Abstract Background Since the use of medicines is strongly correlated to population health needs, higher drug consumption is expected in socio-economical deprived areas. However, no systematic study investigated the relationship between medications use in the treatment of chronic diseases and the socioeconomic position of patients. The purpose of the study is to provide a description, both at national level and with geographical detail, of the use of medicines, in terms of consumption, adherence and persistence, for the treatment of major chronic diseases in groups of population with different level of socioeconomic position. Methods A cross-sectional study design was used to define the “prevalent” users during 2018. A longitudinal cohort study design was performed for each chronic disease in new drug users, in 2018 and the following year. A retrospective population-based study, considering all adult Italian residents (i.e. around 50.7 million people aged ≥ 18 years). Different medications were used as a proxy for underlying chronic diseases: hypertension, dyslipidemia, osteoporosis, diabetes and chronic obstructive pulmonary disease. Only “chronic” patients who had at least 2 prescriptions within the same subgroup of drugs or specific medications during the year were selected for the analysis. A multidimensional measures of socio-economic position, declined in a national deprivation index at the municipality level, was used to identify and estimate the relationship with drug use indicators. The medicine consumption rate for each pharmacological category was estimated for prevalent users while adherence and persistence to pharmacologic therapy at 12 months were evaluated for new users. Results The results highlighted how the socioeconomic deprivation is strongly correlated with the use of medicines: after adjustment by deprivation index, the drug consumption rates decreased, mainly in the most disadvantaged areas, where consumption levels are on average higher than in other areas. On the other hand, the adherence and persistence indicators did not show the same trend. Conclusions This study showed that drug consumption is influenced by the level of deprivation consistently with the distribution of diseases. For this reason, the main levers on which it is necessary to act to reduce disparities in health status are mainly related to prevention. Moreover, it is worth pointing out that the use of a municipal deprivation indicator necessarily generates an ecological bias, however, the experience of the present study, which for the first-time deals with the complex and delicate issue of equity in Italian pharmaceutical assistance, sets the stage for new insights that could overcome the limits.

Abstract Background To face the second COVID-19 wave, Italy implemented a tiered restriction system with different risk levels (yellow=low; orange=medium, red=high). It is unknown whether the effect of the tiers was equal among provinces with varying levels of socioeconomic deprivation (SED). At each restriction level, we analyzed the impact of the province's SED on the SARS-CoV-2 daily reproduction number (Rt). Methods We considered the Rt (Nov 2020-May 2021) as the dependent variable and the SED as the independent variable. The Rt was estimated using daily incidence data from the Civil Protection Department as the instantaneous Rt. The province SED was measured using the percentage of individuals whose yearly income was less than 10,000€ (2019 data from the Ministry of Economy and Finance). We used multilevel linear regression models with random intercepts stratified by restriction level to estimate the effect of the SED on Rt (β) and its Standard Error (SE). Our analyses adjusted the estimates for the number of days into the tier first and then for other covariates. Results We found different levels and trends of Rt by SED in every restriction. Days-adjusted models found a containing effect for the red and the orange tier, while the Rt had an increasing trend in yellow. Higher SED was associated with higher Rt: β was positive and significant in red (β = 0.004 SE = 0.001) and orange (β = 0.002 SE = 0.001) but not in the lowest tier (β = 0.001 SE = 0.001). We found a significant interaction between the number of days into the restriction and the SED in the complete models. Compared to less deprived, more deprived provinces had slower Rt reduction in the highest tier. However, they had steeper Rt reductions in orange and slower increasing trends in yellow. Conclusions The highest restriction had milder effects in more deprived provinces, while lower tiers were more effective. These results underline the importance of accounting for SED when implementing public health measures. Key messages • Area-level deprivation can modify the effects of public health measures. • Socioeconomic characteristics of the areas should be considered when implementing policies aimed to prevent the spread of epidemics.

