Regional indices of socio-economic and health inequalities: a tool for public health programming.

OBJECTIVES: The aim was to provide an affordable method of computing socio-economic (SE) deprivation indices at the regional level, in order to reveal the specific aspects of the relationship between SE inequalities and health outcomes. The Umbria Region Socio-Health Index (USHI) was computed and compared with the Italian National Deprivation Index at the Umbria regional level (NDI-U). METHODS: The USHI was computed by applying factor analysis to census tract SE variables correlated with general mortality and validated through comparison with the NDI-U. RESULTS: Overall mortality presented linear positive trends in USHI, while trends in NDI-U proved non-linear or non-significant. Similar results were obtained with regard to specific causes of death according to deprivation groups, gender and age. CONCLUSIONS: The USHI better describes a local population in terms of health-related SE status. Policy-makers could therefore adopt this method in order to obtain a better picture of SE-associated health conditions in regional populations and to target strategies for reducing health inequalities.

The local Socio-Economic Health Deprivation Index: methods and results.

INTRODUCTION: A socio-economic (SE) deprivation index is a measure that aims to provide an indication of SE hardship and disadvantage in the population. Our aim was constructing 10 Socio-Economonic and Health Deprivation Indexes (SEHDI) by means of the same method. This particular method enables these indexes to be used to investigate the relationships between SE inequalities and aspects of health and prevention in the population. MATERIALS AND METHODS: Data on the demographic and SE situation of the populations were taken from the 2011 Census at the Census Tract (CT) level (2001 for Rome municipality). To construct the SEHDIs, variables displaying a statistically significant correlation with the SMRs of overall mortality were subjected to a tolerance test of linearity, in order to eliminate collinear variables. The variables selected underwent PCA factor analysis, in order to obtain the factors to be linearly combined into the SEHDI. The final values were scaled from minimum to maximum deprivation, and the quantitative scale was converted into five ordinal normalized population groups. The SEHDIs were validated at the SE level by comparing them with the trends of the main SE indexes used in the 2011 Census (2001 for Rome municipality), and at the health level by comparing them with the trends of some causes of death. Both comparisons were made by means of ANOVA. RESULTS: The 10 areas considered were: the municipalities of Cagliari, Ferrara, Florence, Foggia, Genoa, Rome, Palermo, Sassari, Siena, and the ULSS 7 Veneto area. For each one, a specific SEHDI was computed and the different variables comprising each index focused on particular aspects of SE and health deprivation at the area level. The SEHDIs showed good percentages of explained variance (from 72.2% to 49.1%) and a linear distribution of the main statistical SE indices and of overall mortality in each area; these findings were in line with the literature on the relationship between the SE condition and health status of the population. The distribution of cause-specific mortality across the SEHDIs deprivation clusters is analyzed in other articles, which deal with the findings of the study in each area. CONCLUSIONS: The SEHDIs showed good ability to identify the elements of SE inequalities that impact on the health conditions of populations; to depict the distribution of causes of death that are sensitive to SE differences concerning aspects of the social and family support structure. From a public health perspective, these results are relevant because they enable interventions of health promotion and prevention to be implemented on the basis of the characteristics that define deprivation groups.

Analysis of influenza vaccination coverage among the elderly in Genoa (Italy) based on a deprivation index, 2009-2013.

