Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

[A method for identifying people with a high level of frailty by using a population database, Varese, Italy]. / Un metodo per identificare pazienti ad alto grado di fragilità a partire dalla Banca Dati Assistiti nell'ASL di Varese.

Since over 10 years, the Lombardy Region (Italy) has developed a system for classifying all persons registered with the healthcare system (database of persons registered with a general practitioner), according to their use of major healthcare services (hospitalizations, outpatient consultations, pharmaceutical) and whether they are exempt from copayment fees for disease-specific medications and healthcare services. The present study was conducted by the local health authorities of the province of Varese (Lombardy region, Italy) with 894.039 persons registered in the database of whom 258.770 (28.9%) with at least one chronic condition, 104.731 (11.7%) with multiple chronic conditions and 195.296 (21.8%) elderly persons. The aim was to evaluate death rates in different subgroups of patients entered in the database, including persons with chronic diseases and elderly persons. Standardized mortality rates were calculated for the year 2012. Compared with the general population, relative risk for mortality was 4,1 (95% confidence Intervals 4,0-4,2) in the elderly and 1,3 (95% confidence intervals 1,3-1,4) in chronic patients. This confirms that elderly persons have a higher level of frailty with respect to patients with chronic conditions. Mortality was found to be 28 times higher in elderly persons over 74 years of age, affected by high cost conditions such as cancer and cardiac disease, with respect to the general population.

Are occupational repetitive movements of the upper arm associated with rotator cuff calcific tendinopathies?

Calcifying tendinopathy (CT) of the shoulder is a common painful disorder, although the etiology and pathogenesis remain largely unknown. Recent theories about the role of excessive mechanical load in the genesis of CT have been proposed. Driven by the interest for these new theories, we investigated the hypothesis of a relationship between work-related repetitive movements of the upper arm, considered a potential cause of shoulder overload, and the presence of shoulder CT. A secondary aim was to obtain data on CT prevalence in a female sample from the working-age general population, as little data currently exist. 199 supermarket cashiers and 304 female volunteers recruited from the general population underwent a high-resolution ultrasonography of the rotator cuffs of both shoulders, and the presence of tendinopathies, with or without calcification, was recorded. The prevalence of calcific tendinopathy was 22.6 % in the cashiers group and 24.4 % in the control group. There were no statistically significant differences in the prevalence of calcifications between the two groups (p = 0.585), either for the dominant shoulder [OR = 0.841 (95 % CI 0.534-1.326)] or for the non-dominant shoulder [OR = 0.988 (95 % CI 0.582-1.326)]. We observed bilateral calcifications in 8.5 % of cashiers, and 9.6 % of controls, and an increase in prevalence of CT with age in both groups. Work-related repetitive movements of the upper arm did not induce a higher prevalence of shoulder CT compared with the female sample from the general population. If CT etiopathogenesis is related to mechanical load, CT onset may be influenced not only by loading history, but also by individual factors. Level of evidence Prognosis study, Level II.

[Health impact assessment of airport noise on people living nearby six Italian airports]. / Valutazione dell'impatto del rumore aeroportuale sulla salute della popolazione residente nelle vicinanze di sei aeroporti italiani.

BACKGROUND: aircraft noise has been associated with several health effects. Because of the great success of low-cost flights, small airports have been turned into international airports thus exposing nearby residents to an increase in noise levels and potential disturbances and health disorders. OBJECTIVE: to estimate the exposure levels and evaluate the health impact of aircraft noise on residents nearby six airports in Italy (Rome: Ciampino; Milan: Linate and Malpensa; Pisa; Turin; Venice) focusing on hypertension, acute myocardial infarction (AMI), annoyance and sleep disturbances. METHODS: residents in the local Municipalities considered at 31.12.2010 were included in the study and their addresses were geocoded. Aircraft noise exposure in 2011 was defined using the Integrated Noise Model linked to each participant's address. Lden (<55, 55-60, 61-65, 65-70 dB), Lnight, Leq (day and night) were calculated. Available exposure-response relationships were used to estimate the number of additional cases of hypertension, AMI, annoyance and sleep disturbances in the local population. RESULTS: 73,272 persons exposed to aircraft noise levels >55dB were considered: 55,915 (76.3%) were exposed to 55-60 dB; 16,562 (22.6%) to 60-65 dB; 795 (1.2%) to 65-70 dB. Exposure to aircraft noise levels above 55 dB was estimated to be responsible each year of 4,607 (95%CI 0-9,923) additional cases of hypertension; 3.4 (95%CI 0-10.7) cases of AMI; 9,789 (95%CI 6,895-11,962) cases of annoyance; 5,084 (95%CI 1,894-10,509) cases of sleep disturbances. CONCLUSIONS: a significant impact of airport noise on the health of residents nearby six Italian airports was estimated. Epidemiological evaluation and noise mitigation measures should be introduced to protect the health of residents.

