[Effects of high temperature and air pollution on the risk of preterm births. Analysis in six Italian cities, 2001-2010]. / Effetti delle alte temperature e dell'inquinamento atmosferico sul rischio di nascita pretermine. Analisi in sei città italiane, 2001-2010.

OBJECTIVES: to evaluate the association between short term maternal exposure to high temperature and air pollution on preterm births (PBs), which represent the first cause of perinatal mortality and morbidity in developed Countries, and to identify maternal risk factors enhancing individual susceptibility. DESIGN: time series. SETTING E PARTICIPANTS: all singleton live-births occurred in six Italian cities between 1st April and 31st October of each year in the period 2001-2010 were identified through the Certificate of Delivery Care Registry (CedAP). MAIN OUTCOME MEASURES: births occurred between 22nd and 36th week of gestation were defined as preterm births. Daily values were obtained for maximum apparent temperature (MAT), PM10, NO2, and O3. Exposures-preterm births association was estimated using a generalized additive model (GAM) with a Poisson distribution. Exposure and city-specific lag structure were computed using a non-linear distributed lag model (DLNM). RESULTS: 121,797 newborns were enrolled, 6,135 (5.0%) of which were PBs. For MAT, a linear relationship was observed for Turin (Piedmont Region, Northern Italy), Trieste (Friuli Venezia Giulia Region, Northern Italy), Rome (Lazio Region, Central Italy), and Palermo (Sicily Region, Southern Italy), while non-linear relationship was found for Bologna (Emilia-Romagna Region, Northern Italy) and Venice (Veneto Region, Northern Italy). The relative risks (RR) for MAT, computed comparing the 90th vs. the 75th percentile, vary from 1.02 (95%CI 0.95-1.09; lag 0-2) in Palermo to 1.94 (95%CI 1.32-2.85; lag 0-3) in Venice. For pollutants, a significant effect for 10 µg/m3 (IQR) increase of PM10 in Rome (RR: 1.07; 95%CI 1.02-1.12; lag 12-22) and for 16 µg/m3 (IQR) increase of O3 in Palermo (RR: 1.29; 95%CI 1.03-1.62; lag 2-9) was detected. In Rome, a significant effect modification by age and education level of the MAT-PB relationship and by education level and clinical conditions of PM10-PB was found. CONCLUSIONS: results showed a clear positive association between MAT and the risk of NP and a lower and variable effect of pollutants. It is important and necessary to limit the impact of these risk factors on the probability of NP with appropriate prevention programmes.

Temperature in summer and children's hospitalizations in two Mediterranean cities.

BACKGROUND AND OBJECTIVE: Children are potentially vulnerable to hot ambient temperature. However, the evidence on heat-related children's morbidity is still scarce. Our aim was to examine the association between temperatures in summer (May to September) and children's hospitalizations in two Mediterranean cities, Rome and Valencia, during the period 2001-2010. METHODS: Quasi-Poisson generalised additive models and distributed lag non-linear models were combined to study the relationship between daily mean temperature and hospital admissions for all natural, respiratory and gastrointestinal diseases in children under 15 years of age. Associations were summarised as the percentage of change (Ch%) in admissions at 50th, 75th, 90th, 95th and 98th percentiles of temperature in summer compared to 1.) the 50th percentile in the whole year (50th(y)) and 2.) the preceding percentile in the previous series. Cumulated risks were obtained for groups of lags showing a similar pattern: 0-1, 2-7, 8-14 and 15-21 days. RESULTS: Almost whatever increase of temperature from 50th(y) was significantly associated with an increase of paediatric hospitalizations by all natural diseases at short term (lag 0-1), while small increases at high temperatures only had a delayed effect on this outcome. The same pattern was observed in Rome for respiratory admissions, while in Valencia only a delayed association (days 8-14) was observed. The increase of temperature from 50th to 75th percentiles was associated at short time to an increase of gastrointestinal admissions in both cities. CONCLUSION: Children's hospitalizations rose with heat in Rome and Valencia. Patterns of delays and critical windows of exposure mainly varied according the outcome considered.

[Cluster statistical analysis in epidemiology]. / L'analisi statistica dei cluster in epidemiologia.

