Diagnostic accuracy of HPV16 early antigen serology for HPV-driven oropharyngeal cancer is independent of age and sex.

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.

Estimation of per- and polyfluoroalkyl substances (PFAS) half-lives in human studies: a systematic review and meta-analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) constitute a heterogeneous group of synthetic compounds widely used in industrial applications. The estimation of PFAS half-life (t1/2) is essential to quantify their persistence, their toxicity and mechanism of action in humans. OBJECTIVES: The purpose of this review is to summarize the evidence on PFAS half-lives in humans from the available literature, and to investigate the limitations and uncertainties characterizing half-life estimation. METHODS: The search was conducted on PubMed, Scopus, and Embase databases up to July 03, 2023 and was aimed at identifying all papers that estimated PFAS half-life in human populations. We excluded studies on temporal trends or providing estimates of half-life based solely on renal clearance. As persistent and ongoing exposures can influence half-life estimation, we decided to include only studies that were conducted after the main source of exposure to PFAS had ceased. A random-effects meta-analysis was conducted on studies that reported perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) or perfluorohexanesulfonic acid (PFHxS) half-life estimation. Risk of bias was evaluated using the OHAT tool. RESULTS: A total of 13 articles were included in the review, with 5 studies conducted in exposed general populations and 8 studies conducted in exposed workers; the estimated mean half-life ranged from 1.48 to 5.1 years for PFOA, from 3.4 to 5.7 years for total PFOS, and from 2.84 to 8.5 years for PFHxS. High heterogeneity among studies was observed; potential reasons include the variability among the investigated populations, discrepancies in considering ongoing exposures, variability in PFAS isomeric compositions, accounting for background exposure, time since exposure stopped and methods used for half-life estimation. DISCUSSION: Despite the efforts made to better understand PFAS toxicokinetics, further studies are needed to identify important characteristics of these persistent chemicals. Biomonitoring studies should focus on persistent and unaccounted sources of exposure to PFAS and on individual characteristics potentially determining half-life, to ensure accurate estimates.

A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium.

OBJECTIVE: We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. SUBJECTS AND METHODS: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. RESULTS: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. CONCLUSION: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer.

Perfluoroalkyl substance mixtures and cardio-metabolic outcomes in highly exposed male workers in the Veneto Region: A mixture-based approach.

BACKGROUND: Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits. Occupational exposures to multiple PFAS with health outcomes have been poorly investigated. The aim of the present study was to examine these associations among former workers involved in PFAS production. METHODS: We considered 232 male ex-employees who had worked in a factory (Trissino, Veneto Region, Italy), which produced PFAS and other chemicals during 1968-2018. Out of twelve serum PFAS, only four (PFOA, PFOS, PFHxS, and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between serum PFAS mixture and considered outcomes were assessed through linear regression mixed models and Weighted Quantile Sum (WQS) regression, adjusting for potential confounders. RESULTS: PFOA was detected at the highest level, with a median concentration (in ng/mL) of 80.8 (min-max: 0.35-13,033), followed by PFOS (median: 8.55, min-max: 0.35-343), PFHxS (median: 6.8, min-max: 0.35-597) and PFNA (median: 0.8, min-max: 0.35-5). We observed that each A quartile increase in the WQS index was positively associated with the levels of TC (ß: 8.41, 95% IC: 0.78-16.0), LDL-C (ß: 8.02, 95% IC: 1-15.0) and SBP (ß: 3.21, 95% IC: 0.82-5.60). No association of serum PFAS concentration on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although PFOA reported the highest concentration. PFOA and PFOS emerged as chemicals of concern regarding the association with SBP. CONCLUSIONS: The results showed a clear association between serum PFAS levels and markers of cardiovascular risk and support the importance of clinical surveillance of cardiovascular risk factors in population with a high exposure to PFAS, especially in the occupational setting.

How to investigate human health effects related to exposure to mixtures of per- and polyfluoroalkyl substances: A systematic review of statistical methods.

BACKGROUND: Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health. OBJECTIVES: We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect. METHODS: The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers. RESULTS: A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16). CONCLUSION: Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.

Perfluoroalkyl substances and thyroid stimulating hormone levels in a highly exposed population in the Veneto Region.