INTRODUCTION: The elderly suffer the most influenza-related complications, and 90% of deaths due to influenza occur in older subjects. Consequently, the elderly are among the main targets of influenza vaccination campaigns. The use of deprivation indexes can help to identify subgroups with lower vaccination uptake. This study analyzed influenza vaccination coverage in elderly persons living in Genoa (Italy) in relation to a local Index of Socio-Economic and Health Deprivation (SEHDI) in order to identify population subgroups needing specific intervention to improve vaccination coverage. METHODS: The study targeted subjects aged ≥ 65 years living in Genoa in the period 2009-2013. Information on vaccination coverage was provided by general practitioners and Local Health Units. A combination of linear regression, factor analysis and cluster analysis was used to construct the SEHDI at Census Tract (CT) level, on the basis of data from the 2011 Italian census. RESULTS: In 2011, people aged ≥ 65 years accounted for the 27.7% of the population of Genoa. Most elderly subjects were assigned to either the medium (45.3%) or medium-high (32%) deprivation groups, while the percentages in the extreme tails were low (3.6% high deprivation; 1.3% low deprivation). Significant, non-linear (p < 0.05 NL) relationships were observed in both sexes with regard to mortality due to all respiratory diseases (RD) and chronic obstructive pulmonary disease (COPD), with the highest Standardized Mortality Ratio (SMR) values in women in the high deprivation group of women (1.81, p < 0.05 RD; 1.79, p < 0.05 COPD). The SMRs for influenza and pneumonia showed a positive linear trend in women (p < 0.05) with the highest value in the high deprivation group (1.97, p < 0.05), while in men the trend was NL (p < 0.05). A positive linear trend (p < 0.05) was found with regard to vaccination coverage, which grew weakly as deprivation increased, up to the medium-high deprived group (from 34.6% to 44.4%). However, the high deprivation group showed the lowest value (33.3%). CONCLUSIONS: The results revealed a relationship between deprivation and influenza vaccination coverage in the elderly. This finding should be taken into account in the organization of vaccination campaigns and should prompt differentiated intervention in each local area.

Influenza vaccination coverage and deprivation among the elderly in the municipality of Cagliari: results and perspectives.

INTRODUCTION: The elderly are among the main targets of influenza vaccination campaigns. Previous studies have shown that socio-economic status influences compliance with influenza vaccination, particularly in the elderly. Deprivation indexes can therefore be useful in identifying population groups with lower vaccination uptake and guide targeted intervention to improve vaccination coverage. We analysed the correlation between influenza vaccination coverage and levels of socio-economic and health deprivation among the population of Cagliari, by means of an Index of Socio-Economic and Health Deprivation (SEHDI) specifically tailored to the city, in order to identify population subgroups needing specific intervention to improve vaccination coverage. METHODS: A combination of linear regression, factor analysis and cluster analysis was adopted in order to build the SEHDI at the Census Tract (CT) level; data were taken from the 2011 Italian Census. Mortality among subjects aged ≥ 65 years in Cagliari in the period 2013-2015 was used to select the SEHDI variables. On the basis of the SEHDI, his population was classified into five normalised deprivation groups. Information on vaccination coverage was provided by general practitioners and Local Health Units. Cause-specific mortality and information on vaccination coverage in the deprivation groups were analysed by means of ANOVA (F test at p < 0.05). RESULTS: Around 20% of the Cagliari population was seen to be living in disadvantaged conditions. The trends in Standard Mortality Rates (SMRs) for all causes and for respiratory diseases, chronic obstructive pulmonary diseases (COPD), influenza and pneumonia were analysed across the deprivation groups. Pneumonia and flu mortality rates displayed a non-linear trend in men and a positive linear trend in women. Flu vaccination uptake rates were low: 27%. Coverage proved to be lower in the two extreme categories and higher in the medium deprivation ones. CONCLUSIONS: The correlation between low vaccination coverage and socio-economic deprivation not only underlines the important role of vaccination in safeguarding health, but also the fact that it can be considered a factor in ensuring the system's equality, thanks to its role in limiting health impacts on those living in the most problematic or disadvantaged circumstances. It also stresses the characteristics which contribute to low compliance. Therefore, this finding should be taken into account in the organization of vaccination campaigns and should prompt differentiated interventions in each local area.

Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types.

BACKGROUND: Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. PATIENTS AND METHODS: Data on 818 902 Italian cancer patients diagnosed at age 15-74 years in 1985-2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. RESULTS: The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon-rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. CONCLUSIONS: A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective.

