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Background: Cardiovascular trials have revealed the positive impact of GLP‐1 receptor agonists (GLP‐1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP‐1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP‐1 response post‐bariatric surgery on arterial stiffness and renal haemodynamic. Methods: Thirty individuals with morbid obesity and without T2D, scheduled for Roux‐en‐Y Gastric Bypass (RYGB), were included. Clinical parameters, 3‐hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP‐1 and insulin, carotid‐femoral pulse wave velocity (cf‐PWV), carotid distensibility coefficient (carotid‐DC) and renal resistive index (RRI) measurements were conducted pre‐surgery and 1‐year post‐surgery. Participants were categorized into high‐response and low‐response groups based on their post‐surgery increase in GLP‐1 (median increase of 104% and 1%, respectively, pre‐ vs. post‐surgery). Results: Post‐surgery, high‐response group demonstrated a greater reduction in cf‐PWV (p =.033) and a greater increase (p =.043) in carotid DC compared to low‐response group. These enhancements were observed independently of weight loss or blood pressure changes. High‐response group exhibited a reduction in RRI (p =.034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ‐GLP1(AUC)%, was the best predictor of percentage decrease in cf‐PWV (p =.014). Conclusions: Elevated endogenous GLP‐1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio‐renal benefits. The findings underscore the potential role of endogenous GLP‐1 in influencing vascular and renal haemodynamics independent of traditional weight loss. [ABSTRACT FROM AUTHOR]

Background: bariatric surgery stands as an effective intervention for weight loss and improved metabolic control in obesity, although over time there is a proportion of weight regain and type-2-diabetes (T2D) relapse., Aims: to explore the role of physical activity (PA) after surgery and its impact on metabolic parameters during a 5-year follow-up., Methods: 148 individuals who underwent bariatric surgery completed scheduled examinations over 5-years. Physical assessments and laboratory tests were conducted pre-surgery and annually thereafter. PA levels were evaluated using the International Physical Activity Questionnaire., Results: participants were split into the PA group, who engaged in regular physical activity, and No-PA group, who remained sedentary throughout. In T2D individuals before surgery, PA group showed significant reductions in blood pressure and a lower T2D recurrence (6.7 ​% vs 36 ​%) compared to No-PA group. In normoglycemic individuals, the PA group led to sustained BMI reduction and improved blood pressure control (p ​< ​0.001) compared to No-PA group, for the entire duration of follow-up., Conclusions: regular PA demonstrated cardio-metabolic benefits post-bariatric surgery. Integrating PA into post-bariatric care could enhance long-term outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: We declare no financial conflicts of interest. We received grants from the Italian Ministry of Health and from the European Union to conduct research projects on health promotion in the general population and high-risk groups.

The present work describes the cumulative coverage curves by country of birth, sex, age, and area of residence of the adult population residing in the province of Reggio Emilia (Emilia-Romagna Region, Northern Italy).The analyses are stratified by country of birth into HDC (Highly Developed Country), mostly Italians, and HMPC (Highly Migration Pressure Country), as a proxy of migrant status, excluding deaths. Vaccinations carried out up to September 2022 and recorded in the information system were considered, including vaccinations performed outside the province. Vaccinations done abroad are not included when the information is incomplete or the type of vaccine is different from those administered in Italy.Vaccination coverage (%) by number of doses and estimated Hazard Ratio (HR) and related 95% confidence intervals (95%CI) are calculated using Cox models, adjusted for age and stratified by sex.A lower vaccination coverage was detected, delayed by a few weeks, among HMPC, but the differences in vaccination coverage are reversed when the different age structure of the two populations is taken into account. From the estimates of the Cox models, a higher propensity to vaccinate was noted among immigrants, in particular among women (women HR: 1.65; CI95% 1.52-1.78; men HR: 1.39; CI95% 1.28-1.52). Women were vaccinated first, but, at the end of the observation period, there were no particular differences in coverage between the two sexes, either among Italians or immigrants. Focusing on the area of origin, a strong propensity for vaccination was noted, particularly among who came from North Africa. In the mountain areas of the province, a lower propensity for vaccination was observed, perhaps explained by the greater distance of the vaccination centers or by a lower acceptability of the vaccine.