BACKGROUND: Per- and poly-fluoroalkyl substances (PFAS) are persistent and widespread environmental pollutants. People living in Veneto Region (Italy) have been exposed from the late 1970s to 2013 to elevated concentrations of PFAS through drinking water. The effect of PFAS on thyroid function is still controversial and studies focusing on thyroid stimulating hormone (TSH) have shown inconsistent results. The aim of this study was to evaluate the association between serum PFAS and TSH levels and its dose-response relationship in a large population of highly exposed individuals. METHODS: A cross-sectional study was conducted on 21,424 individuals aged 14-39 living in the contaminated area. In the main analysis, participants with prevalent thyroid disease and pregnant women were excluded. Serum levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) were measured. Generalized Additive Models were used to evaluate the association between TSH levels and serum PFAS, using thin plate spline smooth terms to model the potential non-linear relationship. Models were stratified by sex and age group and adjusted for potential confounders. A secondary analysis was conducted to evaluate the association between PFAS with prevalent self-reported thyroid disorders. RESULTS: We found no association between TSH and any type of PFAS among adolescents or women. A decrease in TSH concentration was observed in association with an IQR increase in PFHxS and a mild decrease in TSH at low levels of PFOA, PFOS and PFHxS among male adults. Self-reported thyroid disease was more common among women with higher levels of PFNA concentrations, whereas all other PFAS were not associated with thyroid diseases regardless of sex or age. CONCLUSIONS: Overall there is no evidence of an association between TSH and PFAS. However, some results are suggestive of a possible inverse association of TSH with PFOA, PFOS and PFHxS among adult males.

The association between perfluoroalkyl substances and lipid profile in exposed pregnant women in the Veneto region, Italy.

BACKGROUND: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Serum PFAS levels have been consistently associated with elevated serum lipids, but few studies have been conducted among pregnant women, and none has stratified analyses by trimester of gestation. Elevated serum lipid levels during pregnancy can have both immediate and long-lasting effects on pregnant women and the developing fetus. We evaluated the association between perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluoro-hexanesulfonate (PFHxS) levels in relation to lipid profiles in highly-exposed pregnant women. METHODS: A cross-sectional analysis was conducted in 319 pregnant women (age 14-48 years) enrolled in the Regional health surveillance program. Non-fasting blood samples were obtained in any trimester of pregnancy and analyzed for PFOA, PFOS and PFHxS, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C). Low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFAS (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. RESULTS: The geometric means of PFOA, PFOS and PFHxS were 14.78 ng/mL, 2.67 ng/mL and 1.89 ng/mL, respectively. The plasma levels of TC, HDL-C and LDL-C increased steadily throughout the trimesters. In the 1st trimester, PFOS was positively associated with TC and PFHxS with HDL-C. In the 3rd trimester, instead, an inverse relationship was seen between PFOA and PFHxS and both TC and LDL-C. CONCLUSIONS: Results suggest the associations between PFAS concentrations and lipid profiles in pregnant women might differ by trimesters of pregnancy. In the first trimester, patterns are similar to those of non-pregnant women, while they differ late in pregnancy. Different independent behavior of PFAS and lipid levels throughout the pregnancy might explain our observations. These findings support the ubiquitous exposure to PFAS and possible influence on lipid metabolisms during pregnancy and suggest a careful evaluation of the timing of PFAS measurement, when examining effects of PFAS during pregnancy on gestational outcomes related to serum lipids amounts.

The Barthel index as an indicator of hospital outcomes: A retrospective cross-sectional study with healthcare data from older people.

AIMS: The assessment of functional status is a more appropriate measure in the older people than traditional healthcare outcomes. The present study aimed to analyse the association between functional status assessed using the Barthel Index and length of stay, in-hospital mortality, discharge destination, and Diagnosis-Related Groups-based cost. DESIGN: This study was a retrospective study that used administrative data from patients older than 65 discharged from the University Hospital of Padua (Italy) in 2016. METHODS: A logistic regression model for categorical variables (length of stay, in-hospital mortality, and discharge destination) and a generalized linear model with gamma distributions and log links for continuous variables (cost of hospitalization) were used to evaluate associations with the Barthel Index. RESULTS: A total of 13,484 admissions were included in the analysis. In-hospital mortality, safe discharge, and length of stay were higher in patients with severe dependence than in patients with mild/no dependence with a 12-fold increased risk of death (OR = 12.81; 95% CI 9.22-18.14), a 4 times greater likelihood of safe discharge (OR = 4.64; 95% CI 3.96-5.45), and a 2-fold increase in length of stay (OR = 2.56; 95% CI 2.34-2.81). On the other hand, no significant association was found between the cost of hospitalization and the Barthel Index. CONCLUSIONS: Barthel Index was strongly associated with in-hospital mortality, discharge destination, and length of stay. The costs of hospitalization, however, were not related to patients' functional impairment. IMPACT: The study considers functional status as an indicator of hospital outcomes. Better comprehension of the relationship between functional status and healthcare outcomes may help with early and adequate healthcare planning and resource management.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Perfluoroalkyl substances are associated with elevated blood pressure and hypertension in highly exposed young adults.

