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Biomedical subjects

Franco Merletti

Publications and source records attributed to Franco Merletti.

At least 19 recordsLinked to original sources

Detection of human papillomavirus type 16 integration in pre-neoplastic cervical lesions and confirmation by DIPS-PCR and sequencing.

BACKGROUND: Persistent infections with high-risk types of human papillomavirus (HR-HPV) favour integration of viral DNA into the host cells and are associated with cervical carcinoma. HPV16 is the prevalent HR-type worldwide associated to cervical cancer. Integration of viral DNA promotes a selective cell growth advantage, resulting a risk factor for cancer development. OBJECTIVES: To test physical status of HPV16 infection in pre-neoplastic cervical lesions using a quantitative real time-PCR (QRT-PCR) based method. To investigate reliability of this method in identification of HPV16 integrated sequences, by detection of integrated papillomavirus sequences (DIPS-PCR) assay and sequencing. STUDY DESIGN: One hundred and seventy HR-HPV positive archival cervical specimens were tested for presence of HPV16 DNA. In HPV16 positive samples, viral load and physical status were evaluated. RESULTS: HPV16 DNA was detected in 74/170 (43%) HR-HPV positive specimens. In 52/74 a QRT-PCR was performed, and 3 integrated, 13 mixed and 36 episomal forms were detected. Presence of integrated forms was confirmed by DIPS-PCR and sequencing. CONCLUSIONS: Presence of HPV integrated forms was detected and confirmed in pre-neoplastic cervical lesions. The QRT-PCR method we used is sensitive and specific for identification of HPV integration in cervical samples, and may be suitable for large scale investigations with prognostic and clinical implications in management of cervical cancer.

Base Sequence↗

Short-term effects of Italian smoking regulation on rates of hospital admission for acute myocardial infarction.

AIMS: We used the hospital discharge records of Piedmont region (northern Italy) to evaluate whether a national law banning smoking in public resulted in a short-term reduction in hospital admissions for acute myocardial infarction (AMI). METHODS AND RESULTS: Rates of admission for AMI before the ban (October-December 2004) and during the ban (February-June 2005) were analysed. Each period was compared with the corresponding period 12 months before. Among persons aged under 60, the number of admissions for AMI decreased significantly after the introduction of the ban: from 922 cases in February-June 2004 to 832 cases in February-June 2005 (sex- and age-adjusted rate ratio, 0.89; 95% confidence interval, 0.81-0.98). No decrease was seen before the ban. No effect was found among persons aged at least 60. We estimated that the observed reduction in active smoking after the introduction of the ban could account for a 0.7% decrease in admissions for AMI during the study period, suggesting that most of the observed effect (11%) might be due to the reduction of passive smoking. CONCLUSION: Our study, based on a population of about 4 million inhabitants, suggests that smoke-free policies may result in a short-term reduction in admissions for AMI.

Adult↗

Prevalence of undiagnosed metabolic syndrome in a population of adult asymptomatic subjects.

BACKGROUND: To evaluate in the general population the prevalence of undiagnosed metabolic syndrome (MS), defined according to the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. METHODS: A population-based cross-sectional study of 1175 asymptomatic adults in North-Western Italy. RESULTS: The prevalence of undiagnosed MS was 16.4% (95% CI=14.4-18.6) (NCEP) and 28.0% (25.4-30.6) (IDF), respectively, 5.2% (3.6-7.3) and 8.9% (6.6-11.3) in normal-BMI and 26.6% (23.3-30.2) and 45.3% (41.3-49.2) in overweight/obese individuals. Of the total cohort, 52% were overweight/obese and they accounted for 85% of the cases of MS; a further 19% were normal weight with light physical activity and accounted, respectively, for 12% (NCEP) and 13% (IDF) of the cases. Only 25% (NCEP) and 14% (IDF) of participants showed no component of the MS (respectively, 40 and 26% of those not-overweight and 11 and 3% of those overweight/obese). CONCLUSIONS: More than 97% of unknown MS cases would be identified among apparently healthy individuals when overweight/obese, and normal-BMI subjects with low physical activity were screened. These two criteria might, therefore, be used to prioritise screening programmes in asymptomatic subjects, since even apparently healthy individuals, who are not-overweight, frequently show one or more metabolic abnormalities, whose co-existence has been demonstrated to be hazardous.

