Fast and flexible inference for joint models of multivariate longitudinal and survival data using integrated nested Laplace approximations.

Modeling longitudinal and survival data jointly offers many advantages such as addressing measurement error and missing data in the longitudinal processes, understanding and quantifying the association between the longitudinal markers and the survival events, and predicting the risk of events based on the longitudinal markers. A joint model involves multiple submodels (one for each longitudinal/survival outcome) usually linked together through correlated or shared random effects. Their estimation is computationally expensive (particularly due to a multidimensional integration of the likelihood over the random effects distribution) so that inference methods become rapidly intractable, and restricts applications of joint models to a small number of longitudinal markers and/or random effects. We introduce a Bayesian approximation based on the integrated nested Laplace approximation algorithm implemented in the R package R-INLA to alleviate the computational burden and allow the estimation of multivariate joint models with fewer restrictions. Our simulation studies show that R-INLA substantially reduces the computation time and the variability of the parameter estimates compared with alternative estimation strategies. We further apply the methodology to analyze five longitudinal markers (3 continuous, 1 count, 1 binary, and 16 random effects) and competing risks of death and transplantation in a clinical trial on primary biliary cholangitis. R-INLA provides a fast and reliable inference technique for applying joint models to the complex multivariate data encountered in health research.

Association between professional qualification and adverse events in neonatal and pediatric intensive treatment units.

OBJECTIVE: to verify the association between the qualification of nursing professionals and the occurrence of adverse events in neonatal and pediatric intensive care units. METHOD: Cross-sectional and evaluation study conducted in six intensive care units of five public hospitals in the state of Paraná, Brazil. Data was collected from April/2017 to January/2018 through the use of a questionnaire to be completed by 143 nursing professionals and retrospective analysis of 79 medical records using the Neonatal Trigger Tool and Pediatric Trigger Tool instruments. The prognostic factors were professional training and the existence, or not, of a continuing education service; analysis was performed by logistic regression. RESULTS: Detected 30 adverse events in 22 medical records analyzed. There was a prevalence of infection (n = 12; 40%) and skin damage (n = 9; 30%). Among the prognostic factors, continuing education was identified as a protective factor against adverse events (p≤0.05). CONCLUSION: Continuing education was associated with the prevention of adverse events in neonatal and pediatric intensive care units.

Association between professional qualification and adverse events in neonatal and pediatric intensive treatment units / Asociación entre calificación profesional y eventos adversos en unidades de tratamiento intensivo neonatal y pediátrico / Associação entre qualificação profissional e eventos adversos em unidades de tratamento intensivo neonatal e pediátrico

ABSTRACT Objective: to verify the association between the qualification of nursing professionals and the occurrence of adverse events in neonatal and pediatric intensive care units. Method: Cross-sectional and evaluation study conducted in six intensive care units of five public hospitals in the state of Paraná, Brazil. Data was collected from April/2017 to January/2018 through the use of a questionnaire to be completed by 143 nursing professionals and retrospective analysis of 79 medical records using the Neonatal Trigger Tool and Pediatric Trigger Tool instruments. The prognostic factors were professional training and the existence, or not, of a continuing education service; analysis was performed by logistic regression. Results: Detected 30 adverse events in 22 medical records analyzed. There was a prevalence of infection (n = 12; 40%) and skin damage (n = 9; 30%). Among the prognostic factors, continuing education was identified as a protective factor against adverse events (p≤0.05). Conclusion: Continuing education was associated with the prevention of adverse events in neonatal and pediatric intensive care units.

RESUMEN Objetivo: Verificar la asociación entre la calificación de los profesionales de enfermería y la ocurrencia de eventos adversos en las unidades de cuidados intensivos neonatales y pediátricos Método: Estudio evaluativo y transversal, realizado en seis unidades de cuidados intensivos de cinco hospitales públicos del estado de Paraná, Brasil. La recolección de datos se llevó a cabo de abril / 2017 a enero / 2018 con la aplicación de un cuestionario a 143 profesionales de enfermería y análisis retrospectivo de 79 historias clínicas utilizando los instrumentos Neonatal Trigger Tool y Pediatric Trigger Tool. Los factores pronósticos fueron la formación profesional y la existencia, o no, de un servicio de educación continua; el análisis se realizó mediante regresión logística. Resultados: Detectado 30 eventos adversos en 22 historias clínicas analizadas. Hubo una prevalencia de infección (n = 12; 40%) y daño cutáneo (n = 9; 30%). Entre los factores pronósticos, se identificó la educación continua como factor protector frente a eventos adversos (p≤0,05). Conclusión: La educación continua se asoció con la prevención de eventos adversos en las unidades de cuidados intensivos neonatales y pediátricos.