BACKGROUND: Residents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited, and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. METHODS: The study comprised 16,224 individuals aged 20-39 years. Pregnant women (n = 327), or individuals with missing information on the selected covariates (n = 111) were excluded, leaving 15,786 subjects for the analyses. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP ≥ 140 mmHg)/diastolic blood pressure (DBP ≥ 90 mmHg). Generalized additive models were used to investigate the relation between perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) natural log (ln) transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders. RESULTS: Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61-2.47), 1.60 mmHg (95%CI 0.92-2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and for DBP in women. One unit increase in each In-transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR = 1.06 (1.01-1.11), PFOS OR = 1.13 (1.03-1.23), PFHxS OR = 1.08 (1.02-1.15), PFNA OR = 1.20 (1.02-1.40). CONCLUSIONS: Our findings suggest that serum PFAS concentrations were associated with increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of public health relevance since even small increases in blood pressure levels at the population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.

Avoidable hospitalisation for diabetes mellitus among immigrants and natives: Results from the Italian Network for Longitudinal Metropolitan Studies.

BACKGROUND AND AIMS: Italy has experienced a relevant increase in migration inflow over the last 20 years. Although the Italian Health Service is widely accessible, immigrants can face many barriers that limit their use of health services. Diabetes mellitus (DM) has a different prevalence across ethnic groups, but studies focusing on DM care among immigrants in Europe are scarce. This study aimed to compare the rates of avoidable hospitalisation (AH) between native and immigrant adults in Italy. METHODS AND RESULTS: A multi-centre open cohort study including all 18- to 64-year-old residents in Turin, Venice, Reggio-Emilia, Modena, Bologna and Rome between 01/01/2001 and 31/12/2013-14 was conducted. Italian citizens were compared with immigrants from high migratory pressure countries who were further divided by their area of origin. We calculated age-, sex- and calendar year-adjusted rate ratios (RRs) and 95% confidence intervals (95% CIs) of AH for DM by citizenship using negative binomial regression models. The RRs were summarized using a random effects meta-analysis. The results showed higher AH rates among immigrant males (RR: 1.63, 95% CI: 1.16-2.23), whereas no significant difference was found for females (RR: 1.14, 95% CI: 0.65-1.99). Immigrants from Asia and Africa showed a higher risk than Italians, whereas those from Central-Eastern Europe and Central-Southern America did not show any increased risk. CONCLUSION: Adult male immigrants were at higher risk of experiencing AH for DM than Italians, with differences by area of origin, suggesting that they may experience lower access to and lower quality of primary care for DM. These services should be improved to reduce disparities.

Potentially avoidable hospitalization for asthma in children and adolescents by migrant status: results from the Italian Network for Longitudinal Metropolitan Studies.

