Alessandro Barchielli

Risk of cancer other than Kaposi's sarcoma and non-Hodgkin's lymphoma in persons with AIDS in Italy

Record linkage was carried out between the national Registry of AIDS and 13 Cancer Registries (CRs) covering, in 1991, about 15% of the Italian population. Observed and expected numbers of cancers and standardized incidence ratios (SIRs) were assessed in 6067 persons with AIDS, for a total of 25,759 person-years. Significantly increased SIRs were found for Hodgkins disease [8.9, 95% confidence interval (CI) 4.4-16.0], in which seven of 11 cases were of mixed cellularity type; invasive carcinoma of the cervix uteri (15.5; 95% CI 4.0-40.1); and non-melanomatous skin cancer (3.0, 95% CI 1.3-5.9), in which five of eight cases were basal cell carcinoma. An excess was also seen for brain tumours, but this may be partly due to misdiagnosis of brain non-Hodgkins lymphoma or other brain diseases occurring near the time of the AIDS diagnosis. The risk for all cancer types, after exclusion of Kaposis sarcoma (KS) and non-Hodgkins lymphoma (NHL), was approximately twice the general population risk. An increased SIR for Hodgkins disease in persons with AIDS is thus confirmed, though it is many times smaller than that for NHL. An association with invasive carcinoma of the cervix is also shown at a population level. The excess of non-melanomatous skin cancer seems to be lower than in transplant recipients.

DOSES OF INSULIN AND ITS ANALOGUES AND CANCER OCCURRENCE IN INSULIN-TREATED TYPE 2 DIABETIC PATIENTS

OBJECTIVE Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer. The present study is aimed at assessing the long-term association of different insulin analogues with cancer incidence. RESEARCH DESIGN AND METHODS A nested case-control study dataset was generated from the cohort study dataset (n = 1,340 insulin-treated diabetic outpatients) by sampling control subjects from the risk sets. For each case subject, the control subjects (up to five) were chosen randomly from those members of the cohort who are at risk for the same follow-up time of the case subject. Five-year age classes, sex, and BMI classes (<18.5, 18.5–24.9, 25–29.9, and ≥30 kg/m2) were considered as additional categorical matching variables. RESULTS During a median follow-up of 75.9 months (interquartile range 27.4–133.7), 112 case subjects of incident cancer were compared with 370 matched control subjects. A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects (0.24 IU/kg/day [0.10–0.39] versus 0.16 IU/kg/day [0.12–0.24], P = 0.036). Incident cancer was associated with a dose of glargine ≥0.3 IU/kg/day even after adjusting for Charlson comorbidity score, other types of insulin administration, and metformin exposure (odds ratio 5.43 [95% CI 2.18–13.53], P < 0.001). No association between incident cancer and insulin doses was found for human insulin or other analogues. CONCLUSIONS The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer.

METFORMIN AND CANCER OCCURRENCE IN INSULIN-TREATED TYPE 2 DIABETIC PATIENTS.

OBJECTIVE Metformin is associated with reduced cancer-related morbidity and mortality. The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients. RESEARCH DESIGN AND METHODS A nested case-control study was performed in a cohort of 1,340 patients by sampling, for each case subject, age-, sex-, and BMI-matched control subjects from the same cohort. RESULTS During a median follow-up of 75.9 months, 112 case patients who developed incident cancer and were compared with 370 control subjects. A significantly lower proportion of case subjects were exposed to metformin and sulfonylureas. After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25–0.85], P = 0.014 and 0.75 [0.39–1.45], P = 0.40, respectively). CONCLUSIONS The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.

Risk factors for disability in older persons over 3-year follow-up

BACKGROUND the identification of modifiable risk factors for preventing disability in older individuals is essential for planning preventive strategies. PURPOSE to identify cross-sectional correlates of disability and risk factors for the development activities of daily living (ADL) and instrumental ADL (IADL) disability in community-dwelling older adults. METHODS the study population consisted of 897 subjects aged 65-102 years from the InCHIANTI study, a population-based cohort in Tuscany (Italy). Factors potentially associated with high risk of disability were measured at baseline (1998-2000), and disability in ADLs and IADLs were assessed both at baseline and at the 3-year follow-up (2001-03). RESULTS the baseline prevalence of ADL disability and IADL disability were, respectively, 5.5% (49/897) and 22.2% (199/897). Of 848 participants free of ADL disability at baseline, 72 developed ADL disability and 25 of the 49 who were already disabled had a worsening in ADL disability over a 3-year follow-up. Of 698 participants without IADL disability at baseline, 100 developed IADL disability and 104 of the 199 who already had IADL disability had a worsening disability in IADL over 3 years. In a fully adjusted model, high level of physical activity compared to sedentary state was significantly associated with lower incidence rates of both ADL and IADL disability at the 3-year follow-up visit (odds ratio (OR): 0.30; 95% confidence intervals (CI) 0.12-0.76 for ADL disability and OR: 0.18; 95% CI 0.09-0.36 for IADL disability). After adjusting for multiple confounders, higher energy intake (OR for difference in 100 kcal/day: 1.09; 95% CI 1.02-1.15) and hypertension (OR: 1.91; 95% CI 1.06-3.43) were significant risk factors for incident or worsening ADL disability. CONCLUSIONS higher level of physical activity and lower energy intake may be protective against the development in ADL and IADL disability in older persons.

