Neuroendocrine Tumors (NETs): A population-based study of incidence and survival in Girona province, 1994-2004

Els tumors neuroendocrins (TNEs) són un grup de neoplàsies poc freqüents i heterogènies i amb un ampli espectre d’agressivitat. Hi ha molt poca informació epidemiològica a nivell mundial, l’objectiu d’aquest estudi ha estat el de reportar-ne les dades a la província de Girona. Hem inclòs tots els codis de la ICD-O3 que codifiquen un TNE, període 1994-2002. Hem identificat 698 tumors. Es reporten les dades tant de la casuística com les taxes d’incidència i supervivència de cada TNE per separat. Els resultats són consistents amb les publicacions europees. El fet d’haver reportat la incidència i la supervivència dels TNEs a Girona contribueix a un millor coneixement d’aquestes neoplàsies.

Population based resource allocation: The use of hybrid risk adjustment

The emphasis on integrated care implies new incentives that promote coordinationbetween levels of care. Considering a population as a whole, the resource allocation systemhas to adapt to this environment. This research is aimed to design a model that allows formorbidity related prospective and concurrent capitation payment. The model can be applied inpublicly funded health systems and managed competition settings.Methods: We analyze the application of hybrid risk adjustment versus either prospective orconcurrent risk adjustment formulae in the context of funding total health expenditures for thepopulation of an integrated healthcare delivery organization in Catalonia during years 2004 and2005.Results: The hybrid model reimburses integrated care organizations avoiding excessive risktransfer and maximizing incentives for efficiency in the provision. At the same time, it eliminatesincentives for risk selection for a specific set of high risk individuals through the use ofconcurrent reimbursement in order to assure a proper classification of patients.Conclusion: Prospective Risk Adjustment is used to transfer the financial risk to the healthprovider and therefore provide incentives for efficiency. Within the context of a National HealthSystem, such transfer of financial risk is illusory, and the government has to cover the deficits.Hybrid risk adjustment is useful to provide the right combination of incentive for efficiency andappropriate level of risk transfer for integrated care organizations.

Predictors of death among patients who completed tuberculosis treatment: a population-based cohort study.

Background: Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods: A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995 1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results: Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 4160 years old (HR: 3.5; CI:2.15.7), age greater than 60 years (HR: 14.6; CI:8.924), alcohol abuse (HR: 1.7; CI:1.22.4) and HIV-infected IDU (HR: 7.9; CI:4.713.3). Conclusions: The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival.

Antipsychotic polypharmacy in a regional health service: a population-based study

Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine. Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine.

Development of a population-based cost-effectiveness model of chronic graft versus host disease in Spain

Chronic graft-versus-host disease (cGvHD) is the leading cause of late nonrelapse mortality (transplant-related mortality) after hematopoietic stem cell transplant. Given that there are a wide range of treatment options for cGvHD, assessment of the associated costs and efficacy can help clinicians and health care providers allocate health care resources more efficiently. OBJECTIVE: The purpose of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with rituximab (Rmb) and with imatinib (Imt) in patients with cGvHD at 5 years from the perspective of the Spanish National Health System. METHODS: The model assessed the incremental cost-effectiveness/utility ratio of ECP versus Rmb or Imt for 1000 hypothetical patients by using microsimulation cost-effectiveness techniques. Model probabilities were obtained from the literature. Treatment pathways and adverse events were evaluated taking clinical opinion and published reports into consideration. Local data on costs (2010 Euros) and health care resources utilization were validated by the clinical authors. Probabilistic sensitivity analyses were used to assess the robustness of the model. RESULTS: The greater efficacy of ECP resulted in a gain of 0.011 to 0.024 quality-adjusted life-year in the first year and 0.062 to 0.094 at year 5 compared with Rmb or Imt. The results showed that the higher acquisition cost of ECP versus Imt was compensated for at 9 months by greater efficacy; this higher cost was partially compensated for ( 517) by year 5 versus Rmb. After 9 months, ECP was dominant (cheaper and more effective) compared with Imt. The incremental cost-effectiveness ratio of ECP versus Rmb was 29,646 per life-year gained and 24,442 per quality-adjusted life-year gained at year 2.5. Probabilistic sensitivity analysis confirmed the results. The main study limitation was that to assess relative treatment effects, only small studies were available for indirect comparison. CONCLUSION: ECP as a third-line therapy for cGvHD is a more cost-effective strategy than Rmb or Imt.

