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Abstract Background A time-dependent analysis, usually by means of Poisson and Cox regression models, can be applied to prevent immortal time bias. However, the use of the Poisson model requires the assumption that the event rate is constant over time. This study aims to assess the potential consequences of using the Poisson model to cope with immortal time bias on estimating the exposure-outcome relationship in the case of time-varying risks. Methods A simulation study was carried out. Survival times were assumed to follow a Weibull distribution, and the Weibull parameters were chosen to identify three different scenarios: the hazard of the event is constant, decreases, or increases over time. A dichotomous time-varying exposure in which patients can change at most once from unexposed to exposed was considered. The Poisson model was fitted to estimate the exposure-outcome association. Results Small changes in the outcome risk over time (as denoted by the shape parameter of the Weibull distribution) strongly affected the exposure-outcome association estimate. The estimated effect of exposure was always lower and greater than the true exposure effect when the event risk decreases or increases over time, and this was the case irrespective of the true exposure effect. The bias magnitude was positively associated with the prevalence of and time to exposure. Conclusions Biased estimates were obtained from the Poisson model to cope with immortal time. In settings with a time-varying outcome risk, the model should adjust for the trend in outcome risk. Otherwise, other models should be considered.

Abstract The significant impact of acute respiratory tract infections on healthcare systems is well-documented, given their contribution to emergency department admissions, hospitalizations, and increased use of antibiotics and other medications. However, further research is needed to understand the burden of acute respiratory tract infections in pediatric community care to develop effective public health interventions and improve child health outcomes. Real-world data were retrieved from Pedianet, an Italian network of over 200 family pediatricians. Acute respiratory tract infection visits were identified and analysed using an infection-duration algorithm to extract individual cases. The number of follow-up visits per 100 cases was calculated to assess the burden on the Italian National Health Service. Comparisons were made overall and stratified by type of acute respiratory tract infections and epidemiological season. A total of 1,402,953 acute respiratory infections-related visits were recorded, with an overall rate of 12 visits per 100 cases. Upper respiratory tract infections had an average of 9 visits per 100 cases. Lower respiratory tract infections exhibited a higher burden, with 29 visits per 100 cases. Pneumonia showed a declining trend in the pre-pandemic era (62 to 48 visits) but rebounded in the post-COVID-19 years (32 to 42 visits). This study underscores the importance of monitoring and managing acute respiratory infections, especially lower respiratory tract infections, in pediatric care.

Summary: Background: The proper management of suspicious radiologic findings is crucial to optimize the effectiveness of low-dose computed tomography (LDCT) lung cancer screening trials. In the BioMILD study, we evaluated the utility of combining a plasma 24-microRNA signature classifier (MSC) and LDCT to define the individual risk and personalize screening strategies. Here we aim to assess the utility of repeated MSC testing during annual screening rounds in 1024 participants with suspicious LDCT findings. Methods: The primary outcome was two-year lung cancer incidence in relation to MSC test results, reported as relative risk (RR) with 95% confidence interval (CI). Lung cancer incidence and mortality were estimated using extended Cox models for time-dependent covariates, yielding the respective hazard ratios (HR). Clinicaltrials.gov ID: NCT02247453. Findings: With a median follow-up of 8.5 years, the full study set included 1403 indeterminate LDCT (CTind) and 584 positive LDCT (CT+) results. A lung cancer RR increase in MSC+ compared to MSC- participants was observed in both the CTind (RR: 2.5; 95% CI: 1.4–4.32) and CT+ (RR: 2.6; 95% CI: 1.81–3.74) groups and was maintained when considering stage I or resectable tumors only. A 98% negative predictive value in CTind/MSC− and a 30% positive predictive value in CT+/MSC+ lesions were recorded. At seven years’ follow-up, MSC+ participants had a cumulative HR of 4.4 (95% CI: 3.0–6.4) for lung cancer incidence and of 8.1 (95% CI: 2.7–24.5) for lung cancer mortality. Interpretation: Our study shows that MSC can be reliably performed during LDCT screening rounds to increase the accuracy of lung cancer risk and mortality prediction and supports its clinical utility in the management of LDCT findings of uncertain malignancy. Funding: Italian Association for Cancer Research; Italian Ministry of Health; Horizon2020; National Cancer Institute (NCI); Gensignia LifeScience.