Statistical analysis represents a critical point in cluster analysis, because a methodology able to take into consideration the complexity of this analysis has not yet been developed. However, a common approach in statistical analysis of a suspected cluster is a necessary tool for public health operators who have to face population worries and requests. We propose an approach for the analysis of clusters and discuss the main limitations and strengths of the used methods. To this aim, we present, as a case study, the spatial clustering analysis of acute lymphoblastic leukaemia (ALL) cases among children in Rome between 2000 and 2011. Cases were selected through a record linkage of three different health and administrative current databases. Cases were geocoded at 3 spatial resolutions: 20 districts (D), 155 neighbourhoods (NB), and 5,812 census areas (CA). Indirect standardized incidence ratios (SIR) were computed for the NBs with Rome average incidence rate (IR) of ALL as reference and then smoothed by Besag-York-Mollie (BYM) model. General clustering was tested by Tango statistics, whereas localized clustering was detected through two different statistics: Besag and Newell's, and Kulldorf and Nagarwalla's. Both general and local clustering were tested at city level, using NBs as area units, and at district level, using CAs as area units. We identified 194 ALL cases in the 0-14 age group (IR: 43.7x1,000,000). SIRs ranged between 0.00 and 18.1 among NBs. After smoothing, a significant excess of cases was identified only in 3 Ds. At city level, no general clustering was highlighted (Tango's test p-value: 0.08), while both tests for local clustering were significant in one of the 3 Ds with the highest SIRs. Finally, at district level, although no general cluster was founded, a total of 7 clusters were identified in the 3 Ds with the highest SIRs, each cluster being composed by a number of cases ranging between 2 and 6. Results indicate the presence of clusters in some areas of Rome, which are evident only when the finest spatial resolution is used. This standardised procedure is an important tool to properly analyse potential clusters.

[A systematic review of epidemiological cohort studies based on the Italian Medical Birth Register. Is it time to think of a multicentric birth cohort?] / Una revisione sistematica degli studi epidemiologici basati su coorti CeDAP in Italia. Possibile pensare a una coorte di nascita multicentrica?

INTRODUCTION: birth cohorts are a necessary tool for the study of the effects of exposures which can occur during pregnancy and early life on the development and health status in paediatric and adult life. The Italian Medical Birth Register (CeDAP), linked with other health administrative data, allows to build population based births cohorts to be followed over time. OBJECTIVES: to sistematically review all published scientific papers using data extracted from the (CeDAP) in order to give a picture of their current use for epidemiological aims; to describe advantages and limits of these data and possible future developments for epidemiological purposes. METHODS: a systematic review was conducted using PubMed, identifying all peer-reviewed research papers in English or Italian published by November 2015, by combining of free text and MeSH terms, where available. Features of included papers have been double checked and possible disagreements have been discussed to reach consensus. RESULTS: the research strategy found 720 papers, 35 of which fulfilling the required criteria. Only few Italian regions used CeDAP data for epidemiological studies, particularly Lazio and Umbria (Central Italy) and Emilia-Romagna and Friuli Venezia Giulia (Northern Italy). About half of the included papers were analytical, while the others were descriptive. Occurrence of caesarean deliveries and the prevalence of malformations were the most recurrent topics. Almost all papers used only data at delivery, whereas 5 papers used a longitudinal design with follow-up after birth. CONCLUSIONS: the Italian CeDAP registry is an important source of information for epidemiological research and its use for both aetiological aims and health services assessment should be enhanced. Furthermore, its characteristics, in particular its homogeneity among all Italian regions, might allow to create a multiregional birth cohort to be regularly followed up.

[Literature review of childhood leukaemia cluster investigations]. / Revisione degli studi di cluster di leucemia infantile.