BACKGROUND: Global migration toward Europe is increasing. Providing health assistance to migrants is challenging because numerous barriers limit their accessibility to health services. Migrants may be at a greater risk of developing asthma and receiving lower quality healthcare assistance than non-migrants. We aim to investigate whether immigrants as children and adolescents have higher rates of potentially avoidable hospitalization (PAH) for asthma compared to Italians. METHODS: We performed a retrospective longitudinal study using six cohorts of 2-17-year-old residents in North and Central Italy from 01/01/2001 to 31/12/2014 (N = 1,256,826). We linked asthma hospital discharges to individuals using anonymized keys. We estimated cohort-specific age and calendar-year-adjusted asthma PAH rate ratios (HRRs) and 95% confidence intervals (95%CIs) among immigrants compared to Italians. We applied a two-stage random effect model to estimate asthma PAH meta-analytic rate ratios (MHRRs). We analyzed data by gender and geographical area of origin countries. RESULTS: Three thousand three hundred four and 471 discharges for asthma PAH occurred among Italians and immigrants, respectively. Compared to Italians, the asthma PAH cohort-specific rate was higher for immigrant males in Bologna (HRR:2.42; 95%CI:1.53-3.81) and Roma (1.22; 1.02-1.45), and for females in Torino (1.56; 1.10-2.20) and Roma (1.82; 1.50-2.20). Asthma PAH MHRRs were higher only among immigrant females (MHRRs:1.48; 95%CI:1.18-1.87). MHRRs by area of origin were 63 to 113% higher among immigrants, except for Central-Eastern Europeans (0.80; 0.65-0.98). CONCLUSION: The asthma PAH meta-analytic rate was higher among female children and adolescent immigrants compared to Italians, with heterogeneity among cohorts showing higher cohort-specific PAH also among males, with some differences by origin country. Access to primary care for children and adolescent immigrants should be improved and immigrants should be considered at risk of severe asthma outcomes and consequently targeted by clinicians.

Prevalence of pressure ulcers in hospitalised patients: a cross-sectional study.

OBJECTIVE: The main aim of this study was to estimate the prevalence of pressure ulcers (PU) and related risk factors of PU development in hospitalised patients in Italy. Furthermore, the study investigated the association between risk factors for PU present on admission and the development during hospitalisation (hospital-acquired pressure ulcer, HAPU). METHODS: A cross-sectional study, using two separate designs at two separate timepoints: 2010 and 2015. The methodology used to measure PU prevalence was that recommended by the European Pressure Ulcer Advisory Panel (EPUAP). RESULTS: The total sample was 7681 hospitalised patients (3011 patients in 2010, 4670 in 2015). Prevalence of PU in hospital was 19.5% in 2010 and 17% in 2015. The number of patients with PU present on admission were 9.60% in 2010 and 9.42% in 2015. Patients with HAPU were 5.08% in 2010 and 5.87% in 2015. Older age and comorbidities, and a total Braden score of ≤16 were positively associated with PU present on admission and HAPU in hospitals (p<0.05). A longer length of stay appeared to correlate positively with a better clinical outcome for PU if there were already present on admission. Heterogeneous results emerged for length of stay of >30 days and being admitted to intensive care unit (ICU). CONCLUSION: Our results are comparable with other European and Italian studies. Most of the risk factors associated with PU development have been confirmed. However, further studies are needed to examine the effects of context on PU present on arrival and HAPU, especially regarding hospital length of stay.

Contribution of Italian nursing professors to international Literature: 2000 - 2016 review.

BACKGROUND: The purpose of the study was to assess Italian nurse academics' scientific activity by exploring their publications in international journals. BACKGROUND: The scientific production of a discipline's academics is a requisite for the university accreditation process and for employment in academic positions. It can also be used as an indicator of the maturity and importance of a given discipline in a country. Italian nurse academics' scientific production has not been analyzed recently. METHOD: Quantitative descriptive study on an observation period of 16 years, from 2000 to 2016. METHODS: All Italian full-time academics in the sector of General, Clinical, and Pediatric Nursing Sciences were identified, based on selection criteria. All their publications in indexed international journals were systematically collected between November 2016 and February 2017. FINDINGS: Twenty-five Italian nurse academics were identified, and 450 of their publications met all our inclusion criteria, with a mean of 18 publications per author (range 0-88). There was a steady growth in the number of publications over time. Sixty-five percent of articles were published in nursing journals. Eighty-six percent of the publications were on nursing topics, the most popular being clinical issues (53.8%). Eighty percent of the publications were "applied research articles" and most of them adopted a quantitative approach with a descriptive study design. Hospitals and clinics were the most common settings studied, while patients and caregivers were the participants most often involved. Foreign coauthors contributed to 30% of the articles. DISCUSSION: Italian nursing academics contribute adequately to scientific production in the nursing sector.

Is Adherence to a Gluten-Free Diet by Adult Patients With Celiac Disease Influenced by Their Knowledge of the Gluten Content of Foods?