Several indicators at individual and area level have been used to stratify the population. The aim of this work was to investigate the association between real estate prices, education and health status in Rome. We used the administrative cohort of residents in Rome at the 2011 census. We followed subjects aged 18+ from 2011 to 2016 using anonymous record linkage procedures with administrative databases. The census includes several individual information, comprising sex, age, education, and residential urbanistic zone. From mortality register we collected date and cause of death. Real estate prices (€/m2) were available for each urbanistic zone. We classified the population in five categories according to the quintile of the distribution (1=highest prices, 5=lowest prices). We used adjusted Cox regression models to estimate the hazard ratios (HRs) and 95%CIs. We selected 2,053,668 subjects, not living in institutions at the time of the census survey. Women were 54% of the population; the mean age was 52 years (sd 18), 22.5% had a high education (university degree) and 37% a low education (≤ junior high school). During the follow-up, 126,548 subjects died. As expected educational level was strongly associated with all-cause mortality (39% higher risk of low vs. high educated). The mortality risk increased with decreasing real estate prices, taking account of age and sex. Compared to subjects living in highest prices areas, those living in level 2 areas had a HR = 1.08 (95%CI: 1.06-1.10), those in level 3 had a HR = 1.14 (95%CI: 1.12-1.16), those in level 4 a HR = 1.16 (95%CI 1.14-1.18), and finally those living in the cheapest areas a HR = 1.22 (95%CI: 1.20-1.25). When we considered both education and real estate prizes, the HRs marginally decreased. There is an independent association of both individual education and socioeconomic characteristics of the area of residence and all-cause mortality. There are strong socioeconomic inequalities in Rome. A simple indicator such as real estate prices can be used to tackle inequalities.

OPS 51: Air pollution and mortality: what’s new? Beatrix Theater, August 26, 2019, 4:30 PM - 5:30 PM Background/Aim: Few studies evaluated the association between long-term exposure to ultrafine particles (UFP) and mortality. We aimed to study the association between UFP and mortality in a large administrative cohort (Rome Longitudinal Study, RoLS) and to evaluate whether the role of UFP is independent of other exposures. Methods: We selected 1,009,434 30+ year olds living in the Rome urban area, and we followed them from 2001 to 2013. We used land use regression models for PNC (particle number concentrations) as proxy for UFP, NO2, PM2.5, PM2.5 absorbance (as proxy for soot), and zinc component of PM2.5 (as proxy for non-tail-pipe emissions). We used the acoustic model SoundPLAN7.4 to assess road traffic noise indicators (Lden, Lnight). All exposures were attributed to the residential address of each subject. We analyzed non-accidental, cardiovascular, and ischemic heart disease (IHD) mortality. We applied Cox proportional hazard models adjusted for age, sex, education, place of birth, marital status, occupation, area-level socioeconomic position. We performed single-pollutant and two-pollutant models. Results: The average population exposure was 16,014 (interquartile range, iqr=2,659) n/cm3 PNC, 47 (iqr=8) µg/m3 NO2, 20 (iqr=2) µg/m3 PM2.5, 2.8 (iqr=0.3) 10–5/m PM2.5-absorbance, 25 (iqr=3.4) ng/m3 PM2.5-Zn, 61 (iqr=11) dB. The correlation between UFP and the other exposures ranged from 0.45 (UFP-noise) to 0.61 (UFP-PM2.5). We observed 166,787 deaths for non-accidental causes, 69,034 for cardiovascular causes, and 25,092 for ischemic heart disease. We estimated an increase in non-accidental (Hazard Ratio [HR]=1.010, 95%CI:1.004-1.016), cardiovascular (HR=1.029, 95%CI:1.020-1.038), and IHD (HR=1.032, 95%CI:1.016-1.047) mortality, per iqr increments in PNC. Results were robust to adjustment for all other exposures for cardiovascular and IHD mortality. For non-accidental mortality, adjustment for NO2 and PM2.5-absorbance substantially decreased the PNC effect estimates. Conclusions: We found an effect of UFP exposure on cardiovascular mortality independent of the concomitant exposure to other air pollutants and traffic noise.

