Advancing the Application of Design of Experiments (DOE) to Synthetic Theater Operations Research Model (STORM) Data

NPS NRP Technical ReportThe Navy uses simulation-based campaign analysis to help measure risk for investment options for how best to equip, organize, supply, maintain, train, and employ our naval forces. The Synthetic Theater Operations Research Model (STORM) is a stochastic simulation model used to support campaign analysis by the U.S. Navy, Marine Corps, and Air Force. Building, testing, running, and analyzing campaign scenarios in STORM can be a complex, time-consuming process. The goal of this research is to apply Design Of Experiment (DOE) methods in the selection and creation of Design Points (DPs) to minimize the number of modeling runs required for meaningful comparisons. Another objective is to understand how best DOE methods can complement traditional baseline and excursion modeling. In addition to regular reviews, the research deliverables will include: (1) a final brief and/or technical report, in addition to student theses (if applicable); (2) all findings, methods, and data used in the study; and (3) appropriate conference or journal papers related to this research.N8 - Integration of Capabilities & ResourcesThis research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). https://nps.edu/nrpChief of Naval Operations (CNO)Approved for public release. Distribution is unlimited.

Advancing the Application of Design of Experiments (DOE) to Synthetic Theater Operations Research Model (STORM) Data

NPS NRP Project PosterThe Navy uses simulation-based campaign analysis to help measure risk for investment options for how best to equip, organize, supply, maintain, train, and employ our naval forces. The Synthetic Theater Operations Research Model (STORM) is a stochastic simulation model used to support campaign analysis by the U.S. Navy, Marine Corps, and Air Force. Building, testing, running, and analyzing campaign scenarios in STORM can be a complex, time-consuming process. The goal of this research is to apply Design Of Experiment (DOE) methods in the selection and creation of Design Points (DPs) to minimize the number of modeling runs required for meaningful comparisons. Another objective is to understand how best DOE methods can complement traditional baseline and excursion modeling. In addition to regular reviews, the research deliverables will include: (1) a final brief and/or technical report, in addition to student theses (if applicable); (2) all findings, methods, and data used in the study; and (3) appropriate conference or journal papers related to this research.N8 - Integration of Capabilities & ResourcesThis research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). https://nps.edu/nrpChief of Naval Operations (CNO)Approved for public release. Distribution is unlimited.

Advancing the Application of Design of Experiments (DOE) to Synthetic Theater Operations Research Model (STORM) Data

NPS NRP Executive SummaryThe Navy uses simulation-based campaign analysis to help measure risk for investment options for how best to equip, organize, supply, maintain, train, and employ our naval forces. The Synthetic Theater Operations Research Model (STORM) is a stochastic simulation model used to support campaign analysis by the U.S. Navy, Marine Corps, and Air Force. Building, testing, running, and analyzing campaign scenarios in STORM can be a complex, time-consuming process. The goal of this research is to apply Design Of Experiment (DOE) methods in the selection and creation of Design Points (DPs) to minimize the number of modeling runs required for meaningful comparisons. Another objective is to understand how best DOE methods can complement traditional baseline and excursion modeling. In addition to regular reviews, the research deliverables will include: (1) a final brief and/or technical report, in addition to student theses (if applicable); (2) all findings, methods, and data used in the study; and (3) appropriate conference or journal papers related to this research.N8 - Integration of Capabilities & ResourcesThis research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). https://nps.edu/nrpChief of Naval Operations (CNO)Approved for public release. Distribution is unlimited.

Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.

BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective

Vacina BCG contra tuberculose: efeito protetor e políticas de vacinação

OBJECTIVE: The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies. METHODS: A systematic review of the literature in both English and Spanish was carried out, covering the period 1948 to 2006, using the PubMed database. The main search terms used included BCG vaccine, BCG efficacy, BCG and tuberculosis. The studies were grouped by design, with the main results from the clinic tests, case-control studies and meta-analyses presented separately. RESULTS: The protective effect of the first dose of the BCG vaccine against tuberculosis in its miliary and meningeal forms is high. However, the results vary in relation to the pulmonary form of the disease, with some indicating zero effect and others levels of nearly 80%. Research is being carried out to develop new vaccines that could substitute the BCG or be used as a booster. CONCLUSIONS: There are evidences that the protective effect of the BCG vaccine does not increase with a second dose. In spite of its limitations and the expectation that a new tuberculosis vaccine will be developed in the future, the BCG vaccine remains an important tool in controlling the harmful effects of tuberculosis, particularly in countries with medium or high incidence levels of the disease.OBJETIVO: A vacina BCG é utilizada desde 1921, embora ainda apresente controvérsias e aspectos não esclarecidos. O objetivo do artigo foi analisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e as políticas de vacinação adotadas. MÉTODOS: Foi realizada revisão sistemática da literatura publicada em inglês e espanhol, abrangendo o período compreendido entre 1948 e 2006, na base PubMed. Os principais descritores utilizados foram BCG vaccine, BCG efficacy, BCG e tuberculosis. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e metanálises. RESULTADOS: O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é elevado. No entanto, os resultados são discordantes em relação à forma pulmonar, variando de ausência de efeito a níveis próximos a 80%. Estão sendo conduzidas pesquisas sobre novas vacinas candidatas a substituir a BCG ou serem utilizadas como reforço. CONCLUSÕES: Há evidências de que a segunda dose da BCG não aumenta o seu efeito protetor. Apesar de seus limites e da expectativa futura de nova vacina para tuberculose, a vacina BCG mantém-se como importante instrumento no controle dos efeitos danosos da doença, sobretudo em países com taxas de incidência médias e elevadas

Características dos serviços de saúde associadas à adesão ao tratamento da tuberculose

OBJECTIVE: To analyze characteristics related to adherence to tuberculosis treatment in tuberculosis outpatient clinics. METHODS: An ecological study was conducted in outpatient clinics for the treatment of tuberculosis cases in the sanitary districts of Salvador, Northeastern Brazil, in 2006. The sample was composed of the municipal health units that assisted 67.2% of the 2,283 tuberculosis cases that were reported during the year. The following variables were analyzed: cure, dropout, tests, health team and benefits offered to the patients. Chi-square test or Fisher's exact test was used to verify the association between variables, and associations with pOBJETIVO: Analisar características relacionadas à adesão ao tratamento dos casos de tuberculose em serviços de referência para tuberculose. MÉTODOS: Trata-se de um estudo ecológico nas unidades de referência no tratamento dos casos de tuberculose dos distritos sanitários de Salvador, BA, em 2006. A amostra foi composta pelas unidades de saúde municipais que atenderam 67,2% dos 2.283 casos notificados de tuberculose no ano. Foram analisadas as variáveis: cura, abandono, exames realizados, equipe de saúde e benefícios aos pacientes. Para verificar associação entre as variáveis, foi utilizado o teste qui-quadrado ou exato de Fisher, sendo consideradas estatisticamente significantes as associações com pOBJETIVO: Analizar características relacionadas a la adhesión al tratamiento de los casos de tuberculosis en servicios de referencia para tuberculosis. MÉTODOS: Se trata de estudio ecológico en las unidades de referencia en el tratamiento de los casos de tuberculosis de los distritos sanitarios de Salvador, Noreste de Brasil, en 2006. La muestra fue compuesta por las unidades de salud municipales que atendieron 67,2% de los 2.283 casos notificados de tuberculosis en el año. Fueron analizadas las variables: cura, abandono, exámenes realizados, equipo de salud y beneficios a los pacientes. Para verificar asociación entre las variables, fue utilizada la prueba chi-cuadrado o exacto de Fisher, siendo consideradas estadísticamente significativas las asociaciones con

The need for fast-track, high-quality and low-cost studies about the role of the BCG vaccine in the fight against COVID-19.