Prognostic Stratification of Older Persons Based on Simple Administrative Data: Development and Validation of the “Silver Code,” To Be Used in Emergency Department Triage

BACKGROUND Prognostic stratification of older patients with complex medical problems among those who access the emergency department (ED) may improve the effectiveness of geriatric interventions. Whether such targeting can be performed through simple administrative data is unknown. METHODS We examined the discharge records for 10,913 patients aged 75 years or older admitted during 2005 to the ED of all public hospitals in Florence, Italy. Using information on demographics, drug treatment, previous hospital admissions, and discharge diagnoses, we developed a 1-year mortality prognostic index. The predictive validity of this index was tested in a subsample of patients independent of the subsample used for its original development. Finally, we tested whether patients stratified by the prognostic index had different mortality when admitted to a geriatrics compared with an internal medicine ward. RESULTS In the validation subsample, patients with scores of 4-6, 7-10, and 11+ compared with those with scores less than 4 had hazard ratios (95% confidence interval) for 1-year mortality of, respectively, 1.5 (1.3-1.7), 2.2 (1.3-1.7), and 3.0 (2.6-3.4). Patients in the worse prognostic stratum experienced 33% higher mortality when admitted to an internal medicine compared with a geriatrics ward, although mortality was not significantly affected by the type of ward of admission in all other risk strata. CONCLUSIONS Simple administrative data provide prognostic information on long-term mortality in older patients hospitalized via ED. Patients with worse prognostic index scores appear to benefit from admission in a geriatrics compared with an internal medicine ward.

High suicide mortality soon after diagnosis among cancer patients in central Italy

A high suicide mortality risk has been documented among a population-based cohort of 27 123 cancer patients resident in central Italy where the general suicide rate is low. Forty-one suicides were observed (SMR = 2.36) which were only 0.2% of all deaths. However, the highest risk (SMR = 27.7) during the first 6 months after diagnosis, represents a greater contrast with the general population than has been observed in other studies.

Short-Term Association Between Ambient Air Pollution and Risk of Hospitalization for Acute Myocardial Infarction: Results of the Cardiovascular Risk and Air Pollution in Tuscany (RISCAT) Study

Air pollutant levels have been widely associated with increased hospitalizations and mortality from cardiovascular disease. In this study, the authors focused on pollutant levels and triggering of acute myocardial infarction (AMI). Data on AMI hospitalizations, air quality, and meteorologic conditions were collected in 6 urban areas of Tuscany (central Italy) during 2002-2005. Levels of particulate matter with an aerodynamic diameter ≤10 μm (PM(10)) (range of 4-year mean values, 28.15-40.68 μg/m(3)), nitrogen dioxide (range, 28.52-39.72 μg/m(3)), and carbon monoxide (range, 0.86-1.28 mg/m(3)) were considered, and increases of 10 μg/m(3) (0.1 mg/m(3) for carbon monoxide) were analyzed. A time-stratified case-crossover approach was applied. Area-specific conditional regression models were fitted, adjusting for time-dependent variables. Stratified analyses and analyses in bipollutant models were performed. Pooled estimates were derived from random-effects meta-analyses. Among 11,450 AMI hospitalizations, the meta-analytical odds ratio at lag(2) (2-day lag) was 1.013 (95% confidence interval (CI): 1.000, 1.026) for PM(10), 1.022 (95% CI: 1.004, 1.041) for nitrogen dioxide, and 1.007 (95% CI: 1.002, 1.013) for carbon monoxide. More susceptible subgroups were elderly persons (age ≥75 years), females, and older patients with hypertension and chronic obstructive pulmonary disease. This study adds to evidence for a short-term association between air pollutants and AMI onset, also evident at low pollutant levels, suggesting a need to focus on more vulnerable subjects.