RESUMO Objetivo: Verificar a associação entre a qualificação dos profissionais de enfermagem e a ocorrência de eventos adversos em unidades de terapia intensiva neonatal e pediátrica. Método: Estudo transversal conduzido em seis unidades de cinco hospitais públicos do Estado do Paraná, Brasil. A coleta de dados ocorreu de abril/2017 a janeiro/2018, com análise retrospectiva e aplicação dos instrumentos Neonatal Trigger Tool e Paediatric Trigger Tool a 79 prontuários, para detectar eventos adversos, questionário autoaplicável a 143 profissionais e consulta aos documentos e registros hospitalares. Os fatores prognósticos de eventos adversos foram capacitação profissional e existência, ou não, de serviço de educação continuada; a análise foi realizada por regressão logística. Resultados: Detectou-se 30 eventos adversos, com prevalência de infecção (n=12;40%) e lesão de pele (n=9;30%). A educação continuada foi identificada como fator protetor para eventos adversos (p≤0,05). Conclusão: atividade educativa foi associada à prevenção de eventos adversos em unidades de terapia intensiva neonatal e pediátrica.

Association between nursing work conditions and adverse events in neonatal and pediatric Intensive Care Units. / Associação entre condições de trabalho da enfermagem e ocorrência de eventos adversos em Unidades Intensivas neopediátricas.

OBJECTIVE: To investigate the association between intensive nursing staff's work conditions and the occurrence of adverse events in patients. METHOD: Evaluative documentary study conducted in six public neonatal and pediatric Intensive Care Units from hospitals in Paraná state, from April 2017 to January 2018. The predictive variables concerning staff sizing and work environment were measured through the instruments Nursing Activities Score and Brazilian Nursing Work Index-Revised. The thirty adverse events corresponded to the outcome variable and were detected using the instruments Pediatric and Neonatal Trigger Tool. RESULTS: Two-hundred and three professionals participated in this research. The nursing staff sizing was verified to be appropriate. Work conditions were favorable and Cronbach's Alpha was 0.90 (IC= 0.87 - 0.92). The most frequently detected events in patients were infection and skin lesion. The statistical analysis of correlation and adverse event occurrence was not significant. CONCLUSION: Despite the lack of evidence on statistical significance between the variables, the results reveal commitment by the public sector and professionals with patient safety and assistance quality.

Using Bayesian spatial models to map and to identify geographical hotspots of multidrug-resistant tuberculosis in Portugal between 2000 and 2016.

Multidrug-resistant tuberculosis (MDR-TB) is a major threat to the eradication of tuberculosis. TB control strategies need to be adapted to the necessities of different countries and adjusted in high-risk areas. In this study, we analysed the spatial distribution of the MDR- and non-MDR-TB cases across municipalities in Continental Portugal between 2000 and 2016. We used Bayesian spatial models to estimate age-standardized notification rates and standardized notification ratios in each area, and to delimitate high- and low-risk areas, those whose standardized notification ratio is significantly above or below the country's average, respectively. The spatial distribution of MDR- and non-MDR-TB was not homogeneous across the country. Age-standardized notification rates of MDR-TB ranged from 0.08 to 1.20 and of non-MDR-TB ranged from 7.73 to 83.03 notifications per 100,000 population across the municipalities. We identified 36 high-risk areas for non-MDR-TB and 8 high-risk areas for MDR-TB, which were simultaneously high-risk areas for non-MDR-TB. We found a moderate correlation (ρ = 0.653; 95% CI 0.457-0.728) between MDR- and non-MDR-TB standardized notification ratios. We found heterogeneity in the spatial distribution of MDR-TB across municipalities and we identified priority areas for intervention against TB. We recommend including geographical criteria in the application of molecular drug resistance to provide early MDR-TB diagnosis, in high-risk areas.

Determinants of multidrug-resistant tuberculosis in São Paulo-Brazil: a multilevel Bayesian analysis of factors associated with individual, community and access to health services.

OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) remains a serious public health problem worldwide. Accordingly, this study sought to identify individual, community and access to health services risk factors for MDR-TB. METHODS: Retrospective cohort of all TB cases diagnosed between 2006 and 2016 in the state of São Paulo. A Bayesian spatial hierarchical analysis with a multilevel design was carried out. RESULTS: It was identified that the history of previous TB treatment (Odds Ratios [OR]:13.86, 95% credibility interval [95% CI]:12.06-15.93), positive sputum culture test (OR: 5.26, 95% CI: 4.44-6.23), diabetes mellitus (OR: 2.34, 95% CI: 1.87-2.91), residing at a standard address (OR: 2.62, 95% CI: 1.91-3.60), positive sputum smear microscopy (OR: 1.74, 95% CI: 1.44-2.12), cavitary pulmonary TB (OR: 1.35, 95% CI: 1.14-1.60) and diagnosis performed due to spontaneous request (OR: 1.26; 95% CI: 1.10-1.46) were associated with MDR-TB. Furthermore, municipalities that performed HIV tests in less than 42.65% of patients with TB (OR: 1.50, 95% CI: 1.25-1.79), that diagnosed TB cases only after death (OR: 1.50, 95% CI: 1.17-1.93) and that had more than 20.16% of their population with income between » and ½ of one minimum wage (OR: 1.56, 95% CI: 1.30-1.87) were also related to the MDR-TB. CONCLUSIONS: Knowledge of these predictive factors may help to develop more comprehensive disease prevention strategies for MDR-TB, avoiding the risks expressed regarding drug resistance expansion.

OBJECTIF: La tuberculose multirésistante (TB-MDR) reste un grave problème de santé publique dans le monde. Cette étude visait à identifier les facteurs de risque individuels, communautaires et d'accès aux services de santé pour la TB-MDR. MÉTHODES: Analyse de cohorte rétrospective de tous les cas de TB diagnostiqués entre 2006 et 2016 dans l'Etat de São Paulo par analyse bayésienne spatiale à plusieurs niveaux. RÉSULTATS: Les antécédents de traitements antituberculeux (Rapports de cotes [OR]: 13,86, Intervalle de confiance à 95% [IC95%]: 12.06-15.93), un test de culture d'expectorations positif (OR: 5,26, IC95%: 4,44-6,23), le diabète sucré (OR: 2,34, IC95%: 1,87-2,91), la résidence à une adresse standard (OR: 2,62, IC95%: 1,91-3,60), la microscopie à frottis positif (OR: 1,74, IC95%: 1,44-2,12), la TB pulmonaire (OR: 1,35, IC95%: 1,14-1,60) et le diagnostic réalisé en raison d'une demande spontanée (OR: 1,26; IC95%: 1,10-1,46) étaient associés à la TB-MDR. Les municipalités qui ont effectué des tests de dépistage du VIH chez moins de 42,65% des patients atteints de TB (OR: 1,50, IC95%: 1,25-1,79), qui ont diagnostiqué des cas de TB uniquement après le décès (OR: 1,50, IC95%: 1,17-1,93) et qui avaient plus de 20,16% de leur population avec un revenu entre » et ½ d'un salaire minimum (OR: 1,56, IC95%: 1,30-1,87) étaient également associées à la TB-MDR. CONCLUSIONS: La connaissance de ces facteurs prédictifs peut aider à développer des stratégies plus complètes de prévention des maladies pour la TB-MDR, en évitant les risques d'extension de la résistance aux médicaments.

Associação entre condições de trabalho da enfermagem e ocorrência de eventos adversos em Unidades Intensivas neopediátricas / Asociación entre las condiciones de trabajo en enfermería y la ocurrencia de eventos adversos en Unidades Intensivas neonatales y pediátricas / Association between nursing work conditions and adverse events in neonatal and pediatric Intensive Care Units

RESUMO Objetivo Investigar a associação entre as condições de trabalho da equipe de enfermagem intensivista e a ocorrência de eventos adversos nos pacientes atendidos. Método Pesquisa avaliativa e documental realizada em seis Unidades de Terapia Intensiva neopediátricas públicas de hospitais estaduais do Paraná, de abril de 2017 a janeiro de 2018. As variáveis preditoras, referentes ao dimensionamento de pessoal e ambiente de trabalho, foram mensuradas por meio dos instrumentos Nursing Activities Score e Brazilian Nursing Work Index-Revised. Os 30 eventos adversos corresponderam à variável de desfecho e foram detectados utilizando-se os instrumentos Pediatric e Neonatal Trigger Tool. Resultados Participaram da pesquisa 203 profissionais. Verificou-se que o dimensionamento do pessoal de enfermagem estava adequado. As condições de trabalho mostraram-se favoráveis e o valor do Alfa de Cronbach foi 0,90 (IC= 0,87 - 0,92). Os eventos mais frequentes detectados nos pacientes foram infecção e lesão de pele. A análise estatística de correlação e ocorrência de evento adverso demonstrou não haver significância. Conclusão Apesar de não ser evidenciada associação estatística entre as variáveis, os resultados demonstram comprometimento da gestão pública e dos profissionais com a segurança do paciente e qualidade da assistência.