Bacillus Calmette-Guérin (BCG) vaccination is routine and near-universal in many low- and middle-income countries (LMIC). It has been suggested that BCG can have a protective effect on COVID-19 morbidity and mortality. This commentary discusses the limitations of the evidence around BCG and COVID-19. We argue that higher-quality evidence is necessary to understand the protective effect of the BCG vaccine from existing, secondary data, while we await results from clinical trials currently conducted in different settings

Sensibilidade e especificidade da leitura da cicatriz vacinal do BCG

OBJECTIVE: To validate the BCG scar as a marker of BCG vaccination status. METHODS: A cross-sectional survey was carried out among 53,348 schoolchildren aged 6-14 years who underwent BCG scar examination as part of a large BCG vaccine trial taking place in the city of Manaus, Brazil. Results of BCG scar reading were compared with information on vaccine status of their vaccination cards or provided by parents or guardians. Double-reading was performed in a sub-sample. Data analysis was conducted using Stata 7 and Kappa coefficient. RESULTS: Of 52,348 schoolchildren studied, vaccine status information from parents/guardian letters was available for 29,254 and from vaccination cards for 4,947. There was found a high agreement between the double-readings of the scars (Kappa=0.81). When the agreement between letter and card information was the gold standard, the sensitivity of BCG scar readings was 96.6% (95%CI 96.0-97.1) and the specificity was 71.1% (95%CI 55.7-83.7). The sensitivity was 96.1%, 97.3% and 95.3% for children vaccinated up to one month of age, four months and one year, respectively. CONCLUSIONS: Sensitivity and specificity did not show an association with the child's age at the scar reading. BCG scar was a good marker of BCG vaccination status regardless of age - from the first years of life up to 14 years old.OBJETIVO: Validar a utilização da cicatriz vacinal de BCG como um indicador de vacinação. MÉTODOS: Foi realizado um estudo transversal em 52.348 escolares, entre 6 e 14 anos de idade, que possuíam exame de cicatriz vacinal do BCG e que participaram de um ensaio clínico randomizado e controlado na cidade de Manaus, Brasil. Os dados da leitura da cicatriz vacinal foram comparados com a informação sobre a vacinação passada fornecida pelos cartões vacinais ou informação dos responsáveis. Em uma subamostra foi realizada leitura dupla com cálculo do coeficiente Kappa. Para análise dos dados utilizou-se o Stata 7. RESULTADOS: Do total de 52.348 escolares estudados, 29.254 possuíam informação sobre cicatriz vacinal coletada por meio de carta aos pais, e 4.947 possuíam história de vacinação coletada pelo cartão de vacinas. Observou-se elevada concordância entre a dupla leitura de cicatriz vacinal (Kappa =0,81). A sensibilidade da leitura de cicatriz vacinal foi 96,6% (95% IC 96,0-97,1) e a especificidade foi 71,1% (95% IC 55,7-83,7) quando o padrão ouro utilizado foi a concordância entre a carta aos pais e a informação do cartão de vacinas. A sensibilidade foi de 96,1%, 97,3% e 95,3% para crianças vacinadas até um mês de idade, até 4 meses e até um ano de idade, respectivamente. CONCLUSÕES: Os valores encontrados para sensibilidade e especificidade foram independentes da idade da realização da leitura de cicatriz vacinal. O exame da cicatriz vacinal mostrou ser um bom indicador para avaliar a situação vacinal referente ao BCG

Tuberculose em adolescentes em duas capitais brasileiras

Analisamos o perfil clínico-radiológico da tuberculose (TB) em adolescentes de duas capitais brasileiras, segundo a revisão de 2010 das normas do Programa Nacional de Controle da Tuberculose; estudo descritivo, retrospectivo, transversal de casos notificados de TB em Manaus e Salvador, de 1996 a 2003, em dois grupos: 10 a 14 anos e &#8805; 15 a 19 anos com estatística descritiva. Havia 1.781 adolescentes [928 (52,1%) do sexo masculino]. A média de idade = 16 anos (mediana = 16; DP = 2,3). Encontramos 1.447 (82,9%) pacientes com TB pulmonar; 179 (10,3%) com TB pleural e 81 (4,6%) com ganglionar periférica. A tosse ocorreu mais no grupo &#8805; 15 anos (p < 0,001). A baciloscopia foi positiva em 150 (72,1%) com TB pulmonar no grupo de 10 a 14 anos, e em 870 (84,4%) no grupo de &#8805; 15 anos. Havia radiografias de tórax do tipo adulto em 1.088 (98.6%) no grupo de &#8805; 15 anos, e em 58 (98.1%) no grupo < 15 anos (p < 0.0001). Houve tendência à maior ocorrência de TB bacteriológica do tipo adulto na medida em que o paciente aumentava de idade