The use of prolonged-release melatonin in circadian medicine: a systematic review.

INTRODUCTION: Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is designed to mimic the natural physiological pattern of melatonin release. In circadian medicine, PRM can be used to treat sleep and circadian rhythm disorders, as well as numerous organic diseases associated with sleep disorders. EVIDENCE ACQUISITION: This systematic review analyzed 62 studies and adhered to the PRISMA guidelines, examining the effectiveness of PRM in organic pathologies and mental disorders. EVIDENCE SYNTHESIS: The main evidence concerns primary insomnia in subjects over the age of 55, showing significant improvements in sleep quality. In neurodevelopmental disorders, there is evidence of a positive impact on sleep quality and quality of life for patients and their caregivers. PRM shows efficacy in the treatment of sleep disorders in mood disorders, schizophrenia, and neurocognitive disorders, but requires further confirmation. The additional use of PRM is supported for the withdrawal of chronic benzodiazepine therapies. The tolerability and safety of PRM are excellent, with ample evidence supporting the absence of tolerance and dependence. CONCLUSIONS: Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.

Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Post-selection Inference in Multiverse Analysis (PIMA): An Inferential Framework Based on the Sign Flipping Score Test.

When analyzing data, researchers make some choices that are either arbitrary, based on subjective beliefs about the data-generating process, or for which equally justifiable alternative choices could have been made. This wide range of data-analytic choices can be abused and has been one of the underlying causes of the replication crisis in several fields. Recently, the introduction of multiverse analysis provides researchers with a method to evaluate the stability of the results across reasonable choices that could be made when analyzing data. Multiverse analysis is confined to a descriptive role, lacking a proper and comprehensive inferential procedure. Recently, specification curve analysis adds an inferential procedure to multiverse analysis, but this approach is limited to simple cases related to the linear model, and only allows researchers to infer whether at least one specification rejects the null hypothesis, but not which specifications should be selected. In this paper, we present a Post-selection Inference approach to Multiverse Analysis (PIMA) which is a flexible and general inferential approach that considers for all possible models, i.e., the multiverse of reasonable analyses. The approach allows for a wide range of data specifications (i.e., preprocessing) and any generalized linear model; it allows testing the null hypothesis that a given predictor is not associated with the outcome, by combining information from all reasonable models of multiverse analysis, and provides strong control of the family-wise error rate allowing researchers to claim that the null hypothesis can be rejected for any specification that shows a significant effect. The inferential proposal is based on a conditional resampling procedure. We formally prove that the Type I error rate is controlled, and compute the statistical power of the test through a simulation study. Finally, we apply the PIMA procedure to the analysis of a real dataset on the self-reported hesitancy for the COronaVIrus Disease 2019 (COVID-19) vaccine before and after the 2020 lockdown in Italy. We conclude with practical recommendations to be considered when implementing the proposed procedure.

The perinatal health secondary to pandemic: association between women's delivery concerns and infant's behavioral problems.

BACKGROUND: COVID-19 pandemic characterised a unique and vulnerable social, emotional, and health environment for pregnancy, with potential long-lasting risks to maternal and child health outcomes. In women who were pregnant at the peak of COVID-19 pandemic, we investigated the association between pandemic-related concerns about pregnancy and delivery and both the parent's (i.e. maternal parenting stress) and the infant's (i.e. emotional-behavioral problems) outcomes 12 months after birth. METHODS: A sample of 352 Italian pregnant women completed a web-based survey from 8 April to 4 May 2020 and a follow-up at 12 months after delivery. Maternal assessment in pregnancy covered prenatal measures for: pandemic-related concerns about pregnancy and childbirth, COVID-19 stressful events exposure, pandemic psychological stress, and mental-health symptoms (i.e. depression, anxiety). The 12 months' assessment covered post-partum measures of social support, parenting stress and maternal reports of infants' behavioral problems. RESULTS: The results of the Quasi-Poisson regression models on the association between COVID-19 related influencing factors and parenting stress and infant's behavioral problems showed that the presence of higher pandemic-related concerns about pregnancy and childbirth scores was associated with greater total and internalising behavioral problems but not with parenting stress levels. CONCLUSION: Perinatal mother-infant health has been sensitively threatened by pandemic consequences with maternal concerns about childbirth in pregnancy being associated with 12 months' children's behavioral outcomes. There is a need to invest in psychological support for perinatal women throughout the transition to parenthood to protect risk conditions before they get chronic or severe and influence offspring development.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Chrono-Nutritional Patterns, Medical Comorbidities, and Psychological Status in Patients with Severe Obesity.

