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Abstract Background Health service databases of administrative type can be a useful tool for the study of progression of a disease, but the data reported in such sources could be affected by misclassifications of some patients' real disease states at the time. Aim of this work was to estimate the transition probabilities through the different degenerative phases of liver cirrhosis using health service databases. Methods We employed a hidden Markov model to determine the transition probabilities between two states, and of misclassification. The covariates inserted in the model were sex, age, the presence of comorbidities correlated with alcohol abuse, the presence of diagnosis codes indicating hepatitis C virus infection, and the Charlson Index. The analysis was conducted in patients presumed to have suffered the onset of cirrhosis in 2000, observing the disease evolution and, if applicable, death up to the end of the year 2006. Results The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients was 1.5% per year. The probability of developing HCC is higher in males (OR = 2.217) and patients over 65 (OR = 1.547); over 65-year-olds have a greater probability of death both while still suffering from cirrhosis (OR = 2.379) and if they have developed HCC (OR = 1.410). A more severe casemix affects the transition from HCC to death (OR = 1.714). The probability of misclassifying subjects with HCC as exclusively affected by liver cirrhosis is 14.08%. Conclusions The hidden Markov model allowing for misclassification is well suited to analyses of health service databases, since it is able to capture bias due to the fact that the quality and accuracy of the available information are not always optimal. The probability of evolution of a cirrhotic subject to HCC depends on sex and age class, while hepatitis C virus infection and comorbidities correlated with alcohol abuse do not seem to have an influence.

Abstract Background If spatial representations of hospitalization rates are used, a problem of instability arises when they are calculated on small areas, owing to the small number of expected and observed cases. Aim of this study is to assess the effect of smoothing, based on the assumption that hospitalization rates, when calculated at the municipal level, may be influenced by both the neighboring municipalities and the health service organization, as well as by environmental risk factors associated with the disease under study. Methods To smooth rates we hypothesize that each municipality belongs to two independent hierarchical levels; at one of these levels subjects may belong to a plurality of superior hierarchical objects. Two different models, so-called Multilevel Multimembership Models, are fitted. In the first the structure of random effects was: the municipality heterogeneity, the spatial dependence of the municipalities and the local health service organization. In the second we replaced the local health service organization effect with the environmental risk effect for each municipality area. The models were applied to spatially represent the rates of hospitalization for lung cancer and chronic obstructive pulmonary disease, determined through the hospital discharge forms recorded in Apulia for the year 2006. Results The effect of smoothing was greater in smaller municipalities and in those with a more unstable Risk Adjusted Rate (RAR) due to the small number of cases and of population at risk. When a hierarchical level representing the ASL is inserted, the model fits the data better. Conclusion Maps of hospitalization rates for lung cancer and chronic obstructive pulmonary disease, shaded with the rates obtained at the end of the smoothing procedure, change the visual picture of the disease distribution over the whole territory, and if detected by the model, seem to express a geographical distribution pattern in specific areas of the region. In the case of lung cancer, the models show a clear difference between RAR and smoothed RAR. The inclusion of a random effect indicating the ASL contributed to improve the graphic representation of the results, whereas the environmental risk was not found to be a better hierarchical level than the municipality for fitting of the model.

Abstract Background This study aimed to investigate squamous cellular carcinoma antigen (SCCA) in serum and in tumoral and paired peritumoral tissues. We studied 27 patients with liver cirrhosis (LC) and 55 with HCC: 20 with a single nodule < 3 cm (s-HCC) and 35 with a single nodule > 3 cm or multifocal (l-HCC). Methods Serum SCCA was measured by the ELISA kit, and in frozen tissues by immunohistochemistry, quantified with appropriate imaging analysis software and expressed in square microns. Continuous variables are reported as means and 95% confidence intervals. Comparisons between independent groups were performed with a generalized linear model and Tukey grouping. Pearson's correlation coefficients were determined to evaluate relations between markers. Qualitative variables were summarized as count and percentage. Statistical significance was set at p-value < 0.05. Results Serum SCCA values in LC patients were 0.41 (0.31–0.55) ng/ml and statistically different from both HCC groups: 1.6 (1.0–2.6) ng/ml in s-HCC, 2.2 (1.28–2.74) ng/ml in l-HCC. SCCA in hepatic tissue was 263.8 (176.6–394.01) μm2 in LC patients, statistically different from values in s-HCC: 1163.2 (863.6–1566.8) μm2 and l-HCC: 625.8 (534.5–732.6). All pairwise comparisons between groups yielded statistically significant differences. Tumoral SCCA resulted linearly related with nodule size, showing a statistically significant inverse relation between the two variables (b = -0.099, p = 0.024). Conclusion There was no statistically significant correlation between tissue and serum levels of SCCA. The significantly stronger expression of SCCA in smaller compared to larger HCC could be important for early HCC detection. However, the increased expression in peritumoral tissue could affect the significance of serological detection.