Since the first report of a possible cluster of childhood leukaemia in 1963, many studies have shown a tendency to clustering in space and/or in time of this disease. This paper summarizes the studies about clusters of childhood leukaemia in the international context and in Italy, and discusses the aetiological hypotheses particularly in reference to exposures in the area of residence. Thirty-three cluster studies have been identified through a literature search performed using the PubMed bibliographic database, websites of main national and international health authorities, and relevant reviews published on this topic. Most of leukaemia cluster studies were conducted following an alarm in the nearby areas of a point source of toxic substances as nuclear power plants, chemical-industrial sites, military bases, broadcasting antennas. As alternative explanation, in several clusters an infectious aetiology was hypothesized (population mixing or delayed infection hypothesis). The uncertainty associated with cluster investigations underlines the importance of applying rigorous methods and transparent decision making, involving parents of children with cancer and the local community, and taking into account all potential aetiological factors, especially those for which a biological plausibility exists.

[An example of the integrated use of administrative health databases for the study of childhood cancer clusters]. / Un esempio di uso integrato di banche dati sanitarie correnti per lo studio dei cluster di tumori infantili.

We developed an algorithm to select incident cases of lymphatic and haematopoietic system in children, in order to create a timely and accurate database of incident cases to answer the needs of cluster analysis. This group of cancers is by far the most frequent in the paediatric age. The procedure has been applied to identify incident cases in children aged 0-14 years, resident in Rome (Central Italy), and diagnosed between 2000 and 2011. The algorithm links hospital discharge records (SDO), the hospital registry of the Italian Association of paediatric haematology and oncology (AIEOP), and the Population Registry. We identified 391 cases of cancers of lymphatic and haematopoietic system; among them, the most frequent pathology is the lymphoid leukaemia, which represents 52% of total cases, followed by non-Hodgkin lymphoma (21% of total cases). Results correspond to data from literature and to the estimates from the Italian Association of cancer registries (AIRTUM), giving value to the used procedure.

[Investigative model for the evaluation of spatio-temporal clusters of childhood cancers]. / Modelli di indagine per la valutazione di cluster spazio-temporali di tumori infantili.

This paper describes the conceptual framework and the critical issues of investigations of clusters of childhood cancers and defines an investigative model for the health authorities responsible for assessing a suspected cluster, taking into account the guidelines available and considering the most recent advances of the Geographical Information System and of the specific statistical methodology. Three main investigation phases are identified: the first consists in the preliminary study on the health of population living in the area where the cases are defined and aetiological hypotheses are formulated; the second is the cluster evaluation study using statistical methods assessing the spatial heterogeneity and collecting information about potential risk factors; the third is the analytical epidemiological study to test aetiological hypotheses suggested by the previous phases. The residential cohort approach is the most valid to date to assess long-term effects, and allows to reconstruct the lifetime residential history from the population registry. The researchers' decision on how detailed about a suspected cluster the investigation has to be needs to take into account both the level of alarm in the population and the limited resources available. The concern about a suspected cluster of cancer cases should always be addressed, even if this implies to acknowledge limits of research and uncertainty in results interpretation.

The effect of heat waves on mortality in susceptible groups: a cohort study of a mediterranean and a northern European City.

BACKGROUND: Climate change is projected to increase the number and intensity of extreme weather events, for example heat waves. Heat waves have adverse health effects, especially for the elderly, since chronic diseases are more frequent in that group than in the population overall. The aim of the study was to investigate mortality during heat waves in an adult population aged 50 years or over, as well as in susceptible subgroups of that population in Rome and Stockholm during the summer periods from 2000 to 2008. METHODS: We collected daily number of deaths occurring between 15th May and 15th September each year for the population above 50 as well as the susceptible subgroups. Heat wave days were defined as two or more days exceeding the city specific 95th percentile of maximum apparent temperature (MAT). The relationship between heat waves and all-cause non-accidental mortality was investigated through time series modelling, adjusting for time trends. RESULTS: The percent increase in daily mortality during heat waves as compared to normal summer days was, in the 50+ population, 22% (95% Confidence Interval (CI): 18-26%) in Rome and 8% (95% CI: 3-12%) in Stockholm. Subgroup specific increase in mortality in Rome ranged from 7% (95% CI:-17-39%) among survivors of myocardial infarction to 25% in the COPD (95% CI:9-43%) and diabetes (95% CI:14-37%) subgroups. In Stockholm the range was from 10% (95% CI: 2-19%) for congestive heart failure to 33% (95% CI: 10-61%) for the psychiatric subgroup. CONCLUSIONS: Mortality during heat waves increased in both Rome and Stockholm for the 50+ population as well as in the considered subgroups. It should be evaluated if protective measures should be directed towards susceptible groups, rather than the population as a whole.