Chrono-nutrition studies dietary habits and their role in the onset of metabolic diseases. The aim of this study is to describe chrono-nutritional patterns based on the analysis of the eating habits of patients with severe obesity during the 24-h cycle and investigate a possible relationship between these profiles, the comorbidities, and the psychological status. From the overall evaluation of the chrono-nutritional profiles of 173 patients with severe obesity, four predominant eating patterns were obtained with a refined statistical model. A regression analysis was performed to determine the relationship between chrono-nutritional patterns, medical comorbidities, and psychological status. Profile 1 was the most frequent (46.2%) and characterised by the regular presence of the three main meals. The distribution of the chrono-nutritional profiles did not vary with BMI. Chrono-nutritional profiles affected predominantly psychological variables, with lower performances among chrono-nutritional profiles 3 (to eat during all the 24-h, with nibbling and snacking also during the night) and 4 (like the fourth but without night-eating). This finding could be useful in the assessment and treatment of patients with obesity, allowing the identification of patients with a higher probability of suffering from a psychopathological condition simply by knowing the patients' dietary profiles.

To vaccinate or not to vaccinate? The interplay between pro- and against- vaccination reasons.

BACKGROUND: By mid 2023, European countries reached 75% of vaccine coverage for COVID-19 and although vaccination rates are quite high, many people are still hesitant. A plethora of studies have investigated factors associated with COVID-19 vaccine hesitancy, however, insufficient attention has been paid to the reasons why people get vaccinated against COVID-19. Our work aims to investigate the role of reasons in the decision to get vaccinated against COVID-19 in a representative sample of 1,689 adult Italians (March-April 2021) balanced in terms of age, gender, educational level and area of residence. METHODS: Through an online questionnaire, we asked participants to freely report up to three reasons for and against COVID-19 vaccination, and the weight each had in the decision to get vaccinated. We first investigated the role of emotional competence and COVID-19 risk perception in the generation of both reasons using regression models. Next, we studied the role that the different reasons had in the vaccination decision, considering both the intention to vaccinate (using a beta regression model) and the decision made by the participants who already had the opportunity to get vaccinated (using a logistic regression model). Finally, two different classification tree analyses were carried out to characterize profiles with a low or high willingness to get vaccinated or with a low or high probability to accept/book the vaccine. RESULTS: High emotional competence positively influences the generation of both reasons (ORs > 1.5), whereas high risk perception increases the generation of positive reasons (ORs > 1.4) while decreasing reasons against vaccination (OR = 0.64). As pro-reasons increase, vaccination acceptance increases, while the opposite happens as against-reasons increase (all p < 0.001). One strong reason in favor of vaccines is enough to unbalance the decision toward acceptance of vaccination, even when reasons against it are also present (p < 0.001). Protection and absence of distrust are the reasons that mostly drive willingness to be vaccinated and acceptance of an offered vaccine. CONCLUSIONS: Knowing the reasons that drive people's decision about such an important choice can suggest new communication insights to reduce possible negative reactions toward vaccination and people's hesitancy. Results are discussed considering results of other national and international studies.

Prognostic value of procalcitonin in patients with cirrhosis hospitalized for acute infection.

