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Background: Paclitaxel plus ramucirumab is recommended as a second-line treatment regimen in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer. We aimed to assess whether switch maintenance or early second-line therapy with paclitaxel plus ramucirumab improved outcomes compared with continuation of oxaliplatin and fluoropyrimidine doublet chemotherapy as a first-line strategy., Methods: ARMANI was a multicentre, open-label, randomised, phase 3 trial done in 31 hospitals in Italy. We enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction cancer, who had disease control after 3 months of FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Patients were randomly assigned (1:1) to either paclitaxel 80 mg/m 2 on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days intravenously (switch maintenance group) or continuation of oxaliplatin-based doublet chemotherapy (FOLFOX or CAPOX) for an additional 12 weeks, followed by fluoropyrimidine monotherapy maintenance (control group). Randomisation was stratified by previous gastrectomy (no vs yes), peritoneal carcinomatosis (yes vs no), and primary tumour location (gastro-oesophageal junction vs gastric). Treatment group allocation was done using a web-based system with a minimisation algorithm implementing a random component. The primary endpoint was progression-free survival, analysed on an intention-to-treat basis. The safety population included patients who received at least one dose of the study treatment. This study is registered with ClinicalTrials.gov, NCT02934464, and is complete., Findings: Between Jan 1, 2017, and Oct 2, 2023, 280 patients were randomly assigned to receive paclitaxel plus ramucirumab (switch maintenance group; n=144) or to continue FOLFOX or CAPOX (control group; n=136). All patients were White. 180 (64%) of 280 patients were male and 100 (36%) were female. At a median follow-up of 43·7 months (IQR 24·0-57·9), 253 (90%) of 280 patients had a progression-free survival event: 131 (91%) of 144 patients in the switch maintenance group and 122 (90%) of 136 patients in the control group. Median progression-free survival was 6·6 months (95% CI 5·9-7·8) in the switch maintenance group and 3·5 months (2·8-4·2) in the control group (HR 0·61, 95% CI 0·48-0·79; p=0·0002). The assumption of proportional hazards was violated; in an analysis of 24-month restricted mean survival time, restricted mean progression-free survival was 8·8 months (95% CI 7·7-9·9) in the switch maintenance group and 6·1 months (5·0-7·2) in the control group (p=0·0010). The most frequent grade 3-4 treatment-related adverse events were neutropenia (37 [26%] patients in the switch maintenance group vs 13 [10%] patients in the control group), peripheral neuropathy (eight [6%] vs nine [7%]) and arterial hypertension (nine [6%] vs none). Serious adverse events occurred in 28 (20%) of 141 patients in the experimental group and 15 (11%) of 135 patients in the control group; these events were treatment-related in two (1%) patients in the switch maintenance group (pulmonary embolism) and two (1%) patients in the control group (mucositis and anaemia). No treatment-related deaths occurred., Interpretation: Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents., Funding: Partly funded by Eli Lilly., Competing Interests: Declaration of interests SL reports participation in advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda, Rottapharm, and Beigene; personal honoraria as invited speaker from Amgen, AstraZeneca, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre Fabre, Roche, and Servier; and research funding (to their institution) from Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daichii Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, and Servier. MF reports research funding (to their institution) from Roche, Astellas, and Diaceutics; personal honoraria as an invited speaker from Roche, Astellas, AstraZeneca, Lilly, Incyte, Bristol-Myers Squibb, Sanofi, Agilent, Merck Serono, Pierre Fabre, GSK, Novartis, and Amgen; and participation in advisory boards for Amgen, Astellas, Roche, Merck Serono, GSK, Novartis, and Janssen. EG reports payment or honoraria from Servier, Amgen, Viatris, Pierre Fabre, Daiichi Sankyo, and AstraZeneca and support for attending meetings from Servier, Roche, Ipsen, and Viatris. LF reports grants or contracts from MSD, Bristol-Myers Squibb, AstraZeneca, Incyte, BeiGene, Astellas, Daiichi Sankyo, and Roche; consulting fees from MSD, AstraZeneca, Incyte, Taiho Oncology, Servier, Daiichi Sankyo, Eli Lilly, and BeiGene; and payment or honoraria from Incyte, Bristol-Myers Squibb, Eli Lilly, AstraZeneca, and MSD. FDV reports consulting fees from Daiichi Sankyo and payment or honoraria from Servier, Amgen, Roche, Eli Lilly, Daiichi Sankyo, and AstraZeneca. AS reports honoraria (advisory board member or invited speaker) from AstraZeneca, MSD, Daiichi, Jazz Pharma, and Astellas. FG reports payments or honoraria from Servier, Amgen, Novartis, Lilly, Eisai, and Daichi Sankyo and support for attending meetings and travel from Lilly, Roche, Amgen, and Servier. FM reports honoraria from Pierre Fabre and Servier; research grants from Incyte (to their institution), and travel grants from Amgen and Pierre Fabre. MN reports travel expenses from AstraZeneca, speaker honoraria from Accademia della Medicina and Incyte; honoraria from Sandoz, Medpoint, Incyte, AstraZeneca, and Servier for editorial collaboration; and consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, Astra Zeneca, and Taiho. AR reports honoraria for speaker bureau or advisory board participation from Servier and MSD. FiP repors receiving research funding (to their institution) from Lilly, Bristol-Myers Squibb, Incyte, AstraZeneca, Amgen, and Agenus; personal honoraria as an invited speaker from BeiGene, Daiichi Sankyo, Seagen, Astellas, Ipsen, AstraZeneca, Servier, Bayer, Takeda, Johnson & Johnson, Bristol-Myers Squibb, MSD, Amgen, Merck Serono, Pierre Fabre; and advisory or consultancy fees from Bristol-Myers Squibb, MSD, Amgen, Pierre Fabre, Johnson & Johnson, Servier, Bayer, Takeda, Astellas, GSK, Daiichi Sankyo, Pfizer, BeiGene, Jazz Pharmaceuticals, Incyte, Rottapharm, and Merck Serono. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Considering the growing population of older adults, addressing the influence of loneliness among this demographic group has become imperative, especially due to the link between social isolation and deterioration of mental and physical well-being. Technology has the potential to be used to create innovative solutions to increase socialization and potentially promote healthy aging., Objective: This 6-month study examined the usability and acceptability of a technology-based socialization service and explored how stress and living situation affect older adults' and their ecosystem's perceptions of technology, investigating cross-sectional and longitudinal differences among and across user groups., Methods: Participants were recruited in Tuscany and Apulia (Italy) through a network of social cooperatives and a research hospital, respectively. A total of 20 older adults were provided with the same technology installed on a tablet and on a smart television. The technology has three functionalities: video calling, playing games, and sharing news. Additionally, 20 informal caregivers (IC) and 13 formal caregivers (FC) connected to the older adults were included in the study. After both initial training in the use of the system (T0) and 6 months of using the system (T6), questionnaires on usability, acceptability, and technostress were filled in by older adults, IC, and FC. Nonparametric or parametric tests were conducted to investigate group differences at both time points and changes over time. Additional analyses on older adults were done to assess whether differences in usability and acceptability were related to living situation (ie, alone or with someone). Furthermore, correlation analyses were performed between usability, acceptability, and stress toward technology at T0 and T6., Results: At both T0 and T6, older adults had lower usability scores than IC and FC and higher anxiety than IC. Over time, there was a significant decrease in older adults' attitudes toward technology score, depicting a negative attitude over time (T0 median 4.2, IQR 0.5; T6 median 3.7, IQR 0.8; Cohen d=0.7), while there was no change for IC and FC. At T0, those living alone had lower acceptability than those living with someone but this difference disappeared at T6. People or participants living with someone had a decline in anxiety, attitudes toward technology, enjoyment, and perceived usefulness. Stress toward technology affected usability and acceptability in the older adult group entering the study (ρ=-.85) but this was not observed after 6 months. In the IC group, stress affected trust at T0 (ρ=-.23) but not at T6., Conclusions: At the start of the study, older adults judged the system to be less usable and more stressful than did the caregivers. Indeed, at first, technostress was correlated with usability and acceptability; however, with repeated use, technostress did not influence the perception of technology. Overall, getting accustomed to technology decreased anxiety and stress toward technology., (© Jasmine Pani, Letizia Lorusso, Lara Toccafondi, Grazia D'Onofrio, Filomena Ciccone, Sergio Russo, Francesco Giuliani, Daniele Sancarlo, Novella Calamida, Gianna Vignani, Tarmo Pihl, Erika Rovini, Filippo Cavallo, Laura Fiorini. Originally published in JMIR Aging (https://aging.jmir.org).)

