What to expect and when: benznidazole toxicity in chronic Chagas' disease treatment.

Background: Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies. Objectives: Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax®). Methods: Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly. Results: We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration. Conclusions: There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment.

Population pharmacokinetics of benznidazole in adult patients with Chagas disease.

The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h; V/F, 89.6 liters; and Ka, 1.15 h(-1)). No covariates were found to be significant for CL/F and V/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011-002900-34 and at ClinicalTrials.gov under number NCT01755403.).

Arthritis and benznidazole: more closely related than we thought.

Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug reactions. Although arthralgia is common, arthritis has been reported as a very rare side effect. The objective of this study was to describe arthritis in a cohort of Trypanosoma cruzi-infected patients treated with benznidazole.

Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014.

Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.

Two cases of laboratory-confirmed leptospirosis in travellers returning to Spain from Thailand, September 2013.

In September 2013, leptospirosis was diagnosed in two Spanish travellers returning from Thailand. The first case walked in floodwater in the Phi Phi Islands in pouring rain: 20 days later he presented with fever and acute hepatitis. The second presented with fever and renal failure 17 days after visiting the islands. These cases remind clinicians to consider leptospirosis in febrile patients with a history of contact with flood or fresh water while travelling to tropical countries.

A family cluster of giardiasis with variable treatment responses: refractory giardiasis in a family after a trip to India.

Persistence of giardiasis after some of the recommended drugs is occurring with increasing frequency. We describe the follow-up of four members of a family with giardiasis through microscopic observation, immunochromatography and PCRs of tpi and ß-giardin genes. Three patients did not respond to tinidazole but they were cured after quinacrine. However, PCR became negative at 2 months after negativization of stools in two patients and after 1 year in one patient. In all cases Giardia assemblage B was characterized with high homology between all isolates. Further studies are needed to determine the value of PCR in the diagnosis of Giardia infections.

A case of Japanese encephalitis in a 20 year-old Spanish sportsman, February 2013.

We report a severe case of imported Japanese encephalitis (JE) in a healthy young Spanish traveller who developed symptoms after spending three weeks in a touristic area of Thailand. The patient was diagnosed in Thailand and subsequently transferred to Barcelona, Spain, where the Thai laboratory results were confirmed based on IgM serology. Although JE is a rare disease in travellers, this case illustrates the need for seeking travel medical advice before visiting tropical countries.

Pasos hacia la institucionalización de la evaluación del impacto en salud en España: la percepción de los profesionales de salud pública / Steps towards the institutionalization of health impact assessment in Spain: perception of public health professionals

Fundamento. La actual reforma normativa de la salud pública en España ha previsto la inclusión de la Evaluación del Impacto en Salud (EIS). El objetivo de este estudio es describir la visión de los profesionales de salud pública y planificación sobre la utilidad y aplicabilidad de la EIS en su trabajo diario y con ello reflexionar sobre la mejor manera de institucionalizarla. Metodología. Se han desarrollado 3 talleres de formación en EIS dirigidos a profesionales de las diferentes ramas de la salud pública. Se ofreció un cuestionario para cumplimentar por las personas asistentes. Resultados. El 41% de las personas asistentes contestaron al cuestionario. Entre quienes respondieron, el 92%consideró que el modelo de los determinantes sociales de la salud resulta de gran utilidad en el ámbito de la salud pública. Las principales vías identificadas para introducirla EIS fueron: la obligatoriedad normativa (85%),la integración en otras herramientas de evaluación ya existentes (65%) y la sistematización de esta metodología(40%). En relación a la aplicabilidad de la EIS, se propusieron estrategias específicas para su introducción en las diferentes ramas de la salud pública. Conclusiones. La institucionalización exitosa de la EIS requerirá de la opinión y colaboración del personal técnico. Se constata la aprobación generalizada de esta herramienta para su utilización en la administración. Para garantizar la viabilidad de su implementación, será necesario sensibilizar a los profesionales sobre el modelo de los determinantes sociales de la salud, y recoger sus demandas y sugerencias(AU)

Background. The current normative reform of public health policy in Spain envisages the inclusion of Health Impact Assessment (HIA). This study contributes the vision of public health and planning professionals on the usefulness and applicability of HIA in their daily work and thus reflects on how best to institutionalize it. Methodology. Three training workshop were carried out with public health professionals. Participants were specialists in different branches: epidemiological surveillance, environmental health, food safety and health promotion. In this HIA workshop, a questionnaire was given to the attendees to be completed. Results. Forty-one percent of the people attending answered the questionnaire; 92% of the staff considered that the model of social determinants of health is useful in the field of public health. The principal routes for introducing HIA were: mandatory rules (85%), integration into other existing assessment tools (65%) and the systematization of this methodology (40%). Concerning the applicability of HIA, specific strategies are proposed for its introduction into the different branches of public health. Conclusions. The successful institutionalization of HIA will require the opinion and collaboration of the technical personnel. A widespread approval of this tool for its utilization in the administration was verified. To guarantee the viability of its implementation, it will be necessary to raise the awareness of professionals about the model of the social determinants of health, as well as to attend to their demands and suggestions(AU)

[Steps towards the institutionalization of health impact assessment in Spain: perception of public health professionals]. / Pasos hacia la institucionalización de la evaluación del impacto en salud en España: la percepción de los y las profesionales de salud pública.