Background: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping., Methods: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance., Findings: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting., Interpretation: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years., Funding: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support., Competing Interests: Declaration of interests Maria Benevolo and Paolo Giorgi Rossi as principal investigator and former PI of the NTCC2 study reports nonfinancial support from Roche Diagnostics and Hologic S. r.l., which provided part of the reagents for free or at reduced price. Moreover, Maria Benevolo, Paolo Giorgi Rossi, Simonetta Bisanzi, and Laura De Marco obtained financial and nonfinancial support from Becton & Dickinson. Maria Benevolo also reports financial and nonfinancial support from Arrow S. r.l. for works outside this project. All other authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to map and compare stakeholders' perceptions of barriers towards cervical cancer screening for vulnerable women in seven European countries., Design: In Collaborative User Boards, stakeholders were invited to participate to identify barriers towards participation in cervical cancer screening., Setting: The study is nested in the European Union-funded project CBIG-SCREEN which aims to tackle inequity in cervical cancer screening for vulnerable women (www.cbig-screen.eu). Data collection took place in Bulgaria, Denmark, Estonia, France, Italy, Portugal and Romania., Participants: Participants represented micro-level stakeholders covering representatives of users, that is, vulnerable women, meso-level stakeholders covering healthcare professionals and social workers, and macro-level stakeholders covering programme managers and decision-makers., Methods: Across the seven countries, 25 meetings in Collaborative User Boards with a duration of 2 hours took place between October 2021 and June 2022. The meetings were video recorded or audio recorded, transcribed and translated into English for a qualitative framework analysis., Results: 120 participants took part in the Collaborative User Boards. Context-specific barriers were related to different healthcare systems and characteristics of vulnerable populations. In Romania and Bulgaria, the lack of a continuous screening effort and lack of ways to identify eligible women were identified as barriers for all women rather than being specific for women in vulnerable situations. The participants in Denmark, Estonia, France, Italy and Portugal identified providers' lack of cultural and social sensitivity towards vulnerable women as barriers. In all countries, vulnerable women's fear, shame and lack of priority to preventive healthcare were identified as psychological barriers., Conclusion: The study provides an overview of stakeholders' perceived barriers towards vulnerable women's cervical cancer screening participation in seven European countries. The organisation of healthcare systems and the maturity of screening programmes differ between countries, while vulnerable women's psychological barriers had several similarities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The aim of this study was to examine main risk factors of undocumented Chinese migrants living in Italy when compared with Chinese migrants registered with National Health Service (NHS)., Methods: A cohort of 3435 Chinese first-generation immigrants living in Prato underwent blood pressure (BP) measurement and blood tests. Hypertension was diagnosed for BP ≥ 140/90 mmHg at 2 visits, and/or antihypertensive drug use; type 2 diabetes (T2DM) for fasting glucose ≥ 126 mg/dL at 2 visits, and/or use of hypoglycemic drugs; hypercholesterolemia (HC) for cholesterol ≥ 240 mg/dL and/or statins use. Subjects diagnosed with hypertension, T2DM, or HC unaware of their condition were considered newly diagnosed. Comparisons were performed using multivariable adjusted logistic regression analysis., Results: A large proportion of Chinese migrants were undocumented (1766, 51 %); newly diagnoses of risk factors were performed especially among undocumented migrants; registration with NHS was associated with higher level of awareness for hypertension and T2DM and with 6 times higher rate of treatment for T2DM. Only a small minority of subjects with high cholesterol were treated with statins., Conclusions: Undocumented immigrants had high prevalence of risk factors with lower levels of awareness than migrants registered with the NHS. Health policies targeting this hard-to-reach population needs to be improved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The aim of our study was to test the hypothesis that the community contact tracing strategy of testing contacts in households immediately instead of at the end of quarantine had an impact on the transmission of SARS-CoV-2 in schools in Reggio Emilia Province., Methods: We analysed surveillance data on notification of COVID-19 cases in schools between 1 September 2020 and 4 April 2021. We have applied a mediation analysis that allows for interaction between the intervention (before/after period) and the mediator., Results: Median tracing delay decreased from 7 to 3.1 days and the percentage of the known infection source increased from 34-54.8% (incident rate ratio-IRR 1.61 1.40-1.86). Implementation of prompt contact tracing was associated with a 10% decrease in the number of secondary cases (excess relative risk -0.1 95% CI -0.35-0.15). Knowing the source of infection of the index case led to a decrease in secondary transmission (IRR 0.75 95% CI 0.63-0.91) while the decrease in tracing delay was associated with decreased risk of secondary cases (1/IRR 0.97 95% CI 0.94-1.01 per one day of delay). The direct effect of the intervention accounted for the 29% decrease in the number of secondary cases (excess relative risk -0.29 95%-0.61 to 0.03)., Conclusions: Prompt contact testing in the community reduces the time of contact tracing and increases the ability to identify the source of infection in school outbreaks. Although there are strong reasons for thinking it is a causal link, observed differences can be also due to differences in the force of infection and to other control measures put in place., Funding: This project was carried out with the technical and financial support of the Italian Ministry of Health - CCM 2020 and Ricerca Corrente Annual Program 2023., Competing Interests: OD, EL, MC, SC, EB, DP, LB, MV, FV, PG, PP, AM, EB No competing interests declared, (© 2024, Djuric et al.)