Background: The Pilots for Healthy and Active Ageing (PHArA-ON) project aimsto ensure reality smart and active living for Europe's ageing population by creating a set of integrated and highly customizable interoperable open platforms with advanced services, devices, and technologies and tools. The aim of the present study was to determine the needs and preferences of older people and their caregivers for improving healthy and active aging and guiding the technological development of thePHArA-ON system., Methods: A pre-structured interview was administered to older adults, informal caregivers and professional caregivers (including social operators) taking part in the piloting sessions., Results: Interviews were carried out in Umana Persone Social Enterprise R&D Network (UP) in Tuscany, and Ospedale Casa SollievodellaSofferenza (CSS) in Apulia. A total of 22 older adults, 22 informal caregivers, 13 professional caregivers and 4 social operators were recruited. A prioritization analysis of services, according to the stakeholder's needs, has determined two fundamental need categories: Heath Management (i.e., stimulation and monitoring), and Socialisation (i.e., promoting social inclusion)., Conclusions: The main scientific contributions to this study are the following: to design and evaluate technology in the context of healthy and active ageing, to acquire relevant knowledge on user needs to develop technologies that can handle the real life situations of older people, obtain useful insights about the attitude and availability of end-users in using technologies in clinical practice, and to provide important guidelines to improve the PHArA-ON system. Specific experimentation stages were also carried out to understand which kind of technology is more acceptable, and to obtain feedback regarding the development priority related to the impact of the proposed services. Research through fruitful and continuous interaction with the different subjects involved in the development process of the system, as well as with stakeholders, enabled the implementation of a platform which could be further and easily integrated and improved.

