Algorithmic assessment of cellular senescence in experimental and clinical specimens.

The development of genetic tools allowed for the validation of the pro-aging and pro-disease functions of senescent cells in vivo. These discoveries prompted the development of senotherapies-pharmaceutical interventions aimed at interfering with the detrimental effect of senescent cells-that are now entering the clinical stage. However, unequivocal identification and examination of cellular senescence remains highly difficult because of the lack of universal and specific markers. Here, to overcome the limitation of measuring individual markers, we describe a detailed two-phase algorithmic assessment to quantify various senescence-associated parameters in the same specimen. In the first phase, we combine the measurement of lysosomal and proliferative features with the expression of general senescence-associated genes to validate the presence of senescent cells. In the second phase we measure the levels of pro-inflammatory markers for specification of the type of senescence. The protocol can help graduate-level basic scientists to improve the characterization of senescence-associated phenotypes and the identification of specific senescent subtypes. Moreover, it can serve as an important tool for the clinical validation of the role of senescent cells and the effectiveness of anti-senescence therapies.

Direct costs in diabetic and non diabetic people: the population-based Turin study, Italy.

BACKGROUND AND AIMS: We compared direct costs of diabetic and non diabetic people covered by the Italian National Health System, focusing on the influence of age, sex, type of diabetes and treatment. METHODS AND RESULTS: Diabetic people living in Turin were identified through the Regional Diabetes Registry and the files of hospital discharges and prescriptions. Data sources were linked to the administrative databases to assess health care services used by diabetic (n = 33,792) and non diabetic people(n = 863,123). Data were analyzed with the two-part model; the estimated direct costs per person/year were €3660.8 in diabetic people and €895.6 in non diabetic people, giving a cost ratio of 4.1. Diabetes accounted for 11.4% of total health care expenditure. The costs were attributed to hospitalizations (57.2%), drugs (25.6%), to outpatient care (11.9%), consumable goods (4.4%) and emergency care (0.9%). Estimated costs increased from € 2670.8 in diabetic people aged <45 years to € 3724.1 in those aged >74 years, the latter representing two third of the diabetic cohort; corresponding figures in non diabetic people were € 371.6 and € 2155.9. In all expenditure categories cost ratios of diabetic vs non diabetic people were higher in people aged <45 years, in type 1 diabetes and in insulin-treated type 2 diabetes. CONCLUSION: Direct costs are 4-fold higher in diabetic than in non diabetic people, mainly due to care of the elderly and inpatient care. In developed countries, demographic changes will have a profound impact on costs for diabetes in next years.

[Occupational mortality in Italy during 1992, assessed through record-linkage between pension records and death certificates]. / Mortalità per settore produttivo in Italia nel 1992 secondo le storie lavorative INPS.

BACKGROUND: The creation of a surveillance system of occupational mortality in Italy is limited by the low quality of information on occupation in death certificates, since the information is often incomplete or lacking and because only the occupation at the time of death is registered. OBJECTIVE: To evaluate the possible use of INPS (National Institute of Social Security) records for the purpose of surveillance of occupational mortality, in terms of feasibility of setting up a system and of validity of the results obtained. METHODS: Death records of 218,510 subjects aged 18-74, deceased in the 12 months following the 1991 census, were obtained from ISTAT (Central Statistics Institute). These were combined through record-linkage with the INPS social security archives, which contain the employment records by economic sector going back to 1974, in order to assign these deaths the sector in which they had worked the longest. Mortality by specific causes was evaluated by industry by means of a proportional mortality analysis stratified by sex and occupational status, and adjusted for age, education, marital status, geographical area of birth, drawing a disability pension, employment status at the time of death and work instability. RESULTS: Record-linkage allowed attribution of the longest held job to 70% of the deaths recorded. Results are presented and discussed only on mortality in men due to asbestosis and silicosis, and causes of death with a substantial proportion attributable to occupation: chronic obstructive pulmonary disease (COPD); cancers of the bladder, nasal cavity, larynx, lung and pleura; leukaemia and lymphoma; accidental causes. Among the economic sectors with a significant excess mortality, the following are well documented in the literature: mortality due to COPD in the coal and peat-bog sectors; due to leukaemia among farmers; due to sino-nasal tumours in wood-working and furniture production; due to cancer of the larynx, lung, and pleura in occupations where there was probable exposure to asbestos (fishing and maritime transport, non-metal mining, building industry, and naval, train and aircraft construction); due to silicosis in industries with potential exposure to crystalline silica; due to accidental causes in the building industry and farming. Other mortality excesses and deficits, especially those due to bladder and lympho-haemopoietic cancers, appear to be only partly consistent with those described by other authors. DISCUSSION: The feasibility of developing a surveillance system of occupational mortality based on the INPS source was found to be good, and, at least among males, for 75% of the deceased subjects historical information existed concerning the economic sectors registered in the INPS records. The results obtained would appear to indicate that the system is capable of highlighting risk excesses due to widespread exposure in the industries examined, regarding diseases for which there is a strong association with exposure. On the other hand, due to the inherent limits of the study's design (lack of a complete work history and of precise information on the jobs held) its use is not recommended in the surveillance of diseases with a low proportion attributable to a risk factor, or with wide exposure variability in a given sector among the various jobs.