Assessment of mortality risk in elderly patients after proximal femoral fracture.

Mortality after hip fracture is a major problem in the Western world, but its mechanisms remain uncertain. This study assessed the 2-year mortality rate after hip fracture in elderly patients by including hospital factors (eg, intervention type, surgical delay), underlying health conditions, and, for a subset, lifestyle factors (eg, body mass index, smoking, alcohol). A total of 828 patients (183 men) 70 to 99 years old experiencing a hip fracture in 2009 in the province of Varese were included in the study. The risk factors for death were assessed through Kaplan-Meier analysis and Cox proportional hazards analysis. Hip fracture incidence per 1000 persons was higher in women (8.4 vs 3.7 in men) and in elderly patients (12.4 for 85-99 years vs 4.4 for 70-84 years). The mortality rate after 1, 6, 12, and 24 months was 4.7%, 16%, 20.7%, and 30.4%, respectively. For the province of Varese, sex (hazard ratio, 0.39 for women), age group (hazard ratio, 2.2 for 85-99 years), and Charlson Comorbidity Index score (hazard ratio, 2.06 for score greater than 1) were found to be statistically significant. The 2-year mortality rate in hip fractures is associated with sex, age, and comorbidities. Male sex, age older than 85 years, and Charlson Comorbidity Index score greater than 1 are associated with a higher risk. Surgical delay was significant in the Kaplan-Meier survival time analysis but not in the Cox hazard analysis, suggesting that early surgery reduces risk in patients with numerous comorbidities.

Effectiveness of extracorporeal shock wave therapy in bone marrow edema syndrome of the hip.

There is no gold standard for treatment of bone marrow edema syndrome of the hip (BMESH). Usually, treatment is conservative, owing to the favorable and self limiting prognosis. In musculoskeletal disorders, the effectiveness of extracorporeal shock wave therapy (ESWT) has been widely recognized and recent research supports its use in the treatment of the first stages of avascular osteonecrosis of the proximal femur and in other conditions where bone marrow edema is present. On this basis, we performed a prospective study to evaluate the effectiveness of ESWT in normalizing the symptoms and imaging features of BMESH. Twenty consecutive symptomatic patients underwent two treatments of high-energy ESWT and were followed-up at 2, 3 and 6 months, with a final clinical follow-up at mean 15.52 ± 1.91 months. Patients underwent magnetic resonance imaging of the hip and were evaluated according to the Harris hip score. The mean improvement in HHS over the course of the study was of 58.5 ± 14.9 points (p < 0.0001), and the mean edema area reduced from 981.9 ± 453.2 mm(2) pre-treatment to 107.8 ± 248.1 mm(2) at 6 months. ESWT seems to be a powerful, non-pharmacological tool that produces rapid pain relief and functional improvement and aids the normalization of the vascular and metabolic impairments which characterize BMESH.

Assessment of lung cancer mortality reduction after chest X-ray screening in smokers: a population-based cohort study in Varese, Italy.

BACKGROUND: The effectiveness of screening for lung cancer (LC) in smokers on a population level, as distinct from the special circumstances that may apply in a randomized trial of selected volunteers, has not been thoroughly investigated. Here we evaluate by the standardized mortality ratio (SMR) indicator the impact of a chest X-ray (CXR) screening programme carried out at community level on LC mortality in smokers. METHODS: All smokers of >10 pack-years, of both genders, ages 45-75 years, resident in 50 communities of the Province of Varese, Italy, screening-eligible, in 1997 were invited by their National Health Service (NHS) general practitioner physicians to a nonrandomized programme of five annual CXR screenings. The entire invitation-to-screen cohort (n=5815 subjects) received NHS usual care, with the addition of CXR exams in volunteer participants (21% of invitees), and was observed through December 2006. To overcome participants' selection bias of LC mortality assessment, for the entire invitation-to-screen cohort we estimated the LC-specific SMR, based on the local reference population receiving the NHS usual care. RESULTS: Over the 8-year period 1999-2006, a total of 172 cumulative LC deaths were observed in the invitation-to-screen cohort; 210 were expected based on the reference population. Each year in the invited cohort the observed LC deaths were fewer than expected. The cumulative LC SMR was 0.82 (95% CI, 0.67-0.99; p=0.048), suggesting that LC mortality was reduced by 18% with CXR screening. CONCLUSION: Implementation of a CXR screening programme at community level was associated with a significant reduction of LC mortality in smokers.