The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. Post-hoc analyses in a national context are important because of the differences in disease management across countries. Post-hoc safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted. Patients' quality of life was assessed from baseline to end of treatment. In Italy, 161 patients were enrolled. The median age was 64 years, with a performance status of 0-1. The most common hematological drug-related adverse events ≥grade 3 were neutropenia (41.0%) and anemia (13.7%). The median progression-free survival was reached at 3.0 months, with a disease control rate of 28.6%. The Quality of Life Questionnaire Core 30 score improved in 25.4% of the patients. Safety, efficacy and quality of life results confirmed trifluridine/tipiracil as a feasible and favorable treatment option for metastatic colorectal cancer patients.

Background: More than 70% of elderly people age 80 and older are experiencing problems in personal mobility. Assistive robotics can represent a concrete support providing also a support for caregivers, clinicians and nurses by reducing their burden., Methods: A total of 20 older people and 34 caregivers (formal and informal) were interviewed in Italy and the Netherlands to investigate and prioritize their needs concerning the personal mobility domains and their attitudes towards assistive robots. The data were analysed from a user point of view by means of thematic content analysis by underlying recurrent topics., Results: The results revealed four categories of needs from the perspective of the older individuals: instrumental needs, rehabilitation needs, personal safety and indoor activities of daily life. Additionally, the results underline how personal mobility issues influence different aspects of daily life. Complementarily, three categories of caregiver needs were also distinguished: instrumental needs, rehabilitation monitoring needs and checkup needs. The highest percentage of participants showed a positive expectation towards assistive robotics., Conclusions: The results were clustered according to the robot abilities (i.e., motion, interaction, manipulation, decision support and perception abilities) as a list of functional and technical requirements that should be developed to address all the needs related to the personal mobility. Robotic developer teams that work in this context could take advantage of this research. Additionally, this work can be used as a basis for clinicians and nurses working in geriatric units to understand how the robots can support and enhance their work. Implications for rehabilitation The incidence of personal mobility limitations affects 35% of adults age 70 and older and 72% of people over 80 years of age. Assistive robots can support elderly people during daily tasks: they could promote their personal mobility acting as a supporting tool. The results of the needs analysis revealed four categories of needs from the perspective of the older individuals: instrumental needs, rehabilitation needs, personal safety, and indoor activities of daily life. Three categories of caregiver needs were also distinguished: instrumental needs, rehabilitation monitoring needs, and check-up needs.