Changes in the effects of heat on mortality among the elderly from 1998-2010: results from a multicenter time series study in Italy.

BACKGROUND: This multicenter study is aimed at estimating changes in the effect of high temperatures on elderly mortality before and after the 2003 heat waves and following the introduction of heat prevention activities. METHODS: A total of sixteen cities were included in the study. City-specific relationships between maximum apparent temperature (MAT) and elderly daily mortality before (1998-2002) and after (2006-2010) intervention were modelled through non-linear distributed lag models and estimates were combined using a random effect meta-analysis. We estimated the percentage change in daily mortality for 3°C variations in MAT above the 25th percentile of the June city-specific 1998-2002 distribution. A time-varying analysis was carried out to describe intra-seasonal variations in the two periods. RESULTS: We observed a reduction in high temperatures' effect post intervention; the greatest reduction was for increases in temperature from 9°C to 12°C above the 25th percentile, with a decrease from +36.7% to +13.3%. A weak effect was observed for temperatures up to 3°C above the 25th percentile only after. Changes were month-specific with a reduction in August and an increase in May, June and September in 2006-2010. CONCLUSIONS: A change in the temperature-mortality relationship was observed, attributable to variations in temperature distributions during summer and to the introduction of adaptation measures. The reduction in the effect of high temperature suggests that prevention programs can mitigate the impact. An effect of lower temperature remains, indicating a relevant impact of temperature at the beginning of summer when the population has not yet adapted and intervention activities are not fully operational.

Effectiveness of therapies for heroin addiction in retaining patients in treatment: results from the VEdeTTE study.

Treatment is effective in reducing heroin use and clinical and social problems among heroin addicts. The effectiveness is related to the duration of treatment. "VEdeTTE" is an Italian longitudinal study funded by the Ministry of Health to evaluate the effectiveness of treatments provided by the National Health Services. The study involved 115 drug treatment centers and 10,454 heroin users. Clinical and personal information were collected at intake through a structured interview. Treatments were recorded using a standardized form. Survival analysis and Cox Proportional Hazard model were used to evaluate treatment retention. Five thousand four hundred and fifty-seven patients who started a treatment in the 18 months of the study were included in the analysis: 43.2% received methadone maintenance therapy (MMT), 10.5% therapeutic community, and 46.3% abstinence-oriented therapy (AOT). The likelihood of remaining in treatment was 0.5 at 179 days. The median daily dose of methadone was 37 mg. Psychotherapy was provided in 7.6% of patients receiving methadone and 4.9% of those in therapeutic community. Type of therapy was the strongest predictor of retention, with AOT showing the lowest retention. In MMT patients, retention improved according to dose. Living alone, psychiatric comorbidity and cocaine use increased the risk of dropout. Psychotherapy associated halved the risk of dropout.

Temporal and geographic heterogeneity of the association between socioeconomic position and hospitalisation in Italy: an income based indicator.

BACKGROUND: The inverse association between socioeconomic position (SEP) and health has been extensively explored in Italy; however few studies have been carried out on the relationship between income inequalities and health status or health services utilisation, particularly at a local level.The objective of this study is to test the association between the demand for hospital care and a small area indicator based on income in four Italian cities, over a four-year period (1997-2000), in the adult population. METHODS: Census Block (median 260 residents) Median per capita Income (CBMI) was computed through record linkage between 1998 national tax and local population registries in the cities of Rome, Turin, Milan and Bologna (total population approximately 5.5 million). CBMI was linked to acute hospital discharges among residents, based on patient's residence.Age-standardized gender-specific hospitalisation rates were computed by CBMI quintiles (first quintile indicating lowest income), overall, and by city and year. Heterogeneity of the association between income level and hospitalisation was analysed through a Poisson model. RESULTS: We found an inverse association between small area income level and hospitalisation rates, which decreased continuously from 153 per 1000 inhabitants in the first quintile to 107 per 1000 inhabitants in the fifth quintile. Income differences in hospitalisation were confirmed in each city and year. However, the magnitude of the association and the absolute level of hospitalisation rates were quite different in each city and tended to slightly decrease over time in all cities considered, except Bologna. CONCLUSION: Our study confirms an inverse association between income level and the use of hospitalization in four Italian cities, using a small area economic indicator, based on population tax data. Further analysis of the association between income and cause-specific hospitalization rates will allow to better understand the capability of the Italian National Health System to compel with socio-economic inequalities in health needs.Furthermore the SEP indicator we propose can represent a contribution to the improvement of tools for monitoring inequalities in health and in health services utilization.