Abstract Background The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD. Methods Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP. Results Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination. Conclusion We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.

Abstract Background The analysis of non-fatal recurring events is frequently found in studies on chronic-degenerative diseases. The aim of this paper is to estimate the probability of readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) or with Respiratory Failure (RF). Methods The Repeated hospital admissions of a patient are considered as a Markov Chain. The transitions between the states are estimated using the Nelson-Aalen estimator. The analysis was carried out using the Puglia Region hospital patient discharge database for the years 1998–2005. Patients were selected on the basis of first admission between 01/01/2001 and 31/12/2005 with ICD-9-CM code of COPD or RF as principal and/or secondary diagnosis. For those selected two possible transitions were considered in the case they had the second and third admission with an ICD-9-CM code of COPD or RF as principal diagnosis. Results The probability of readmission is increased in patients with a diagnosis of RF (OR = 1.618 in the first transition and 1.279 in the second) and also in those with a diagnosis of COPD or RF as the principal diagnosis at first admission (OR = 1.615 in the first transition and 1.193 in the second). The clinical gravity and the ward from which they were discharged did not significantly influence the probability of readmission. Conclusion The time to readmission depends on the gravity of the pathology at onset. In patients with a grave clinical picture, either COPD or Respiratory Failure, when treated and controlled after the first admission, they become minor problems and they are indicated among secondary diagnoses in any further admission.

Abstract Background Thyroid nodules and thyroid cancer occur more frequently in people exposed to radiation for therapeutic purposes, and to nuclear fallout. Furthermore, it is known that a moderate degree of iodine deficiency may be responsible for an increased prevalence of thyroid nodules, while it is suspected that radiation exposure could induce changes in thyroid autoimmunity. The iodine intake of people resident in Bari, S. Italy, is mildly deficient, which could be presumed to cause a higher prevalence of thyroid pathology. This study was conducted to evaluate the prevalence of thyroid nodules in a population occupationally exposed to radiation, in an area of mild iodine deficiency. Methods A cross-sectional study was designed to evaluate the prevalence of thyroid nodules in radiation exposed workers, compared with a stratified sample of non exposed workers. After giving written consent to participate in the study, all the recruited subjects (304 exposed and 419 non exposed volunteers) were interviewed to fill in an anamnestic questionnaire, and underwent a physical examination, ultrasound thyroid scan, serum determinations of fT3, fT4 and TSH, fine needle aspiration biopsy. The sample was subdivided into one group exposed to a determined quantity of radiation (detected by counter), one group exposed to an undetectable quantity of radiation, and the non exposed control group. Results The prevalence of thyroid nodules Instead, the prevalence of thyroid nodules > 1 cm in diameter resulted statistically different in exposed and non exposed health staff: 18.68% in non exposed males vs exposed: 3.76% (determined dose) and 9.09% (undetectable dose) in males, and 20.30% in non exposed females versus 3.23% (detected dose) and 9.52% (undetectable dose) in exposed females. There was a higher proportion of healthy staff in the exposed group than in the non exposed: (80.45% vs 68.68% in males; 80.65% vs 57.87% in females). Conclusion In our study, occupational exposure to radiation combined with mild iodine deficiency did not increase the risk of developing thyroid nodules. The statistically significant higher prevalence of thyroid nodules in the non exposed group could be explained by the high percentage (22%) of people with a familial history of, and hence a greater predisposition to, thyroid disease. The endemic condition of mild iodine deficiency, demonstrated in other studies, played a major role in determining the thyroid pathology in our study groups.