Objectives: COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients' outcomes is still poorly understood., Design: Observational, prospective, multicentre study., Setting: Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards., Participants: Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded., Interventions: Anthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101-200 mm Hg); mild (PaO2/FiO2 201-300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg)., Primary and Secondary Outcome Measures: The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay., Results: 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55-76) years with a PaO2/FiO2 at admission of 262 (140-343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04)., Conclusions: A moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality., Trial Registration Number: NCT04307459., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project., Design: Population-based cohort study, the INTERGROWTH-21st Project., Setting: Brazil, India, Italy, Kenya and the UK., Participants: 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes., Primary Measures: Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones., Results: Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA's cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA's negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22-30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges., Conclusions: From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

We studied neurodevelopmental outcomes and behaviours in healthy 2-year old children (N = 1306) from Brazil, India, Italy, Kenya and the UK participating in the INTERGROWTH-21 st Project. There was a positive independent relationship of duration of exclusive breastfeeding (EBF) and age at weaning with gross motor development, vision and autonomic physical activities, most evident if children were exclusively breastfed for ≥7 months or weaned at ≥7 months. There was no association with cognition, language or behaviour. Children exclusively breastfed from birth to <5 months or weaned at >6 months had, in a dose-effect pattern, adjusting for confounding factors, higher scores for "emotional reactivity". The positive effect of EBF and age at weaning on gross motor, running and climbing scores was strongest among children with the highest scores in maternal closeness proxy indicators. EBF, late weaning and maternal closeness, associated with advanced motor and vision maturation, independently influence autonomous behaviours in healthy children.

Purpose: There is no consensus on the use of cetuximab in elderly patients with metastatic colorectal cancer. To this end, a survey was carried in 17 Italian oncology centers., Methods: The centers answered a 29-item questionnaire structured as follows: (i) demographic characteristics; (ii) medical history; (iii) assessment of RAS/BRAF mutations and DPD/UGT polymorphism before treatment; (iv) treatment schemes and side effects; (v) geriatric assessment and customization of treatment., Results: One-third of patients are over 80 years old. The RAS/BRAF mutational status is not primarily evaluated by 17.6% of the centers, while DPD and UGT polymorphism is not evaluated by 82.4% and 76.5% of the centers. The most common therapeutic scheme is cetuximab/FOLFIRI and diarrhea is the main cause of suspension/reduction of treatment. The 70% of centers use systemic tetracyclines for skin toxicity. The 23.5% of the centers do not carry out any geriatric evaluation before the start of the therapy and those who perform it prefer the G8 (70.6%) and VES-13 (29.4%) scales., Conclusions: Greater efforts should be made to improve the evaluation of the patient both about mutational and genetic procedures with geriatric evaluation. As for cetuximab in elderly patients, randomized studies are needed to provide guidance to physicians.

Background/aim: Technological solutions can support the elderly, improve their quality of life and reduce isolation and loneliness. The Euro-Japan ACCRA (Agile Co-Creation for Robots and Aging) project has the objective of building a reference co-creation methodology for the development of robotic solutions for ageing. The aim of this study is to provide a pilot qualitative analysis of the real needs of elderly people and their caregivers when exposed to conversational activities with robots and to identify priority needs that should be developed from end-user perspectives., Methods: A qualitative research design was adopted to define a pre-structured questionnaire that was administered to the elderly taking part in the piloting sessions. Three groups of end-users were included: subjects with an age ≥ 60 years, informal caregivers and formal caregivers., Results: The interviews were carried out in Italy and Japan. A total of 17 elderly and 36 caregivers were recruited. Common needs in the two sites were categorized into 3 groups: Communication; Emotion Detection and Safety. General robot acceptance level is good and perception is positive among participants in the pilot sites., Conclusion: A positive perception of the elderly on the application of a robotic solution was found and many are the needs that could be addressed by an appropriate and careful robotic development taking into account the real needs and capabilities of the involved subjects.

Introduction: Italy is prone to major earthquakes and has experienced several devastating earthquakes in the far and recent past. The objectives of this study were to assess the level of Italian households' preparedness for earthquakes and to measure the public's perception of the risk and its impact on preparedness behavior., Hypothesis: Italian households' preparedness for earthquakes is insufficient and is influenced by different threat perception components that were assessed., Methods: A cross-sectional study, using an online questionnaire, was conducted in early 2018. The sample included 1,093 responders from a diverse sociodemographic background. The primary outcome was the Preparedness Index (PI), a score indicating the number of preparedness actions complied-with out of 10., Results: The PI's mean was 5.26 (SD = 2.17). The recommendation most complied-with was keeping a flashlight at home (87.7%) and the least was securing the kitchen cupboards (15.1%). The PI was positively correlated with a higher sense of preparedness (r = 0.426; P &lt;.001). The PI was higher for responders residing in high-seismic-risk areas and those who experienced a major earthquake before. The predictors of PI were: gender, age, prior experience, sense of preparedness, searching for information, and threat intrusiveness (negatively)., Conclusions: The findings demonstrate a medium-level of preparedness; however, this might be circumstantial. Italians perceive major earthquakes to be unlikely, yet severe if and when they do occur. A validated tool in Italian now exists and can be used in future studies.Bodas M, Giuliani F, Ripoll-Gallardo A, Caviglia M, Dell'Aringa MF, Linty M, Della Corte F, Ragazzoni L. Threat perception and public preparedness for earthquakes in Italy. Prehosp Disaster Med. 2019;34(2):114-124.

