Analysis of human immune responses in quasi-experimental settings: tutorial in biostatistics

<p>Abstract</p> <p>Background</p> <p>Human immunology is a growing field of research in which experimental, clinical, and analytical methods of many life science disciplines are utilized. Classic epidemiological study designs, including observational longitudinal birth cohort studies, offer strong potential for gaining new knowledge and insights into immune response to pathogens in humans. However, rigorous discussion of methodological issues related to designs and statistical analysis that are appropriate for longitudinal studies is lacking.</p> <p>Methods</p> <p>In this communication we address key questions of quality and validity of traditional and recently developed statistical tools applied to measures of immune responses. For this purpose we use data on humoral immune response (IR) associated with the first cryptosporidial diarrhea in a birth cohort of children residing in an urban slum in south India. The main objective is to detect the difference and derive inferences for a change in IR measured at two time points, before (pre) and after (post) an event of interest. We illustrate the use and interpretation of analytical and data visualization techniques including generalized linear and additive models, data-driven smoothing, and combinations of box-, scatter-, and needle-plots.</p> <p>Results</p> <p>We provide step-by-step instructions for conducting a thorough and relatively simple analytical investigation, describe the challenges and pitfalls, and offer practical solutions for comprehensive examination of data. We illustrate how the assumption of time irrelevance can be handled in a study with a pre-post design. We demonstrate how one can study the dynamics of IR in humans by considering the timing of response following an event of interest and seasonal fluctuation of exposure by proper alignment of time of measurements. This alignment of calendar time of measurements and a child's age at the event of interest allows us to explore interactions between IR, seasonal exposures and age at first infection.</p> <p>Conclusions</p> <p>The use of traditional statistical techniques to analyze immunological data derived from observational human studies can result in loss of important information. Detailed analysis using well-tailored techniques allows the depiction of new features of immune response to a pathogen in longitudinal studies in humans. The proposed staged approach has prominent implications for future study designs and analyses.</p

Parasitism of Lepidopterous Stem Borers in Cultivated and Natural Habitats

Plant infestation, stem borer density, parasitism, and parasitoid abundance were assessed during two years in two host plants, Zea mays (L.) (Cyperales: Poaceae) and Sorghum bicolor (L.) (Cyperales: Poaceae), in cultivated habitats. The four major host plants (Cyperus spp., Panicum spp., Pennisetum spp., and Sorghum spp.) found in natural habitats were also assessed, and both the cultivated and natural habitat species occurred in four agroecological zones in Kenya. Across habitats, plant infestation (23.2%), stem borer density (2.2 per plant), and larval parasitism (15.0%) were highest in maize in cultivated habitats. Pupal parasitism was not higher than 4.7% in both habitats, and did not vary with locality during each season or with host plant between each season. Cotesia sesamiae (Cameron) and C. flavipes Cameron (Hymenoptera: Braconidae) were the key parasitoids in cultivated habitats (both species accounted for 76.4% of parasitized stem borers in cereal crops), but not in natural habitats (the two Cotesia species accounted for 14.5% of parasitized stem borers in wild host plants). No single parasitoid species exerted high parasitism rates on stem borer populations in wild host plants. Low stem borer densities across seasons in natural habitats indicate that cereal stem borer pests do not necessarily survive the non-cropping season feeding actively in wild host plants. Although natural habitats provided refuges for some parasitoid species, stem borer parasitism was generally low in wild host plants. Overall, because parasitoids contribute little in reducing cereal stem borer pest populations in cultivated habitats, there is need to further enhance their effectiveness in the field to regulate these pests

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Impacto do Programa Fica Vivo na redução dos homicídios em comunidade de Belo Horizonte Impacto del Programa Permanezca Vivo en la reducción de los homicidios en comunidad de Belo Horizonte, Sureste de Brasil Impact of the Staying Alive Program on the reduction of homicides in a community in Belo Horizonte