Risk of non-Hodgkin's lymphoma and residential exposure to air pollution in an industrial area in northern Italy: a case-control study.

The aim of this study was to evaluate the risk of non-Hodgkin's lymphoma (NHL) in an adult population residing in an area in northern Italy exposed to industrial air pollution from a big power plant, a coke oven, 2 chemical factories, and some minor plants. The design was a population-based case-control study and information about residential history and the main risk factors for NHL was obtained interviewing 133 cases and 279 controls using a structured questionnaire. Three exposure categories (heavy, moderate, and slight) were defined on the basis of the location of the major facilities with respect to the subject residence. NHL risk was not associated either with location or duration of residence in the heavily polluted area. However, the unavoidable limitations of this study prevent us from drawing definitive conclusions.

Subclinical functional and structural renal abnormalities predict new onset type 2 diabetes in patients with primary hypertension.

Recent studies suggest a close relationship between renal dysfunction and new onset diabetes (NOD). The aim of the study was to investigate the association between subclinical functional and structural renal abnormalities and NOD in primary hypertension (PH). This observational prospective study (9.1 ± 2.2 years follow-up) includes 231 consecutive untreated non-diabetic patients with PH and without overt nephropathy. The primary end point was NOD. Albuminuria (albumin to creatinine ratio, ACR), glomerular filtration rate (eGFR), and renal structure and hemodynamics (ultrasound scan and Doppler) were evaluated at baseline. During 2106 person-years of follow-up, 10 patients developed diabetes (incidence rate 4.7/1000 person-years). Patients with NOD showed a higher body mass index, serum uric acid, serum creatinine and ACR, and lower eGFR and renal volume (RV) to resistive index (RI) ratio (RV/RI) at baseline, as compared with the 221 controls that did not develop diabetes. When all renal variables were taken into consideration, RV/RI was the only variable significantly related to diabetes (hazard ratio 1.04, P=0.0342). Patients in the lowest tertile of RV/RI were more likely to develop diabetes (10.4 vs 2.6 vs 0%, P=0.0044). For each s.d. decrease of RV/RI, the risk of NOD increased by 68% (P=0.0012). Subclinical functional and structural renal abnormalities are independent predictors of diabetes in PH.

Metabolic syndrome and microalbuminuria predict renal outcome in non-diabetic patients with primary hypertension: the MAGIC study.

Metabolic syndrome (MS) has recently been shown to be a forerunner of chronic kidney disease (CKD). Microalbuminuria (MA) is associated with both MS and CKD. This study aimed to prospectively investigate the relationship among MA, MS and renal outcome in non-diabetic patients with primary hypertension. A total of 790 hypertensive patients enrolled in the MAGIC study between 1993 and 1997 (mean age 49.3±10.7 years) were included in the analysis. Renal outcome was defined as the first hospitalization with a diagnosis of CKD. At baseline, 146 (19%) and 60 (7.6%) patients met MS and MA criteria, respectively. A total of 20 patients (2.5%) concomitantly showed MS and MA. After a median follow-up of 11.6 years (interquartile range 3.2 years), renal end point was reached in 15.8% of patients with MS and in 8.9% of those without it (P=0.0087). The incidence of renal events increased progressively starting from patients with neither MS nor MA, to patients with only one of these abnormalities and then to those with both. Significant interaction was observed between MS and MA. Patients with concomitant occurrence of MS and MA at baseline showed a greater than fivefold risk of renal outcome, as compared with patients with neither of these two risk factors (hazard ratio 5.46; 95% confidence interval 2.34-12.75). This risk became even higher when data were adjusted for potential confounders. MS and MA are independent and interactive predictors of renal outcome in non-diabetic patients with primary hypertension.

Incidence of thyroid cancer in Italy, 1991-2005: time trends and age-period-cohort effects.

