Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study.

AIMS: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. METHODS: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. RESULTS: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and,  of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. CONCLUSIONS: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.

Clinical Asthma Remission Obtained with Biologics in Real Life: Patients' Prevalence and Characteristics.

BACKGROUND: The prevalence of clinical asthma remission with biologics in severe asthma has not been well understood yet. We do not even know whether there might be characteristics that identify subjects prone to remission of the disease. MATERIALS AND METHODS: Retrospectively, four groups of severe asthmatics already treated with Omalizumab, Mepolizumab, Benralizumab and Dupilumab (302, 55, 95 and 34 patients, respectively) for at least 12 months were considered. The number of individuals with clinical asthma remission was sought in each group. This was considered when patients, after a treatment of at least 1 year with one of the aforesaid biologics, showed the disappearance of asthma symptoms (ACT ≥ 20), zero exacerbations, suspension of oral corticosteroids and a FEV1% ≥ 80%. Baseline characteristics of patients with and without remission were also taken into account. RESULTS: The prevalence of asthma remission after a mean of 37.8 ± 19.2, 13.5 ± 1.7, 15.4 ± 5.5 and 12 ± 0 months of Omalizumab, Mepolizumab, Benralizumab and Dupilumab treatments was 21.8%, 23.6%, 35.8% and 23.5%, respectively. For each biologic, different baseline characteristics, seem to be associated with failure to achieve clinical asthma remission. Older age, higher BMI, a later age of asthma onset, rhinitis/sinusitis/nasal polyposis, comorbidities and a greater asthma severity may be the characteristics of a suboptimal response to biologic treatments. CONCLUSION: All biologics have the potential to induce disease remission in severe asthmatics. For each biologic, there may be several markers that can identify the patients who will not achieve asthma remission. It would be important to detect them (by carrying out targeted studies) as they would allow us to select the best biologic that may induce clinical asthma remission on a larger number of patients.

COVID-19 severity appears to be reduced in spring/summer.

BACKGROUND: because of different human behaviours, SARS-CoV-2 spread may be lower in spring/summer. On the contrary, it is not clearly known whether the clinical course/severity of hospitalized patients infected by SARS-CoV-2 can be different in the various seasons.. OBJECTIVES: to understand whether there were differences in severity of COVID-19 in patients who had contracted the infection in winter versus those infected in spring/summer. DESIGN: observational retrospective cohort study. SETTING AND PARTICIPANTS: from the administrative database of the SARS-CoV-2 surveillance system and that of hospital discharge, a cohort of patients (8,221, 653 of which were hospitalized) who tested positive to the RT-PCR test for SARS-CoV-2 between 01.12.2020 and 31.07.2021 in the Grosseto province (Tuscany Region, Central Italy) was selected and analysed. MAIN OUTCOME MEASURES: hospitalization rate and length, continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) use, Intensive Care Unite (ICU) admissions, intra-hospital mortality and PaO2/FiO2 values were measured and compared between subjects infected in winter and those who developed COVID-19 in spring/summer. Viral load (cycle threshold, Ct), vitamin D, serum ferritin, IL-6, procalcitonin, D-dimer, and C-reactive protein measured in the two periods were also compared. RESULTS: in the considered months, the hospitalization rate among 8,221 patients with COVID-19 was 8%: 370 (8.5%) individuals were hospitalized in winter and 283 (7,3%; p=0.31) in spring/summer; 62 (16.8%), 88 (23.8%), and 63 (17%) in winter and 28 (9.9%), 40 (14.1%), and 36 (12.7%) in spring/summer were admitted in ICU (p=0.01), used CPAP/NIV (p=0.002) and died (p=0.13), respectively. Hospitalization days were 14.5±11.6 in winter and 10.3±8.84 in spring/summer (p=0.001), while minimum PaO2/FiO2, measured during hospital stays was 123.2±38.6 in spring/summer and 112.6±40.8 in winter (p=0.054). Multivariate analysis (adjusted for all confounding factors) also confirmed reduced risks of having ICU admissions (0.53; 95%CI 0.32;0.88; p=0.01) and of using CPAP/NIV (0.48; 95%CI 0.32;0.75; p=0.001) in spring/summer when compared to winter. Hospitalization days and minimum PaO2/FiO2 were also lower in spring/summer (ß= -3.9; 95%CI -5.5;-2.2; p=0.001) and winter (ß= -17; 95%CI -0.93;35; p=0.06), respectively. The adjusted hazard ratio of mortality in winter, obtained with a Cox model, was higher of about 38% compared to spring/summer. No Ct values (viral load) differences were found either in winter (19.45±6.18) or spring/summer (20.3±6.7; p=0.343). IL-6, ferritin, procalcitonin, D-dimer were similar. Conversely, CRP was lower whereas vitamin D was higher in the warmer seasons. CONCLUSIONS: COVID-19 may be less severe during spring/summer in hospitalized patients. This does not seem to be influenced by different SARS-CoV-2 viral load in the different periods considered. C-reactive protein was found to be lower whereas vitamin D higher in the warmer months. It can be hypothesized that higher levels of vitamin D in spring/summer, compared to winter, may be associated to a positive modulation of COVID-19 induced inflammation with a possible disease severity reduction during spring/summer.