OBJETIVO: Avaliar o impacto de programa de prevenção de homicídios. MÉTODOS: Com base nos dados do Programa Fica Vivo, de prevenção de homicídios, foi realizado um estudo quase experimental com análise de séries temporais da ocorrência de homicídios no aglomerado Morro das Pedras, em Belo Horizonte, MG, de 2002 a 2006. Comparou-se o número de homicídios ocorridos nessa localidade com os de outras favelas violentas e não violentas e outros bairros da cidade, em cada uma das fases do Programa. Para testar a hipótese de que a redução dos homicídios resultou das ações implementadas pelo Programa, foi elaborado um modelo estatístico baseado em modelos lineares generalizados. RESULTADOS: Nos primeiros seis meses obteve-se 69% de redução no número médio de homicídios. Nos períodos de refluxo e retomada parcial do Programa, o efeito de redução dos homicídios diminuiu, mas a diferença entre coeficientes com aquele do período inicial não foi estatisticamente significante. Mesmo com a retomada integral do Programa, o efeito continuou similar aos dos períodos anteriores, provavelmente porque o Programa foi implantado em outras favelas violentas da cidade. CONCLUSÕES: Os resultados apontam que o modelo do Programa Fica Vivo pode constituir uma importante alternativa para prevenção de homicídios contra jovens em comunidades que apresentem características semelhantes às da experiência piloto no Morro das Pedras.<br>OBJETIVO: Evaluar el impacto del programa de prevención de homicidios. MÉTODOS: Con base en los datos del Programa "Fica Vivo" (Permanezca Vivo), de prevención de homicidios, fue realizado un estudio quasi experimental con análisis de series temporales de la ocurrencia de homicidios en el región urbanizada Morro das Pedras en Belo Horizonte, Sureste de Brasil, de 2002 a 2006. Se comparó el número de homicidios ocurridos en esa localidad con los de otros barrios violentos y no violentos y otras urbanizaciones de la ciudad, en cada una de las fases del Programa. Para evaluar la hipótesis de que la reducción de los homicidios resultó de las acciones implementadas por el Programa, fue elaborado un modelo estadístico basado en modelos lineales generalizados. RESULTADOS: En los primeros seis meses se obtuvo 69% de reducción en el número promedio de homicidios. En los períodos de retroceso y retomada parcial del Programa, el efecto de reducción de los homicidios disminuyó, pero la diferencia entre coeficientes con el obtenido en el período inicial no fue estadísticamente significativo. Aún con la retomada integral del Programa, el efecto continuó similar a los dos períodos anteriores, probablemente porque el programa fue implantado en otros barrios violentos de la ciudad. CONCLUSIONES: Los resultados señalan que el modelo del Programa Fica Vivo puede constituir una importante alternativa para prevención de homicidios contra jóvenes en comunidades que presenten características semejantes a las de la experiencia piloto en el Morro das Pedras.<br>OBJECTIVE: To evaluate the impact of a homicide prevention program. METHODS: A quasi-experimental study was performed using time series analysis of homicide incidence in the Morro das Pedras area in the city of Belo Horizonte, Southeastern Brazil, from 2002 to 2006. The number of homicides occurring in this location was compared to other violent and non-violent favelas and to other neighborhoods of the city, during each of the Program phases. To test the hypothesis that homicide reduction was caused by the actions implemented by the program, a statistical model was developed based on generalized linear models. RESULTS: In the first six months a 69% reduction in the number of homicides was obtained. During the other Program periods, the effect on the reduction of homicides lessened, but the difference among coefficients compared to the initial period was not statistically significant. Even with full Program implementation, the effect continued to be similar to the previous periods, probably because the program was implemented in other violent favelas in the city. CONCLUSIONS: The results suggest that the Staying Alive Program model can be an important alternative for the prevention of youth homicides in communities that have characteristics similar to the pilot program in Morro das Pedras