Objective: To evaluate the association between maternal migration status and preterm birth, and whether a better adherence to antenatal care during pregnancy mitigates the risk of preterm birth. Design: Population-based cohort. Setting: Administrative databases of the Lombardy region, Italy. Population: First singleton births of women aged 15–55 years at 22–42 gestational weeks, between 2016 and 2021. Methods: Assessed the risk of preterm birth (

Background. Left ventricular hypertrabeculation (LVHT) is a myocardial disorder with different clinical manifestations, from total absence of symptoms to heart failure, arrhythmias, sudden cardiac death (SCD), and thromboembolic events. It is challenging to distinguish between the benign and pathological forms of LVHT. The aim of this study was to describe the arrhythmic manifestations of LVHT in a large group of pediatric patients and to correlate them with genetic results or other clinical markers. Methods. We retrospectively enrolled 140 pediatric patients with diagnosis of LVHT followed at our Institution from 2013 to 2023. Data regarding family history, instrumental exams, cardiac magnetic resonance, genetic testing and outcomes were collected. Most of them had isolated LVHT (80.7%); in other patients, mixed phenotypes (hypertrophic or dilated cardiomyopathy or congenital heart disease) were present. Results. Arrhythmias were found in 33 children (23.6%): 13 (9.3%) supraventricular tachyarrhythmias; 14 (10%) ventricular arrhythmias (five frequent PVCs (premature ventricular contractions), eight patients with ventricular tachycardia (VT), one ventricular fibrillation (VF)); two (1.4%) sinus node disfunctions; two (1.4%) complete atrio-ventricular blocks (AVB), three (2.1%) paroxysmal complete AVB, one (0.7%) severe I degree AVB. Three patients received an ICD (implantable cardioverter defibrillator). Comparison between LVHT patients with (33 pts) and without (107 pts) arrhythmias as regards genetic testing showed a statistical significance for the presence of class 4 or 5 genetic variants and arrhythmic manifestation (p = 0.037). Conclusions. In our pediatric cohort with LVHT, good outcomes were observed, but arrhythmias were not so rare (23.6%); no SCD occurred.

Background/Objectives: Seasonal influenza annually puts a significant burden on the pediatric population, especially the youngest, causing severe illness and death. Additionally, associated healthcare costs cause a significant financial strain on healthcare systems. While vaccination is the most effective prevention method, its cost-effectiveness for healthy children remains unassessed. Methods: Using the Pedianet database spanning from 2009 to 2019, we analyzed influenza cases among 6-month-olds to 14-year-olds in Italy. Data included influenza-related medical visits, prescriptions, exams, emergency visits, hospitalizations, and costs. Adverse events and quality-adjusted life years (QALYs) were considered from the existing literature. A static decision-tree model compared annual vaccination strategies, assessing probabilities for influenza or influenza-like illnesses by vaccination status. Incremental cost-effectiveness ratios (ICERs) were calculated, along with sensitivity analyses and cost-effectiveness acceptability curve generation. Results: Mean total influenza costs for vaccinated children averaged EUR 18.6 (range 0–3175.9, including EUR 15.79 for the influenza vaccination), whereas costs for unvaccinated children were consistently lower at around EUR 4.6 (range 0–3250.1). The average ICER for years where vaccine and virus strains are matched was EUR 29,831 per QALY, which is below the EUR 40,000 threshold set by the Italian National Health Services. The ICER values range from EUR 13,736 (2017/2018) to EUR 72,153 (2013/2014). Averted influenza costs averaged EUR 23 per case, with fluctuations over the years. In most observed years, influenza vaccination was cost-effective from the healthcare providers’ standpoint. The exception was 2009–2010, due to a mismatch between vaccine and virus strains. Conclusions: This study highlights the economic viability of influenza vaccination, especially when virus and vaccine strains align. It demonstrates the potential of vaccination programs in preserving children’s health and well-being while managing healthcare costs.