It is unclear whether early child development is, like skeletal growth, similar across diverse regions with adequate health and nutrition. We prospectively assessed 1307 healthy, well-nourished 2-year-old children of educated mothers, enrolled in early pregnancy from urban areas without major socioeconomic or environmental constraints, in Brazil, India, Italy, Kenya and UK. We used a specially developed psychometric tool, WHO motor milestones and visual tests. Similarities across sites were measured using variance components analysis and standardised site differences (SSD). In 14 of the 16 domains, the percentage of total variance explained by between-site differences ranged from 1.3% (cognitive score) to 9.2% (behaviour score). Of the 80 SSD comparisons, only six were >±0.50 units of the pooled SD for the corresponding item. The sequence and timing of attainment of neurodevelopmental milestones and associated behaviours in early childhood are, therefore, likely innate and universal, as long as nutritional and health needs are met.

Background: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21 st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age., Objective: The purpose of this study was to determine whether the babies in the INTERGROWTH-21 st Project maintained optimal growth and development in childhood., Study Design: In the Infant Follow-up Study of the INTERGROWTH-21 st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites., Results: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21 st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21 st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions., Conclusion: The cohort enrolled in the INTERGROWTH-21 st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Turin, Italy, was one of the two European sites for the INTERGROWTH-21(st) Project. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two obstetric hospitals that together account for 79% of the city's approximately 12,000 births per year. Women were recruited for the Fetal Growth Longitudinal Study (FGLS) from ten antenatal clinics serving the city's largest obstetric hospital, Azienda Ospedaliera OIRM-S. Anna. Special activities to encourage participation and raise awareness of the project in this population included obtaining an endorsement from the coordinator of the city's antenatal care service, and disseminating information about the project to women through posters and leaflets in antenatal clinics. One of the major challenges at this site was the low recruitment rate in the early phase of FGLS because of the high prevalence of smoking and of women >35 years old in the population. The addition of six extra recruiting clinics served to increase the pool of potentially eligible women who could be screened and led to a marked improvement in the recruitment rate., (© 2013 Royal College of Obstetricians and Gynaecologists.)

Background and Objective: This was a nationwide prospective study carried out in Italy between 2005 and 2007, involving 34 centers with a neonatal intensive care unit. The study reports the Italian Neonatal Study charts for weight, length, and head circumference of singletons born between 23 and 42 gestational weeks, comparing them with previous Italian data and with the most recent data from European countries., Patients and Methods: Single live born babies with ultrasound assessment of gestational age within the first trimester, and with both parents of Italian origin. Only fetal hydrops and major congenital anomalies diagnosed at birth were excluded. The reference set consists of 22,087 girls and 23,375 boys., Results: At each gestational age, boys are heavier than girls by about 4%. Later-born neonates are heavier than firstborn neonates by about 3%. The effects of sex and birth order on length and head circumference are milder. No differences were observed between babies born in central-north Italy and southern Italy. A large variability emerged among European neonatal charts, resulting in huge differences in the percentage of Italian Neonatal Study neonates below the 10th centile, which is traditionally used to define small-for-gestational-age babies. In the last 2 decades prominent changes in the distribution of birth weight emerged in Italy and in the rest of Europe, in both term and preterm neonates., Conclusions: The existing European neonatal charts, based on more or less recent data, were found to be inappropriate for Italy. Until an international standard is developed, the use of national updated reference charts is recommended.

Preterm Infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. These neonates constitute the large majority of the population in neonatal intensive care units. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth,specifically in relation to the charts used. At present the available charts in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. An international multicentric project has recently started a study aiming at building a prescriptive standard for the evaluation of postnatal growth of preterm infants and it will be available in the next years. At present, while an international longitudinal standard for evaluating preterm infant postnatal growth is lacking, in Italy the best compromise in clinical practice is likely to be as follows: new Italian INeS (Italian Neonatal Study) charts up to term; International longitudinal charts WHO 2006 or CDC 2002 from term to two years; finally, the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP) 2006 growth charts could be suitable for monitoring the growth of these infants from two years up to 20 years of age.