Alcohol versus combined alcohol and energy drinks consumption: Risk behaviors and consumption patterns among European students.

INTRODUCTION: Recent research found that drinking alcohol mixed with energy drinks (AmED) could be riskier than drinking alcohol alone. Our aim was to compare rates of risk behaviors in consumers of AmED versus exclusive alcohol drinkers, matching them based on their drinking frequency. METHODS: Data about 16-year-old students who reported the number of occasions on which they had drunk AmED or alcohol only in the preceding 12 months (n = 32,848) were drawn from the 2019 ESPAD study. After matching for consumption frequency, the sample consisted of 22,370 students (11,185 AmED consumers and 11,185 exclusive alcohol drinkers). Key predictors comprised substance use, other individual risk behaviors, and family characteristics (parental regulation, monitoring, and caring). RESULTS: The multivariate analysis showed significantly higher odds of being AmED consumers compared to being exclusive alcohol drinkers in the majority of the investigated risk behaviors, including: daily tobacco smoking, illicit drug use, heavy episodic drinking, truancy at school, engaging in physical fights and serious arguments, having troubles with the police, and having unprotected sexual intercourse. Instead, lower odds were found for reporting high parents' educational level, medium and low family economic status, perceived possibility to freely talk about problems to family members, spending free time reading books or other hobbies. CONCLUSIONS: Our study shows that, given the same consumption frequency in the past year, AmED consumers typically reported higher associations with risk-taking behaviors compared to exclusive alcohol drinkers. These findings advance past research that failed to control for the frequency of AmED use versus exclusive alcohol consumption.

E-cigarette use and conventional cigarette smoking among European students: findings from the 2019 ESPAD survey.

BACKGROUND AND AIMS: Representative data on e-cigarette use among European adolescents are scant. This study reports current vaping and tobacco smoking individual and country-specific correlates among European students. DESIGN: Cross-sectional survey: 2019 European School Survey Project on Alcohol and Other Drugs (ESPAD) collecting data on risk behaviours on a representative sample of 16-year-old students. SETTING: A total of 35 European countries, 25-30 with Tobacco Control Scale (TCS) and TCS components PARTICIPANTS: A total of 99 648 students (49.1% males) turning 16 years in the survey year. MEASUREMENTS: Data on current cigarette and e-cigarette use were gathered through a self-administered questionnaire which also collected socio-demographics and individual and family characteristics. ESPAD data were integrated with country-level data on TCS and selected TCS parameters to assess their association with the prevalence of current cigarette and e-cigarette use. FINDINGS: Of the 99 648 participating students, 12.4% were current e-cigarette users, from 5.5% in Serbia to 41.4% in Monaco; 19.3% current smokers, from 5.1% in Iceland to 32.4% in Italy. Compared with non-users, current e-cigarette users less frequently came from an average well-off family [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.80-0.90] and lived in countries with higher cigarette prices (OR = 0.71, 95% CI = 0.50-0.99), restrictive measures on tobacco advertising and promotion (OR = 0.79, 95% CI = 0.63-0.99) and intermediate implementation of tobacco control measures (OR = 0.57, 95% CI = 0.38-0.85). Current vapers were more frequently life ever smokers (OR = 7.31, 95% CI = 6.47-8.25), were early smokers (OR = 4.35, 95% CI = 3.66-5.17), males (OR = 1.61, 95% CI = 1.55-1.67), from non-traditional families (OR = 1.43, 95% CI = 1.34-1.53), with relatively low parental education (OR = 1.15, 95% CI = 1.10-1.20). Compared with non-smokers, current smokers had similar family characteristics to vapers, and were less likely to live in countries with higher cigarette prices (OR = 0.70, 95% CI = 0.49-0.99) and higher spending on public anti-tobacco media campaigns (OR = 0.23, 95% CI = 0.10-0.50). CONCLUSIONS: E-cigarette use among European adolescents is associated with weaker tobacco control measures, particularly on tobacco price, advertising and promotion. Besides preventing tobacco smoking, the adoption of governmental tobacco control policies in European countries also seems to contribute to the prevention of vaping among adolescents.