BackgroundChildhood obesity is a significant public health problem representing the most severe challenge in the world. Antibiotic exposure in early life has been identified as a potential factor that can disrupt the development of the gut microbiome, which may have implications for obesity. ObjectiveThis study aims to evaluate the risk of developing obesity among children exposed to antibiotics early in life. MethodsAn Italian retrospective pediatric population-based cohort study of children born between 2004 and 2018 was adopted using the Pedianet database. Children were required to be born at term, with normal weight, and without genetic diseases or congenital anomalies. We assessed the timing of the first antibiotic prescription from birth to 6, 12, and 24 months of life and the dose-response relationship via the number of antibiotic prescriptions recorded in the first year of life (none, 1, 2, and ≥3 prescriptions). Obesity was defined as a BMI z score >3 for children aged ≤5 years and >2 for children aged >5 years, using the World Health Organization growth references. The obese incidence rate (IR) × 100 person-years and the relative 95% CI were computed using infant sex, area of residence, preschool and school age, and area deprivation index, which are the covariates of interest. A mixed-effect Cox proportional hazards model was used to estimate the hazard ratio and 95% CI for the association between antibiotic exposure in early life and child obesity between 24 months and 14 years of age, considering the family pediatricians as a random factor. Several subgroup and sensitivity analyses were performed to assess the robustness of our results. ResultsAmong 121,540 children identified, 54,698 were prescribed at least an antibiotic within the first year of life and 26,990 were classified as obese during follow-up with an incidence rate of 4.05 cases (95% CI 4.01-4.10) × 100 person-year. The risk of obesity remained consistent across different timings of antibiotic prescriptions at 6 months, 1 year, and 2 years (fully adjusted hazard ratio [aHR] 1.07, 95% CI 1.04-1.10; aHR 1.06, 95% CI 1.03-1.09; and aHR 1.07, 95% CI 1.04-1.10, respectively). Increasing the number of antibiotic exposures increases the risk of obesity significantly (P trend

Abstract There is growing evidence that inflammatory, immunologic, and metabolic status is associated with cancer patients survival. Here, we built a simple algorithm to predict lung cancer outcome. Perioperative routine blood tests (RBT) of a cohort of patients with resectable primary lung cancer (LC) were analysed. Inflammatory, immunologic, and metabolic profiles were used to create a single algorithm (RBT index) predicting LC survival. A concurrent cohort of patients with resectable lung metastases (LM) was used to validate the RBT index. Charts of 2088 consecutive LC and 1129 LM patients undergoing lung resection were evaluated. Among RBT parameters, C-reactive protein (CRP), lymphocytes, neutrophils, hemoglobin, albumin and glycemia independently correlated with survival, and were used to build the RBT index. Patients with a high RBT index had a higher 5-year mortality than low RBT patients (adjusted HR 1.93, 95% CI 1.62–2.31). High RBT patients also showed a fourfold higher risk of 30-day postoperative mortality (2.3% vs. 0.5%, p 0.0019). The LM analysis validated the results of the LC cohort. We developed a simple and easily available multifunctional tool predicting short-term and long-term survival of curatively resected LC and LM. Prospective external validation of RBT index is warranted.