Population-based incidence of myeloid malignancies: fifteen years of epidemiological data in the province of Girona, Spain

Myeloid malignancies (MMs) are a heterogeneous group of hematologic malignancies presenting different incidence, prognosis and survival.1–3 Changing classifications (FAB 1994, WHO 2001 and WHO 2008) and few available epidemiological data complicate incidence comparisons.4,5 Taking this into account, the aims of the present study were: a) to calculate the incidence rates and trends of MMs in the Province of Girona, northeastern Spain, between 1994 and 2008 according to the WHO 2001 classification; and b) to predict the number of MMs cases in Spain during 2013. Data were extracted from the population-based Girona Cancer Registry (GCR) located in the north-east of Catalonia, Spain, and covering a population of 731,864 inhabitants (2008 census). Cases were registered according to the rules of the European Network for Cancer Registries and the Manual for Coding and Reporting Haematological Malignancies (HAEMACARE project). To ensure the complete coverage of MMs in the GCR, and especially myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS), a retrospective search was performed. The ICD-O-2 (1990) codes were converted into their corresponding ICD-O-3 (2000) codes, including MDS, polycythemia vera (PV) and essential thrombocythemia (ET) as malignant diseases. Results of crude rate (CR) and European standardized incidence rate (ASRE) were expressed per 100,000 inhabitants/year

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

INTRODUCTION: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. METHODS: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. DISCUSSION: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.

The Employment Precariousness Scale (EPRES): psychometric properties of a new tool for epidemiological studies among waged and salaried workers

Background: Despite the fact that labour market flexibility has resulted in an expansion of precarious employment in industrialized countries, to date there is limited empirical evidence about its health consequences. The Employment Precariousness Scale (EPRES) is a newly developed, theory-based, multidimensional questionnaire specifically devised for epidemiological studies among waged and salaried workers. Objective: To assess acceptability, reliability and construct validity of EPRES in a sample of waged and salaried workers in Spain. Methods: Cross-sectional study, using a sub-sample of 6.968 temporary and permanent workers from a population-based survey carried out in 2004-2005. The survey questionnaire was interviewer administered and included the six EPRES subscales, measures of the psychosocial work environment (COPSOQ ISTAS21), and perceived general and mental health (SF-36). Results: A high response rate to all EPRES items indicated good acceptability; Cronbach’s alpha coefficients, over 0.70 for all subscales and the global score, demonstrated good internal consistency reliability; exploratory factor analysis using principal axis analysis and varimax rotation confirmed the six-subscale structure and the theoretical allocation of all items. Patterns across known groups and correlation coefficients with psychosocial work environment measures and perceived health demonstrated the expected relations, providing evidence of construct validity. Conclusions: Our results provide evidence in support of the psychometric properties of EPRES, which appears to be a promising tool for the measurement of employment precariousness in public health research.

Changes in leisure time and occupational physical activity over 8 years: The Cornellà health Interview Survey Follow-Up Study

Aim: To describe changes in leisure time and occupational physical activity status in an urban Mediterranean population-based cohort, and to evaluate sociodemographic, health-related and lifestyle correlates of such changes. Methods: Data for this study come from the Cornellè Health Interview Survey Follow-Up Study, a prospective cohort study of a representative sample (n¿=¿2500) of the population. Participants in the analysis reported here include 1246 subjects (567 men and 679 women) who had complete data on physical activity at the 1994 baseline survey and at the 2002 follow-up. We fitted Breslow-Cox regression models to assess the association between correlates of interest and changes in physical activity. Results: Regarding leisure time physical activity, 61.6% of cohort members with ¿sedentary¿ habits in 1994 changed their status to ¿light/moderate¿ physical activity in 2002, and 70% who had ¿light/moderate¿ habits in 1994 did not change their activity level. Regarding occupational physical activity, 74.4% of cohort members who were ¿active¿ did not change their level of activity, and 64.3% of participants with ¿sedentary¿ habits in 1994 changed to ¿active¿ occupational physical activity. No clear correlates of change in physical activity were identified in multivariate analyses. Conclusion: While changes in physical activity are evident in this population-based cohort, no clear determinants of such changes were recognised. Further longitudinal studies including other potential individual and contextual determinants are needed to better understand determinants of changes in physical activity at the population level.

Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.

Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.

A monolithic glass chip for active single-cell sorting based on mechanical phenotyping

The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetrically etched glass plates, combines exact optical fiber alignment, low laser damage threshold and high imaging quality with the possibility of several microfluidic inlet and outlet channels. We show the utility of such a custombuilt optical stretcher glass chip by measuring and sorting single cells in a heterogeneous population based on their different mechanical properties and verify sorting accuracy by simultaneous fluorescence detection. This offers new possibilities of exact characterization and sorting of small populations based on rheological properties for biological and biomedical applications.