Biomedical subjects

Vincenzo Bagnardi

Publications and source records attributed to Vincenzo Bagnardi.

8 recordsLinked to original sources

PubMed2006

Empirical-Bayes adjustment improved conventional estimates in postmarketing drug-safety studies.

OBJECTIVES: Empirical-Bayes adjustment was used to investigate the effects of antibacterials on risk of arrhythmia in a large cohort study based upon automated record linkage. STUDY DESIGN AND SETTING: The Prescription Drug Database of the Varese Province, Italy, was used to form a population-based cohort of patients who received at least one prescription of antibacterials for systemic use. All cohort members were followed-up from the beginning of each antibacterial therapeutic cycle up to 60 days afterward, identifying the first prescription of an antiarrhythmic drug and/or the first admission for arrhythmia. Standardized incidence ratios for eight classes of antibacterials, as well as for the specific antibacterial drugs, were estimated using both conventional methods and empirical-Bayes (EB) adjustment. RESULTS: Using EB adjustment, overall precision was greatly enhanced compared to the conventional analysis. Statistical evidence of drug-induced dysrhythmic events was found for 17 drugs mostly belonging to Macrolides and Quinolones. Strongest proarrhythmic effects were found for Ciprofloxacin (standardized incidence ratio [SIR]: 1.98; 95% CI: 1.67, 2.34) and Erythromycin (SIR: 1.91; 95% CI: 1.20, 2.88). CONCLUSION: Empirical-Bayes may mitigate some problems inherent the conventional analysis. Macrolides and Quinolones were associated with the highest number of positive signals of dysrhythmic events. This requires further investigation by other types of epidemiologic studies.

Adult↗

PubMed2005

Estimating dose-response relationship between ethanol and risk of cancer using regression spline models.

Cancers of the upper aero-digestive tract (i.e., oral cavity, pharynx, larynx and oesophagus) are largely attributable to smoking and drinking habits, but the correct estimation of the dose-response relationship between alcohol and cancer risk is challenging. Step functions are widely used to estimate risks and to evaluate trends of continuous exposure. However, results are influenced by the selection of the reference category and cutpoints. More flexible models, like spline regression and fractional polynomial models, may be an attractive alternative for avoiding strict assumptions about the dose-response relationship. Data from a large series of hospital-based case-control studies conducted in Italy and the Swiss Canton of Vaud in the last 2 decades were reassessed to compare findings from logistic regression spline models and standard step function analysis. For all examined cancers, the risk increased to the consumption of 150 grams of ethanol per day (1.5 litre/day of wine), with a possible threshold effect emerging for cancer of the pharynx and larynx (<50 grams of ethanol per day) only. For higher consumptions, the risks flattened. Our study suggests that regression spline models can be useful to estimate the pattern of risk of a continuous exposure variable, such as alcohol consumption, and provide more accurate estimates than categorical analysis when ORs within each interval, especially in the reference category, are not homogeneous.

Adult↗

PubMed2005

Generating signals of drug-adverse effects from prescription databases and application to the risk of arrhythmia associated with antibacterials.

BACKGROUND: Although it is well known that a variety of antibacterials may incidentally cause malignant arrhythmia, the list of drugs causing arrhythmia and the impact of these adverse effects are still uncertain. We investigated on this topic by using a large prescription database with different observational designs. METHODS: Prescription data on all incident users of several antibacterial and antiarrhythmic drugs over the period July 1997 through December 1999 were retrieved from the Drug Prescription Database (DPD) of the Italian Province of Varese. The association between the use of antibacterial and antiarrhythmic drugs was investigated by applying prescription sequence symmetry, cohort and nested case-control designs. RESULTS: Lower proarrhythmic effects were on an average obtained from prescription sequence symmetry approach with respect to both cohort and nested case-control. Evidence of association between exposure to drugs (erythromycin and ciprofloxacin) and the risk of arrhythmia was consistently found by the three approaches. No other signals were generated from the prescription sequence symmetry analysis. Two drugs (clarithromycin and levofloxacin) showed patterns compatible with an arrhythmic effect according to both cohort and nested case-control designs. CONCLUSIONS: Prescription databases are useful tools to explore drug safety through both conventional and emerging observational designs. In spite of its appealing features, prescription sequence symmetry design shows lower sensitivity with respect to conventional designs. Evidence about the association between the use of certain macrolides and fluoroquinolones and the onset of arrhythmia is confirmed by this study.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

Short-acting inhaled beta-2-agonists increased the mortality from chronic obstructive pulmonary disease in observational designs.

OBJECTIVE: The effect of short-acting inhaled beta(2)-agonists on mortality from chronic obstructive pulmonary disease (COPD) is controversial. Different observational designs were used to investigate about this topic. STUDY DESIGN AND SETTING: A population-based case-control design was performed, by linking automated health databases from the Varese Province of Italy. Deaths of COPD generated from the cohort of 135,871 patients for whom at least one prescription for drugs used to treat COPD had been dispensed between 1997 and 1999 entered into the study as cases. Up to 20 controls were randomly selected for each case from the cohort after matching on gender, age, and date of cohort entry. Risk ratios were estimated using the case-control, case-crossover, and case-time-control approaches. RESULTS: A total of 222 cases and 3022 controls met the inclusion criteria. Odds ratios (and corresponding 95% confidence intervals) corresponding to more than 0.5 defined-daily-doses were 2.6 (1.7, 4.0), 1.9 (1.1, 3.3), 2.1 (1.1, 4.0), and 2.3 (1.2, 4.6) by using crude and adjusted case-control, case-crossover, and case-time-control estimates, respectively. CONCLUSION: Evidence that higher doses of short-acting inhaled beta(2)-agonists are associated with higher mortality from COPD was consistently supplied by three observational approaches.