Objectives: The study aims to explore the risk factors, clinical characteristics, and outcomes of mpox infection in Abu Dhabi, United Arab Emirates (UAE). Methods: A prospective cohort study was conducted at two communicable disease centers in Abu Dhabi, UAE and patients admitted with confirmed mpox infections between May 01, 2022 and December 31, 2022 were included in our study. Results: A total of 176 mpox patients were admitted, of which 93% (n = 164) were men and mean age was 30.4 ± 7 years. Individuals presented with mucocutaneous lesions, most commonly on the genital and anal regions (n = 157; 89%). Only 70 (39.8%) gave a history of sexual exposure. The most common systemic symptoms reported were fever (n = 91; 52%), exanthema (n = 92; 52%), and inguinal lymphadenopathy (n = 60; 34%). Median timeframe from systemic symptoms to appearance of lesions was 4 days (interquartile range 4-6 days). Complications were observed in seven (4%) participants; two (1.1%) individuals developed conjunctivitis, four (2.3%) patients developed penile edema, and one (0.6%) case of myocarditis was reported. In 60% (n = 106) of patients, a potential source of sexual exposure was not identified. Conclusion: The clinical characteristics of mpox cases in the UAE are similar to those in other countries. However, cultural and religious factors likely prevent patient disclosure of sexual exposure and symptoms, contributing to the limited information about the disease in the Middle East.

This population-based study aimed at providing an overview of drug prescription patterns during pregnancy in the Italian region of Lombardy from 2010 to 2020. The cohort consisted of 780,075 deliveries identified from the regional healthcare utilization databases. The prevalence of drugs’ dispensed prescriptions was estimated as the proportion of pregnant women with at least one prescription out of the total deliveries over the entire pregnancy and by trimester. Drugs were classified according to the Anatomical Therapeutic Chemical code. In addition, interrupted time series analysis was conducted to investigate temporal trends of antibiotics’ use during the onset of the COVID-19 pandemic. A total of 497,515 women (63.8%) used at least a drug, including vitamins and minerals, at some point during pregnancy. Vitamins, minerals, and anti-anaemic preparations were prescribed in 20.8%, 13.3%, and 18.3% of deliveries over the trimesters of pregnancy. Folic acid was the most prescribed drug, with about one woman out of four, followed by iron preparations, progestogen, and antibiotics (prescription rate, respectively: 15.9%, 10.2%, and 9.8%). A decreasing trend in the dispensing of antibiotics emerged during the entire study period; however, a significant further decrease following the spread of the pandemic was observed. Further evidence is needed to monitor the use of drugs during pregnancy, determinants, and implications.

Abstract Background As Canada and other high-income countries continue to welcome newcomers, we aimed to 1) understand newcomer parents’ attitudes towards routine-childhood vaccinations (RCVs), and 2) identify barriers newcomer parents face when accessing RCVs in Alberta, Canada. Methods Between July 6th—August 31st, 2022, we recruited participants from Alberta, Canada to participate in moderated focus group discussions. Inclusion criteria included parents who had lived in Canada for

Background:Preterm birth may affect maternal mental health. We explored the relationship between preterm birth and the risk of initiating antidepressant use during the year after birth.Methods:We conducted a population-based investigation using regional healthcare utilization databases. The exposure considered was preterm birth. The outcome was having at least one prescription for antidepressant medications during the year after birth. We used a log-binomial regression model including terms for maternal age at birth, nationality, educational level, parity, modality of conception, modality of delivery, use of other psychotropic drugs, and diabetes to estimate relative risk (RR) and 95% confidence intervals (CI) for the association between preterm birth and the initiation of antidepressant use. In addition, the absolute risk differences (ARD) were also computed according to the timing of birth.Results:The cohort included 727,701 deliveries between 2010 and 2020 in Lombardy, Northern Italy. Out of these, 6,522 (0.9%) women had at least one prescription for antidepressant drugs during the year after birth. Preterm births were related to a 38% increased risk of initiation of antidepressant use during the year after birth (adjusted RR = 1.38; 95% CI: 1.25–1.52) for moderate to late preterm and to 83% (adjusted RR = 1.83; 95% CI: 1.46–2.28) for extremely and very preterm. Excluding women with only one antidepressant prescription, the association was consistent (adjusted RR = 1.41, 95%CI: 1.23–1.61 for moderate to late preterm and adjusted RR = 1.81, 95% CI: 1.31–2.49 for extremely and very preterm). Also, excluding women who used other psychotropics, the association remained consistent (adjusted RR = 1.39, 95%CI: 1.26–1.54 and adjusted RR = 1.91, 95% CI: 1.53–2.38, respectively for moderate to late and extremely and very preterm).Conclusion:Women who delivered preterm may have an excess risk of initiation of antidepressant consumption during the first year after birth.