Atrial Function Impairments after Pediatric Cardiac Surgery Evaluated by STE Analysis.

Background: Applications of atrial speckle tracking echocardiography (STE) strain (ε) analysis in pediatric cardiac surgery have been limited. This study aims to evaluate the feasibility of atrial STE ε analysis and the progression of atrial ε values as a function of post-operative time in children after pediatric cardiac surgery. Methods: 131 children (mean 1.69 ± 2.98; range 0.01−15.16 years) undergoing cardiac surgery were prospectively enrolled. Echocardiographic examinations were performed pre-operatively and at 3 different post-operative intervals: Time 1 (24−36 h), Time 2 (3−5 days), Time 3 (>5 days, before discharging). The right and left atrium longitudinal systolic contractile (Ct), Conduit (Cd), and Reservoir (R) ε were evaluated with a novel atrial specific software with both P- and R-Gating methods. One hundred and thirty-one age-matched normal subjects (mean 1.7 ± 3.2 years) were included as controls. Results: In all, 309 examinations were performed over the post-operative times. For each post-operative interval, all STE atrial ε parameters assessed were significantly lower compared to controls (all p < 0.0001). The lowest atrial ε values were found at Time 1, with only partial recovery thereafter (p from 0.02 to 0.04). All atrial ε values at discharge were decreased compared to the controls (all p < 0.0001). Significant correlations of the atrial ε values with cardio-pulmonary-bypass time, left and right ventricular ε values (p < 0.05), and ejection fraction (p < 0.05) were demonstrated. Conclusions: Atrial ε is highly reduced after surgery with only partial post-operative recovery in the near term. Our study additionally demonstrates that post-surgical atrial and ventricular ε responses correlated with each other.

A pharmacogenetic interaction analysis of bevacizumab with paclitaxel in advanced breast cancer patients.

To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1, and TSP-1 SNPs and their role on progression-free survival (PFS) in metastatic breast cancer (MBC) patients treated with bevacizumab plus first-line paclitaxel or with paclitaxel alone. Analyses were performed on germline DNA, and SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction (MDR) methodology was applied to investigate the interaction between SNPs. The present study was an explorative, ambidirectional cohort study: 307 patients from 11 Oncology Units were evaluated retrospectively from 2009 to 2016, then followed prospectively (NCT01935102). Two hundred and fifteen patients were treated with paclitaxel and bevacizumab, whereas 92 patients with paclitaxel alone. In the bevacizumab plus paclitaxel group, the MDR software provided two pharmacogenetic interaction profiles consisting of the combination between specific VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes. Median PFS for favorable genetic profile was 16.8 vs. the 10.6 months of unfavorable genetic profile (p = 0.0011). Cox proportional hazards model showed an adjusted hazard ratio of 0.64 (95% CI, 0.5-0.9; p = 0.004). Median OS for the favorable genetic profile was 39.6 vs. 28 months of unfavorable genetic profile (p = 0.0103). Cox proportional hazards model revealed an adjusted hazard ratio of 0.71 (95% CI, 0.5-1.01; p = 0.058). In the 92 patients treated with paclitaxel alone, the results showed no effect of the favorable genetic profile, as compared to the unfavorable genetic profile, either on the PFS (p = 0.509) and on the OS (p = 0.732). The pharmacogenetic statistical interaction between VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes may identify a population of bevacizumab-treated patients with a better PFS.

Left Ventricular Systolic Impairment after Pediatric Cardiac Surgery Assessed by STE Analysis.