Cross-Sectional Studies↗

Late deaths among five-year survivors of childhood cancer. A population-based study in Piedmont Region, Italy.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze late mortality among 5-year survivors of childhood cancer, in Piedmont (Italy), in terms of risk factors and causes of death. DESIGN AND METHODS: From 1967 to 1999, the Childhood Cancer Registry of Piedmont recorded 3164 incident cases. Patients identified only by a death certificate (n = 59), lost to follow-up (n = 32), alive with a period of observation shorter than 5 years at the end of follow-up (n = 65) and records corresponding to a second malignant tumor during childhood (n = 9) were excluded from the analyses. RESULTS: Within 5 years after diagnosis, 1301 children died, and among the 1698 5- year survivors, 144 children subsequently died. Among 5-year survivors, cumulative mortality percentages increased from 5.1% (95% CI 4.0-6.2) at 10 years after diagnosis to 16.0% (12.2-19.8) at 35 years. Period of diagnosis (p = 0.006), age at diagnosis (p = 0.002), and tumor type (p = 0.003) were associated with late mortality. Most deaths were related to cancer recurrence (62.2%) and treatment-related sequelae (22.4%), including second malignant neoplasms, cardiac diseases and other late effects. Compared to the general population, children included in this study had a 9-fold increased risk of overall mortality, and experienced an absolute excess of 4.4 deaths per 1000 person-years. INTERPRETATION AND CONCLUSIONS: Among 5-year survivors, patients treated more recently (after 1979) had a statistically significant lower risk of late death than those treated earlier. However, long-term survivors still experienced higher mortality rates than those in the general population, and recurrence or progression of the primary tumor was the first cause of death.

Child↗

Accessibility as a major determinant of radiotherapy underutilization: a population based study.

BACKGROUND AND PURPOSE: A survey was conducted of radiotherapy (RT) resources and utilization in a northwestern Italian Region in order to assess geographical variations in radiotherapy utilization rates, and the effects of infrastructure supply on accessibility. MATERIALS AND METHODS: The survey was conducted by analysing standardized utilization rates based on administrative records. The data were analysed at both Regional and Local Health Unit (LHU) level. RESULTS: Wide variation was found among LHUs RT utilization rates--the sex- and age-standardized rates varied from 1.8/1000 inhabitants to more than 3/1000 inhabitants. Patients resident in LHUs with no RT service showed a lower probability of accessing RT (standardized rate ratio (SRR), 0.82; 95%IC, 0.80-0.85). The utilization rate decreased in relation to the distance between a patient's residence and the nearest RT service; the reduction was greater for patients > or =70 years of age. CONCLUSION: The wide geographic variation implies lack of equity in access to services. Utilization levels decreased significantly with increasing distance from the nearest RT service, distance being a barrier to access particularly for older persons. The heterogeneous distribution of services on the Regional territory seems a relevant explanation of differences in utilization rates.

Community Health Planning↗

Updating long-term childhood cancer survival trend with period and mixed analysis: good news from population-based estimates in Italy.

An empirical evaluation of long-term period survival analysis was performed using data from the Childhood Cancer Registry of Piedmont, Italy. The aim was to update survival time trends and provide 25-year projections for children currently diagnosed with cancer. The observed survival experiences up to 15 years after diagnosis of five quinquennial cohorts (cohort analysis) were compared to the corresponding estimates obtained by period analysis. The two methods generally produced very similar findings, although period analysis estimates were slightly lower than those obtained from cohort analysis. We then used mixed analysis to assess time trends in long-term survival. This showed that the probability of surviving 25 years after a cancer in childhood has more than doubled compared to cohort analysis estimates from patients diagnosed more than 25 years ago (73% vs. 32%), providing further evidence of an ongoing improvement in prognosis.

Child↗

Human papillomavirus typing with GP5+/6+ polymerase chain reaction reverse line blotting and with commercial type-specific PCR kits.

