Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study.

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.

What are the barriers towards cervical cancer screening for vulnerable women? A qualitative comparative analysis of stakeholder perspectives in seven European countries.

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.

Cardiovascular risk and access to primary care: Comparisons among Chinese documented and undocumented immigrants.

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.

Effect of an enhanced public health contact tracing intervention on the secondary transmission of SARS-CoV-2 in educational settings: The four-way decomposition analysis.

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.

COVID-19 incidence in women of reproductive age: a population-based study in Reggio Emilia, northern Italy.

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.

[Young researchers no more young: who are we?] / I giovani ricercatori non più giovani: chi siamo?

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.

[Millennials looking for their place in epidemiology.] / I millennials alla ricerca del proprio posto nell'epidemiologia.

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.

[Protect your data and protect yourself: balancing privacy and health protection in Public health.] / Proteggi i tuoi dati e proteggi te stesso: alla ricerca dell'equilibrio tra tutela della privacy e tutela della salute in Sanità pubblica.

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 effect of diabetes on COVID-19 incidence and mortality: Differences between highly-developed-country and high-migratory-pressure-country populations.

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.

Validation of the Italian version of the Tool to Measure Parenting Self-Efficacy questionnaire using data from an intervention study.

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.

Surveillance, contact tracing and characteristics of SARS-CoV-2 transmission in educational settings in Northern Italy, September 2020 to April 2021.

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.

Effectiveness of mobile health interventions targeting parents to prevent and treat childhood Obesity: Systematic review.

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.

Specific miRNAs Change After 3 Months of GH treatment and Contribute to Explain the Growth Response After 12 Months.

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.

Performance of HPV E6/E7 mRNA assay as primary screening test: Results from the NTCC2 trial.

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

Synthesizing quantitative and qualitative information on multiple comparisons of health interventions to facilitate knowledge transfer: an example from an EUnetHTA multi-HTA.

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.

A nationwide study of air pollution from particulate matter and daily hospitalizations for respiratory diseases in Italy.

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 PM2.5 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 PM10 and PM2.5 concentrations over the study period were 23.3 and 17 µg/m3, respectively. For each 10 µg/m3 increases in PM10 and PM2.5 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.

The Effect of Diffuse Liver Diseases on the Occurrence of Liver Metastases in Cancer Patients: A Systematic Review and Meta-Analysis.

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.

p16/ki67 and E6/E7 mRNA Accuracy and Prognostic Value in Triaging HPV DNA-Positive Women.

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.

Evaluation of an intervention aimed at supporting new parents: the Baby Newsletter project.

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 .

Source-related components of fine particulate matter and risk of adverse birth outcomes in Northern Italy.

BACKGROUND/AIM: The aim of the present study was to assess the association between PM2.5, 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 PM2.5 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 PM2.5 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 PM2.5 mass (OR 1.03, 95% CI 1.002-1.058 per 1 µg/m3). 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 PM2.5 components or the residual PM2.5 related to all other sources. CONCLUSION: This study found an association between PTB and PM2.5. Traffic, secondary sulfates, and organic and oil combustion were the sources with most consistent association.