BACKGROUND: In patients with cirrhosis, infections significantly increase the risk of short and long-term mortality. During infection, the levels of procalcitonin increase, but it has not yet been clarified its prognostic value in subjects with cirrhosis. Therefore, the aim of this study was to evaluate the prognostic role of procalcitonin in patients with liver cirrhosis hospitalized for acute infection, and to compare it with other markers of infection. PATIENTS: We included 279 patients hospitalized because of infection, 133 with liver cirrhosis. At admission the levels of the main biochemical parameters of infection, i.e. leukocytes, procalcitonin, C reactive protein and lactate, were considered. RESULTS: The duration of hospitalization and antibiotic therapy were longer in patients with cirrhosis, while no difference was observed for mortality. In both groups, a correlation with the duration of hospitalization and antibiotic therapy was observed for high levels of procalcitonin. In the cirrhotic population, in particular, higher procalcitonin values were associated with an increase in the length of hospitalization and antibiotic therapy, suggesting an even greater predictive value for those patients. High levels of leucocytes and lactate were positively associated with the duration of hospitalization, but not with the duration of antibiotic therapy. For mortality, the strongest correlation was found for high serum lactate levels, regardless of the presence of cirrhosis. CONCLUSION: In patients with cirrhosis and acute infection, the value of procalcitonin at admission is a good prognostic indicator for the course of hospitalization, and could be useful for guiding the management and treatment of hospitalized patients.

The Impact of Crohn's Perianal Fistula on Quality of Life: Results of an International Patient Survey.

Background: Crohn's perianal fistula is a disabling manifestation of Crohn's disease. However, the additional burden of perianal fistula on patients with only Crohn's disease remains to be addressed. This patient-reported survey considered outcomes of two domains: "diagnosis" (eg, symptoms) and "living with the disease" (eg, quality of life, well-being, and relationships). Methods: Patients with perianal fistula and Crohn's disease completed an online, self-selective, anonymous, 46-item survey available in 11 languages hosted on the European Federation of Crohn's & Ulcerative Colitis Associations and national patient association websites. The survey was conducted between July and December 2019 in Europe and other regions. Likert scales and closed questions were used to assess outcomes. Results: Of the 820 respondents with Crohn's disease (67.2% women; median age, 40.0 years), 532 (64.9%) reported the presence of perianal fistula. Patients with perianal fistula reported a greater impact on overall quality of life (P < .001), well-being (P < .001), relationships (P < .001), social life (P = .001), and work life (P = .012) than patients with only Crohn's disease. Conclusions: Perianal fistulas impact several domains of the life of patients with Crohn's disease. These results may help healthcare practitioners plan therapeutic strategies that address the symptomatic and psychological burden experienced by patients with perianal fistulizing Crohn's disease.

First steps into the pupillometry multiverse of developmental science.

Pupillometry has been widely implemented to investigate cognitive functioning since infancy. Like most psychophysiological and behavioral measures, it implies hierarchical levels of arbitrariness in preprocessing before statistical data analysis. By means of an illustrative example, we checked the robustness of the results of a familiarization procedure that compared the impact of audiovisual and visual stimuli in 12-month-olds. We adopted a multiverse approach to pupillometry data analysis to explore the role of (1) the preprocessing phase, that is, handling of extreme values, selection of the areas of interest, management of blinks, baseline correction, participant inclusion/exclusion and (2) the modeling structure, that is, the incorporation of smoothers, fixed and random effects structure, in guiding the parameter estimation. The multiverse of analyses shows how the preprocessing steps influenced the regression results, and when visual stimuli plausibly predicted an increase of resource allocation compared with audiovisual stimuli. Importantly, smoothing time in statistical models increased the plausibility of the results compared to those nested models that do not weigh the impact of time. Finally, we share theoretical and methodological tools to move the first steps into (rather than being afraid of) the inherent uncertainty of infant pupillometry.

DRD2, DRD3, and HTR2A Single-Nucleotide Polymorphisms Involvement in High Treatment Resistance to Atypical Antipsychotic Drugs.