The aim of this study was to investigate adherence to a gluten-free diet and potentially associated factors, focusing on the relationship between adherence and knowledge of the gluten content of foods and of celiac disease in general. A questionnaire was completed by adult patients diagnosed with celiac disease including demographics, dietary practices, sources of information, and attitude to the disease. Their knowledge of disease and gluten-free diet was assessed using a newly developed scale comprising 31 statements on celiac disease in general and foods appropriate in a gluten-free diet. A validated questionnaire was used to measure adherence to diet. One hundred four patients with celiac disease took part in the study, 65% of them reported strictly adhering to a gluten-free diet. Factors associated with adherence were membership of the Italian Celiac Association and receiving support from this association, Internet, and social media. Patients' knowledge regarding celiac disease and gluten-free diet was generally poor: one patient answered all questions correctly. Knowledge of celiac disease and gluten-free diet was strongly and significantly associated with adherence to a gluten-free diet. The association between knowledge of celiac disease and gluten-free diet in patients with celiac disease and their adherence to the diet suggests the promotion of education and behavioral programs.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Two Relevant Diseases of the Endocrine System: Diabetes Mellitus and Thyroid Disorders.

BACKGROUND: diabetes mellitus (DM) and thyroid disorders (TDs) are two of the most prevalent and relevant endocrine disorders worldwide, and determining their occurrence and their follow-up pathways is essential. In Italy, due to the presence of a universal health care system, administrative data can be effectively used to determine these measurements. DM is an ideal model for surveillance with administrative data, due to its specific pharmacologic treatment, high rate of hospitalization, and specific care units. The identification of TDs, conversely, is more challenging: they are less frequently managed in a hospital setting, and even if the treatment is highly specific, subclinical forms often do not need any pharmacological treatment. OBJECTIVES: to identify and to describe all DM and TD caseidentification algorithms by means of Italian Healthcare Administrative Databases (HADs), through the review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for "primary objectives" (I disease occurrence; II population/cohort selection; III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. Algorithms were divided between those identifying type 2/not specified DM and type 1 DM, and those created to identify hypo- and hyperthyroidism. RESULTS: of the 780 articles identified for DM, 77 were included and a further 14 papers were added by screening the references. For TD, 65 articles were identified through the search string and 5 of them were included. Of the selected articles, 64% and 80% were published after 2014 for DM and TD, respectively, and 33% (for DM) and 20% (for TD) used multicentric national or international data. Forty original algorithms for DM (29 for type 2 DM/not-specified DM, and 11 for type 1 DM) and 9 for TD (6 for hypo- and 3 for hyperthyroidism) were extracted. In 6 algorithms, specific selections were made so as not to include gestational diabetes. With regard to type 2 DM, the most commonly used sources were the drug prescription database (DPD, 27 cases), hospital discharge record database (HDD, 23 cases), and exemption from healthcare co-payment database (ECD, 19 cases). Other sources were the ambulatory care services database (ACD), birth register, and mortality record database (MRD). Among the 11 algorithms to identify type 1 DM, 9 used DPD, 7 ECD, and 6 HDD; in one case ACD codes were added, and all 11 algorithms but one was applied to a population of young people (always <35 years old). With regard to TDs, 2 algorithms from one paper for hypo and hyperthyroidism relied on DPD as the only source, the other 7 original algorithms combined DPD with HDD (5 cases), ECD (3 cases), and ACD (1 case). One paper identified autoimmune/iodine deficiency hypothyroidism by subtracting iatrogenic hypothyroidism cases (identified through records of previous procedures from HDD and ACD) from the whole hypothyroid population (identified through DPD). External validation was performed for two algorithms for DM and none for TD. The first algorithm for DM was obtained through HDD only and its sensitivity ranged from 61% to 70%, the second had a sensitivity of 71%. CONCLUSION: Italian literature on the use of administrative healthcare data for case identification of diabetes is vast; the proposed algorithms are quite similar to one another, and the differences between them are rarely accompanied by clinical justification. On the contrary, the literature concerning thyroid disorders is relatively poor. Further validations of the proposed algorithms, as well as their further implementation, are needed.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Three Relevant Diseases of the Digestive and Genitourinary System: Inflammatory Bowel Diseases, Celiac Disease, and Chronic Kidney Disease.