[Differences of perceived health and lifestyle by occupational groups in the Italian ISTAT (Central Statistic Institute) health survey]. / Differenze occupazionali nello stato di salute e negli stili di vita nell'indagine ISTAT sulla salute 1999-2000.

BACKGROUND: Little is known about the distribution by occupation of chronic illness, disability, morbidity, and lifestyles which put health at risk. OBJECTIVES: To provide a map of the social inequalities in various dimensions of health and lifestyle by social class and for specific occupational groups. To formulate a hypothesis about the mechanisms which generate these inequalities. METHODS: Prevalence rate ratios and prevalence odds ratios of perceived health, chronic illness, disability, absenteeism, trauma, smoking, and obesity calculated with data from the 1999-2000 Italian ISTAT (Central Statistics Institute) health survey; the study population includes adults (aged over 18 years) employed, or searching for a job, or withdrawn from the workforce. RESULTS: Among workers in manual unskilled labour, construction and agriculture are noted for worse health and more unhealthy lifestyles than average. For example, perceived bad health is more widespread among agricultural labourers (OR = 1.63), masons and construction machine operators (OR = 1.75), transport drivers (OR = 1.40), male caretakers, custodians, janitors and domestic help (OR = 1.46), electro-technicians (OR = 1.44), leatherworkers and shoemakers (OR = 3.58), miners and quarrymen (OR = 2.60), earthenware and stone workers (OR = 2.14), garment and furnishings workers (OR = 1.86); in female workers excess risk for perceived bad health was present among agricultural labourers (OR = 2.08), caretakers, custodians, janitors and domestic helpers (OR = 1.49), waitresses, cooks and bartenders, (OR = 1.44), and textile workers (OR = 1.67). Smoking was more widespread among chemical workers (OR = 1.41), and in miners and quarrymen (OR = 1.30). An excess risk of smoking of 20-25% was evident in spinners, weavers and finishers; masons, (and) builders; waiters, cooks and bartenders; garment and furnishings workers; porters and warehouse workers. The risk was 10% higher among foundry workers and forgers, plumbers, carpenters and welders, and transport drivers. Among women the propensity to smoke was higher among waitresses, cooks and bartenders (OR = 1.37), cleaners, commerce and service workers (OR = 1.22). Other occupational groups with an increased smoking prevalence, where women were less represented, included: chemical workers (OR = 2.25), butchers (OR = 1.97), postwomen (OR = 1.58), plastics workers (OR = 1.56), shippers (OR = 1.37). CONCLUSIONS: It can be hypothesized on the one hand that there are factors and mechanisms common to the various occupational groups belonging to the same social class; on the other, there are factors and mechanisms specific to certain occupational categories. The latter can generate specific health subcultures. A greater integration between qualitative and quantitative research is recommended, which would yield better explanations of the observed inequalities.

[Workplace injuries and professional mobility correlated with health problems. The potential and limitations of the ISTAT Labour Force survey--July 1999]. / Infortuni e mobilità lavorativa correlata a problemi di salute. Potenzialità e limiti della Rilevazione Trimestrale sulle Forze di Lavoro--luglio 1999 dell'ISTAT.