RESUMEN Objetivo Investigar la asociación entre las condiciones de trabajo del equipo de enfermería de cuidados intensivos y la ocurrencia de eventos adversos en los pacientes atendidos. Método Evaluación e investigación documental realizada en seis Unidades de Cuidados Intensivos públicas neonatales y pediátricas de hospitales estatales de Paraná, desde abril de 2017 hasta enero de 2018. Las variables predictoras, referidas al tamaño del personal y al ambiente de trabajo, se midieron utilizando el puntaje de las actividades de los instrumentos Nursing Activities Score y Brazilian Nursing Work Index-Revised. Los 30 eventos adversos correspondieron a la variable de resultado y se detectaron utilizando los instrumentos Pediatric y Neonatal Trigger Tool. Resultados 203 profesionales participaron en el estudio. Se verificó que el dimensionamiento del personal de enfermería era adecuado. Las condiciones de trabajo fueron favorables y el valor Alfa de Cronbach fue de 0,90 (CI = 0,87 - 0,92). Los eventos más frecuentes detectados en los pacientes fueron la infección y la lesión de la piel. El análisis estadístico de la correlación y la ocurrencia del evento adverso no mostró ninguna significación. Conclusión Aunque no se evidencia una asociación estadística entre las variables, los resultados demuestran el compromiso de la administración pública y los profesionales con la seguridad del paciente y la calidad de la atención.

ABSTRACT Objective To investigate the association between intensive nursing staff's work conditions and the occurrence of adverse events in patients. Method Evaluative documentary study conducted in six public neonatal and pediatric Intensive Care Units from hospitals in Paraná state, from April 2017 to January 2018. The predictive variables concerning staff sizing and work environment were measured through the instruments Nursing Activities Score and Brazilian Nursing Work Index-Revised. The thirty adverse events corresponded to the outcome variable and were detected using the instruments Pediatric and Neonatal Trigger Tool. Results Two-hundred and three professionals participated in this research. The nursing staff sizing was verified to be appropriate. Work conditions were favorable and Cronbach's Alpha was 0.90 (IC= 0.87 - 0.92). The most frequently detected events in patients were infection and skin lesion. The statistical analysis of correlation and adverse event occurrence was not significant. Conclusion Despite the lack of evidence on statistical significance between the variables, the results reveal commitment by the public sector and professionals with patient safety and assistance quality.

Spatiotemporal diffusion of influenza A (H1N1): Starting point and risk factors.

Influenza constitutes a major challenge to world health authorities due to high transmissibility and the capacity to generate large epidemics. This study aimed to characterize the diffusion process of influenza A (H1N1) by identifying the starting point of the epidemic as well as climatic and sociodemographic factors associated with the occurrence and intensity of transmission of the disease. The study was carried out in the Brazilian state of Paraná, where H1N1 caused the largest impact. The units of spatial and temporal analysis were the municipality of residence of the cases and the epidemiological weeks of the year 2009, respectively. Under the Bayesian paradigm, parametric inference was performed through a two-part spatiotemporal model and the integrated nested Laplace approximation (INLA) algorithm. We identified the most likely starting points through the effective distance measure based on mobility networks. The proposed estimation methodology allowed for rapid and efficient implementation of the spatiotemporal model, and provided evidence of different patterns for chance of occurrence and risk of influenza throughout the epidemiological weeks. The results indicate the capital city of Curitiba as the probable starting point, and showed that the interventions that focus on municipalities with greater migration and density of people, especially those with higher Human Development Indexes (HDIs) and the presence of municipal air and road transport, could play an important role in mitigation of effects of future influenza pandemics on public health. These results provide important information on the process of introduction and spread of influenza, and could contribute to the identification of priority areas for surveillance as well as establishment of strategic measures for disease prevention and control. The proposed model also allows identification of epidemiological weeks with high chance of influenza occurrence, which can be used as a reference criterion for creating an immunization campaign schedule.

Does community deprivation determine longevity after the age of 75? A cross-national analysis.