S21: When the Answer is "Big(ger) Data" in Environmental Epidemiology: What are the Questions?, Room 315, Floor 3, August 26, 2019, 1:30 PM - 3:00 PM Aim: Multi-center collaborations provide the opportunity for harmonized epidemiological analyses in large data sets that increase statistical power to detect associations. We assessed methodological approaches for the analysis of multi-level survival data within the framework of the ELAPSE project that pooled data from nine European cohorts to assess the association of long term residential exposure to air pollutants with mortality. Methods: After harmonizing individual and area-level variables between cohorts, we applied Cox proportional hazard models adjusting for these covariates. The data presented two levels of clustering: one corresponding to the initial cohort and one to the residential neighborhood level. We assessed five approaches to account for the first level: 1) not accounting for the cohort or using 2) dummies for cohorts, 3) strata per cohort, 4) a frailty term for cohort identification, 5) a random intercept per cohort under a mixed Cox. We further assessed second level clustering by applying 1) a random intercept per neighborhood and 2) a variance correction method -recognizing that approaches have different interpretations. We finally assessed the frailty vs the stratified approach for cohort adjustment through 1,000 simulations under nine scenarios for varying amount of heterogeneity between cohorts and pollutants' effects. Results: Our results support that effect estimates derived from any of the approaches to account for different initial cohorts are stable except absence of any adjustment, while adjustment for the neighborhood clustering increased the estimates' standard errors. Simulations confirmed the identical results between the stratified and frailty model except in the case of large heterogeneity between the underlying hazards and the pollutant effects that resulted in a difference of 0.0001 in the pollutant coefficient between methods. Conclusions: It is important to account for across cohort heterogeneity although the specific approach may be less important. We encourage investigators to consider study-specific conditions and objectives.

PDS 74: Pregnancy outcomes, Exhibition Hall (PDS), Ground floor, August 26, 2019, 1:30 PM - 3:00 PM Background/Aim: The health effects of particulate matter (PM) could depend on its chemical composition. Few studies examined the associations between maternal exposure to chemical constituents of PM and pregnancy outcomes. Our aim was to investigate the association between elemental constituents of PM and term low birth weight (LBW: weight < 2,500 g among births after 37 weeks of gestation), preterm births, and small for gestational age (SGA, according to the Italian curves). Methods: We considered all singleton livebirths from mother who lived in Rome for the entire pregnancy in the period 2006-2014. We used land-use regression models to estimate annual average concentrations of elemental constituents of PM ≤ 2.5 and ≤ 10 μm (PM2.5 and PM10) at maternal home addresses during pregnancy. We considered eight elements: copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc. We used logistic regression to evaluate the association between exposure and outcomes, taking account of maternal age, parity, maternal education, season of conception, sex of the newborn, census block index of socioeconomic position. Results: Among the 172,325 singleton livebirths, 2.31% were term low birth weight, 6.07% were preterm births, and 8.59% were SGA. All the elemental constituents considered were associated to LBW and SGA. A 200-ng/m3 increase in sulfur in PM10 was associated with an increased risk of LBW (OR = 1.38; 95%: 1.22-1.57), an increased risk in SGA (OR=1.13; 95%CI: 1.06-1.21), and an increased risk in preterm births (OR=1.09; 95%CI: 1.01-1.17). The association was independent of PM10. Conclusions: The association between PM and pregnancy outcomes can be attributed to several components. Sulfur and Nickel components seem to be important.