BACKGROUND: Knowledge on the occupational and social factors that influence the relationship between illness, absence from work and occupational mobility is at present insufficient. OBJECTIVES: To map out, by social class and occupational group, the impact of health problems on work and the distribution of accidents and morbidity associated with occupation. METHODS: Using data from the National Survey of the Italian Labour Force (ISTAT, 1999), covering a sample of 200,384 subjects, prevalence odds ratios of morbidity, work injuries and change of occupation due to health problems were calculated by social class and occupation, adjusting for age and residence. RESULTS: The working class showed a higher risk, due to health problems, of a reduction in time worked (OR = 3.70 in men and OR = 4.10 in women), of choosing to work part-time (OR = 2.04 in men and OR = 2.27 in women), or of withdrawing from the workforce (for artisans, skilled manual workers, farmers and agricultural labourers OR = 1.63 in men and OR = 1.47 in women). This class was also at a greater disadvantage not only with respect to accident rates (OR = 1.85 in men and OR = 1.88 in women), but also with respect to the time needed for post-trauma rehabilitation and return to work (for absences of one week to one month: OR = 1.67 and 1.83 for men and women, respectively; for absences of more than one month: OR = 1.29 and OR = 1.69). Moreover, the working class, when compared to other social classes, had a higher rate of suffering from illness, physical impairment or other physical and psychological problems caused or aggravated by working activity (25% in men and 32% in women). CONCLUSIONS: The ISTAT National Survey provides an estimate of minor accidents with prognoses of less than three days, including those not reported to the National Institute for Insurance against Occupational Accidents and Diseases (INAIL). This allows a preliminary exploration of the relationship between health problems and occupational mobility; however, it seems necessary to collect more detailed information in order to more exhaustively explore the mechanisms which generate the inequalities observed.

The role of individual and contextual socioeconomic circumstances on mortality: analysis of time variations in a city of north west Italy.

STUDY OBJECTIVE: To evaluate the independent and mutual effects of neighbourhood deprivation and of individual socioeconomic conditions on mortality and to assess the trends over the past 30 years and the residual neighbourhood heterogeneity. DESIGN: General and cause specific mortality was analysed as a function of time period, highest educational level achieved, housing conditions, and neighbourhood deprivation, using multilevel Poisson models stratified by gender and age class. SETTING: The study was conducted in Turin, a city in north west Italy with nearly one million inhabitants and consisting of 23 neighbourhoods. PARTICIPANTS: The study population included three cohorts of persons aged 15 years or older, recorded in the censuses of 1971, 1981, and 1991 and followed up for 10 years after each census. MAIN RESULTS: Individual and contextual socioeconomic conditions showed an independent and significant impact on mortality, both among men and women, with significantly higher risks for coronary heart and respiratory diseases among people, aged less than 65 years, residing in deprived neighbourhoods (9% and 15% excess for coronary heart diseases, 20% and 24% for respiratory diseases, respectively for men and women living in deprived neighbourhoods compared with rich). The decreasing time trend in general mortality was less pronounced among men with lower education and poorer housing conditions, compared with their more advantaged counterparts; the same was found in less educated women aged less than 65 years. CONCLUSIONS: These results and further developments in the evaluation of impact and mechanisms of other contextual effects can provide information for both health and non-health oriented urban policies.

Mortality of a cohort of road construction and maintenance workers with work disability compensation.

BACKGROUND: Surveillance systems of occupational mortality are useful tools to identify cases of diseases suspected as occupational and to monitor their occurrence over time, in space and in population subgroups. Many surveillance systems make use of administrative data in which information about occupations and/or economic sectors of the subjects enrolled is reported, such as death certificates, hospital discharge data, census data, tax and pension records, and workers' compensation archives. OBJECTIVES: In the present study we analyzed the mortality of a cohort of road construction and maintenance workers enrolled through the Italian national archive of work disability compensations, also in order to evaluate the possible use of this administrative source to monitor occupational mortality. METHODS: 8,000 subjects (7,879 males) receiving a disability compensation while working in the "road construction and maintenance" sector were identified from INAIL (National Institute for Insurance of Accidents at Work) archives. Vital status of these subjects was ascertained using the information available in INAIL archives and in the national tax register. For those found to be deceased from INAIL or tax archives, or without any information on vital status, a mail follow-up was started. We considered as observation period the years from 1980 to 1993. A record linkage with the ISTAT (Italian Institute of Statistics) national mortality registry was performed and the cause of death was retrieved for 964 out of 1,259 subjects. The analysis was restricted to males, leaving altogether 863 observed deaths with ascertained cause (84.7% of 1,019 total male deaths). SMR for overall mortality and PMR for specific cause mortality were computed, using the general Italian male population as reference. RESULTS: Overall mortality was significantly reduced (SMR = 79.0; 95% CI = 74.2-84.0). Proportional mortality analysis revealed significant excess risks for all malignant tumours (332 deaths, PMR = 1.08) and for digestive diseases (87 deaths, PMR = 1.34), while mortality for cardiovascular diseases was significantly decreased (288 deaths, PMR = 0.90). Among specific causes of death, significant excess mortality was found for cancer of testicles (2 deaths, PMR = 5.98), liver and biliary ducts (32 deaths, PMR = 1.40), and for silicosis (10 deaths, PMR = 3.07) and cirrhosis (64 deaths, PMR = 1.40). CONCLUSIONS: The excess mortality observed for all cancers, digestive diseases and silicosis, and the decreased risk for cardiovascular diseases are in agreement with the results of other studies conducted on workers in road construction and maintenance. As expected, the low overall mortality and the reduced risk from cardiovascular diseases indicate that these workers present a strong "healthy worker effect".