OBJECTIVES: Analyze the association between socioeconomic deprivation and old-age survival in Europe, and investigate whether it varies by country and gender. METHODS: Our study incorporated five countries (Portugal, Spain, France, Italy, and England). A 10-year survival rate expressing the proportion of population aged 75-84 years who reached 85-94 years old was calculated at area-level for 2001-11. To estimate associations, we used Bayesian spatial models and a transnational measure of deprivation. Attributable/prevention fractions were calculated. RESULTS: Overall, there was a significant association between deprivation and survival in both genders. In England that association was stronger, following a dose-response relation. Although lesser in magnitude, significant associations were observed in Spain and Italy, whereas in France and Portugal these were even weaker. The elimination of socioeconomic differences between areas would increase survival by 7.1%, and even a small reduction in socioeconomic differences would lead to a 1.6% increase. CONCLUSIONS: Socioeconomic deprivation was associated with survival among older adults at ecological-level, although with varying magnitude across countries. Reasons for such cross-country differences should be sought. Our results emphasize the importance of reducing socioeconomic differences between areas.

The influence of socioeconomic deprivation, access to healthcare and physical environment on old-age survival in Portugal.

Spatial inequalities in old-age survival exist in Portugal and might be associated with factors pertaining to three distinct domains: socioeconomic, physical environmental and healthcare. We evaluated the contribution of these factors on the old-age survival across Portuguese municipalities deriving a surrogate measure of life expectancy, a 10-year survival rate that expresses the proportion of the population aged 75-84 years old who reached 85-94. As covariates we used two internationally comparable multivariate indexes: the European deprivation index and the multiple physical environmental deprivation index. A national index was developed to evaluate the access to healthcare. Smoothed rates and odds ratios (OR) were estimated using Bayesian spatial models. Socioeconomic deprivation was found to be the most relevant factor influencing old-age survival in Portugal [women: least deprived areas OR=1.132(1.064-1.207); men OR=1.044(1.001- 1.094)] and explained a sizable amount of the spatial variance in survival, especially among women. Access to healthcare was associated with old-age survival in the univariable model only; results lost significance after adjustment for socioeconomic circumstances [women: higher access to healthcare OR=1.020(0.973- 1.072); men OR=1.021(0.989-1.060)]. Physical environmental deprivation was unrelated with old-age survival. In conclusion, socioeconomic deprivation was the most important determinant in explaining spatial disparities in old-age survival in Portugal, which indicates that policy makers should direct their efforts to tackle socioeconomic differentials between regions.

The influence of socioeconomic, biogeophysical and built environment on old-age survival in a Southern European city.

Old-age survival is a good indicator of population health and regional development. We evaluated the spatial distribution of old-age survival across Porto neighbourhoods and its relation with physical (biogeophysical and built) and socioeconomic factors (deprivation). Smoothed survival rates and odds ratio (OR) were estimated using Bayesian spatial models. There were important geographical differentials in the chances of survival after 75 years of age. Socioeconomic deprivation strongly impacted old-age survival (Men: least deprived areas OR=1.31(1.05-1.63); Women OR=1.53(1.24-1.89)), explaining over 40% of the spatial variance. Walkability and biogeophysical environment were unrelated to old-age survival and also unrelated to socioeconomic deprivation, being fairly evenly distributed through the city.

Where do people live longer and shorter lives? An ecological study of old-age survival across 4404 small areas from 18 European countries.

BACKGROUND: Further increases in life expectancy in high-income countries depend to a large extent on advances in old-age survival. We aimed to characterise the spatial distribution of old-age survival across small areas of Europe, and to identify areas with significantly high or low survivorship. METHODS: This study incorporated 4404 small areas from 18 European countries. We used a 10-year survival rate to express the proportion of population aged 75-84 years who reached 85-94 years of age (beyond average life expectancy). This metric was calculated for each gender using decennial census data (1991, 2001 and 2011) at small geographical areas. To address problems associated with small areas, rates were smoothed using a Bayesian spatial model. Excursion sets were defined to identify areas with significantly high (>95th centile) and low (<5th) survival. RESULTS: In 2011, on average, 47.1% (range: 22.5-71.5) of the female population aged 75-84 years had reached 85-94 years of age, compared to 34.2% (16.4-49.6) of the males. These figures, however, hide important and time-persistent spatial inequalities. Higher survival rates were concentrated in northern Spain, Andorra and northeastern Italy, and in the south and west of France. Lower survival was found in parts of the UK, Scandinavia and the Netherlands, and in some areas of southern Europe. Within these regions, we detected areas with significantly high and low old-age survival. CONCLUSIONS: Clear and persistent spatial inequalities in old-age survival exist, suggesting that European social unity is still to be accomplished. These inequalities could arise from a myriad of population health determinants (eg, poverty, unhealthy lifestyles), which merit further study.