BACKGROUND: Speckle-tracking echocardiography (STE) has gained increasing value in the evaluation of congenital heart diseases (CHD); however, its use in pediatric cardiac surgery is limited. AIM: To evaluate left ventricular (LV) systolic impairment after biventricular pediatric cardiac surgery by STE strain (ε) analysis. METHODS: We prospectively enrolled 117 children undergoing cardiac surgery for CHD. Echocardiography was performed at four different times: pre-operatively, 12-36 h (Time 1), 3-5 days (Time 2), and 6-8 days (Time 3). Images were obtained in the 4-2-and 3 apical chamber's views to derive LV global and regional (basal/mid/apical) ε values. RESULTS: At different postoperative times, we performed 320 examinations in 117 children (mean age: 2.4 ± 3.9, range: 0-16 years); 117 age-matched healthy children served as controls. All global, basal, and mid LVε values decreased after surgery; the lowest values being at Time 1 (p < 0.0001), which increased thereafter. At discharge, all global, basal, and mid LVε values remained lower than in pre-operative and healthy children (p < 0.05). Instead, apical segments (lowest at baseline) increased after surgery (p < 0.0001) but remained lower compared to controls. LV ejection fraction (LVEF) decreased at Time 1 (p = 0.0004) but promptly recovered to Time 2 and normalized at Time 3. CONCLUSIONS: STE ε analysis revealed a significant LV systolic impairment after surgery with amelioration thereafter but incomplete normalization at discharge. Base-apex differences emerged with apical segments that, contrary to all the other regions, showed relative hypercontractility after surgery. The slower recovery of LVε values compared to LVEF suggests that STE ε analysis may be more accurate for the follow-up of mild LV post-surgical impairment.

A real-world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma.

Carfilzomib-lenalidomide-dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We conducted a retrospective analysis of 197 RRMM patients (pts) between January 2016 and March 2018 in six Italian hematologic centers, with the aim to evaluate efficacy and safety of KRd in real-life. At KRd initiation 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)], median number of prior lines of therapy was 2 (1-8), nearly all pts (96%) received prior bortezomib (18% refractory) while 45% were exposed to lenalidomide (R; 22% refractory). At the median of 12.5 months, 52% of the pts had discontinued treatment, mainly (66%) for progression. Main grade 3-4 adverse events were neutropenia (21%), infections (11%), and hypertension (6%). Overall, the response rate was 88%. The median progression-free survival (PFS) was 19.8 months and 1-year overall survival (OS) rate was 80.6%. By subgroup analysis, extended PFS and OS were observed for pts who received ≤2 prior lines of therapy (HR = 0.42, p < 0.001 and HR = 0.35, p = 0.001, respectively), not refractory to prior R (HR = 0.37, p < 0.001, and HR = 0.47, p = 0.024), without HRCA (HR = 0.33, p = 0.005 and HR = 0.26, p = 0.016) and achieving ≥ very good partial response (VGPR; HR = 0.17, p < 0.001 and HR = 0.18, p < 0.001). In conclusion, KRd demonstrated to be effective in RRMM pts treated in real-world setting, without new safety concerns. Better survival outcomes emerged for pts with ≤2 prior lines of therapy, achieving at least a VGPR, and without HRCA.

Validity of the STOP-Bang Questionnaire in Identifying OSA in a Dental Patient Cohort.

Background and objectives: Obstructive Sleep Apnea represents a widespread problem in the population, but it is often not diagnosed and not considered a true pathology. Different diagnostic tools are available for the diagnosis of sleep apnea. This study aims to demonstrate the ability of the STOP-Bang (Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender) questionnaire in identifying subjects with Obstructive Sleep Apnea (OSA) Syndrome, highlighting the role of dentists as epidemiological sentinels. Materials and methods: the STOP-Bang questionnaire was administered to a cohort of 1000 patients, assessing three private dental clinics in Italy. Excessive daytime sleepiness was measured using Epworth Sleepiness Scale (ESS) and defined as ≥ 10. Subjects were considered at risk of OSA if they had three or more positive items at STOP-Bang and were invited to undergo further examination with a type 3 polygraph. Presence of OSA was measured with the apnea-hypopnea index (AHI) and defined as AHI ≥ 5. Results: 482/1000 subjects (48.2%) had three or more positive items in the STOP-Bang questionnaire and were considered at risk for Obstructive Sleep Apnea Syndrome (OSAS). Excessive daytime sleepiness (EDS ≥ 10) was more frequent among subjects at risk for OSAS (73/482, 15.1%) vs. those not at risk for OSAS (30/518, 5.8%) (p < 0.0001). Moreover, 153/482 subjects at risk for OSAS (31.7%) accepted further examination with a type 3 polygraph. Presence of OSAS (AHI ≥ 5) was suggested in 121/153 subjects (79.1%, 95% CI 71.6% to 85.1%), with 76/121 subjects (62.8%) needing treatment (AHI ≥ 15). Conclusion: the high prevalence of OSAS highlights the role of dentists as "epidemiological sentinels". The STOP-Bang questionnaire is a simple and efficacious instrument for screening sleep apnea patients.

