Receiver Operating Characteristic (ROC) Curves: The Basics and Beyond.

Diagnostic tests and clinical prediction rules are frequently used to help estimate the probability of a disease or outcome. How well a test or rule distinguishes between disease or no disease (discrimination) can be measured by plotting a receiver operating characteristic (ROC) curve and calculating the area under it (AUROC). In this paper, we review the features of ROC curves and interpretation of ROC curves and AUROC values. We highlight 5 underappreciated features of ROC curves: (1) the slope of the ROC curve over a test result interval is the likelihood ratio for that interval; (2) the optimal cutoff for calling a test positive depends not only on the shape of the ROC curve, but also on the pretest probability of disease and relative harms of false-positive and false-negative results; (3) the AUROC measures discrimination only, not the accuracy of the predicted probabilities; (4) the AUROC is not a good measure of discrimination if the slope of the ROC curve is not consistently decreasing; and (5) the AUROC can be increased by including a large number of people correctly identified as being at very low risk for the outcome of interest. We illustrate this last concept using 3 published studies.

A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity.

BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility.

Determining the Association Between the Origin of Sepsis and the Severity of Sepsis in Intensive Care Unit (ICU) Patients Using Acute Physiology and Chronic Health Evaluation (APACHE) IV.

Objective The objective of this study is to compare the outcomes of hospital mortality, the requirement of invasive ventilation, vasopressor requirement, duration of vasopressor requirement, and duration of intensive care unit (ICU) stay among the different causes of sepsis and to determine which cause of sepsis had the most severe outcomes. Methods A retrospective chart review was done in critically ill adult patients who were admitted with sepsis to the ICU from July 2017 until July 2019. Acute Physiology and Chronic Health Evaluation (APACHE) IV scores were calculated on patients admitted to ICU on day one of ICU admission. Each patient was then evaluated for outcomes of hospital mortality, need for invasive ventilation, requirement of vasopressors, duration of vasopressors, and duration of ICU stay. The outcomes were then compared between the different sources of sepsis to determine which source of sepsis had the highest severity. Results In total, 176 patients were included in the study. Ninety-three patients were admitted with respiratory sepsis, 26 patients were admitted with gastrointestinal sepsis, 31 patients were admitted with urosepsis, and 26 patients were admitted with other miscellaneous causes of sepsis. The hospital mortality was highest in the respiratory sepsis group at 32%, with a trend towards statistical significance with a P value of 0.057. ICU stay duration was highest in patients with respiratory sepsis at six days, with a statistically significant P value of < 0.001. The need for invasive ventilation was highest in patients with respiratory sepsis at 64%, with a statistically significant P value of < 0.001. The requirement of vasopressor support was highest in patients with respiratory sepsis at 47% and the duration of vasopressors was highest in both respiratory and gastrointestinal sepsis at three days, however, there was no statistical significance. Conclusion Among the different origins of sepsis, the patients with respiratory sepsis had the most severe outcomes, with the highest need for invasive ventilation and the highest ICU stay duration.

Delineando a pesquisa clínica: uma abordagem epidemiológica / Designing clinical research: an epidemiologic approach

Um guia prático para o planejamento e a implementação da pesquisa clínica. Direto e de fácil leitura, o texto oferece a médicos e a investigadores clínicos descrições rigorosas dos componentes básicos, enfatizando o bom senso como o ingrediente fundamental do sucesso. Diferenciais dessa segunda edição: exemplos e idéias sobre o que há de novo na pesquisa clínica; expansão dos tópicos relativos ao delineamento e à implementação de ensaios clínicos randomizados; novas abordagens para estimativas de tamanho de amostra, abrangendo novas opções de delineamento; atualização nas questões éticas e na condução responsável da pesquisa clínica; novos capítulos sobre estudos de testes médicos, dados secundários (incluindo estudos suplementares e metanálise), gerenciamento de dados e pesquisa comunitária e internacional.