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Background: The COVID-19 pandemic has likely affected the most vulnerable groups of patients and those requiring time-critical access to healthcare services, such as patients with cancer. The aim of this study was to use time trend data to assess the impact of COVID-19 on timely diagnosis and treatment of head and neck cancer (HNC) in the Italian Piedmont region., Methods: This study was based on two different data sources. First, regional hospital discharge register data were used to identify incident HNC in patients ≥18 years old during the period from January 1, 2015, to December 31, 2020. Interrupted time-series analysis was used to model the long-time trends in monthly incident HNC before COVID-19 while accounting for holiday-related seasonal fluctuations in the HNC admissions. Second, in a population of incident HNC patients eligible for recruitment in an ongoing clinical cohort study (HEADSpAcE) that started before the COVID-19 pandemic, we compared the distribution of early-stage and late-stage diagnoses between the pre-COVID-19 and the COVID-19 period., Results: There were 4,811 incident HNC admissions in the 5-year period before the COVID-19 outbreak and 832 admissions in 2020, of which 689 occurred after the COVID-19 outbreak in Italy. An initial reduction of 28% in admissions during the first wave of the COVID-19 pandemic (RR 0.72, 95% CI 0.62-0.84) was largely addressed by the end of 2020 (RR 0.96, 95% CI 0.89-1.03) when considering the whole population, although there were some heterogeneities. The gap between observed and expected admissions was particularly evident and had not completely recovered by the end of the year in older (≥75 years) patients (RR: 0.88, 0.76-1.01), patients with a Romano-Charlson comorbidity index below 2 (RR 0.91, 95% CI: 0.84-1.00), and primary surgically treated patients (RR 0.88, 95% CI 0.80-0.97). In the subgroup of patients eligible for the ongoing active recruitment, we observed no evidence of a shift toward a more advanced stage at diagnosis in the periods following the first pandemic wave., Conclusions: The COVID-19 pandemic has affected differentially the management of certain groups of incident HNC patients, with more pronounced impact on older patients, those treated primarily surgically, and those with less comorbidities. The missed and delayed diagnoses may translate into worser oncological outcomes in these patients., 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 Popovic, Fiano, Moirano, Chiusa, Conway, Garzino Demo, Gilardetti, Iorio, Moccia, Ostellino, Pecorari, Ramieri, Ricardi, Riva, Virani and Richiardi.)

Background: Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight., Methods: DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7-17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva., Results: None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10 th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR)., Conclusion: Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

Objectives: to estimate the population prevalence of COVID-19-like symptoms in children and adults during the first SARS-CoV-2 epidemic wave hitting Italy in the spring 2020; to assess their geographical correlation with the cumulative number of COVID-19 cases by province; to analyse their clustering within families; to estimate their sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2., Design: cross-sectional study nested within a birth cohort., Setting and Participants: mothers participating in an Italian birth cohort (NINFEA) were invited to complete an online questionnaire on COVID-19-like symptoms in their household., Main Outcome Measures: population prevalence of COVID-19-like symptoms in children and adults, geographical correlation of COVID-19-like symptoms with the cumulative number of COVID-19 cases by province, clustering of COVID-19-like symptoms within families, and sensitivity, PPV and NPV of COVID-19-like symptoms for COVID-19 diagnosis in individuals tested for SARS-CoV-2., Results: information was collected on 3,184 households, 6,133 adults, and 5,751 children. In the period March-April 2020, 55.4% of the NINFEA families had at least one member with at least one COVID-19-like symptom. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing difficulties in adults (Spearman's rho >=0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio (PR) of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5°C; PR 4.54; 95%CI 2.20-9.40) and anosmia/dysgeusia in children. Among adults with COVID-19 diagnosis, fatigue, muscle pain, and fever had a sensitivity >=70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing difficulties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%., Conclusions: the geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of confirmed COVID-19 cases could help identify the intra-familial spread of the virus and its further propagation in the community. Low-grade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection.

Background: health literacy may contribute to the strategies to control the Coronavirus disease 2019 (COVID-19), as individuals need to acquire promptly new health information, understand the reasons behind recommendations, and adapt their behaviour accordingly., Objectives: to investigate sociodemographic and disease-related factors that can influence self-perceived knowledge (poor/medium vs high) about COVID-19 in women of the Italian NINFEA birth cohort., Design: cross-sectional study., Setting and Participants: a web-based anonymous survey on COVID-19 was sent in April 2020 to women participating in the NINFEA cohort. A total of 3,129 women were included in the study., Main Outcome Measures: using multiple weighted logistic regression models, self-perceived knowledge level was analysed in relation with the following variables: age, education level, family size, cumulative incidence of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) cases until 7 April 2020 by province, presence of COVID-19-like symptoms, SARS-CoV-2 testing, and COVID-19 diagnosis., Results: the prevalence of self-perceived poor/medium knowledge was 57%. In multivariable logistic regression analyses, the odds ratio (OR) of self-perceived poor/medium COVID-19 knowledge level was increased for low/medium compared with high education level (OR 1.57; 95%CI 1.34-1.84), and decreased for SARS-CoV-2 testing (OR 0.25; 95%CI 0.16-0.39) and COVID-19 diagnosis (OR 0.20; 95%CI 0.07-0.60). There was no evidence of association between the other analysed variables and self-perceived knowledge level., Conclusions: the findings of this study suggest that low educational level is a determinant of low self-perceived knowledge on COVID-19 in middle-aged women.