Impact of Postprandial Hypoglycemia on Weight Loss After Bariatric Surgery.

INTRODUCTION: Postprandial hypoglycemia (PPHG) is a well-known complication after bariatric surgery (BS). However, it is not known whether PPHG affects weight loss after BS. AIMS: To assess the impact of PPHG on weight loss after BS in subjects without and with type 2 diabetes mellitus (T2D). METHODS: Data from 338 subjects who had undergone gastric bypass (RYGB) or sleeve gastrectomy (LSG) and were followed up for at least 2 years were analyzed. At each follow-up visit, the patient's anthropometric and biochemical characteristics were recorded and the Edinburgh Questionnaire was performed to evaluate the presence of PPHG symptoms. RESULTS: Before surgery: younger age and lower BMI predicted PPHG after BS (p = 0.02 and p = 0.0008, respectively). Also, the baseline OGTT indicated that subjects who developed PPHG had an earlier glucose peak and more often had low glucose levels at 2 h compared with the no-PPHG group (p = 0.03 and p = 0.004, respectively). After surgery: Mild-to-moderate PPHG occurred equally after RYGB and LSG (38% vs 25%, p = ns when accounting for confounders), and in T2D who achieved remission and those who did not (29.5% vs 28.6%, ns). At the 2-year follow-up, occurrence of PPHG was independently associated with smaller weight loss (p = 0.0006). CONCLUSIONS: Mild-to-moderate PPHG is a frequent complication after bariatric surgery and results in smaller weight loss after 2 years. Age, baseline BMI, and an earlier glucose peak during OGTT predict PPHG after bariatric surgery.

Prognostic Value of a New Lung Ultrasound Score to Predict Intensive Care Unit Stay in Pediatric Cardiac Surgery.

BACKGROUND: Lung ultrasound (LUS) in pediatric cardiac surgery is gaining consensus. We (1) evaluated the prognostic value of a new LUS-score in pediatric cardiac surgery, and (2) compared LUS-score to conventional risk factors including age, The Society of Thoracic Surgeons/European Association of Cardio-Thoracic Surgery (STAT) score, cardiopulmonary bypass time, and prognostic biomarkers including brain natriuretic peptide and cystatin-C. METHODS: LUS examinations were performed in 237 children (median age, 0.55 years; interquartile range, 0.09-4.15 years) at 12 to 36 hours after surgery. For each hemithorax, 3 areas (anterior/lateral/posterior) were evaluated in the upper and lower halves, constituting 12 total scanning areas. For each site a score was assigned: 0 (rare B lines), 1 (separated B lines), 2 (coalescent B lines), 3 (loss of aeration), and total LUS score was calculated as sum of all sites. The primary endpoints were intensive care unit length of stay and extubation time. RESULTS: The mean total LUS score was 12.88 ± 6.41 (range, 0-26) and was higher in newborns (16.77 ± 5.25) compared with older children (5.36 ± 5.57; P < .001). On univariate analysis, LUS score was associated inversely with age (beta 0.26; P = .004) and body surface area (beta 3.41 P = .006) and positively with brain natriuretic peptide (beta 1.65; P < .001) and cystatin-C (beta 2.41; P < .001). The LUS score, when added as continuous predictor to a conventional risk model (age, STAT score, and cardiopulmonary bypass time) emerged significant both for intensive care unit length of stay (beta 0.145, P = .047) and extubation time (beta 1.644; P = .024). When single quadrants were analyzed, only anterior LUS score was significant (intensive care unit length of stay beta, 0.471; P = .020; extubation time beta 5.530; P = .007). CONCLUSIONS: Our data show the prognostic incremental value of a new LUS score over traditional risk factors in pediatric cardiac surgery.

Paper-and-pencil versus computerized administration mode: Comparison of data quality and risk behavior prevalence estimates in the European school Survey Project on Alcohol and other Drugs (ESPAD).