A population-based cohort study of chest x-ray screening in smokers: lung cancer detection findings and follow-up.

BACKGROUND: Case-control studies of mass screening for lung cancer (LC) by chest x-rays (CXR) performed in the 1990s in scarcely defined Japanese target populations indicated significant mortality reductions, but these results are yet to be confirmed in western countries. To ascertain whether CXR screening decreases LC mortality at community level, we studied a clearly defined population-based cohort of smokers invited to screening. We present here the LC detection results and the 10-year survival rates. METHODS: The cohort of all smokers of > 10 pack-years resident in 50 communities of Varese, screening-eligible (n = 5,815), in July 1997 was invited to nonrandomized CXR screening. Self-selected participants (21% of cohort) underwent screening in addition to usual care; nonparticipants received usual care. The cohort was followed-up until December 2010. Kaplan-Meier LC-specific survival was estimated in participants, in nonparticipants, in the whole cohort, and in an uninvited, unscreened population (control group). RESULTS: Over the initial 9.5 years of study, 67 LCs were diagnosed in screening participants (51% were screen-detected) and 178 in nonparticipants. The rates of stage I LC, resectability and 5-year survival were nearly twice as high in participants (32% stage I; 48% resected; 30.5% 5-year survival) as in nonparticipants (17% stage I; 27% resected; 13.5% 5-year survival). There were no bronchioloalveolar carcinomas among screen-detected cancers, and median volume doubling time of incidence screen-detected LCs was 80 days (range, 44-318), suggesting that screening overdiagnosis was minimal. The 10-year LC-specific survival was greater in screening participants than in nonparticipants (log-rank, p = 0.005), and greater in the whole cohort invited to screening than in the control group (log-rank, p = 0.001). This favourable long-term effect was independently related to CXR screening exposure. CONCLUSION: In the setting of CXR screening offered to a population-based cohort of smokers, screening participants who were diagnosed with LC had more frequently early-stage resectable disease and significantly enhanced long-term LC survival. These results translated into enhanced 10-year LC survival, independently related to CXR screening exposure, in the entire population-based cohort. Whether increased long-term LC-specific survival in the cohort corresponds to mortality reduction remains to be evaluated. TRIAL REGISTRATION NUMBER: ISRCTN90639073.

Medication use in relation to noise from aircraft and road traffic in six European countries: results of the HYENA study.

OBJECTIVES: Studies on the health effects of aircraft and road traffic noise exposure suggest excess risks of hypertension, cardiovascular disease and the use of sedatives and hypnotics. Our aim was to assess the use of medication in relation to noise from aircraft and road traffic. METHODS: This cross-sectional study measured the use of prescribed antihypertensives, antacids, anxiolytics, hypnotics, antidepressants and antasthmatics in 4,861 persons living near seven airports in six European countries (UK, Germany, the Netherlands, Sweden, Italy, and Greece). Exposure was assessed using models with 1 dB resolution (5 dB for UK road traffic noise) and spatial resolution of 250×250 m for aircraft and 10×10 m for road traffic noise. Data were analysed using multilevel logistic regression, adjusting for potential confounders. RESULTS: We found marked differences between countries in the effect of aircraft noise on antihypertensive use; for night-time aircraft noise, a 10 dB increase in exposure was associated with ORs of 1.34 (95% CI 1.14 to 1.57) for the UK and 1.19 (1.02 to 1.38) for the Netherlands but no significant associations were found for other countries. For day-time aircraft noise, excess risks were found for the UK (OR 1.35; CI: 1.13 to 1.60) but a risk deficit for Italy (OR 0.82; CI: 0.71 to 0.96). There was an excess risk of taking anxiolytic medication in relation to aircraft noise (OR 1.28; CI: 1.04 to 1.57 for daytime and OR 1.27; CI: 1.01 to 1.59 for night-time) which held across countries. We also found an association between exposure to 24hr road traffic noise and the use of antacids by men (OR 1.39; CI 1.11 to 1.74). CONCLUSION: Our results suggest an effect of aircraft noise on the use of antihypertensive medication, but this effect did not hold for all countries. Results were more consistent across countries for the increased use of anxiolytics in relation to aircraft noise.

Annoyance due to aircraft noise has increased over the years--results of the HYENA study.