OBJECTIVES: to identify and describe all Inflammatory Bowel Disease (IBD), Celiac Disease (CD), and Chronic Kidney Disease (CKD) case-identification algorithms by means of Italian Healthcare Administrative Databases (HADs), through a review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers; exclusion criteria were the following: no details of algorithms reported, algorithm not developed in the Italian context, exclusive use of data from the death certificate register, or from general practitioner or pediatrician databases. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for primary objectives (I disease occurrence, II population/cohort selection, III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, followback periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. RESULTS: the search string led to the identification of 98 articles for IBD, 42 articles for CD, and 390 for CKD. By screening the references, one paper for IBD was added. Finally, this led to 5, 9, and 8 pertinent papers respectively for IBD, CD, and CKD. Considering the papers on IBD and CD, specific age selections were applied to focus on children and young adult populations. When a selection on age was applied for CKD, instead, it mostly considered individuals aged more than 18 years. Three algorithms for IBD, 4 for CD, and 5 for CKD were extracted from papers and characterized. Drug prescription databases were used for both IBD and CKD algorithms, whereas the hospital discharge database and co-payment exemption database were used for IBD and CD. Pathology records and specialist visit databases were also used for CD and CKD, respectively. For each disease only one algorithm applied criteria for the exclusion of prevalent cases. External validation was performed only for Crohn's disease among IBDs, in one algorithm. CONCLUSIONS: the results of this review indicate that case identification for IBD and CD from routinely collected data can be considered feasible and can be used to perform different kinds of epidemiological studies. The same is not true for CKD, which requires further efforts, mainly to improve the detection of early stage patients.

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Three Relevant Diseases of the Nervous System: Parkinson's Disease, Multiple Sclerosis, and Epilepsy.

BACKGROUND: Parkinson's Disease (PD), Multiple Sclerosis (MS), and Epilepsy are three highly impactful health conditions affecting the nervous system. PD, MS, and epilepsy cases can be identified by means of Healthcare Administrative Databases (HADs) to estimate the occurrence of these diseases, to better monitor the adherence to treatments, and to evaluate patients' outcomes. Nevertheless, the absence of a validated and standardized approach makes it hard to quantify case misclassification. OBJECTIVES: to identify and describe all PD, MS, and epilepsy case-identification algorithms by means of Italian HADs, through the review of papers published in the past 10 years. METHODS: this study is part of a project that systematically reviewed case-identification algorithms for 18 acute and chronic conditions by means of HADs in Italy. PubMed was searched for original articles, published between 2007 and 2017, in Italian or English. The search string consisted of a combination of free text and MeSH terms with a common part that focused on HADs and a disease-specific part. All identified papers were screened by two independent reviewers. Pertinent papers were classified according to the objective for which the algorithm had been used, and only articles that used algorithms for primary objectives (I disease occurrence; II population/cohort selection; III outcome identification) were considered for algorithm extraction. The HADs used (hospital discharge records, drug prescriptions, etc.), ICD-9 and ICD-10 codes, ATC classification of drugs, follow-back periods, and age ranges applied by the algorithms have been reported. Further information on specific objective(s), accuracy measures, sensitivity analyses and the contribution of each HAD, have also been recorded. RESULTS: the search strategy led to the identification of 70 papers for PD, 154 for MS, and 100 for epilepsy, of which 3 papers for PD, 6 for MS, and 5 for epilepsy were considered pertinent. Most articles were published in the last three years (2014-2017) and focused on a region-wide setting. Out of all pertinent articles, 3 original algorithms for PD, 4 for MS, and 4 for epilepsy were identified. The Drug Prescription Database (DPD) and Hospital Discharge record Database (HDD) were used by almost all PD, MS, and epilepsy case-identification algorithms. The Exemption from healthcare Co-payment Database (ECD) was used by all PD and MS case-identification algorithms, while only 1 epilepsy case-identification algorithm used this source. All epilepsy case-identification algorithms were based on at least a combination of electroencephalogram (EEG) and drug prescriptions. An external validation had been performed by 2 papers for MS, 2 for epilepsy, and only 1 for PD. CONCLUSION: the results of our review highlighted the scarce use of HADs for the identification of cases affected by neurological diseases in Italy. While PD and MS algorithms are not so heterogeneous, epilepsy case-identification algorithms have increased in complexity over time. Further validations are needed to better understand the specific characteristics of these algorithms.