PURPOSE: The aim of this experimental study was to investigate whether paper-and-pencil and computerized surveys administered in the school setting yield equivalent data quality indicators and risk behavior prevalence estimates. METHODS: Data were drawn from the European School Survey Project on Alcohol and Other Drugs (ESPAD®) carried out in Italy to monitor drug, alcohol, tobacco use and other risk-behaviors among Italian high school students aged 15-19 years. A sub-sample of schools was recruited for the study (1673 pupils). For each school, two entire randomly selected courses (from the first to the fifth grade) participated and were assigned randomly to the self-administered paper-and-pencil (N = 811) or computerized survey (N = 862). Differences in data quality were assessed using the following indicators: questionnaire completeness (missing gender and/or 50% of missing answers) and internal consistency (repetitive extreme response patterns). Separate logistic regression models were used to estimate the mode effect on the reporting of each risk behavior, controlling for gender and age. Finally, the prevalence estimates of the experimental study were compared to the results of the national ESPAD® study. RESULTS: The computerized administration mode produced a higher proportion of invalid questionnaires, but the prevalence estimates generated from responses to the paper-and-pencil and computerized surveys were generally equivalent. Nevertheless, comparing these results with those of the national ESPAD® study, some differences in the prevalence rates were found. CONCLUSIONS: The findings suggest that in a proctored school setting, the computerized survey mode yields almost the same results as the paper-and-pencil mode. However, because of the reliance on existing informatics facilities until when all schools in the country will be sufficiently equipped for the computerized data collection, they should be given the opportunity to choose between paper-and-pencil and computerized survey modes, in order to avoid a possible selection bias.

Prevalence of youth gambling and potential influence of substance use and other risk factors throughout 33 European countries: first results from the 2015 ESPAD study.

BACKGROUND AND AIMS: Although generally prohibited by national regulations, underage gambling has become popular in Europe, with relevant cross-country prevalence variability. This study aimed to estimate the prevalence of underage gambling in Europe stratified by type of game and on-/off-line mode and to examine the association with individual and family characteristics and substance use. DESIGN: Our study used data from the 2015 European School Survey Project on Alcohol and Other Drugs (ESPAD) cross-sectional study, a survey using self-administered anonymous questionnaires. SETTING: Thirty-three European countries. PARTICIPANTS: Sixteen-year-old-year-old students (n = 93 875; F = 50.8%). MEASUREMENTS: The primary outcome measure was prevalence of past-year gambling activity. Key predictors comprised individual behaviours, substance use and parenting (regulation, monitoring and caring). FINDINGS: A total of 22.6% of 16-year-old students in Europe gambled in the past year: 16.2% on-line, 18.5% off-line. High prevalence variability was observed throughout countries both for mode and types of game. With the exception of cannabis, substance use shows a higher association with gambling, particularly binge drinking [odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.39-1.53), life-time use of inhalants (OR = 1.57, 95% CI = 1.47-1.68) and other substances (OR = 1.78, 95% CI = 1.65-1.92)]. Among life habits, the following showed a positive association: truancy at school (OR = 1.26, 95% CI = 1.18-1.35), going out at night (OR = 1.32, 95% CI = 1.26-1.38), participating in sports (OR = 1.30, 95% CI = 1.24-1.37). A negative association was found with reading books for leisure (OR = 0.82%, 95% CI = 0.79-0.86), parents' monitoring of Saturday night activities (OR = 0.81, 95% CI = 0.77-0.86) and restrictions on money provided by parents as a gift (OR = 0.89, 95% CI = 0.84-0.94). CONCLUSIONS: Underage gambling in Europe appears to be associated positively with alcohol, tobacco and other substance use (but not cannabis), as well as with other individual behaviours such as truancy, going out at night and active participation in sports, and is associated negatively with reading for pleasure, parental monitoring of evening activities and parental restriction of money.

Reference values and correlates of right atrial volume in healthy adults by two-dimensional echocardiography.

