiving an effective painkiller therapy at triage, leading to substantial patient satisfaction. In moderate pain, orosoluble paracetamol 1000 mg provided a reduction of NRS score by 2 points in 67.6% of the patients, confirming to be the analgesic of choice in ED.

Background and PURPOSE: In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy. Methods: STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score. Results: Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC 95% ]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively). Conclusions: C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and β=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.