Background: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence.Methods: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis.Results: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 125; 95% Cl, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m3), PMio S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PMio and PM2.5 and lung cancer were largely explained by PM2.5 S.Conclusions: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important. (C) 2015 Elsevier Ltd. All rights reserved.

speckle tracking echocardiography, regional metabolism by FDG-PET and regional perfusion by SPECT. Regional LV work was estimated from loop area of segmental LV pressure-strain loops, using a previously validated method to estimate LV pressure. Segmental values of glucose metabolism, perfusion and work were expressed as percentage of the peak value in the ventricle. The figure shows bull’s eye plots for regional glucose uptake (A), regional perfusion (B) and non-invasive pressure-strain loop area (C) in a representative patient. The figure illustrates that glucose metabolism (p< 0.01) as well as perfusion (p < 0.01) were markedly reduced in the septum. The negative values for segmental work in the septum imply that the septum produced no contribution to LV work. Pooled data support these findings with good correlations between segmental values of work and glucose uptake, r=0.82 (p< 0.01) and perfusion, r=0.59 (p< 0.01). Conclusions: Reduced septal perfusion in patients with normal coronaries and LBBB was attributed to reduced septal work which caused reduced metabolic demand. This abnormal distribution of myocardial energy metabolism is a reflection of the inefficient contractile function during LBBB and contributes to the understanding of the heterogeneous LV remodelling seen in this patient group.

Introduction: The Aphekom project aimed to provide new, clear, and meaningful information on the health effects of air pollution in Europe. Among others, it assessed the health and monetary benefits of reducing short and long-term exposure to particulate matter (PM) and ozone in 25 European cities.Method: Health impact assessments were performed using routine health and air quality data, and a common methodology. Two scenarios were considered: a decrease of the air pollutant levels by a fixed amount and a decrease to the World Health Organization (WHO) air quality guidelines. Results were economically valued by using a willingness to pay approach for mortality and a cost of illness approach for morbidity.Results: In the 25 cities, the largest health burden was attributable to the impacts of chronic exposure to PM2.5. Complying with the WHO guideline of 10 mu g/m(3) in annual mean would add up to 22 months of life expectancy at age 30, depending on the city, corresponding to a total of 19,000 deaths delayed. The associated monetary gain would total some (sic)31 billion annually, including savings on health expenditures, absenteeism and intangible costs such as well-being, life expectancy and quality of life.Conclusion: European citizens are still exposed to concentrations exceeding the WHO recommendations. Aphekom provided robust estimates confirming that reducing urban air pollution would result in significant health and monetary gains in Europe. This work is particularly relevant now when the current EU legislation is being revised for an update in 2013. (C) 2013 Elsevier B.V. All rights reserved.

Purpose: The fibroblast growth factor-23 (FGF-23) is a key player in the regulation of calcium-phosphate and vitamin D metabolism and has a causal role in the pathogenesis of LV hypertrophy, a major determinant of cardiovascular events. We evaluated the association between circulating levels of FGF-23 / vitamin D, slight abnormalities in LV mass and mortality in elderly people.

Objectives Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. Methods The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998–2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. Results Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m3 (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. Conclusions Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

OBJECTIVE:To investigate the association between circulating cardiac biomarkers and minor abnormalities in cardiac phenotype [left ventricular (LV) mass and midwall fractional shortening (MFS)] in elderly individuals in a general population sample. DESIGN AND SETTING:We examined the relationship between plasma concentrations of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal probrain natriuretic peptide (NT-proBNP) and elevated LV mass (LV mass/body surface area >95 g m(-2) for women and 115 g m(-2) for men), reduced MFS (<15%) or isolated LV diastolic dysfunction in 1973 elderly subjects (mean age 73 ± 5 years, range 65-84) resident in the Lazio region of Italy and enrolled in the PREDICTOR study. RESULTS:Overall, 24.8% of subjects had elevated LV mass, and 30.4% had reduced MFS. Median [quartile 1-3] plasma concentrations of hs-cTnT and NT-proBNP were higher in individuals with elevated than those with normal LV mass: 6.6 [3.5-11.6] and 147 [64-296] ng L(-1) vs. 4.6 [3.0-8.1] and 79 [41-151] ng L(-1) respectively (P < 0.001). There was a graded increase in median hs-cTnT concentrations across clinical categories of LV hypertrophy: 4.6 [3.0-8.1], 5.8 [3.1-10.2], 7.6 [3.8-13.7] and 8.4 [3.8-17.6] ng L(-1) for subjects with normal LV mass and mild, moderate or severe LV hypertrophy respectively (P < 0.0001); hs-cTnT also increased with increasing quartiles of MFS or grades of isolated LV diastolic dysfunction. CONCLUSIONS:Within an extremely low range of concentrations, increased hs-cTnT amongst community-dwelling elderly subjects is associated with subtle alterations in cardiac phenotype, suggesting that minor injury to cardiac myocytes and subsequent release of troponin reflect subclinical pathophysiological LV deterioration in this population.