BACKGROUND: Right atrial (RA) volume is an important parameter in the evaluation of patients with pulmonary hypertension. Aim of this study was to define reference ranges for RA volume by two-dimensional echocardiography (2DE) in healthy adults. METHODS: A total of 596 healthy subjects [mean age 45.7 ± 14.6 years, range 18-88 years; 60.1% women] underwent a transthoracic echocardiography. In addition, a meta-analysis was performed of published studies measuring RA volume in healthy subjects, using 2DE single plane area-length (A-L) and/or method of disks (MOD) at end-systole in apical four-chamber view. RESULTS: In our cohort, RA volume was higher in men than women but did not vary with age. Body surface area (BSA), stroke volume (SV), and tricuspid annular plane systolic excursion (TAPSE) were the only independent variables associated with RA volume (ß coefficient 0.569, 0.123, and 0.131, respectively; all P < .001). In the pooled analysis, normalized RA volume was 25.7 ± 7.0 mL/m2 in men and 21.2 ± 5.8 mL/m2 in women for A-L, 21.6 ± 5.6 mL/m2 in men and 18.2 ± 5.4 mL/m2 in women for MOD (all P values < .0001). The upper limit was about 36 mL/m2 in men and 31 mL/m2 in women for A-L and 31 mL/m2 in men and 27 mL/m2 in women for MOD. CONCLUSIONS: RA volume was found to be higher in men but not influenced by age. It was mainly correlated with larger BSA, indices of preload (SV) and RV longitudinal function (TAPSE). A statistically significant difference was found between A-L and MOD.

Normative Data for Left and Right Ventricular Systolic Strain in Healthy Caucasian Italian Children by Two-Dimensional Speckle-Tracking Echocardiography.

BACKGROUND: There is an increasing interest in echocardiographic strain (ε) measurements for the assessment of ventricular myocardial function in children; however, pediatric nomograms remain limited. Our aim was to establish pediatric nomograms for the left ventricular (LV) and the right ventricular (RV) ε measured by two-dimensional speckle-tracking echocardiography (2D-STE) in a large cohort of healthy children prospectively enrolled. METHODS: Echocardiographic measurements included STE LV longitudinal and circumferential and RV longitudinal global end-systolic ε. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Echocardiograms were performed by Philips-iE33 systems (Philips, Bothell, WA) and offline measurements on Philips-Q-Lab-9. RESULTS: In all, 721 subjects (age 31 days to 17 years; 48% female) were studied. Low coefficients of determination (R2) were noted among all of the ε parameters evaluated and adjusted for age, weight, height, BSA, and HR (i.e., R2 all ≤ 0.10; range, 0.01-0.088). This hampered the possibility of performing z-scores with a sufficient reliability. Thus, we are limited to presenting data as mean values (±SD) stratified for age groups and divided by gender. LV longitudinal ε values decreased with age (P < .001), while no significant age-related variations were noted for RV longitudinal ε. A significant base-to-apex (lowest to highest) gradient in circumferential LV ε values was noted at all ages (P < .001). CONCLUSIONS: We report pediatric echocardiographic normative data for 2D-STE for the LV and RV ε by using vendor-specific software. Our results confirm previous observations, showing only little variations of strain parameters with age and gender.

Lung ultrasound reclassification of chest X-ray data after pediatric cardiac surgery.

INTRODUCTION: Lung ultrasound is gaining consensus for the diagnosis of some pulmonary conditions. Pulmonary complications are common in pediatric cardiac surgery. However, its use remains limited in this setting. Our aim was to test the feasibility of lung ultrasound following pediatric cardiac surgery and to compare lung ultrasound and chest X-ray findings, assessing whether lung ultrasound may provide additional information. METHODS: One hundred and thirty-eight lung ultrasound examinations were performed in 79 children (median age 9.3 months) at different time points after surgery. For each hemithorax, 3 areas (anterior/lateral/posterior) have been evaluated in the upper and lower halves of the chest (for a total of 6 scanning sites per side). Pleural effusion, atelectasis, and the number of B-lines were investigated. RESULTS: Lung ultrasound was feasible in all cases in at least 1 of the 3 areas. Feasibility was different for the lateral, posterior, and anterior areas (100%, 90%, and 78%, respectively). The posterior areas were more sensitive than anterior and lateral ones in the diagnosis of effusion/atelectasis. In 81 cases, lung ultrasound allowed reclassification of chest X-ray findings, including 40 new diagnoses (diagnosis of effusion/atelectasis with negative chest X-ray reports) and 41 changes in diagnosis (effusions reclassified as atelectasis/severe congestion or vice versa). Although new diagnosis of small-to-moderate effusion/atelectasis was of limited clinical value, in 29 cases the new diagnosis changed the therapeutic approach. CONCLUSION: Lung ultrasound is feasible and accurate for the diagnosis of common pulmonary conditions after pediatric cardiac surgery, allowing reclassification of chest X-ray findings in a significant number of patients.

Diagnostic accuracy and prognostic valued of plasmatic Cystatin-C in children undergoing pediatric cardiac surgery.