BACKGROUND: In Italy, some of the highest incidence rates (IRs) of thyroid cancer (TC) worldwide have been reported. PATIENTS AND METHODS: TC cases <85 years of age reported to Italian cancer registries during 1991-2005 were included. Age-standardized IRs were computed for all TC and age-period-cohort effects were estimated for papillary TC. RESULTS: IRs of TC were twofold higher in 2001-2005 than in 1991-1995 (18 and 8 per 100,000 women, 6 and 3 per 100,000 men, respectively). Increases were similar in the two sexes and nearly exclusively due to papillary TC. Increases of papillary TC by birth cohort were found in both sexes and among all age groups between 20 and 79 years. Age-period-cohort models showed a strong period effect in both sexes (rate ratio for 2001-2009 versus 1991-1995 = 2.5 in women and 2.3 in men), although IRs peaked at an earlier age in women (45-49 years) than men (65-69 years). CONCLUSION: The strength of the period effect in both sexes and the earlier onset in women than men strongly implicated increased medical surveillance in the upward trends of papillary TC incidence in Italy. The consequences of the current intense search for TC on morbidity and possible overtreatment, especially among young women, should be carefully evaluated.

Pattern of cancer risk in persons with AIDS in Italy in the HAART era.

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16-69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997-2004 compared with 1986-1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997-2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

Decline in pneumonia and acute otitis media after the introduction of childhood pneumococcal vaccination in Liguria, Italy.

The effect of the pneumococcal conjugate vaccine immunization programme on pneumococcal-associated or potentially pneumococcal-associated hospital admissions in the Italian region of Liguria was assessed. Hospital admission rates were compared in subjects belonging to birth cohorts before and after the introduction of widespread immunization for 0 - 2-year old children with a seven-valent conjugate vaccine (PCV7). Significant reductions in hospitalization rates for all-cause and pneumococcal pneumonia and for acute otitis media were observed in subjects born after widespread uptake of the vaccine. The preventive fraction (a measure of vaccine effectiveness) ranged from 15.2% for all cause pneumonia to 70.5% for pneumococcal pneumonia. This study contributes to the growing body of information that supports the beneficial effect of PCV7 vaccination.

Ozone air pollution and daily mortality in Genoa, Italy between 1993 and 1996.

The association between ozone (O3) and daily mortality was investigated in Genoa, an Italian city characterized by a Mediterranean climate and a high prevalence of elderly inhabitants. The O3 effect, adjusted for long time trend, seasonality and weather, was assessed using Poisson regression modelling, allowing for overdispersion and autocorrelation, and expressed as mean variation percent of daily mortality per 50 microg/m3 increase (MV). Significant MVs for overall (+4.0%) and cardiovascular (+7.2%) mortality were detected at 1-day lag. The effects were stronger in the warmer season (May-October). Similar estimates were found after restricting the analyses to the elderly (>or=75 years). Furthermore, in this group, higher MVs were observed for total mortality at 2-day lag. A statistically significant synergistic effect between O3 and temperature was observed for cardiovascular mortality, particularly in elderly people, with an evident increase in mortality risk above 26 degrees C (MV +30.0% for the whole population and +40.0% for the elderly, respectively). This investigation highlights the importance of taking local climatic and demographic features into account when comparing different time-series studies, and substantiates the influence of photochemical pollution on mortality trends in small urban areas.

Classic Kaposi's sarcoma in Italy, 1985-1998.

To evaluate incidence rates (IRs) of classic Kaposi's sarcoma (CKS) in Italy after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using an 'ad hoc' record linkage procedure between 15 Cancer Registries (CRs) (21% of the Italian population) and the national AIDS Registry. Between 1985 and 1998, 874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS accounted for 16 and 27% of KS cases below 55 years of age in men and women, respectively, but for 91 and 100% of those above age 55. The IRs for CKS were 1.0/ in men and 0.4/100,000 in women, but they varied between 0.3 in Umbria and 4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs of CKS in both genders were stable between 1985-1987 and 1993-1998. In Northern and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in individuals born in the same area, but 1.6 in individuals born in Southern Italy or in the Islands (rate ratio = 3.2) suggesting that KS-associated herpesvirus, the cause of KS, is acquired early in life.