BACKGROUND: The current normative reform of public health policy in Spain envisages the inclusion of Health Impact Assessment (HIA). This study contributes the vision of public health and planning professionals on the usefulness and applicability of HIA in their daily work and thus reflects on how best to institutionalize it. METHODOLOGY: Three training workshop were carried out with public health professionals. Participants were specialists in different branches: epidemiological surveillance, environmental health, food safety and health promotion. In this HIA workshop, a questionnaire was given to the attendees to be completed. RESULTS: Forty-one percent of the people attending answered the questionnaire; 92% of the staff considered that the model of social determinants of health is useful in the field of public health. The principal routes for introducing HIA were: mandatory rules (85%), integration into other existing assessment tools (65%) and the systematization of this methodology (40%). Concerning the applicability of HIA, specific strategies ere proposed for its introduction into the different branches of public health. CONCLUSIONS: The successful institutionalization of HIA will require the opinion and collaboration of the technical personnel. A widespread approval of this tool for its utilization in the administration was verified. To guarantee the viability of its implementation, it will be necessary to raise the awareness of professionals about the model of the social determinants of health, as well as to attend to their demands and suggestions.

Mortality in small geographical areas and proximity to air polluting industries in the Basque Country (Spain).

OBJECTIVES: To study the association between proximity to air polluting industrial facilities and mortality in the Basque Country (Spain) in the 1996-2003 period. METHODS: A cross-sectional ecological study with 1465 census sections (CS) as units of analysis with a mean population of 1257 inhabitants. Association of CS mortality with proximity of industries of the European Pollutant Emission Register was studied by type of industrial activity and adjusted for social deprivation. Two distance thresholds (1 km and 2 km) were used as proxies for exposure in a 'near versus far' analysis. Causes of mortality studied were: all causes; tracheal, bronchial, and lung cancer; haematological tumours; ischaemic heart disease; cerebrovascular diseases; chronic diseases of the lower respiratory tract; and breast cancer (in women). Poisson's generalised linear mixed models (GLMM) with two random effects (heterogeneity and structured spatial variability) were used in a fully Bayesian environment. RESULTS: Men living in sections within 1 km from energy production industries had greater mortality from tracheal, bronchial, and lung cancer [CI(90%) 6% to 53%] as compared with people living further. Women had greater mortality from ischaemic heart disease [CI(90%) 1% to 17%] and respiratory illness [CI(90%) 1% to 24%] within 2 km from metal-processing industries. On the contrary, within the 1 km buffer from mineral industries, mortality was lower for all causes [CI(90%) -20% to -6%] and for ischaemic heart disease [CI(90%) -40% to -10%] in women, and from respiratory diseases in men [CI(90%) -39% to -4%], while it was greater for breast cancer in women [CI(90%) 2% to 28%] within the 2 km buffer. CONCLUSIONS: Analysis of mortality by census sections is a helpful exploratory tool for investigating environmental risk factors and directing actions to sites and risk factors with a greater impact on health. Further epidemiological and environmental investigations around metal-processing and energy-producing plants are required.

Health impact assessment of an urban regeneration project: opportunities and challenges in the context of a southern European city.

BACKGROUND: Social values and the political context have an influence on the use and spread of health impact assessment (HIA). In Spain, there is little experience in HIA but some regional governments are already introducing it. The aim of this article is to describe the health impacts of a local regeneration project to improve accessibility in a neighbourhood of Bilbao (Spain), and discuss the main difficulties, opportunities and challenges of the process, considering the specificities of the social and political context. METHODS: A concurrent and prospective assessment, based on a broad model of health, was carried out following the Merseyside guidelines. A literature review, community profiling and qualitative data collection were undertaken. Profound involvement of members of the community and key informants was judged as essential in the HIA process. RESULTS: The overall expected effect of the new lifts, roads, park and the rainwater collection system was positive. Uncertain or negative impacts were identified in some of those areas, and also concerning the burying of four high-voltage power lines. Historical and current characteristics of the community were highly influential on the way local people perceived the project and its impacts. Likewise, the way in which processes of planning and implementation were developing also played an important role. CONCLUSION: The spread of HIA in southern European countries will depend on the progressive introduction of values underlying HIA, as well as on the promotion of intersectoral work, a better knowledge of the social model of health and community's participation in policy making.

[Variability in the in-hospital management of acute myocardial infarction in Spain. IBERICA Study (Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda)]. / Variabilidad en el manejo hospitalario del infarto agudo de miocardio en España. Estudio IBERICA (Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda)

Introduction and objective. Although some in-hospital studies have described the management of acute myocardial infarction (MI) patients in Spain, none has been able to guarantee the exhaustiveness of patient registry. This study sought to determine the clinical characteristics and in-hospital management of patients with MI in eight Spanish population registries.Methods. The IBERICA study is a population-based MI registry carried out in the 25 to 74 year-old population, in eight Spanish regions in 1997. A standardized methodology was used to register and investigate all MI arriving alive to a hospital. Clinical characteristics, cardiovascular risk factors prevalence, pharmacological treatment, invasive and non-invasive procedures performed and complications at 28 days of evolution were recorded. A descriptive analysis was performed and the variation coefficient (VC) was calculated.Results. In 1997, 4,041 MI patients were registered, 79.9% were men with a mean age of 61.1 years. Although 10.9% (95% CI: 9.9-11.9%) were not admitted to the coronary care unit, a large variability existed among different areas (VC = 53%). There was a high variability in the utilization and performance of non-invasive and invasive procedures among regions, as well as in the use of pharmacological treatment. Only the use of antiaggregants (91.5%) and thrombolytic therapy (41.8%) showed a low variability (VC < 10%). Twenty-eight day mortality was 16.2% (95% CI: 15.1-17.4%) with a high variability being observed among the different regions (VC = 20.6%).Conclusion. Patient characteristics vary among the different Spanish regions. The differences in management and prognosis suggest a lack of equality in the health care provided to MI patients in the different regions in Spain.