Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

BACKGROUND: Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. RESULTS: We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. CONCLUSION: The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes

Efetividade do treinamento de resistência à fadiga dos músculos dos membros inferiores dentro e fora d'água no equilíbrio estático e dinâmico de idosos Effectiveness of aquatic and non-aquatic lower limb muscle endurance training in the static and dynamic balance of elderly people

CONTEXTUALIZAÇÃO: O envelhecimento compromete a habilidade do sistema nervoso central (SNC) de realizar a manutenção do equilíbrio corporal bem como diminui a capacidade das reações adaptativas. Para prevenir as quedas, é necessário aprimorar as condições de recepção de informações sensoriais. OBJETIVOS: Comparar o impacto de um programa estruturado de exercícios de resistência muscular dos membros inferiores dentro e fora d'água no equilíbrio estático e dinâmico em idosos. MÉTODOS: Trata-se de um estudo clínico, prospectivo, aleatório, em que as variáveis utilizadas foram avaliadas antes e após o programa de treinamento. Foram avaliados 36 idosos por meio de quatro testes: Escala de Equilíbrio de Berg, Dynamic Gait Index, velocidade da marcha, Marcha Tandem. Posteriormente, houve a alocação dos voluntários em três grupos: grupo de exercício na piscina terapêutica, grupo de exercício no solo e grupo controle. Os grupos de exercícios foram submetidos a um programa de resistência muscular dos membros inferiores aplicado durante seis semanas, duas sessões semanais com 40 minutos de duração. Os voluntários foram reavaliados após seis semanas. Os dados foram analisados estatisticamente pelo teste ANOVA univariada para comparação entre os três grupos antes e após a intervenção. RESULTADOS: O programa de resistência muscular dos membros inferiores promoveu aumento significativo do equilíbrio dos idosos (p<0,05) nos testes avaliados após o programa de treinamento. CONCLUSÃO: O programa de resistência muscular proporcionou uma melhora significativa no equilíbrio estático e dinâmico de idosos comunitários. Foi possível inferir também que essa melhora ocorreu independentemente do meio em que o programa foi realizado, ou seja, se dentro ou fora d'água.<br>BACKGROUND: Aging compromises the ability of the central nervous system to maintain body balance and reduces the capacity for adaptive reactions. To prevent falls, the reception conditions for sensory information need to be improved. OBJECTIVES: To evaluate the impact of a structured aquatic and a non-aquatic exercise program for lower-limb muscle endurance on the static and dynamic balance of elderly people. METHODS: This was a prospective randomized clinical study in which the variables were assessed before and after the training program. Thirty-six elderly people were evaluated using four tests: the Berg Balance Scale, Dynamic Gait Index, gait speed and tandem gait. The participants were randomized into three groups: aquatic exercise group, non-aquatic exercise group and control group. The exercise groups underwent a program for lower-limb muscle endurance that consisted of 40-minute sessions twice a week for six weeks. The participants were reevaluated after six weeks. The data were analyzed statistically using the univariate ANOVA test for comparisons between the groups before and after the intervention. RESULTS: The program for lower-limb muscle endurance significantly increased balance (p<0.05) in the evaluation tests after the training program. CONCLUSION: The muscle endurance program provided a significant improvement in static and dynamic balance among community-dwelling elderly people. It was also possible to infer that this improvement occurred regardless of the environment, i.e. aquatic or non-aquatic

Validation of a Culturally Relevant Snakebite Envenomation Clinical Practice Guideline in Brazil

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases

Performance of broilers experimentally inoculated with Salmonella Typhimurium and fed diets with addition of lactulosis

The objective of this experiment was to evaluate the influence of lactulose on performance as well as its ability to prevent colonization by Salmonella Typhimurium in broilers orally inoculated with this pathogen. The design adopted was completely randomized, with 630 one-day-old male chicks distributed into six treatments, with seven replications and 15 birds per experimental unit. The treatments comprised the following procedures: T1 (control group) - no S. Typhimurium inoculation or supply of lactulosis; T2 - only inoculation of S. Typhimurium; T3 - only lactulosis supply; T4 supply of lactulosis and S. Typhimurium inoculation on the first day of life; T5 - supply of lactulosis 48 hours before S. Typhimurium inoculation; and T6 - supply of lactulosis 48 hours after inoculation of S. Typhimurium. Performance variables were evaluated on the seventh, 14th, 21st and 28th days of age; fragments of the duodenum and jejunum were collected and sent to histomorphometric assessment at 14 days of age, and S. Typhimurium excretion was verified in cloacal swabs on the 10th, 24th and 35th days of age. Performance data were analyzed by ANOVA and Tukey's test (5%) and fecal excretion data were assessed by non-parametric chi-square test. Better weight gain and feed conversion were observed in groups fed lactulosis with or without challenge of S. Typhimurium up to 21 days of age. Reduced duodenum villous height was verified on the 14th day in groups challenged with the pathogen. Reduction of S. Typhimurium fecal excretion was verified in broilers fed lactulosis from the first day of life on and 48 hours before receiving S. Typhimurium directly into the crop. Lactulosis increases broiler performance up to one week after its inoculation, influences duodenum villous height and reduces the fecal excretion of Salmonella Typhimurium

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease