An unintended consequence of COVID-19 immunity passports-quasi-experimental evidence of moral hazard observed after implementing the domestic Green Pass policy during the second wave of the COVID-19 pandemic in Italy.

Objectives: Amidst the second wave of the COVID-19 pandemic, Italian policymakers mandated to exhibit evidence of vaccination or immunity (the Green Pass) as a condition to access retail premises and public offices. This study aims to offer evidence, in a quasi-experimental setting, suggesting that an unintended consequence of this policy was the emergence of moral hazard.

Methods: Google visit duration data measured the time customers typically spend on retail premises or public offices.

From 15 Minutes to 15 Seconds: How the Delta Variant Changed the Risk of Exposure to COVID-19. A Comparative Epidemiological Investigation Using Community Mobility Data From the Metropolitan Area of Genoa, Italy.

The Delta variant became dominant during the second wave of the Covid-19 pandemic due to its competitive advantage, the ability to reduce close contact duration from minutes to seconds, and, consequently, increase the risk of exposure to COVID-19. We used game theory to model the most effective public health response to this new threat. We compared the absolute and relative risk of exposure to COVID-19 before and after the emergence of the Delta variant.

Risk of Exposure to COVID-19: Visit Duration Data Can Inform Our Daily Activities Choices: An Epidemiological Investigation Using Community Mobility Data from the Metropolitan Area of Genoa, Italy.

COVID-19 spreads mainly among people who are in close contact. Policymakers mostly resorted to normative measures to limit close contacts and impose social distancing. Our study aimed to estimate the risk of exposure to COVID-19 by location and activity in crowded metropolitan areas.

Cross-regional variations of Covid-19 mortality in Italy: an ecological study.

Background: Disparities in cross-regional coronavirus disease 2019 (Covid-19) mortality remain poorly understood. The association between pre-epidemic health and epidemic mortality can inform a policy response to future outbreaks.

Method: We conducted an ecological study of the association between the cumulative deaths attributed to Covid-19 epidemic in the 20 Italian regions and nine determinants of population health derived from a systematic review of the literature.

Evaluation of the relationship between lactacidemia and postoperative complications after surgery for peritoneal carcinomatosis.

Background: Cytoreductive surgery was developed as a treatment for peritoneal carcinomatosis. However, this surgery is associated with important complications. The present study aimed to assess the relationship between lactacidemia and the rate of associated complications during the immediate postoperative period in the intensive care unit (ICU) in patients undergoing cytoreductive surgery.

Quality of life of Portuguese and Spanish adolescents. A comparative study between natives and immigrants.

The aim of this study was to analyse differences in quality of life (QOL) between Spanish and Portuguese immigrant and native adolescents. In total, 475 native and immigrant adolescents (52% boys) from Algarve (Portugal) and Huelva (Spain), aged between 12 and 17 years old, were assessed with the KIDSCREEN-52. QOL dimensions were not related to most academic variables, with the exception of number of school failures, Financial Resources and Social Support from Peers.

Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult volunteers with mild or moderate hepatic impairment.

Aims: To evaluate the pharmacokinetics and pharmacodynamics after a single dose of liposomal mifamurtide (liposomal muramyl tripeptide phospatidyl ethanolamine; MEPACT(®)) in adult subjects with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment in comparison with age-, weight- and sex-matched healthy subjects with normal hepatic function.

Methods: Subjects received a 4 mg dose of liposomal mifamurtide via 1 h intravenous infusion. Blood samples were collected over 72 h for pharmacokinetic and pharmacodynamic assessments (changes in serum interleukin-6, tumour necrosis factor-α and C-reactive protein).

Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult volunteers with mild or moderate renal impairment.

Aims: To evaluate the pharmacokinetics and pharmacodynamics following a single dose of liposomal mifamurtide (L-MTP-PE, MEPACT(®)) in adult subjects with mild (calculated creatinine clearance [CLcr ] of 50-80 ml min(-1)) or moderate (CLcr 30-50 ml min(-1)) renal impairment in comparison with age-, weight- and gender-matched healthy subjects with normal renal function (CLcr >80 ml min(-1)).

Methods: Subjects received a 4 mg dose of liposomal mifamurtide via 1 h intravenous infusion. Blood samples were collected over 72 h for analysis of plasma pharmacokinetics of total and non-liposome-associated (free) mifamurtide and assessment of pharmacodynamics (changes in serum interleukin-6 [IL-6], tumour necrosis factor-α [TNF-α], C-reactive protein [CRP]).

Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

Purpose: Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).

Patients And Methods: This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC.

Double-blind, randomized, placebo-controlled study of safety, tolerability, pharmacokinetics and pharmacodynamics of TAK-683, an investigational metastin analogue in healthy men.

Aims: Two randomized, double-blind, placebo-controlled studies were performed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the investigational metastin analogue, TAK-683, in healthy men.

Methods: We first investigated a single subcutaneous (s.c.

A pharmacokinetic, pharmacodynamic, and electrocardiographic study of liposomal mifamurtide (L-MTP-PE) in healthy adult volunteers.

Purpose: This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety/tolerability, and cardiac safety of liposomal muramyl tripeptide phosphatidyl-ethanolamine [mifamurtide (L-MTP-PE)] in healthy adults.

Methods: L-MTP-PE 4 mg was administered intravenously over 30 min. Study participants were monitored from 24 h preinfusion until 72 h postinfusion.

Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial.

Objectives: A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2(+) previously treated advanced breast cancer or metastatic breast cancer (MBC). Here, we report final analyses of overall survival.

Patients And Methods: Women with HER-2(+) MBC who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab, were randomized to lapatinib (1,250 mg/day) plus capecitabine (2,000 mg/m(2)) or capecitabine monotherapy (2,500 mg/m(2)) on days 1-14 of a 21-day cycle.

Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer.

Purpose: Cross-talk between human epidermal growth factor receptors and hormone receptor pathways may cause endocrine resistance in breast cancer. This trial evaluated the effect of adding lapatinib, a dual tyrosine kinase inhibitor blocking epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2), to the aromatase inhibitor letrozole as first-line treatment of hormone receptor (HR) -positive metastatic breast cancer (MBC).

Patients And Methods: Postmenopausal women with HR-positive MBC were randomly assigned to daily letrozole (2.

Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as first-line treatment in HER2-negative or unknown metastatic breast cancer.

Purpose: Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) with activity in HER2-amplified metastatic breast cancer (MBC). Its role in non-HER2-amplified MBC remains unclear. EGF30001, a phase III trial of lapatinib and paclitaxel versus paclitaxel and placebo, demonstrated lapatinib does not significantly benefit HER2-negative or HER2-unselected patients with MBC.

Mitogen-activated protein kinase phosphatase-1 in human breast cancer independently predicts prognosis and is repressed by doxorubicin.

Purpose: Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) dephosphorylates mitogen-activated protein kinase [extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38], mediates breast cancer chemoresistance, and is repressible by doxorubicin in breast cancer cells. We aimed to characterize doxorubicin effects on MKP-1 and phospho-MAPKs in human breast cancers and to further study the clinical relevance of MKP-1 expression in this disease.

Experimental Design: Doxorubicin effects on MKP-1, phospho-ERK1/2 (p-ERK1/2), phospho-JNK (p-JNK), and phospho-p38 were assayed in a panel of human breast cancer cells by Western blot and in human breast cancer were assayed ex vivo by immunohistochemistry (n = 50).

Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer.

Purpose: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial.

HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer.

Purpose: Biomarkers from two randomized phase III trials were analyzed to optimize selection of patients for lapatinib therapy.

Experimental Design: In available breast cancer tissue from EGF30001 (paclitaxel +/- lapatinib in HER-2-negative/unknown metastatic breast cancer, n = 579) and EGF100151 (capecitabine +/- lapatinib in HER-2-positive metastatic breast cancer, n = 399), HER-2 gene amplification by fluorescence in situ hybridization (FISH), HER-2 mRNA by reverse transcription-PCR (RT-PCR), HER-2 protein expression by HercepTest immunohistochemistry (IHC), epidermal growth factor receptor (EGFR) mRNA level by RT-PCR, and EGFR protein by IHC were analyzed and compared with clinical outcome. HER-2 was determined by FISH in an academic reference/research laboratory and in a large, high-volume commercial reference laboratory.