Objective To examine the association between socioeconomic status (SES) and eight selected surgical outcomes after hysterectomy and asses the role of lifestyle, co-morbidity and clinical conditions on the relationship. Methods All 22 150 women registered with a benign elective hysterectomy code in the national Danish Hysterectomy Database (DHD) from 2004 to 2008 were included in the study. Data from DHD were linked to several central registers providing information on education, employment, income, lifestyle factors, co-morbidities and surgical outcome. Data were analysed using multilevel logistic regression models. Results Overall 17% of the women experienced a clinical complication in relation to hysterectomy. Four per cent were re-operated, 6% readmitted and 6% experienced prolonged hospitalisation ≥5 days. Women with short education had a higher risk of complications than women with higher education after adjusting for patient characteristics (OR=1.15, 95% CI 1.02 to 1.31). They also had a higher risk of peroperative bleeding after adjusting for lifestyle factors and co-morbidity (OR=1.60, CI 1.15 to 2.22). Furthermore, a higher risk of infection and readmission was observed however, these relations seemed fully explained by lifestyle factors and co-morbidity. Women out of employment had a higher risk of infection, organ lesion, prolonged hospitalisation and readmission than women in employment. We found no association between income and surgical outcome after hysterectomy. Conclusion This study suggests that women with low SES have a significant worse surgical outcome after hysterectomy than women with high SES when differences in lifestyle factors and co-morbidity are taking into account.

Background and aims: Few studies have evaluated the association between long-term exposure to air pollution and incidence or prognosis of stroke. We investigated the association between nitrogen dioxide (NO2) exposure at residence and incidence of stroke (total and by subtype) and its prognosis within a large cohort study. Methods: The Rome Longitudinal Study (RoLS) is a fixed cohort enrolled at the 2001 census. We selected subjects aged 45-80 years at the baseline who had not changed their address nor had a hospital admission for stroke in the previous five years (n=677,909). Incident cases of stroke occurred between October 2001 and December 2004 were selected from administrative databases. NO2 exposure was estimated for residence's coordinates through a land use regression model (R2=0.66). Subjects were followed till December 31st, 2006. We used Cox regression models to evaluate the association between NO2 exposure and incidence of stroke and survival taking account of education, occupation, place of birth, and area-based socioeconomic position (SEP). Results: During the period 2001-2004 there were 4455 new cases of stroke (76% ischemic) in the cohort . Average exposure of NO2 was 44 (sd 8) μg/m3. There was no evidence of association between NO2 at residence and incidence of stroke in the study population, both for ischemic and hemorrhagic forms. Stroke incident cases in the highest quintile of exposure (>50.2μg/m3) had 23% (95%CI:3%-47%) risk of dying for natural causes than those living in the lowest quintile (<35.7μg/m3). After first stroke there was a 9% (95%CI:3%-17%) higher risk of dying for 10μg/m3 increase of NO2 at residence. Conclusions: Although there was no evident association between air pollution exposure at residence and incidence of stroke, we found a strong evidence of association between NO2 exposure and survival after first stroke.