Adrenergic beta-Agonists↗

PubMed2004

Flexible meta-regression functions for modeling aggregate dose-response data, with an application to alcohol and mortality.

In this paper, the authors describe fractional polynomials and cubic splines with which to represent smooth dose-response relations in summarizing meta-analytical aggregate data. Use of these two curve-fitting families can help prevent the problems arising from inappropriate linearity assumptions. These methods are illustrated in the problem of estimating the shape of the dose-response curve between alcohol consumption and all-cause mortality risk. The authors considered aggregate data from 29 cohort studies investigating this issue (1966-2000). J-shaped curves with a nadir at approximately 5-7 g/day of alcohol consumption and a last protective dose of 47-60 g/day were consistently obtained from fractional polynomials and cubic splines. The authors conclude that both of the curve-fitting families are useful tools with which to explore dose-response epidemiologic questions by means of meta-analytical approaches, especially when important nonlinearity is anticipated.

Alcohol Drinking↗

PubMed2004

A meta-analysis of alcohol consumption and the risk of 15 diseases.

BACKGROUND: To compare the strength of evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 14 major alcohol-related neoplasms and non-neoplastic diseases, plus injuries. METHODS: A search of the epidemiological literature from 1966 to 1998 was performed by several bibliographic databases. Meta-regression models were fitted considering fixed and random effect models and linear and nonlinear effects of alcohol intake. The effects of some characteristics of the studies, including an index of their quality, were considered. RESULTS: Of the 561 initially reviewed studies, 156 were selected for meta-analysis because of their a priori defined higher quality, including a total of 116,702 subjects. Strong trends in risk were observed for cancers of the oral cavity, esophagus and larynx, hypertension, liver cirrhosis, chronic pancreatitis, and injuries and violence. Less strong direct relations were observed for cancers of the colon, rectum, liver, and breast. For all these conditions, significant increased risks were also found for ethanol intake of 25 g per day. Threshold values were observed for ischemic and hemorrhagic strokes. For coronary heart disease, a J-shaped relation was observed with a minimum relative risk of 0.80 at 20 g/day, a significant protective effect up to 72 g/day, and a significant increased risk at 89 g/day. No clear relation was observed for gastroduodenal ulcer. CONCLUSIONS: This meta-analysis shows no evidence of a threshold effect for both neoplasms and several non-neoplastic diseases. J-shaped relations were observed only for coronary heart disease.

Alcohol Drinking↗

PubMed2002

Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels.

UNLABELLED: A retrospective evaluation of asymptomatic subjects with persistent elevation of serum creatine kinase (CK) levels (hyperCKemia) was made in order to verify the presence of subclinical myopathy or idiopathic hyperCKemia and to define the most appropriate diagnostic pathway. Persistently increased serum CK levels are occasionally encountered in healthy individuals. In 1980 Rowland coined for them the term idiopathic hyperCKemia. Despite the increase of scientific knowledge, several healthy subjects with hyperCKemia still represent a problem for the clinician. We made a retrospective evaluation of 114 asymptomatic or minimally symptomatic individuals with incidentally detected persistent hyperCKemia. They underwent neurological examination and laboratory/instrumental evaluation. Skeletal muscle biopsy was performed and thoroughly investigated. Biochemical and genetic investigations were added in selected cases. Logistic regression analysis was applied. We diagnosed a neuromuscular disorder in 21 patients (18.4%), and found, by muscle biopsy and/or EMG, pathological but not conclusive findings in 57 subjects (50%). The statistic correlation between elevated serum CK levels and the probability of making a diagnosis changed according to the age of the patient. CONCLUSIONS: Muscle biopsy is the basic tool for screening asymptomatic subjects with hyperCKemia. It allowed us to make a diagnosis of disease in 18.4% of patients, and to detect skeletal muscle abnormalities in 38.6% of the subjects. Interestingly, 31.6% of individuals had completely normal muscle findings. These best fit the "diagnosis" of idiopathic hyperCKemia.

Adolescent↗

PubMedDate not supplied

Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies.

BACKGROUND: Moderate consumption of alcohol is inversely related with coronary disease, but its association with mortality is controversial. We performed a meta-analysis of prospective studies on alcohol dosing and total mortality. METHODS: We searched PubMed for articles available until December 2005, supplemented by references from the selected articles. Thirty-four studies on men and women, for a total of 1 015 835 subjects and 94 533 deaths, were selected. Data were pooled with a weighed regression analysis of fractional polynomials. RESULTS: A J-shaped relationship between alcohol and total mortality was confirmed in adjusted studies, in both men and women. Consumption of alcohol, up to 4 drinks per day in men and 2 drinks per day in women, was inversely associated with total mortality, maximum protection being 18% in women (99% confidence interval, 13%-22%) and 17% in men (99% confidence interval, 15%-19%). Higher doses of alcohol were associated with increased mortality. The inverse association in women disappeared at doses lower than in men. When adjusted and unadjusted data were compared, the maximum protection was only reduced from 19% to 16%. The degree of association in men was lower in the United States than in Europe. CONCLUSIONS: Low levels of alcohol intake (1-2 drinks per day for women and 2-4 drinks per day for men) are inversely associated with total mortality in both men and women. Our findings, while confirming the hazards of excess drinking, indicate potential windows of alcohol intake that may confer a net beneficial effect of moderate drinking, at least in terms of survival.

Alcohol Drinking↗