BACKGROUND: Infection with human papillomavirus (HPV) is a necessary step in the progression to cervical cancer. Many methods for HPV testing are currently available, most developed to detect pools of HPV types. OBJECTIVES: To evaluate the HPV typing by molecular methods and to compare commercial kits with an established laboratory method. STUDY DESIGN: Eighty-four cervical samples found to be positive for HPV DNA by GP5+/6+-polymerase chain reaction-enzyme immunoassay-reverse line blotting (PCR-EIA-RLB) were re-tested with two commercial methods, INNO-LiPA and Amplisense HPV typing, able to identify the HPV type predicted by PCR-EIA-RLB in 76 and 67 samples, respectively. RESULTS: The INNO-LiPA assay revealed HPV DNA in 75/76 samples (98.7%; 95% CI, 0.93-0.99) that would contain HPV types identifiable by this assay. The Amplisense HPV assay revealed HPV DNA in 58/67 samples (86.6%; 95% CI, 0.76-0.93) containing HPV types detectable by this assay. For samples with a single infection, the unweighted kappa for concordance of HPV typing was 0.87 (95% CI, 0.78-0.97) for PCR-EIA-RLB versus INNO-LiPA, 0.94 (95% CI, 0.87-0.99) for INNO-LiPA versus Amplisense HPV, and 0.82 (95% CI, 0.70-0.94) for PCR-EIA-RLB versus Amplisense HPV typing. PCR-EIA-RLB revealed 12 multiple infections, INNO-LiPA revealed 14, and Amplisense HPV revealed 5. The agreement among tests for samples with multiple infections was lower, giving kappa values of 0.44 (95% CI, 0.18-0.70) for PCR-EIA-RLB versus INNO-LiPA, 0.52 (95% CI, 0.19-0.85) for PCR-EIA-RLB versus Amplisense HPV and 0.43 (95% CI, 0.12-0.74) for INNO-LiPA versus Amplisense HPV. CONCLUSIONS: In HPV-positive samples, the agreement among tests for HPV typing was high for single infections but markedly lower for infections with multiple HPV types.

Adult↗

Occupational factors and risk of adult bone sarcomas: a multicentric case-control study in Europe.

We investigated the association between occupational factors and risk of bone sarcoma, a rare tumor with a largely unknown aetiology. A multicentric case-control study was conducted in 7 European countries in 1995-97. Ninety-six cases aged 35-69 years with a centrally reviewed diagnosis of bone sarcoma (68 chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or colon cancer (32%) controls. Subjects were interviewed to obtain information on occupational, medical and reproductive history, smoking and alcohol consumption and selected exposures including use of pesticides. Response proportions were 90% among cases and 66% among controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for selected categories of job titles and branches of industry and for use of pesticides. We found an increased OR for bone sarcoma among blacksmiths, toolmakers, machine-tool operators (OR = 2.14, 95% CI 1.08-4.26), woodworkers (OR = 2.68, 95% CI 1.36-5.29) and construction workers (OR = 1.62, 95% CI 0.92-2.87). Ever users of pesticide had an OR of 2.33 (95% CI 1.31-4.13), with similar risks for exposure to insecticides and exposure to herbicides. Neither duration of employment in any of the analyzed occupational categories nor duration of use of pesticides showed an increasing trend in the risk of bone sarcoma. ORs of bone sarcoma were 1.03 (95% CI 0.23-4.57), 3.13 (95% CI 1.26-7.76) and 1.44 (95% CI 0.43-4.85) for the first, second and third tertile of days of use of pesticides. Our study suggests that novel and previously reported (woodworking) occupational factors play a role in the aetiology of bone sarcomas.

Adult↗

Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy).

Survival after childhood cancer has been improving since the late 1970s in most developed countries. The Childhood Cancer Registry of Piedmont has been recording malignant tumors in children (0-14 years) throughout Piedmont since 1967. The present paper is based on the records of the 2,970 children diagnosed during the period 1970-2001; survival rates are estimated up to June 30, 2004. Based on records from the Registrar Offices of the relevant towns of residence, 1,698 children were reported to be alive, 1,252 deceased, and 20 were of unknown vital status. Over the period 1970-2001, 5-year survival rates for all tumor types combined showed a statistically significant increasing trend (p<0.0001). For acute lymphocytic leukemia, the survival rate increased steadily from 24.7% (95% CI 15.0-34.3) in 1970-1974 to 87.8% (82.1-93.6) in 1995-1999. Five-year survival rates for central nervous system tumors increased from 32.8% (21.0-44.6) in 1970-1974 to 80.3% (72.6-88.0) in 1990-1994 and decreased thereafter. Age of less than 1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma and ganglioneuroblastoma. The extent of disease at diagnosis was related to prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid tumors. A white blood cell count greater than 50,000 x 10(6) cells/l was associated with decreased survival in children with acute lymphocytic leukemia and acute non-lymphocytic leukemia. We have found positive trends in survival for all tumor types in Piedmont, similar to those reported by other population-based cancer registries. Age, extent of disease, and white blood cell count at diagnosis are prognostic factors for selected cancer sites.