In the HYENA study (HYpertension and Exposure to Noise near Airports) noise annoyances due to aircraft and road traffic noise were assessed in subjects that lived in the vicinity of 6 major European airports using the 11-point ICBEN scale (International Commission on Biological Effects of Noise). A distinction was made between the annoyance during the day and during the night. L(den) and L(night) were considered as indicators of noise exposure. Pooled data analyses showed clear exposure-response relationships between the noise level and the noise annoyance for both exposures. The exposure-response curves for road noise were congruent with the EU standard curves used for predicting the number of highly noise annoyed subjects in European communities. Annoyance ratings due to aircraft noise, however, were higher than predicted by the EU standard curves. The data supports other findings suggesting that the people's attitude towards aircraft noise has changed over the years, and that the EU standard curve for aircraft noise should be modified.

[Descriptive study of cancer incidence in the area around the Ispra Joint Research Centre (JCR)]. / Studio descrittivo sull'incidenza di tumori maligni nell'area circostante al Centro comune di ricerca (CCR) di Ispra.

OBJECTIVE: to assess the effects of radioactive emissions from the EU Joint Research Centre (JRC) (nuclear) at Ispra, the Local Health Authority (ASL) of Varese carried out an ecological study to measure any excess incidence of cancer in the surrounding population. DESIGN AND SETTING: after estimation of historical exposure levels in the surrounding population, the incidence rates of leukaemia and other exposure-related tumours were calculated from data in the population based Lombardy Cancer Registry (Varese Province). By indirect standardization, the expected cases (based on incidence rate in the Province) were compared with observed cases in the close-by municipality of Ispra, in municipalities within a 5 km radius of the JRC (5kmArea) and in the area covered by the District of Sesto Calende (DistrictArea). RESULTS: in the period 1982-1998, mean populations were 4,687 (Ispra), 32,120 (5kmArea) and 43,707 (DistrictArea); the population of the Province was 793,752. The numbers of cancers registered were 374, 2,920, 4,099 and 72,246 respectively. Significant excesses of leukaemia were not found in Ispra (SIR 0.33, 95% CI 0.07-0.96) or the 5kmArea (SIR 0.83, 95% CI 0.63-1.08). For all cancers combined and for the commonest cancers (breast, colo-rectal) the numbers of incident cases were lower than expected. CONCLUSIONS: consistent with the low levels of exposure detected, and despite the fears of the local people, no incidence excesses of cancers was found in Ispra, the town closest to the JRC, or inforin the surrounding areas. It may be worth searching for excess cancer among exposed workers.

Descriptive epidemiology of selected birth defects, areas of Lombardy, Italy, 1999.

BACKGROUND: Birth defects are a leading cause of neonatal and infant mortality in Italy, however little is known of the etiology of most defects. Improvements in diagnosis have revealed increasing numbers of clinically insignificant defects, while improvements in treatment have increased the survival of those with more serious and complex defects. For etiological studies, prevention, and management, it is important to have population-based monitoring which provides reliable data on the prevalence at birth of such defects. METHODS: We recently initiated population-based birth defect monitoring in the Provinces of Mantova, Sondrio and Varese of the Region of Lombardy, northern Italy, and report data for the first year of operation (1999). The registry uses all-electronic source files (hospital discharge files, death certificates, regional health files, and pathology reports) and a proven case-generation methodology, which is described. The data were checked manually by consulting clinical records in hospitals. Completeness was checked against birth certificates by capture-recapture. Data on cases were coded according to the four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). We present data only on selected defects. RESULTS: We found 246 selected birth defects in 12,008 live births in 1999, 148 among boys and 98 among girls. Congenital heart defects (particularly septal defects) were the most common (90.8/10,000), followed by defects of the genitourinary tract (34.1/10, 000) (particularly hypospadias in boys), digestive system (23.3/10,000) and central nervous system (14.9/10,000), orofacial clefts (10.8/10,000) and Down syndrome (8.3/10,000). Completeness was satisfactory: analysis of birth certificates resulted in the addition of two birth defect cases to the registry. CONCLUSION: This is the first population-based analysis on selected major birth defects in the Region. The high birth prevalences for septal heart defect and hypospadias are probably due to the inclusion of minor defects and lack of coding standardization; the latter problem also seems important for other defects. However the data produced are useful for estimating the demands made on the health system by babies with birth defects.

[Use of healthcare services by elderly people in a local health authority in Varese (Italy)]. / I consumi di prestazioni sanitarie negli anziani dell'ASL della provincia di Varese.