Background: Despite being at higher risk of severe disease and pregnancy complications, evidence on susceptibility to SARS-CoV-2 infection in pregnancy is still limited. The aim of the study is to compare the likelihood of undergoing a SARS-CoV-2 test and testing positive for COVID-19 in pregnancy and puerperium with that of the general female population of reproductive age., Methods: This is a retrospective population-based cohort study including 117,606 women of reproductive age (March 2020-September 2021) with 6608 (5.6%) women having ≥ 1 pregnancy. Women were linked to the pregnancy registry to be classified as "non-pregnant", "pregnant", and "puerperium"; then, according to the national case-based integrated COVID-19 surveillance system, all women undergoing a SARS-CoV-2 test during the study period were identified. The Incidence Rate Ratio was calculated to compare the likelihood of being tested for SARS-CoV-2 in pregnant, puerperium and non-pregnant women among all women included. The likelihood of having a COVID-19 diagnosis was calculated using two comparators (not-pregnant women and the person-time before/after pregnancy) by means of Cox proportional hazards models, adjusting for age and with the cluster option to control standard error calculation in repeated pregnancies. Only first infection and swabs before the first one positive were included., Results: The probability of being tested for SARS-CoV-2 was 4.9 (95% CI: 4.8-5.1) and 3.6 times higher (95%CI: 3.4-3.9) in pregnancy (including spontaneous miscarriages) and in the puerperium, respectively. The Hazard Ratio (HR) of covid-19 diagnosis during pregnancy vs. non-pregnancy was 1.17 (95% CI 1.03-1.33) with similar results when comparing the risk during pregnancy with that of the same women outside pregnancy (puerperium excluded), with an HR of 1.13 (95% CI 0.96-1.33); the excess decreased when excluding the test performed at admission for delivery (HR 1.08 (95%CI 0.90-1.30). In the puerperium, the HR was 0.62 (95% CI 0.41-0.92) comparing women with ≥ 1childbirth with all other women and excluding the first two weeks of puerperium., Conclusions: Women during pregnancy showed a small increase in the risk of infection, compatible with a higher likelihood of being tested. A lower probability of infection during the puerperium was observed during the entire pandemic period, suggesting likely protective behaviors which were effective in reducing their probability of infection., (© 2023. BioMed Central Ltd., part of Springer Nature.)

To reflect on the present and the future of the "millennial" epidemiologists in Italy, the starting question is who are we? The online survey "I giovani ricercatori non più giovani: chi siamo? #GIOVANIDENTRO" was launched in 2022 and advertised at conferences of the Italian association of epidemiology to gather voices from all over Italy. Information on training, job position, attitudes and difficulties encountered in our profession and in scientific production activity has been collected and contextualized to answer the starting question and provide food for thought for the perspectives of our profession.

The General data protection regulation (Gdpr) of 2016, implemented since 2018, has become a crucial issue in the field of epidemiology. The Gdpr concerns the protection of personal data, which includes all information that identifies or can identify a natural person, providing information about their habits, health status, and lifestyle, and regulates their processing. Epidemiological studies rely on the use of personal data and their interconnection. The introduction of this regulation is marking an important transition for the work of epidemiologists. There is a need to understand how this can coexist with the research activities that have always been carried out in epidemiology and public health. This section aims to lay the foundations for a discussion on the topic and provide a framework for researchers and epidemiologists that answers some of the doubts that accompany daily work.

The "millennial" epidemiologists, born between the beginning of the 80s and the end of the 90s, are the generation that most of all, today, lives between the present and the future of this discipline. This issue of Recenti Progressi in Medicina aims to talk about what young (and no longer young) epidemiologists and public health researchers are dealing with and to reflect on the most relevant topics in our field, with an eye to the future. Starting from the profile of the "millennial" epidemiologists in Italy and the topics on which they work, the issue develops through three parts dealing with relevant topics for the present and the future of Public health. The first part deals with the important issue of finding a balance between the protection of personal data and the protection of health through a dialogue between researchers, jurists and citizens. The second part aims to clarify the issue of big data and its implications for producing health. The third part touches on four relevant topics for the perspectives of epidemiology through reflections and application examples of machine learning, integration between pharmacoepidemiology and environmental epidemiology, health prevention and promotion involving citizens and other stakeholders, and epidemiology of mental health. In a constantly changing world, challenges for those who work to produce health are not lacking, as is the determination to face them. With this issue, we hope to contribute to the awareness of who we are and our potential, to help millennials (but not only) find their place in epidemiology, today and tomorrow.

The objective of this study was to compare the effect of diabetes and pathologies potentially related to diabetes on the risk of infection and death from COVID-19 among people from Highly-Developed-Country (HDC), including Italians, and immigrants from the High-Migratory-Pressure-Countries (HMPC). Among the population with diabetes, whose prevalence is known to be higher among immigrants, we compared the effect of body mass index among HDC and HMPC populations. A population-based cohort study was conducted, using population registries and routinely collected surveillance data. The population was stratified into HDC and HMPC, according to the place of birth; moreover, a focus was set on the South Asiatic population. Analyses restricted to the population with type-2 diabetes were performed. We reported incidence (IRR) and mortality rate ratios (MRR) and hazard ratios (HR) with 95% confidence interval (CI) to estimate the effect of diabetes on SARS-CoV-2 infection and COVID-19 mortality. Overall, IRR of infection and MRR from COVID-19 comparing HMPC with HDC group were 0.84 (95% CI 0.82-0.87) and 0.67 (95% CI 0.46-0.99), respectively. The effect of diabetes on the risk of infection and death from COVID-19 was slightly higher in the HMPC population than in the HDC population (HRs for infection: 1.37 95% CI 1.22-1.53 vs. 1.20 95% CI 1.14-1.25; HRs for mortality: 3.96 95% CI 1.82-8.60 vs. 1.71 95% CI 1.50-1.95, respectively). No substantial difference in the strength of the association was observed between obesity or other comorbidities and SARS-CoV-2 infection. Similarly for COVID-19 mortality, HRs for obesity (HRs: 18.92 95% CI 4.48-79.87 vs. 3.91 95% CI 2.69-5.69) were larger in HMPC than in the HDC population, but differences could be due to chance. Among the population with diabetes, the HMPC group showed similar incidence (IRR: 0.99 95% CI: 0.88-1.12) and mortality (MRR: 0.89 95% CI: 0.49-1.61) to that of HDC individuals. The effect of obesity on incidence was similar in both HDC and HMPC populations (HRs: 1.73 95% CI 1.41-2.11 among HDC vs. 1.41 95% CI 0.63-3.17 among HMPC), although the estimates were very imprecise. Despite a higher prevalence of diabetes and a stronger effect of diabetes on COVID-19 mortality in HMPC than in the HDC population, our cohort did not show an overall excess risk of COVID-19 mortality in immigrants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ottone, Bartolini, Bonvicini, Giorgi Rossi and Reggio Emilia COVID-19 working group.)