Adolescent↗

Spatial variation of mortality for common and rare cancers in Piedmont, Italy, from 1980 to 2000: a Bayesian approach.

A Bayesian hierarchical model was used to study the spatial variation in mortality risk from lung and pleural cancer in both sexes, and breast and soft tissue sarcoma (STS) in women in Piedmont (north-west Italy, average population 4 349 411) from 1980 to 2000. Of these four neoplasms, two are common (lung and breast) and two rare (pleura and STS); two have well recognized risk factors (lung and pleura) while the other two (breast and STS) have no single strong risk factor. Data were analysed at a small-area level (1206 municipalities, population 39 to 989 663), using both standardized mortality ratios and Bayesian-estimated mortality risks. The Bayesian model allowed for both heterogeneity (through spatially independent random effects) and clustering (through spatially correlated random effects) and, by borrowing information from neighbouring areas, provided stable estimates for areas with sparse data. The aim was to reduce the noise in the disease maps to highlight the true underlying mortality distribution. Lung cancer in men showed strong spatial structure with a marked east-west gradient, but no appreciable urban-rural differences. In contrast, high mortality areas for female lung cancer were observed around conurbations. Female breast cancer and STS appeared to be spread uniformly across the region. Pleural cancer mortality clusters were evident around areas with major asbestos manufacturers, or natural asbestiform fibre pollution. Maps of Bayesian-estimated mortality risk provided appreciably clearer pictures of risk distribution than did maps of the standardized mortality ratio.

Bayes Theorem↗

Occupational sun exposure and mycosis fungoides: a European multicenter case-control study.

OBJECTIVE: We sought to study the association between occupational sun exposure and mycosis fungoides (MF), a peripheral T-cell lymphoma. SUBJECTS AND METHODS: A European multicenter case-control study including seven rare cases (one being MF) was conducted between 1995 and 1997. From the 118 accepted cases, 104 were interviewed, of which 76 were definite cases. Population controls were selected randomly from the regions of case ascertainment. Information based on occupational experiences was coded according to industry types. A job exposure matrix was created according to the expected exposure to sunlight. RESULTS: Once exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3; 95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures to solar radiation. CONCLUSION: It would appear that workers exposed to sunlight have a higher risk of MF. However, this factor is not the only one involved.

Aged↗

Lifestyle habits as prognostic factors in survival of laryngeal and hypopharyngeal cancer: a multicentric European study.

Little information is available on the role of tobacco, alcohol and diet in the survival of upper aero digestive cancers. Our study analysed the survival of 931 laryngeal and hypopharyngeal cancer patients, enrolled in a population based case-control study conducted at 5 centres in southeast Europe during 1979-1982. Age at the time of diagnosis and site of origin of tumour were observed to be predictors of the survival. Cigarette smoking, and to a limited extent alcohol drinking, before the diagnosis of tumour seem to influence the overall survival whereas high intakes of vegetables and vitamin C were observed to favourably affect the prognosis. For mortality from upper aerodigestive cancer protective effects of high intakes of vegetables, fibres and vitamin C were observed. Our results support the hypothesis that there is a role for dietary intervention to improve survival of laryngeal and hypopharyngeal cancer patients.

Aged↗

Bayesian methods for early detection of changes in childhood cancer incidence: trends for acute lymphoblastic leukaemia are consistent with an infectious aetiology.

Published data on time trends in the incidence of childhood leukaemia show inconsistent patterns, with some studies showing increases and others showing relatively stable incidence rates. Data on time trends in childhood cancer incidence from the Childhood Cancer Registry of Piedmont, Italy were analysed using two different approaches: standard Poisson regression and a Bayesian regression approach including an autoregressive component. Our focus was on acute lymphoblastic leukaemia (ALL), since this is hypothesised to have an infectious aetiology, but for purposes of comparison we also conducted similar analyses for selected other childhood cancer sites (acute non-lymphoblastic leukaemia (AnLL), central nervous system (CNS) tumours and neuroblastoma (NB)). The two models fitted the data equally well, but led to different interpretations of the time trends. The first produced ever-increasing rates, while the latter produced non-monotonic patterns, particularly for ALL, which showed evidence of a cyclical pattern. The Bayesian analysis produced findings that are consistent with the hypothesis of an infectious aetiology for ALL, but not for AnLL or for solid tumours (CNS and NB). Although sudden changes in time trends should be interpreted with caution, the results of the Bayesian approach are consistent with current knowledge of the natural history of childhood ALL, including a short latency time and the postulated infectious aetiology of the disease.