Susceptibility to heat wave-related mortality: a follow-up study of a cohort of elderly in Rome.

BACKGROUND: Few studies have identified specific factors that increase mortality during heat waves. This study investigated socio-demographic characteristics and pre-existing medical conditions as effect modifiers of the risk of dying during heat waves in a cohort of elderly residents in Rome. METHODS: A cohort of 651,195 residents aged 65 yrs or older was followed from 2005 to 2007. During summer, heat wave days were defined according to month-specific thresholds of maximum apparent temperature. The adjusted relative risk of dying during heat waves was estimated using a Poisson regression model including all the considered covariates. Risk differences were also calculated. All analyses were run separately for the 65-74 and 75+ age groups. RESULTS: In the 65-74 age group the risk of dying during heat waves was higher among unmarried subjects and those with a previous hospitalization for chronic pulmonary disease or psychiatric disorders. In the 75+ age group, women, and unmarried subjects were more susceptible to heat. Furthermore, a higher susceptibility to heat among those with previous hospitalization for diabetes, diseases of the central nervous system (CNS), psychiatric disorders and cerebrovascular diseases resulted from risk differences. DISCUSSION: Results showed a higher susceptibility to heat among those older than seventy-five years, females and unmarried. Pre-existing health conditions play a different role among the two considered age groups. Moreover, compared with previous studies the pattern of susceptibility factors have slightly changed over time. For the purposes of public health programmes, susceptibility should be considered as time, space and population specific.

Income level and chronic ambulatory care sensitive conditions in adults: a multicity population-based study in Italy.

BACKGROUND: A relationship between quality of primary health care and preventable hospitalizations has been described in the US, especially among the elderly. In Europe, there has been a recent increase in the evaluation of Ambulatory Care Sensitive Conditions (ACSC) as an indicator of health care quality, but evidence is still limited. The aim of this study was to determine whether income level is associated with higher hospitalization rates for ACSC in adults in a country with universal health care coverage. METHODS: From the hospital registries in four Italian cities (Turin, Milan, Bologna, Rome), we identified 9384 hospital admissions for six chronic conditions (diabetes, hypertension, congestive heart failure, angina pectoris, chronic obstructive pulmonary disease, and asthma) among 20-64 year-olds in 2000. Case definition was based on the ICD-9-CM coding algorithm suggested by the Agency for Health Research and Quality - Prevention Quality Indicators. An area-based (census block) income index was used for each individual. All hospitalization rates were directly standardised for gender and age using the Italian population. Poisson regression analysis was performed to assess the relationship between income level (quintiles) and hospitalization rates (RR, 95% CI) separately for the selected conditions controlling for age, gender and city of residence. RESULTS: Overall, the ACSC age-standardized rate was 26.1 per 10.000 inhabitants. All conditions showed a statistically significant socioeconomic gradient, with low income people being more likely to be hospitalized than their well off counterparts. The association was particularly strong for chronic obstructive pulmonary disease (level V low income vs. level I high income RR = 4.23 95%CI 3.37-5.31) and for congestive heart failure (RR = 3.78, 95% CI = 3.09-4.62). With the exception of asthma, males were more vulnerable to ACSC hospitalizations than females. The risks were higher among 45-64 year olds than in younger people. CONCLUSIONS: The socioeconomic gradient in ACSC hospitalization rates confirms the gap in health status between social groups in our country. Insufficient or ineffective primary care is suggested as a plausible additional factor aggravating inequality. This finding highlights the need for improving outpatient care programmes to reduce the excess of unnecessary hospitalizations among poor people.