Background: Parent self-efficacy (PSE), parents' confidence in their ability to successfully raise their children, has proved to be a powerful direct predictor of specific positive parenting practices. The aim of this study was to validate the Italian version of the Tool to Measure Parenting Self-Efficacy (TOPSE) using data from the questionnaires previously completed in a controlled before-after study conducted in 2015 to evaluate a newsletter programme to help improve parenting. Mothers and fathers of newborns were asked to complete the TOPSE at the child's birth (t0), at 6 months (t1) and at 12 months (t2): 265 TOPSE questionnaires were collected at t0 (43%), 158 at t1 (26%) and 188 at t2 (31%)., Methods: We measured internal reliability using Cronbach's alpha for each of the eight domains of the TOPSE. The intracluster correlation coefficient (ICC) was used to evaluate the external reliability only for parents with more than one child. Responsiveness was measured by testing the ability of the questionnaire to detect differences between groups and times that we expected to be measurable, based on consolidated findings in the literature. Mean scores of PSE improved from t0 to t2 (Hypothesis 1), PSE was lower at baseline for first-time parents than for those with multiple children (Hypothesis 2) and the improvement from t0 to t2 was stronger for first-time parents than for parents with multiple children (Hypothesis 3)., Results and Conclusion: Based on our sample of questionnaires, the Italian version of the TOPSE was reliable for almost all of the domains except for Emotion, Self-acceptance and Learning, which could be refined by re-framing or dropping one item. External reliability was moderate, bearing in mind that the questionnaire was repeated at different times over 12 months, during which parents normally change. Responsiveness was good, especially for the Emotion and Empathy domains., (© 2022 John Wiley & Sons Ltd.)

Background: The role of school contacts in the spread of the virus and the effectiveness of school closures in controlling the epidemic is still debated. We aimed to quantify the risk of transmission of SARS-CoV-2 in the school setting by type of school, characteristics of the index case and calendar period in the Province of Reggio Emilia (RE), Italy. The secondary aim was to estimate the speed of implementation of contact tracing., Methods: A population-based analysis of surveillance data on all COVID-19 cases occurring in RE, Italy, from 1 September 2020, to 4 April 2021, for which a school contact and/or exposure was suspected. An indicator of the delay in contact tracing was calculated as the time elapsed since the index case was determined to be positive and the date on which the swab test for classmates was scheduled (or most were scheduled)., Results: Overall, 30,184 and 13,608 contacts among classmates and teachers/staff, respectively, were identified and were recommended for testing, and 43,214 (98.7%) underwent the test. Secondary transmission occurred in about 40% of the investigated classes, and the overall secondary case attack rate was 4%. This rate was slightly higher when the index case was a teacher but with almost no differences by type of school, and was stable during the study period. Speed of implementation of contact tracing increased during the study period, with the time from index case identification to testing of contacts being reduced from seven to three days. The ability to identify the possible source of infection in the index case also increased., Conclusions: Despite the spread of the Alpha variant during the study period in RE, the secondary case attack rate remained stable from school reopening in September 2020 until the beginning of April 2021., Competing Interests: The authors have declared that no competing interests exist.

As the primary screening test, E6/E7 mRNA has shown similar sensitivity for CIN3+ and lower positivity rate than the HPV DNA test. Nevertheless, the overall mRNA positivity is too high for immediate colposcopy, making a triage test necessary. The aim was to estimate the mRNA performance as a primary test with different triage strategies. All HPV DNA-positives were tested for mRNA, cytology and p16/ki67. A sample of HPV DNA-negatives was also tested for mRNA to estimate test specificity. We included all CIN3+ histologically diagnosed within 24 months since recruitment. Of the 41 127 participants, 7.7% were HPV DNA-positive, of which 66.4% were mRNA-positive. Among the HPV DNA-negatives, 10/1108 (0.9%) were mRNA-positive. Overall, 97 CIN3+ were found. If mRNA was used as the primary test, it would miss about 3% of all CIN3+ with a 22% reduction of positivity compared with HPV DNA. The weighted specificity estimate for