Background: socioeconomic inequalities in reproductive outcomes have been consistently reported in several countries. In a European collaborative study conducted in 2012 whose aim was to investigate the association between socioeconomic position (SEP), measured through maternal education, and preterm delivery inconsistent results were found for the NINFEA birth cohort. However, NINFEA contributed to that study with the first 2,500 pregnancies only, and estimates were not adjusted for any potential confounders assuming that SEP is a distal exposure, that could not be affected by other preterm risk factors., Objectives: to investigate the relationship between SEP and the reproductive outcomes using the entire NINFEA cohort and compare the results with the population-based Piedmont Birth Registry (PBR), accounting for potential baseline collider bias both in the cohort and in the registry., Design: observational study., Setting and Particpants: 5,323 NINFEA singletons, whose mothers registered into the study before the 36th week of gestation, were analysed. Analyses on maternal education were replicated in the 2011 PBR of 35,318 singletons live births. Factors affecting the likelihood of being a member of the NINFEA study or becoming pregnant in the general population were treated as potential confounders to adjust for baseline collider bias., Main Outcome Measures: the association of maternal education and a recently developed household income indicator with both preterm delivery (<37th weeks of gestation) and low birth weight (<2,500 gr) were analysed., Results: in the NINFEA cohort, low SEP was positively associated with both preterm delivery and low birth weight, with slightly stronger associations for household income, especially on low birth weight. Results were consistent with those obtained in the PBR data, where an inverse relationship between maternal education and the two reproductive outcomes was found. In both populations, there was confounding due to maternal age and parity, showing that independently of the nature of the source population, baseline factors that affect the probability of being a member of such source population have to be accounted for to allow causal inference., Conclusions: low SEP is associated with adverse reproductive outcomes in a contemporary Italian population.

Background: Wheezing and infections are common during infancy, and the role of early-life exposures in their development is still under investigation. We examined associations between maternal mental health in pregnancy and after delivery and subsequent offspring wheezing and infections., Methods: We studied 2314 mother-child pairs recruited in the Piccolipiù birth cohort (Italy) from 2011 to 2015. Maternal mental health was assessed in pregnancy and 12 months after delivery via the General Health Questionnaire-12 (GHQ-12). GHQ-12 Likert scores were collapsed into low (below the upper tercile) and high (above). Risk ratios (RR) and 95% confidence intervals (CI) between each combination of scores-during pregnancy and 1 year after delivery-and outcomes were computed by log-binomial regression models., Results: High scores both in pregnancy and after delivery, compared with low scores in both periods, were associated with wheezing (RR: 1.35; 95% CI: 1.08, 1.69), recurrent (≥2 episodes) wheezing (1.35; 0.99, 1.83), any and recurrent (≥4 episodes) upper respiratory infections (1.20; 1.04, 1.41, and 1.45; 1.07, 1.97, respectively), lower respiratory infections (1.31; 1.08, 1.61), and diarrhea (1.49; 1.23, 1.80). High scores either during pregnancy or 1 year after delivery only were less consistently associated with outcomes., Conclusions: Maternal mental health problems extending from pregnancy to the first year after delivery are associated with development of both wheezing and infections. As wheezing is mostly triggered by infections, increased infection susceptibility could represent a possible common biologic mechanism. This study confirms the importance of early-life exposures on childhood health., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Epigenetics may play a role in wheezing and asthma development. We aimed to examine infant saliva DNA methylation in association with early childhood wheezing., Methods: A case-control study was nested within the NINFEA birth cohort with 68 cases matched to 68 controls by sex, age (between 6 and 18 months, median: 10.3 months) and season at saliva sampling. Using a bumphunting region-based approach, we examined associations between saliva methylome measured using Illumina Infinium HumanMethylation450k array and wheezing between 6 and 18 months of age. We tested our main findings in independent publicly available data sets of childhood respiratory allergy and atopic asthma, with DNA methylation measured in different tissues and at different ages., Results: We identified one wheezing-associated differentially methylated region (DMR) spanning ten sequential CpG sites in the promoter-regulatory region of PM20D1 gene (family-wise error rate < 0.05). The observed associations were enhanced in children born to atopic mothers. In the publicly available data sets, hypermethylation in the same region of PM20D1 was consistently found at different ages and in all analysed tissues (cord blood, blood, saliva and nasal epithelia) of children with respiratory allergy/atopic asthma compared with controls., Conclusion: This study suggests that PM20D1 hypermethylation is associated with early childhood wheezing. Directionally consistent epigenetic alteration observed in cord blood and other tissues at older ages in children with respiratory allergy and atopic asthma provides suggestive evidence that a long-term epigenetic modification, likely operating from birth, may be involved in childhood atopic phenotypes., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

A study was performed to assess the prevalence of specific antibodies to human T cell lymphotropic retrovirus (HTLV-III) in patients with lymphadenopathy syndrome, patients with the acquired immune deficiency syndrome (AIDS), and those at risk of AIDS. Serum samples were obtained from these groups and from healthy controls in selected cities in Italy, and antibodies to HTLV-III were measured by immunofluorescence assay and, in a few patients, by Western blotting. In addition, IgM antibody values were measured in 82 of those positive for HTLV-III. Altogether, 235 out of 320 patients with lymphadenopathy syndrome had antibodies to HTLV-III, the proportions being highest in haemophiliacs, homosexuals, and drug addicts from Rome; 11 out of 12 patients with AIDS had antibodies; 78 out of 439 subjects at risk for AIDS had antibodies; and six out of 30 patients with lymphadenopathy syndrome and positive for HTLV-III antibodies and nine of 52 patients at risk of AIDS had a detectable titre of IgM. HTLV-III is widespread in groups at risk of AIDS in Italy, and antibodies to HTLV-III are highly prevalent in patients with lymphadenopathy syndrome. A higher proportion of drug abusers were positive for antibodies than in previous studies. HTLV-III "infection" would appear to be spread mainly in compromised hosts, as none of the controls were positive for antibodies.