This independent, population-based surveillance study monitored the efficacy and safety of interferon beta (IFNbeta) products in 1033 patients with relapsing-remitting multiple sclerosis (RRMS) from 15 centres in Italy. Relapses, Expanded Disability Status Scale (EDSS) scores, and adverse events were evaluated for up to 24 months. Data of patients with a baseline EDSS score < or = 3.5 are reported. The proportions of relapse-free patients were similar among the groups at 12 and 24 months (P = 0.10). IFNbeta products produced significant reductions from baseline in relapse rates at 12 and 24 months (P < 0.001), with no differences among treatments (P = 0.2). There were no significant differences in mean EDSS change among groups at 12 or 24 months. The IFNbeta-1b group showed a higher incidence of adverse events during the first year of treatment (P < 0.05) than IFNbeta-1a groups, and more withdrawals (10%) compared with Avonex (5%) at 24 months. IFNbeta products are equally effective in low disability RRMS, but IFNbeta-1a may have a more favorable efficacy/tolerability ratio.

Age at onset of multiple sclerosis (MS) can vary from childhood to adult life. Many reports have been carried out over the years concerning the role of age at onset in determining the disease outcome. In a sporadic MS population of 1463 patients with homogeneous clinical and demographic features, derived from three Italian neurological centres (Bari, Cagliari and Sassari), we analysed the relative weights of current age and age at onset on disease severity according to the expanded disability status scale (EDSS) score, by fixing the disease duration. The results of present study demonstrate that clinical disability in MS is influenced by the patient's age (p < 0.01) and not by the age at onset. Therefore, these data do not confirm the hypothesis that an early age at onset should be considered a favourable prognostic factor of the disease outcome.

This article reports on a general method of evaluating exposure to infrared radiation (IR-A, IR-B, IR-C) from high temperature (T > 1000 degrees C) black body sources, simply by performing measurements with a luxometric and/or near IR detector. The method, which may be applied to any black body source, uses the universality of the Planck formula for the black body spectrum, which allows estimation of the radiated power in any wavelength range by measuring the power radiated in another range. This capability may be very useful when the range of interest is one in which radiometers are expensive and difficult to calibrate, as for the IR-B and IR-C ranges, because a more commonly available luxometer can be used instead. The results of measurements and evaluations in two traditional Italian glass factories are reported and compared with the threshold limit value given by the American Conference of Governmental Industrial Hygienists. Intense exposures in the IR-B and IR-C ranges has been found for some workers, exceeding the limit by a large factor. This exposure must be reduced, as it has been shown by epidemiologic studies that there is indeed a correlation between cataractogenesis and work with fused glass and metals.

A total of 71 patients with advanced gastric carcinoma were randomized to receive either folinic acid + fluorouracil (arm A) or the same combination with the addition of 4-epidoxorubicin (arm B). Of the 62 evaluable patients (31 in both arms), six patients achieved a CR (10%) and 16 a PR (25.5%) with an overall response rate of 35.5% (29% in arm A and 42% in arm B; p = .28). Median duration of response was 6 and 7 months for arm A and B, respectively (p = .6). Responder patients showed a significantly better median survival duration than nonresponders (p = .01); in arm B the median survival duration was 16 months for responder patients in contrast to 7 months for nonresponders (p = .004). Toxicity was mild without significant differences between the two groups. There was one death due to hematological toxicity (arm A). The EPI-FA-FU combination appears effective and well tolerated with the additional advantage of being able to be administered in the outpatient clinic.

A total of 101 patients with advanced colorectal cancer in two consecutive Southern Italian Oncology Groups (GOIM) studies (8501 and 8801--arm A) were treated with a sequential combination of high dose methotrexate (HDMTX) and fluorouracil (FU). Of the 92 eligible patients, 2 achieved complete response (2%) and 27 partial response (30%), with a median duration of 7 months. When classified according to the time interval between administration of the two drugs, retrospective analysis showed significant improvement (p = 0.04) in overall survival in the shorter time interval group (6 hours). The observed toxicities were generally mild and transient. Our data confirm the efficacy of the synergism between the two chemotherapeutic agents, in particular when administered with a 6-hour interval. Further studies are necessary to establish the possibility of enhancing the efficacy of sequential treatment with the modulation of FU with high-dose folinic acid.