Risk of cancer in persons with AIDS in Italy, 1985-1998.

A record linkage was carried out between the Italian Registry of AIDS and 19 Cancer Registries (CRs), which covered 23% of the Italian population, to estimate the overall cancer burden among persons with HIV or AIDS (PWHA) in Italy, according to various characteristics. Observed and expected numbers of cancer and standardised incidence ratios (SIRs) were assessed until 1998 in 12 104 PWHA aged 15-69 years, for a total of 60 421 person-years. Significantly increased SIRs were observed for Kaposi's sarcoma (KS, 1749-fold higher than the general population), non-Hodgkin's lymphomas (NHL, 352), and invasive cervical cancer (22). SIR was significantly elevated also for cancer of the anus (34), lung cancer (2.4), brain tumours (4.4), Hodgkin's disease (16), and leukaemias (5.3). The majority of lung and brain cancers were not histologically confirmed, and the possibility of misclassification with KS or NHL cannot be ruled out. The SIR for all non-AIDS-defining cancers was 2.2 in men and 2.5 in women. Intravenous drug users showed significantly more elevated SIRs for lung cancer (9.4), and brain tumours (6.7) than other transmission categories (SIR=1.4 and 2.3, respectively). This study confirmed increased SIRs for haemolymphopoietic neoplasms other than NHL in PWHA, although many-fold smaller than for NHL. An association with human papillomavirus-related cancers was also confirmed.

Prostate cancer in Italy before and during the 'PSA era': survival trend and prognostic determinants.

The aim of the study was to investigate the variations in prostate cancer prognosis during a period of major diagnostic change, such as the introduction of the prostate-specific antigen (PSA) test. Data were provided by 14 Italian cancer registries (CRs). Incidence and follow-up information was collected for patients diagnosed from 1978 to 1994. Relative survival was computed taking into account incidence period, age, tumour stage and grade at diagnosis. A multivariate analysis was carried out to evaluate the independent simultaneous effect on survival of some prognostic determinants. A large geographical variability was observed: in 1993-1994 Italian survival rates ranged from 76% to 52%, with a north-south gradient. A striking prognostic improvement (up to +27 percentage points) between the late 1980s and the early 1990s occurred in almost all CRs, particularly with regard to younger patients. Multivariate analysis showed a strong influence of incidence period on survival, also after correction by tumour stage. The slowdown of metastatic cancers suggests that the survival improvement could be due both to the introduction of an effective opportunistic screening and to a quantitative change in the application of clinical treatment, even if the effect of the lead-time bias phenomenon has to be taken into account.

Differences in the epidemic rise and decrease of prostate cancer among geographical areas in Southern Europe. an analysis of differential trends in incidence and mortality in France, Italy and Spain.

This is a population-based study aimed at evaluating incidence and mortality trends for prostate cancer in France, Italy and Spain, during the prostate-specific antigen (PSA) era, considering elderly people aged 70 years and over and younger adults aged between 40 and 69 years. Trends were estimated by a log-linear Poisson regression model and expressed as an Estimated Annual Percent Change (EAPC). Incidence increased sharply in almost all areas. Spain showed the lowest increases. Incidence started to rise around 1985 in France and after 1990 in Italy and Spain. Mortality increased until the late 1980s in all countries, then declined in France and Italy (-2.5% in 40-69 year age group), but not in Spain. Younger people showed a much higher rise in incidence than the elderly, while mortality decreased mainly in the younger adults. The decrease in mortality was more marked in those areas and the younger age group where the rise in incidence was higher and started earlier, i.e. in France and in younger people, suggesting that the PSA test may have had a positive effect on mortality, although other clinical advances also have to be taken into account.

Lymphohaematopoietic system cancer incidence in an urban area near a coke oven plant: an ecological investigation.