[Inequalities in mortality in the Italian longitudinal studies]. / Le diseguaglianze di mortalità negli studi longitudinali italiani.

The article presents some of the most relevant results on inequalities in mortality, obtained by the two Italian longitudinal studies carried out in Turin, and Tuscany (in Leghorn and Florence). The two studies share the same methodology. Each database contains census data, information from population register and from death certificates. The authors approach this issue not in an analytical way (as they did in the works cited in the reference list), but answering some questions, relevant both from a scientific and a political point of view. How big are the health inequalities in Italy? Are the health inequalities in Italy increasing or decreasing? Are the health inequalities due to absolute or to relative deprivation? Does the mortality profile of the Italian population express the presence of old or new health inequalities? Can the health inequalities be reduced? The study's results prove that the health inequalities in Italy are deep and strictly related to individuals' position in the social fabric. Facing the other questions the authors focus only in the Turin data. From the 1970's to the 1990's the health inequalities in Turin have increased, despite of general improvement of population's health condition and the progressive reduction of the size of deprived groups. Turin data support both the hypotheses on the source of health inequalities, using long term unemployment as absolute deprivation's indicator, and status' inconsistency as (a row) indicator of relative deprivation. The growth of drug-related causes of death (AIDS and overdose) shows that in the Turin and--quite reasonably--Italian population old and new health inequalities live together. The essay closes offering evidence on the possibility to reduce health inequalities. For this purpose the authors analyses the Turin trend of avoidable deaths and infant and adolescent mortality.

[Social inequalities in the mortality due to cardiovascular diseases in Italy]. / Le diseguaglianze sociali nella mortalità per malattie cardiovascolari in Italia.

Social inequalities in cardiovascular disease mortality are described in this paper focusing on the results of the Studio Longitudinale Torinese (SLT), an investigation that links census data with the statistical data that are currently available. The overall results confirm that cardiovascular disease mortality is higher in less-advantaged socioeconomic groups, irrespectively of the social indicator used: education, social class, housing quality, job security. Stratified data shows less important inequalities among ischemic heart disease as compared to cerebrovascular mortality. The differences are even more complex when the age groups in the two genders are analyzed, revealing cohort effects. Overall, the results agree with the previous survey carried out by ISTAT on 1981 Italian mortality, which confirmed the variations in inequalities according to geographical areas, gender and age. Differences in access to the health system are likely to be related to the differences detected for geographical areas, while differences in personal history and attitude towards health-associated behavior should explain age and gender variations in inequalities. Equity must be included in the evaluation of preventive programs and health-care models. Epidemiological and social research should be encouraged to better understand the factors that influence inequalities in cardiovascular disease mortality and in the health status of the population at large.

[Social differences in infant mortality in a longitudinal Turin study]. / Differenze sociali nella mortalità infantile nello studio longitudinale torinese.

The Turin longitudinal study enables to study the one-year survival of children born to any member of the study population and to relate the still-born and infant mortality to the parents' census characteristics. In this paper 25,108 children, born between 1981 and 1985 of parents residents in Turin at the 1981 population census, were followed up with respect to one-year survival. The numbers of infant deaths have been observed according to parents' education, housing ownership, occupational status and professional position. Only parents' education showed consistent differential in the still-born and infant mortality risks, adjusted for maternal age.