Childhood obesity is a high prevalence condition that causes a high burden of disease in adulthood. Mobile phone app are increasingly used to prevent it. We summarized the evidence on the effectiveness of mobile apps for devices used by parents to prevent and treat childhood and adolescent obesity. An update of a systematic review of the literature (De Lepeleere et al., 2017) was carried out. PubMed, Embase, Cochrane, CINAHL, PsycINFO, Scopus, and ERIC were searched up to 2020. The included studies should target children 1-18 years, compare an app aimed at preventing or treating overweight and obesity, as stand-alone intervention or as part of a complex program, installed on parents' mobile devices, to no intervention or an intervention without the app. Outcomes related to weight status, diet, and physical activity (PA) behaviors were considered. Nineteen studies (14 RCTs and 5 non-randomized trials) were included. The app was mainly used to record food consumption and PA, to set goals, to view progress, and send health promotion messages. One study reported a significant decrease and one a suggestive decrease in anthropometric measures in obese and overweight children, while other studies observed no effect. One study reported a significant increase in PA. Six interventions proved to be effective in changing dietary behaviors. Interventions targeting overweight and/or obese children had the most positive results. All studies reported high acceptability and feasibility of interventions. The differences between interventions and the small sample size of the studies did not allow this review to reach conclusion on effectiveness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Context: There is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role., Objective: The aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response., Design and Methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response., Results: Sixteen miRNAs were upregulated and 2 were downregulated at t+3 months. MiR-199a-5p ( p = 0.020), miR-335-5p ( p = 0.001), and miR-494-3p ( p = 0.026) were confirmed to be upregulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters., Conclusions: MiR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months of GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Catellani, Ravegnini, Sartori, Righi, Lazzeroni, Bonvicini, Poluzzi, Cirillo, Predieri, Iughetti, Giorgi Rossi, Angelini and Street.)

Background/aim: The relationship between air pollution and respiratory morbidity has been widely addressed in urban and metropolitan areas but little is known about the effects in non-urban settings. Our aim was to assess the short-term effects of PM10 and PM2.5 on respiratory admissions in the whole country of Italy during 2006-2015., Methods: We estimated daily PM concentrations at the municipality level using satellite data and spatiotemporal predictors. We collected daily counts of respiratory hospital admissions for each Italian municipality. We considered five different outcomes: all respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), lower and upper respiratory tract infections (LRTI and URTI). Meta-analysis of province-specific estimates obtained by time-series models, adjusting for temperature, humidity and other confounders, was applied to extrapolate national estimates for each outcome. At last, we tested for effect modification by sex, age, period, and urbanization score. Analyses for PM 2.5 were restricted to 2013-2015 cause the goodness of fit of exposure estimation., Results: A total of 4,154,887 respiratory admission were registered during 2006-2015, of which 29% for LRTI, 12% for COPD, 6% for URTI, and 3% for asthma. Daily mean PM 10 and PM 2.5 concentrations over the study period were 23.3 and 17 μg/m 3 , respectively. For each 10 μg/m 3 increases in PM 10 and PM 2.5 at lag 0-5 days, we found excess risks of total respiratory diseases equal to 1.20% (95% confidence intervals, 0.92, 1.49) and 1.22% (0.76, 1.68), respectively. The effects for the specific diseases were similar, with the strongest ones for asthma and COPD. Higher effects were found in the elderly and in less urbanized areas., Conclusions: Short-term exposure to PM is harmful for the respiratory system throughout an entire country, especially in elderly patients. Strong effects can be found also in less urbanized areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Presenting an approach to synthesize quantitative and qualitative information from systematic reviews of multiple health interventions., Methods: Within the context of an EUnetHTA multi-health technology assessment of twenty-three surgical techniques, we developed synthetic single tables, using color gradients and abbreviations, with information on which technologies had been compared, estimates of the size of differences for available comparisons, their clinical relevance, and certainty of the related evidence., Results: The proposed methodology provided, through a single depiction, information normally included in multiple figures/tables such as network plots, league tables, and summary of findings tables., Conclusion: Transferring information on benefits, risks, and certainty of the available evidence on health interventions may be challenging, especially when assessing multiple treatments: more pieces of information need to be integrated in order to show an overall picture for each of the chosen outcomes, and usual reporting tools may be targeted to researchers more than to different kinds of decision makers. While more in-depth layers of information can always be added to satisfy needs of different audiences, the proposed tools could favor a quick interpretation of articulated scientific data by both decision makers and researchers.

This systematic review with meta-analysis aimed to assess the effect of diffuse liver diseases (DLD) on the risk of synchronous (S-) or metachronous (M-) liver metastases (LMs) in patients with solid neoplasms. Relevant databases were searched for systematic reviews and cross-sectional or cohort studies published since 1990 comparing the risk of LMs in patients with and without DLD (steatosis, viral hepatitis, cirrhosis, fibrosis) in non-liver solid cancer patients. Outcomes were prevalence of S-LMs, cumulative risk of M-LMs and LM-free survival. Risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale. We report the pooled relative risks (RR) for S-LMs and hazard ratios (HR) for M-LMs. Subgroup analyses included DLD, primary site and continent. Nineteen studies were included ( n = 37,591 patients), the majority on colorectal cancer. ROB appraisal results were mixed. Patients with DLD had a lower risk of S-LMs (RR 0.50, 95% CI 0.34-0.76), with a higher effect for cirrhosis and a slightly higher risk of M-LMs (HR 1.11 95% CI, 1.03-1.19), despite a lower risk of M-LMs in patients with vs without viral hepatitis (HR 0.57, 95% CI 0.40-0.82). There may have been a publication bias in favor of studies reporting a lower risk for patients with DLD. DLD are protective against S-LMs and slightly protective against M-LMs for viral hepatitis only.