BACKGROUND: The objective of this study was to investigate the DRD2 rs1800497, rs1799732, rs1801028, DRD3 rs6280, and HTR2A rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders. METHODS: We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership. RESULTS: A diagnosis of schizophrenia significantly predicted the HTR membership compared to other diagnoses. Other predictors were the DRD3 rs6280 C|T (OR = 22.195) and T|T (OR = 18.47) vs. C|C, HTR2A rs7997012 A|G vs. A|A (OR = 6.859) and vs. G|G (OR = 2.879), and DRD2 rs1799732 I|I vs. D|I (OR = 12.079) genotypes. CONCLUSIONS: A diagnosis of schizophrenia and the DRD2 rs1799732, DRD3 rs6280, and HTR2A rs7997012 genotypes can predict high treatment resistance to SGAs.

Estimating Overall and Cause-Specific Excess Mortality during the COVID-19 Pandemic: Methodological Approaches Compared.

During the COVID-19 pandemic, excess mortality has been reported worldwide, but its magnitude has varied depending on methodological differences that hinder between-study comparability. Our aim was to estimate variability attributable to different methods, focusing on specific causes of death with different pre-pandemic trends. Monthly mortality figures observed in 2020 in the Veneto Region (Italy) were compared with those forecasted using: (1) 2018-2019 monthly average number of deaths; (2) 2015-2019 monthly average age-standardized mortality rates; (3) Seasonal Autoregressive Integrated Moving Average (SARIMA) models; (4) Generalized Estimating Equations (GEE) models. We analyzed deaths due to all-causes, circulatory diseases, cancer, and neurologic/mental disorders. Excess all-cause mortality estimates in 2020 across the four approaches were: +17.2% (2018-2019 average number of deaths), +9.5% (five-year average age-standardized rates), +15.2% (SARIMA), and +15.7% (GEE). For circulatory diseases (strong pre-pandemic decreasing trend), estimates were +7.1%, -4.4%, +8.4%, and +7.2%, respectively. Cancer mortality showed no relevant variations (ranging from -1.6% to -0.1%), except for the simple comparison of age-standardized mortality rates (-5.5%). The neurologic/mental disorders (with a pre-pandemic growing trend) estimated excess corresponded to +4.0%/+5.1% based on the first two approaches, while no major change could be detected based on the SARIMA and GEE models (-1.3%/+0.3%). The magnitude of excess mortality varied largely based on the methods applied to forecast mortality figures. The comparison with average age-standardized mortality rates in the previous five years diverged from the other approaches due to the lack of control over pre-existing trends. Differences across other methods were more limited, with GEE models probably representing the most versatile option.

The Interplay of Perceived Risks and Benefits in Deciding to Become Vaccinated against COVID-19 While Pregnant or Breastfeeding: A Cross-Sectional Study in Italy.

The present study examined the role of the perception of risks and benefits for the mother and her babies in deciding about the COVID-19 vaccination. In this cross-sectional study, five hypotheses were tested using data from a convenience sample of Italian pregnant and/or breastfeeding women (N = 1104, July-September 2021). A logistic regression model estimated the influence of the predictors on the reported behavior, and a beta regression model was used to evaluate which factors influenced the willingness to become vaccinated among unvaccinated women. The COVID-19 vaccination overall risks/benefits tradeoff was highly predictive of both behavior and intention. Ceteris paribus, an increase in the perception of risks for the baby weighed more against vaccination than a similar increase in the perception of risks for the mother. Additionally, pregnant women resulted in being less likely (or willing) to be vaccinated in their status than breastfeeding women, but they were equally accepting of vaccination if they were not pregnant. COVID-19 risk perception predicted intention to become vaccinated, but not behavior. In conclusion, the overall risks/benefits tradeoff is key in predicting vaccination behavior and intention, but the concerns for the baby weigh more than those for the mother in the decision, shedding light on this previously neglected aspect.