BACKGROUND: Diagnosis and treatment of acute kidney injury (AKI) is often delayed in children after cardiac surgery due to the lack of an early biomarker of renal damage. Our aim was to evaluate the diagnostic accuracy of plasma cystatin-C as an early biomarker of AKI and its prognostic value in pediatric cardiac surgery. METHODS: Cystatin-C and creatinine were measured pre-operatively and at 2-6-12h post-surgery. The primary outcome was: AKI (defined as an increase of ≥1.5 of plasma creatinine from baseline) and a composite marker, including major complications and/or extubation time>15days. Risk was evaluated using Cox proportional hazards regression analysis, considering some continuous predictors in the basal model (i.e., age, body surface area and Aristotle-score) to which cystatin-C peak values were added. Discrimination, calibration, and reclassification tests were also performed. RESULTS: 248 children (140 males) undergoing cardiac surgery (median age 6.5months; IQR: 1.7-40.1months; range 0-17years) have been enrolled. Post operatory Cystatin-C values were found to be an early diagnostic marker of AKI showing the best area under the ROC curve value (AUC) at 12h (0.746, CI 95% 0.674-0.818). In the multivariable analyses, peak cystatin-C values showed a significant hazard ratio (HR=2.665, CI 95% 1.750-4.059, p<0.001). Finally, post operatory cystatin-C at 12h significantly improved the AUC (p=0.017) compared to basal model, resulting a net gain in reclassification proportion (NRI=0.417, p<0.001). CONCLUSIONS: Our data show that cystatin-C should be considered an early biomarker of AKI, improving the risk prediction for complicated outcome in pediatric cardiac surgery.

Energy Drink and Alcohol mixed Energy Drink use among high school adolescents: Association with risk taking behavior, social characteristics.

PURPOSE: The aims of the study were to: a) examine the prevalence of energy drink (ED) and alcohol mixed with energy drink (AmED) consumption; b) investigate the relationships between ED and AmED with alcohol, binge drinking and drugs accounting for at risk behaviors among a representative sample of Italian adolescents. METHODS: A representative sample of 30,588 Italian high school students, aged 15-19years, was studied. Binary and multivariate logistic regression analyses were performed to determine the independent association of the potential predictors' characteristics with the ED and AmED drinking during the last year. RESULTS: Respectively 41.4% and 23.2% of respondents reported drinking EDs and AmEDs in the last year. Multivariate analysis revealed that consumption of EDs and AmEDs during the last year were significantly associated with daily smoking, binge drinking, use of cannabis and other psychotropic drugs. Among life habits and risky behaviors the following were positively associated: going out with friends for fun, participating in sports, experiencing physical fights/accidents or injury, engaging in sexual intercourse without protection and being involved in accidents while driving. CONCLUSIONS: This study demonstrates the popularity of ED and AmED consumption among the Italian school population aged 15-19years old: 4 out of 10 students consumed EDs in the last year and 2 out of 10 AmED. Multivariate analysis highlighted the association with illicit drug consumption and harming behaviors, confirming that consumption of EDs and AmEDs is a compelling issue especially during adolescence, as it can effect health as well as risk taking behaviors.

Cardiac safety of adjuvant non-pegylated liposomal doxorubicin combined with cyclophosphamide and followed by paclitaxel in older breast cancer patients.

PURPOSE: To investigate the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) combined to Cyclophosphamide (CTX) and followed by weekly Paclitaxel, in older patients (≥65 years) with diagnosis of high risk breast cancer. The main end point of this prospective study was the detection of early episodes of symptomatic congestive heart failure (CHF). METHODS: The cardiac function was evaluated by left ventricular ejection fraction (LVEF) measurements with repeated echocardiograms, performed 2 weeks before the beginning of chemotherapy and every 6 months, until 30 months after the study entry; then yearly for at least 5 years. RESULTS: Forty-seven patients were enrolled from two Italian Divisions of Medical Oncology. Final results revealed no early episodes of symptomatic CHF within the first 12 months from the enrolment. Only two cardiac events were observed: an episode of atrial flutter after the first cycle of NPL-DOX and CTX, with a quick return to normal rhythm, and a grade 3 (scored to NCI-CTCAE, version 3.0) CHF episode, 18 months later chemotherapy start. No other relevant toxicities were reported. CONCLUSIONS: This adjuvant combination including NPL-DOX in elderly patients, resulted in a low rate of cardiac toxic effects. Comparative trials should be encouraged to confirm these findings.