Older people use more healthcare than younger people and aging of the population is considered to be one of the main factors leading to consumption of healthcare resources. The aim of this study was to evaluate rates of hospitalization, use of out-patient services and medicine confections among the elderly population (>65 years) in the local health authority of Varese (Italy), in the three-year period from 2003-2005, and to calculate the trend for the years 2006 and 2007. Rates of hospitalization and drug use remained stable while use of out-patient services showed an increasing trend. In spite of the influence of aging on consumption of healthcare resources, the use of medical services is determined mainly by the health state of the population: monitoring of the burden of morbidity in the population should therefore be improved.

Prevalence of anti-poliovirus type 1, 2 and 3 antibodies in unvaccinated Italian travelers.

BACKGROUND: Immunization against poliomyelitis is recommended for international travelers to developing countries. However, the level of antibodies varies even in previously unvaccinated persons, due to wild-type or vaccine-type infections in the eldest travelers. METHODS: In 1999, we conducted a seroprevalence study in the Lombardy region (northern Italy), using sera collected in 1994 from a population aged 50 to 59 years. The study subjects were consecutive, randomly selected travelers enrolled in an anti-hepatitis A virus antibody study. Neutralizing antibodies were titrated on Vero cells in microtiter plates. Each serum dilution (1:8 to 1:256) was challenged against 100 tissue culture infective doses of the three Sabin strains. Titers> 1:8 were considered to be protective. RESULTS: We studied 98 travelers, 59 male and 39 female, of mean age 54 years. Seventy-three (74.4%) reported previous travel abroad, but none had been vaccinated against polio. Dietary habits included consumption of seafood in 74.4% and raw vegetables from their own garden in 52.1%. The seroprevalences for neutralizing antibodies against poliovirus type 1, type 2 and type 3 were 86.7%, 89.9%, and 86.7%, respectively. All travelers presented protective antibody titers against at least one of the three viral types. Protective antibody titers were unrelated to travel history or dietary habit. CONCLUSIONS: A high proportion of the previously unvaccinated adults in our sample presented protective immunity to polioviruses. This observation may have implications for cost-effectiveness analysis of generalized polio vaccination in adult Italian travelers.

[Epidemiologic study Salus domestica: evaluation of health damage in a sample of women living near the Malpensa 2000 airport]. / Studio epidemiologico Salus domestica: valutazione dei danni di salute in un campione di donne residenti nei pressi dell'aeroporto Malpensa 2000.

The opening of the new Malpensa 2000 Airport worried people living in the neighbouring towns about possible effects of acoustic and air pollution on health status. For this reason, Varese Health Unit set up a study involving housewives and General Practitioners. This study has been carried out in 3 Areas: A Area, bordering the airport, B Area, at intermediate distance, and C Area, at long distance. On the whole, 932 housewives (18 to 64 years old) and 92 General Practitioners, were involved. The questionnaire, distributed to housewives between May 1st and November 30th 2000, was filled out in the doctor's surgery who furthermore added clinical data. Chi-square statistics were calculated to test the association between living area and personal data, behavioural and environmental characteristics, and reported disorders. To describe possible interrelationships between living Area and the answers supplied by housewives and General Practitioners the multiple correspondence multivariate analysis technique was applied. The housewives living next to the airport (A area) frequently report insomnia, nocturnal waking, anxiety and difficulty in hearing words. The multivariate analysis has shown a relationship between recently increasing noise noted by the housewives, and the area where they live, as well as a noticeable coherence between the answers given by the housewives and those given by the General Practitioners, who reported higher frequencies of cephalgy, allergies, anxiety neurosis, medical consultation, benzodiazepine's and sleeping disorder's prescriptions in A Area compared to C Area. The airport's presence seems to be associated with the onset of subjective disorders in neighbouring population. Some of these disorders, in particular neuropsychological ones, are clinically confirmed by General Practitioners, and are consistent with different noise exposure levels.

[Public health consumption at the Varese health trust]. / I consumi di prestazioni sanitarie nella Asl della Provincia di Varese.

This study is based on a provincial Atlas assessing territorial differences in hospital admissions and out-patient services. The authors have analysed consumer distribution per District as compared to overall provincial consumption. Results show some geographical inequities that are not always associated to epidemiological reasons. As a matter of fact, some services happen to be more crowded than others, which obviously entails the need for more adequate offers and different diagnostic behaviours as regards treatments. It would therefore be advisable if high consumption levels were assessed to be effectively useful in terms of health production.