A multivariate approach to investigate the associations of electrophysiological indices with schizophrenia clinical and functional outcome.

BACKGROUND: Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). METHODS: Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers' decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. RESULTS: The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. CONCLUSIONS: These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.

Behavioral outcomes and exposure to perfluoroalkyl substances among children aged 6-13 years: The TEDDY child study.

BACKGROUND: Although some studies report that exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy and early life stages of a child could adversely impact neurodevelopment, literature shows mixed evidence. OBJECTIVES: Using an ecological framework for human development, we assessed the association of risk factors for environmental PFAS exposure and childhood PFAS concentrations with behavioral difficulties among school-age children exposed to PFAS from birth, while also controlling for the important influence of the parenting and familial environment. METHODS: The study participants included 331 school-age children (6-13 years) born in a PFAS-contaminated area in the Veneto Region (Italy). We study the associations between environmental risk factors of maternal PFAS exposure (residential time, consumption of tap water, residence in Red zone A or B), and breastfeeding duration with parent assessments of children's behavioral problems (using the Strengths and Difficulties Questionnaire [SDQ]), adjusting for socio-demographic, parenting and familial variables. The direct relationships between serum blood PFAS concentrations and SDQ scores was evaluated in a subset of children (n = 79), both with single PFAS and weighted quantile sum (WQS) regressions. RESULTS: Poisson regression models reported positive associations between high consumption of tap water and externalizing SDQ scores (Incidence Rate Ratio [IRR]: 1.18; 95% confidence interval [CI]: 1.04-1.32) and total difficulty scores (IRR: 1.14; 95% CI: 1.02-1.26). Childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with higher internalizing SDQ scores (4th vs. 1st quartile, PFOS IRR: 1.54, 95% CI: 1.06-2.25), externalizing scores (4th vs. 1st quartile, PFHxS IRR: 1.59, 95% CI: 1.09-2.32), and total difficulty scores (4th vs. 1st quartile, PFOS IRR: 1.37, 95% CI: 1.05-1.71; PFHxS IRR: 1.54, 95% CI: 1.09-1.90). The WQS regressions confirmed the associations reported by single-PFAS analyses. CONCLUSIONS: We observed cross-sectional associations of tap water consumption and childhood PFOS, and PFHxS concentrations with greater behavioral difficulties.

Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy. METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE). RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE. CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

An SEIR Model with Time-Varying Coefficients for Analyzing the SARS-CoV-2 Epidemic.

In this study, we propose a time-dependent susceptible-exposed-infected-recovered (SEIR) model for the analysis of the SARS-CoV-2 epidemic outbreak in three different countries, the United States, Italy, and Iceland using public data inherent the numbers of the epidemic wave. Since several types and grades of actions were adopted by the governments, including travel restrictions, social distancing, or limitation of movement, we want to investigate how these measures can affect the epidemic curve of the infectious population. The parameters of interest for the SEIR model were estimated employing a composite likelihood approach. Moreover, standard errors have been corrected for temporal dependence. The adoption of restrictive measures results in flatten epidemic curves, and the future evolution indicated a decrease in the number of cases.

Psychological well-being during the COVID-19 pandemic in Italy assessed in a four-waves survey.

COVID-19 pandemic had a negative impact on the mental health and well-being (WB) of citizens. This cross-sectional study included 4 waves of data collection aimed at identifying profiles of individuals with different levels of WB. The study included a representative stratified sample of 10,013 respondents in Italy. The WHO 5-item well-being scale (WHO-5) was used for the assessment of WB. Different supervised machine learning approaches (multinomial logistic regression, partial least-square discriminant analysis-PLS-DA-, classification tree-CT-) were applied to identify individual characteristics with different WB scores, first in waves 1-2 and, subsequently, in waves 3 and 4. Forty-one percent of participants reported "Good WB", 30% "Poor WB", and 28% "Depression". Findings carried out using multinomial logistic regression show that Resilience was the most important variable able for discriminating the WB across all waves. Through the PLS-DA, Increased Unhealthy Behaviours proved to be the more important feature in the first two waves, while Financial Situation gained most relevance in the last two. COVID-19 Perceived Risk was relevant, but less than the other variables, across all waves. Interestingly, using the CT we were able to establish a cut-off for Resilience (equal to 4.5) that discriminated good WB with a probability of 65% in wave 4. Concluding, we found that COVID-19 had negative implications for WB. Governments should support evidence-based strategies considering factors that influence WB (i.e., Resilience, Perceived Risk, Healthy Behaviours, and Financial Situation).