Background: The study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis., Methods: Women aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided., Results: 40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both)., Conclusions: p16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anticipatory guidance for parents is commonly used to improve parenting skills. The objective of this pre/post-intervention controlled study was to evaluate the effectiveness of a periodic newsletter with advice on childcare and development in improving parenting self-efficacy., Methods: This was a non-randomized pre/post-intervention controlled study. All the parents of children born between September 2014 and December 2015 resident in the S. Ilario d'Enza municipality (Italy) received eight Baby Newsletters. Parents resident in other municipalities of the same Health District were the control. Parents with linguistic barriers or with preterm or hospitalized children were excluded. Improvement in parenting self-efficacy was measured through the TOPSE (Tool to Measure Parenting Self-Efficacy) questionnaire during the first week (t0) after delivery and at 5 (t1) and 12 months (t2) of life at two vaccination appointments. A score ranging from 0 to 60 was computed for each of the eight domains investigated by the TOPSE. Variations of each TOPSE score between delivery and 12 months in the two groups were compared, adjusting for parity, education, age of parents, and child's sex, and stratifying by parity and education., Results /findings: One hundred thirty-six families accepted to participate in the study. Scores at 12 months were higher than 1 week after delivery in both groups for all TOPSE domains. The improvement was slightly stronger in the Newsletter group for almost all the skills except learning and knowledge [difference in the mean of variation: -0.48 (95% CI: - 3.17; 2.21)]; the difference was significant only for play and enjoyment [2.18 (95% CI: 0.12; 4.25)]. The increase in scores in almost all domains was more pronounced for parents with high education level at first child., Conclusions: The intervention was effective in improving parents' ability to play. However, it risks worsening existing differences between parents with high and with low education levels., Trial Registration: Clinical trial registration: NCT03268408 .

Objectives: to explain differences in effectiveness of paediatrician-led motivational interviewing (MI) in decreasing body mass index (BMI) between children of mothers with low or high education level., Design: secondary analysis of a randomised control trial., Setting and Participants: individually randomized controlled trial previously conducted from 2011 to 2013 in the province of Reggio Emilia (Emilia-Romagna Region, Northern Italy). Eligible participants included in the trial were 372 (187 in the MI group and 185 in the control group) overweight children (BMI percentile >= 85th and < 95th) aged between 4 and 7 years, residing in the province of Reggio Emilia and under the care of paediatrician for >= 12 months. The intervention included 5 MI sessions based on the transtheoretical model of addiction and behavioural change delivered at 1, 4, 7, and 12 months after the baseline visit, when families had to define specific goals in changing physical activity (PA) and diet behaviours., Main Outcome Measures: primary: BMI score variation (ΔBMI) from baseline to 12 months; secondary: percentage of changes in parent-reported PA and dietary behaviours., Results: a significant effect of MI on ΔBMI in children whose mothers had high education level (ΔBMI = -0.62; 95%CI -0.92;-0.32) were observed. Children of women with high education level in MI group had more improvements in set unstructured PA, decreasing screen time and sweet snacks consumption, while children with less educated mothers had improvements in consuming more vegetable soup and less desserts, sweet snacks, and sugary beverages. Highly educated mothers chose for their children to drink fewer sugary beverages and to increase PA. Less educated mothers most frequently chose as goals having breakfast, eating more fruit and vegetables, eating fewer snacks, and having less screen time. Overall achievement was similar in the two strata for diet goals, but higher for PA goals in the high education level stratum., Conclusions: MI intervention was not effective in reducing BMI in children of mothers with low education level. This does appear to be weakly or not associated with goal choices and achievement within MI, it is rather an effect of unmeasured behaviours which possibly mediate association between MI and BMI reduction.