AIMS: To evaluate the incidence risk of lymphohaematopoietic cancers for the 1986-94 period in Cornigliano, a district of Genoa (Italy), where a coke oven is located a few hundred metres from the residential area. METHODS: The whole of Genoa and one of its 25 districts (Rivarolo) were selected as controls. The trend of risk around the coke oven was evaluated via Stone's method, while the geographic pattern of such risks across the Cornigliano district was evaluated by computing full Bayes estimates of standardised incidence ratio (FBE-SIR). RESULTS: In males, elevated relative risks (RR) were observed for all lymphohaematopoietic cancers (RR 1.7 v Rivarolo and 1.6 v Genoa), for NHL (RR 2.4 v Rivarolo and 1.7 v Genoa), and for leukaemia (RR 2.4 v Rivarolo and 1.9 v Genoa). In females, statistically non-significant RR were observed. In males no excess of risk was found close to the coke oven. In females, a rising risk for NHL was observed approaching the plant, although statistical significance was not reached, while the risk for leukaemia was not evaluable due to the small number of cases. Analysis of the geographic pattern of risk suggested the presence of a cluster of NHL in both sexes in the eastern part of the district, where a foundry had been operational until the early 1980s. A cluster of leukaemia cases was observed in males in a northern part of the area, where no major sources of benzene seemed to be present. CONCLUSIONS: The estimated risks seem to be slightly or not at all related to the distance from the coke oven. The statistically significant higher risks observed in males for NHL and leukaemia, and the clusters of leukaemia in males and of NHL in both sexes deserve further investigations in order to trace the exposures associated with such risks.

Survival of cancer patients in Italy in the nineties: the importance of population based data.

This monograph shows 5-year survival data for over 200,000 cancer patients diagnosed within 1994 and followed-up to 31.12.99. These population based figures are provided by the Italian network of cancer registries, which covers over 7 million inhabitants. The overall survival rate is 37% in men and 56% in women, with an increase of about 6 percentage points in comparison to the previous period. Survival increases for cancers at good prognosis, as for example breast, colorectal and melanoma. No improvement is observed for more lethal cancers, like liver, pancreas or brain. These results are better than the corresponding ones recently observed in greater London, but worse, particularly in men, of those observed in the USA and Switzerland. A comparison within the country confirms the previous observations of less good results for southern Italy and homogeneous results in other regions.

Mortality trend for multiple sclerosis in Italy (1974-1993).

The prevalence of multiple sclerosis (MS) in Italy is one of the highest in Europe, estimated proportions ranging between 32 and 69 cases per 100,000. An update of mortality time trend analyses can help trace a picture of the evolution of the disease and contribute to the interpretation of differences related to latitude and gender. Standardized mortality ratios (SMR) were computed for the 1974-1993 calendar period, using the pooled data set as standard. World population was the standard used to estimate age-adjusted rates for all Italy, while for selected regions the 1991 Italian population was utilized. Time trend analysis was performed using the Poisson regression model and the variation of mortality rates in time was expressed as mean difference per cent per year. Age-adjusted rates per million inhabitants were 4.1 for males and 5.0 for females. Northern Italian regions showed higher MS mortality rates than Central and Southern regions and Sicily, particularly in females; the effect was less evident in Sardinia. Time trend analysis by area showed a mortality decrease in Northern Italy (-1.15%) that reached statistical significance for men. In central regions a slight increase of borderline statistical significance (+1.03%) was observed only in women. while in the South and Sicily a statistically significant increase was seen in both males (+2.14%) and females (+3.09%). The analysis of the time trend for all Italy did not reveal significant variations in male mortality; by contrast, a slight, but statistically significant, increase (+0.88%) was observed in female mortality. Analysis of age-adjusted MS mortality rates in each region suggested the presence of an effect due to latitude. The occurrence of an increasing trend in Southern Italian regions and Sicily deserves further investigation.