People's perspectives about COVID-19 vaccination certificate: Findings from a representative Italian sample.

In Italy, like in other countries, issues still exist regarding how to reach high vaccine coverage and several countries have considered policies to increase vaccine uptake. In the present study, we focused on people who have a favorable attitude towards vaccination. In March-April 2021, we asked a representative sample of Italian participants (N = 1,530) to assess to what extent they would support the adoption of a COVID-19 vaccination certificate, excluding unvaccinated people from participating in public and cultural events. Furthermore, as the vaccination coverage increases, severe forms of COVID-19 requiring hospitalization more likely involve unvaccinated individuals, who might be perceived as those who don't contribute to ending the pandemic and who constitute a significant health cost for society. We then asked participants to assess to what extent they would favor the idea of requiring people who refuse the vaccine to pay for their own medical expenses in case of hospitalization. We hypothesized that support for the adoption of the vaccination certificate would be predicted by the COVID-19 vaccination status (received, booked, high-, medium-, low-willingness to be vaccinated, or refused) and by the same factors that are known to affect the willingness to get vaccinated. These factors were also tested in a model aimed at investigating if a vaccinated person would favor a measure requiring the unvaccinated individuals to pay for medical expenses. Results confirmed that the support towards the vaccination certificate policy was strongly predicted by the vaccination status and by factors known to affect the willingness to get vaccinated. Interestingly (and surprisingly), a similar pattern was observed for the support of the policy about medical expenses. In conclusion, support for a COVID-19 vaccination certificate was high among the Italian population in the early phases of the vaccination rollout. The findings are discussed considering potential policies to tackle the pandemic.

Insomnia in primary care: a survey conducted on Italian patients older than 50 years-results from the "Sonno e Salute" study.

Insomnia affects one-third of the adult population and is associated with multiple medical conditions. We conducted an observational epidemiological survey to assess (1) the prevalence of insomnia in an Italian group of patients aged over 50 years, presenting directly to the general physician (GP); (2) the association of insomnia with sleepiness and comorbidities; and (3) the pharmacological treatment. The study was carried out by GPs. Each GP was asked to enroll the first patient over 50 years old spontaneously presenting for any medical problems for 5 consecutive days. The Italian version of the Sleep Condition Indicator (SCI) was administered; daytime sleepiness was evaluated by a visual analogic scale (VAS). For every patient, GPs collected information regarding comorbidities and pharmacological treatment for insomnia and evaluated the severity of insomnia using the Clinical Global Impression Severity (CGI-S) scale. A total of 748 patients (mean age 65.12 ± 9.45 years) were enrolled by 149 GPs. Prevalence of insomnia was 55.3%. SCI, VAS, and CGI-S scores were highly correlated between each other (p < 0.0001). At general linear model analysis, the comorbidities more associated with the presence of insomnia were anxiety-depressive disorder (p < 0.001), other psychiatric disorders (p = 0.017), cardiovascular disorders (p = 0.006), and dementia (p = 0.027). A statistically significant correlation was found between SCI score and the use of benzodiazepines (p < 0.001), z-drugs (p = 0.012), antidepressants (p < 0.001), and melatonin-prolonged release (p < 0.001). Insomnia affects half of Italian primary care patients over 50 years and is frequently associated with different medical conditions, sleepiness, and use of multiple-often off-label-drugs.