Background/aim: The aim of the present study was to assess the association between PM 2.5 , its sources, and preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) in a large open residential cohort (Supersito Project in the Emilia-Romagna Region - Northern Italy)., Methods: We collected 2012-2014 pregnancy and childbirth data from Birth Assistance Certificates and selected the pregnancies of interest. PTBs (gestational age < 37 weeks), LBW (weight < 2500 g), and SGA (newborns weighing ≤ 10th age and pregnancy week-specific percentile) were considered. Three-year measurements of daily concentrations and constituents of PM 2.5 were available at four sites and were analyzed through a source apportionment approach identifying 6 sources (traffic, biomass burning, oil combustion, anthropogenic mix, and two secondary factors). Exposure to PM 2.5 and sources was calculated at address level. Using logistic regression models, associations between exposure and outcomes were derived, applying single-pollutant and two-pollutant models, to verify the independent effect of each source., Results: The study included 23,708 neonates born to 23,415 women, among whom 1,311 PTB, 424 LBW, and 1,354 SGA occurred. PTB was the only outcome associated with PM 2.5 mass (OR 1.03, 95% CI 1.002-1.058 per 1 μg/m 3 ). Traffic, oil combustion and secondary sulfates and organics showed independent effects on PTB. Exposure to secondary nitrates was associated with a lower risk of PTB. There was no association between LBW or SGA and source-specific PM 2.5 components or the residual PM 2.5 related to all other sources., Conclusion: This study found an association between PTB and PM 2.5 . Traffic, secondary sulfates, and organic and oil combustion were the sources with most consistent association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Childhood obesity prevention is a public health priority in industrialized countries. The Reggio Emilia Local Health Authority has implemented a program involving primary and secondary prevention as well as the care of obese children. There are many health-promoting mobile apps, but few are targeted to children and very few are sponsored by public health agencies., Objective: The goal of the research was to describe the process and tools adopted to cocreate a mobile app sponsored by the Reggio Emilia Local Health Authority to be installed in parents' phones aimed at promoting child health and preventing obesity., Methods: After stakeholder mapping, a consulting committee including relevant actors, stakeholders, and users was formed. Key persons for childhood obesity prevention were interviewed, focus groups with parents and pediatricians were conducted, and community reporting storytelling was collected. The results of these activities were presented to the consulting committee in order to define the functionalities and contents of the mobile app., Results: Three key trends emerged from community reporting: being active, playing, and being outdoors; time for oneself, family, and friends; and the pressures of life and work and not having time to be active and socialize. In focus groups, interviews, and labs, mothers showed a positive attitude toward using an app to manage their children's weight, while pediatricians expressed concerns that the app could increase their workload. When these findings were explored by the consulting committee, four key themes were extracted: strong relationships with peers, family members, and the community; access to safe outdoor spaces; children's need for age-appropriate independence; and professional support should be nonjudgmental and stigma-free. It should be a dialogue that promotes family autonomy. The app functions related to these needs include the following: (1) newsletter with anticipatory guidance, recipes, and vaccination and well-child visit reminders; (2) regional map indicating where physical activity can be done; (3) information on how to manage emergencies (eg, falls, burns, fever); (4) module for reinforcing the counseling intervention conducted by pediatricians for overweight children; and (5) a function to build a balanced daily diet., Conclusions: The pilot study we conducted showed that cocreation in health promotion is feasible, with the consulting committee being the key co-governance and cocreation tool. The involvement of stakeholders in this committee made it possible to expand the number of persons and institutions actively contributing to the project., (©Paolo Giorgi Rossi, Francesca Ferrari, Sergio Amarri, Andrea Bassi, Laura Bonvicini, Luca Dall'Aglio, Claudia Della Giustina, Alessandra Fabbri, Anna Maria Ferrari, Elena Ferrari, Marta Fontana, Marco Foracchia, Teresa Gallelli, Giulia Ganugi, Barbara Ilari, Sara Lo Scocco, Gianluca Maestri, Veronica Moretti, Costantino Panza, Mirco Pinotti, Riccardo Prandini, Simone Storani, Maria Elisabeth Street, Marco Tamelli, Hayley Trowbridge, Francesco Venturelli, Alessandro Volta, Anna Maria Davoli, Childhood Obesity Prevention Working Group. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 08.06.2020.)

Background: Anticoagulant concentration in plasma units is extremely variable. Understanding the underlying causes of this variability could help personalise plasmapheresis procedures in order to optimise the risk-benefit ratio. We studied the association between anticoagulant solution A (usually ACD-A, Citrate Dextrose Solution A) volume in plasma units and donor characteristics to build a model to determine the needed weight of the final plasma unit to have an 80% probability of reaching 600 mL net plasma., Materials and Methods: We experimentally measured ACD-A in 296 plasma units from an Italian blood donor centre, where machines are set for the collection of 700 g of plasma. Next, we built a statistical model to predict how the final volume of the unit should be set to obtain 50%, 80% or 90% probability of having at least 600 mL net plasma., Results: ACD-A volume was associated with haemoglobin, total proteins and triglycerides. Donors with low haemoglobin reach an 80% probability of at least 600 mL net plasma with units of approximately 690 g, while 720 g are needed for donors with high haemoglobin levels. For total proteins and triglycerides, plasma units may vary within a range of ±20 g., Discussion: Our model, based on easily measurable individual characteristics, makes it possible to customise plasmapheresis procedures by determining the blood volume to be processed for each donor. Tailored plasma donations might result in both a reduction in adverse events and an increase in the quality of collected plasma.