Background/Objectives: Seasonal influenza annually puts a significant burden on the pediatric population, especially the youngest, causing severe illness and death. Additionally, associated healthcare costs cause a significant financial strain on healthcare systems. While vaccination is the most effective prevention method, its cost-effectiveness for healthy children remains unassessed. Methods: Using the Pedianet database spanning from 2009 to 2019, we analyzed influenza cases among 6-month-olds to 14-year-olds in Italy. Data included influenza-related medical visits, prescriptions, exams, emergency visits, hospitalizations, and costs. Adverse events and quality-adjusted life years (QALYs) were considered from the existing literature. A static decision-tree model compared annual vaccination strategies, assessing probabilities for influenza or influenza-like illnesses by vaccination status. Incremental cost-effectiveness ratios (ICERs) were calculated, along with sensitivity analyses and cost-effectiveness acceptability curve generation. Results: Mean total influenza costs for vaccinated children averaged EUR 18.6 (range 0–3175.9, including EUR 15.79 for the influenza vaccination), whereas costs for unvaccinated children were consistently lower at around EUR 4.6 (range 0–3250.1). The average ICER for years where vaccine and virus strains are matched was EUR 29,831 per QALY, which is below the EUR 40,000 threshold set by the Italian National Health Services. The ICER values range from EUR 13,736 (2017/2018) to EUR 72,153 (2013/2014). Averted influenza costs averaged EUR 23 per case, with fluctuations over the years. In most observed years, influenza vaccination was cost-effective from the healthcare providers' standpoint. The exception was 2009–2010, due to a mismatch between vaccine and virus strains. Conclusions: This study highlights the economic viability of influenza vaccination, especially when virus and vaccine strains align. It demonstrates the potential of vaccination programs in preserving children's health and well-being while managing healthcare costs. [ABSTRACT FROM AUTHOR]

An online questionnaire attempted to reveal the heuristics and biases used when participants reflected on their trust ina healthcare system. Participants answered quantitative questions related to six different heuristics and biases, whichrevealed their propensity for exhibiting each heuristic, before rating healthcare systems on seven trust-related metrics: re-source allocation; access to treatment; honesty, integrity and intention; competence; quality; safety; and equality. Multipleregressions tested whether the predictive power of heuristics and biases on trust ratings was significantly moderated bythe relative proportion of patients receiving service in the public and private sector. Results revealed that heuristics andbiases significantly impacted thought processes when arriving at assessments of participants willingness to trust. As trustin major institutions declines, this presents the scientific and medical communities with relevant data to potentially alterpractices and communication approaches in a way that fosters trust.

BackgroundBronchiolitis is the most common lower respiratory tract infection (LRTI) in children and is mainly caused by the Respiratory Syncytial Virus (RSV). Bronchiolitis presents seasonally and lasts about five months, usually between October to March, with peaks of hospitalizations between December and February, in the Northern Hemisphere. The burden of bronchiolitis and RSV in primary care is not well understood.Materials and methodsThis retrospective analysis used data from Pedianet, a comprehensive paediatric primary care database of 161 family paediatricians in Italy. We evaluated the incidence rates (IR) of all-cause bronchiolitis (ICD9-CM codes 466.1, 466.11 or 466.19), all-cause LRTIs, RSV-bronchiolitis and RSV-LRTIs in children from 0 to 24 months of age, between January 2012 to December 2019. The role of prematurity (