Adolescent↗

Risk factors for the development of second primary tumors among men after laryngeal and hypopharyngeal carcinoma.

BACKGROUND: Second primary tumors (SPT) constitute a major threat to the survival of patients with laryngeal carcinoma. However, to the authors' knowledge little is known regarding the risk factors for developing SPTs or about the strategy to be followed to avoid them. METHODS: Eight hundred seventy-six male patients with laryngeal/hypopharyngeal carcinoma enrolled in a population-based, case-control study in 5 centers from South Europe during 1979-1982 were followed up to ascertain the occurrence of SPTs. Standardized incidence ratios were calculated to estimate the risk of SPT occurring in the cohort. Cox proportional hazard models were fitted to estimate the hazard ratio for development of SPTs in relation to use of tobacco smoking, alcohol consumption, and dietary habits before the first primary tumor. RESULTS: One hundred forty-five patients developed an SPT with an annual average rate of 2.1%. An excess risk of developing an SPT of the tongue, mouth, esophagus, and lung was observed. No elevated risks of SPTs were observed in other organs. Alcohol consumption strongly increased the risk of developing an SPT of the upper aerodigestive tract (UADT). Heavy cumulative cigarette smoking increased the risk of developing a lung SPT. A protective effect of high intake of citrus fruit was noticed for SPT in the lung, whereas high butter intake was associated with an increased risk for SPT of the UADT. CONCLUSIONS: Continuous medical surveillance was essential in the UADT and lung to reduce the risk from an SPT after initial laryngeal/hypopahryngeal carcinoma. Alcohol consumption before the first primary tumor was a risk factor for SPT of the UADT. The study suggested a protective role of citrus fruits in the development of a lung SPT.

Adult↗

Guidelines for preoperative assessment: impact on clinical practice and costs.

OBJECTIVE: To describe preoperative evaluation in the San Giovanni Battista Hospital in Turin and to forecast the economic impact when preoperative assessment guidelines are implemented. DESIGN: We enrolled, in a month, 702 consecutive patients, excluding cardiac, thoracic, neuro- and vascular surgery, as well as emergency operations. Preoperative assessment data were collected individually, followed by simulating various applications of guidelines based on: (i) preoperative tests relying on full medical history and physical examination to discriminate preoperative risk patients; (ii) organization of a preoperative evaluation unit and tests before patient hospitalization. MAIN MEASURES: Mean number of tests prescribed, preoperative assessment cost per patient. RESULTS: The application of preoperative guidelines would decrease the mean number of tests prescribed from 20 laboratory and 1.9 instrumental to, respectively, 3 and 1.4 per patient. Tests deemed inappropriate by guidelines did not add any relevant clinical information to our study. Economic analysis estimates a reduction of 63% in cost per patient for preoperative tests by introducing guideline criteria (from 69 euros to 26 euros). As regards the cost per patient for preoperative evaluation and hospital stay (115 euros considering only variable costs, 580 euros including all costs), the application of the guidelines would reduce costs by 41-52% according to different cost evaluation approaches for hospital stay. CONCLUSION: Preoperative guidelines fully introduced in practice could notably increase efficiency without affecting the quality of care.

Adolescent↗

European multi-centre case-control study on risk factors for rare cancers of unknown aetiology.

To search for occupational risk factors, we conducted a case-control study in nine European countries of cancers of the small intestine, male gall bladder, thymus, bone, male breast, melanoma of the eye, and mycosis fungoides. Recruitment was population based in Denmark, Latvia, France, Germany, Italy, and Sweden, from hospital areas in Spain and Portugal, and from one United Kingdom (UK) hospital. We recruited 1457 cases (84% interviewed). Numbers identified corresponded to those in the EUROCIM database for Denmark, but were below those observed for France, Italy and Sweden in the database. We recruited 3374 population (61% interviewed) and 1284 colon cancer controls (86% interviewed). It was possible to undertake this complicated study across Europe, but we encountered three main problems. It was difficult to ensure complete case ascertainment, for population controls, we found a clear divide in the response rate from 75% in the South to only 55% in the North, and a somewhat selective recruitment was noted for the colon cancer controls. The study showed there is a clear dose-response relationship between alcohol intake and the risk of male breast cancer, and an excess risk of mycosis fungoides among glass formers, pottery and ceramic workers. Further data are expected.

Adult↗