Childhood obesity is a major public health problem in industrialized countries. The aim of this study was to estimate the risk of obesity at age 5 based on BMI categories at age 3 and changes in BMI z-score from birth to 3 years of age. In this population-based study BMI data of 5173 children were collected at ages 3 and 5 and were linked to information relative to birth weight. The prevalence of obesity at age 5 was 3.8%. The risk of obesity for children born large for gestational age was 6.5%, while it was 18.6% for children overweight at age 3 and 62% for children who were obese at 3. An increase in BMI z-score from birth to 3 years increases the risk of obesity at age 5 (OR for increase of one standard deviation 2.8%; 95% CI: 2.46-3.20), but adjusting for BMI z-score at age 3, the effect of trajectory disappears (OR 1.08 95% CI: 0.9-1.29). In other words, if one targeted early preventive interventions to 3-year-olds affected by overweight/obesity (only 9.8% of the study cohort), one could possibly address 71% of children potentially affected by obesity at age 5., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Childhood obesity has a strong social gradient. This scoping review aims to synthesize the evidence on the impact on inequalities of non-targeted interventions to reduce the prevalence of childhood and adolescent obesity in high-income countries. We updated a review by Hillier-Brown, searching up to 31 December 2017 on MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO, with no limitations on study design. Fifty-eight studies describing 51 interventions were included: 31 randomized clinical trials and 27 non-randomized trials, with sample sizes from 67 to 2,700,880 subjects. The majority were implemented in the school setting at a community level; the others were in health services or general population setting and targeting individuals or the system. Twenty-nine interventions proved to be effective overall; seven others had an effect only in a subgroup, while 15 proved not to be effective. All types of included interventions can increase inequalities. Moreover, some interventions had opposite effects based on the socioeconomic characteristics. Any kind of intervention can reduce equity. Consequences are difficult to predict based on intervention construct. Complex interventions acting on multiple targets, settings, and risk factors are more effective and have a lower risk of increasing inequalities., (© 2019 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: Describing and monitoring socioeconomic inequalities in health are the prerequisite for planning equity policies. In Italy, some cities have integrated personal information from the municipal registries with Census data and with data from healthcare information systems to set up Longitudinal Metropolitan Studies (LMS). Under the coordination of the Italian National Institute for Health, Migration, and Poverty (NIHMP), six cities in the LMS network have contributed to the present monograph: Turin, Venice, Reggio Emilia, Modena, Bologna, and Rome. MORTALITY RESULTS. Significant socioeconomic differences by level of education were seen in all the participating centres. People who live alone or in single-parent households are more likely to die, as are those living in a substandard dwelling. Immigrants resident in the six cities included in the study showed lower all-cause mortality than Italians (males: MRR 0.83; 95%CI 0.78-0.90 - females: MRR 0.70; 95%CI 0.64-0.77). Sub-Saharan Africans experienced a significant higher mortality than Italians (males: MRR 1.33; 95%CI 1.12-1.59 - females: MMR 1.69; 95%CI 1.31-2.17). Immigrants had a neonatal and post-neonatal mortality risk about 1.5 times higher than Italians (neonatal: OR 1.71; 95%CI 1.22-2.39 - post-neonatal: OR 1.63; 95%CI 1.03-2.57). A difference between Italians and immigrants was also observed for mortality in children aged 1-4 years, though less marked (OR 1.24; 95%CI 0.73-2.11). Excesses concerned particularly immigrants from North Africa and from sub-Saharan Africa as well as those residing in Italy for >5 years. HOSPITALISATION RESULTS. Hospitalisation rates are lower for immigrants than for Italians, except when due to infectious diseases, blood disorders, and, among women, for reasons linked to pregnancy and childbirth. Avoidable hospitalisation rates of adults from low migratory pressure Countries are lower than or equal to those of Italians. On the contrary, adults from low migratory pressure Countries show higher avoidable hospitalisation rates compared to Italians in every cohort, with the exception of Rome (RR 0.81; 95%CI 0.78-0.85), with RR ranging from 1.08 (95%CI 0.96-1.22) in Venice to 1.64 (95%CI 1.47-1.83) in Modena., Conclusions: Maternal and child health is the most critical area of health for immigrant population. Considering the importance that the issue of health equity has taken on in the political agenda, the data presented in this volume are a great asset, particularly in light of the long recession and the social crisis that have impacted the Country.

Background: To date, the quantification of the anticoagulant (ACD-A) in plasma units has been based on theoretical calculations. An accurate quantification could help minimize the risks associated with plasmapheresis, given that the total ACD-A used during the procedure is distributed between the donor and the plasma unit. Our aim was to experimentally quantify the volume of ACD-A in units collected by plasmapheresis., Study Design and Methods: We used proton nuclear magnetic resonance spectroscopy to measure the ACD-A volume in 295 plasma units collected by the Azienda USL-IRCCS of Reggio Emilia, Italy. We analyzed the determinants of the differences between estimated and measured ACD-A through multivariate regression models., Results: The experimentally measured ACD-A in plasma units was variable, with 45% of the samples showing a discrepancy of more than 15 mL compared to the manufacturer's estimate. ACD-A was underestimated for higher density of the units (p < 0.0005); a weak association was also observed with triglycerides (underestimated for higher levels, p = 0.015) and sex (overestimated in females, p = 0.008), but our model explained only 35% of the individual variability., Conclusion: The manufacturer's algorithms do not accurately estimate the ACD-A in units collected by plasmapheresis. Donor-related characteristics may affect ACD-A distribution between donor and plasma unit, thereby explaining the discrepancies between estimate and measurement. Errors in the estimate of the ACD-A actually received by donors could hamper studies on dose-response relationship between anticoagulant and adverse reactions. Our work should stimulate research on tailored procedures aimed at minimizing the anticoagulant received by donors and increasing plasmapheresis safety., (© 2019 AABB.)