LONG-TERM SEQUELAE OF BREAST CANCER SURGERY

Background Quality of care is today a major issue in oncology, and much attention is given to research on the outcome of breast cancer care. Too little attention has been devoted in the scientific literature to the consequences of treatment in long-term survivors, and in particular to the possible side effects. The specific aim of this contribution is to present population-based data about the long-term impact of breast cancer care in women who had an incident cancer in 1985/1986. Patients and Methods The cases are 476 breast cancers incident in the City of Florence in 1985-86. Women still living 5 years later were invited to have an interview and a physical examination. Lymphedema, peripheral nerve lesions and damage to the shoulder were assessed. Results Of the 346 5-year survivors, 238 accepted our invitation: 35.2% of the women reported some early postoperative sequelae, 30.2% had a chronic lymphedema and 18.9% a shoulder deficit. Comparing breast-conserving surgery with radical mastectomy, the risk of chronic lymphedema (OR=1.62; 95% CI: 0.91-2.88) and other lesions was higher for women who had a radical surgery. Women who had a breast-conserving surgery more often reported an early lymphedema (OR=1.60; 95% CI: 0.88-2.88). Conclusions The proportion of women who complained of (or manifested at the physical examination) a minor or major disability of the arm in our study was high. The impact of these functional problems in terms of quality of life should also be assessed, but it is our impression that there is need for much greater attention to the issue of long-term survivor sequelae.

Determinants of treatment strategies and survival in acute myocardial infarction: a population-based study in the Florence district, Italy: results of the acute myocardial infarction Florence registry (AMI-Florence).

AIMS The Florence Acute Myocardial Infarction Registry is a prospective, observational study aimed at identifying the determinants of use of primary PCI and of prognosis in patients with STE-AMI, in an unselected population-based setting. METHODS AND RESULTS Nine hundred and thirty cases of STE-AMI (mean age: 70.5 years) were prospectively recorded. Factors associated with use of revascularization, or influencing survival were identified through multivariate analyses (respectively: logistic and Cox regression). Primary PCI was the preferred reperfusion therapy in the study district, with 50% of STE-AMI cases admitted within 24h, and 58% of those admitted within 12h from symptom onset treated; about 5% of patients undergone fibrinolysis (overall revascularization being 55% and 63%, respectively). Availability of PCI facilities at admission hospital was the strongest independent positive predictor of subsequent primary PCI. Advanced age, comorbidities, Killip class 3, delayed hospitalisation and other factors independently reduced the probability of receiving reperfusion. In the whole series, in-hospital mortality was 6.6% for revascularization and 15.6% for conservative therapy, 6-month mortality was 10.1% and 26.0% respectively. The independent, protective effect of primary PCI persisted at the multivariate analysis, being 44% the reduction in the risk of death at 6 months. CONCLUSION In this unselected series of patients, primary PCI, routinely performed in high volume centres, achieved good results in terms of survival even outside the setting of a randomised clinical trial. However, the relatively high number of untreated subjects and the tendency to select less severe cases of AMI for reperfusion treatment confirm the need for an accurate reassessment of behavioural patterns in selecting patients for revascularization.

Arrhythmias in mitral valve prolapse: Relation to anterior mitral leaflet thickening, clinical variables, and color Doppler echocardiographic parameters

Atrial and ventricular arrhythmias have been reported with variable incidence in symptomatic patients with mitral valve prolapse (MVP). The role of clinical and echocardiographic parameters as predictors for arrhythmias still needs to be clarified. One hundred nineteen consecutive patients (56 women and 63 men, mean age 40 +/- 17 years) with echocardiographically diagnosed MVP were examined. A complete echocardiographic study (M-mode, two-dimensional, and Doppler) and 24-hour electrocardiographic monitoring were performed in all patients. Complex atrial arrhythmias (CAAs) included atrial couplets, atrial tachycardia, and paroxysmal or sustained atrial flutter or fibrillation. Complex ventricular arrhythmias (CVAs) included multiform ventricular premature contractions (VPCs), VPC couplets, and runs of three or more sequential VPCs (salvos of ventricular tachycardia). The relation between complex arrhythmias and clinical parameters (age and gender) and echocardiographic parameters (left atrial and left ventricular dimensions, anterior mitral leaflet thickness [AMLT], and presence and severity of mitral regurgitation) was evaluated by multiple logistic regression analysis. CAA were present in 14% of patients and CVA in 30%. According to multiple logistic modeling, CAA correlated separately in the univariate analysis with age, presence of MR, and left ventricular and left atrial diameters; age was the only independent predictor (p < 0.001). CVA, in the univariate analysis, correlated with age, female gender, left ventricular end-diastolic diameter, and AMLT; only female gender and AMLT were independent predictors in the multivariate analysis (p < 0.01). The incidence of mitral regurgitation (59%) was higher than expected in a general population of MVP patients.(ABSTRACT TRUNCATED AT 250 WORDS)