Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable : an illustrative case study of cancer risk of patients on glucose-lowering therapies

Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through substantially different risk levels between exposure groups at the start of follow-up when exposure is deemed too short to have any plausible biological effect of the drug. The restrictive proportional hazards assumption with its arbitrary choice of baseline hazard function renders the commonly used Cox proportional hazards model of limited use for revealing such potential bias. We demonstrate a fully parametric approach using accelerated failure time models with an illustrative safety study of glucose-lowering therapies and show that its results are comparable against other methods that allow time-varying exposure effects. Our approach includes a wide variety of models that are based on the flexible generalized gamma distribution and allows direct comparisons of estimated hazard functions following different exposure-specific distributions of survival times. This approach lends itself to two alternative metrics, namely relative times and difference in times to event, allowing physicians more ways to communicate patient's prognosis without invoking the concept of risks, which some may find hard to grasp. In our illustrative case study, substantial differences in cancer risks at drug initiation followed by a gradual reduction towards null were found. This evidence is compatible with the presence of protopathic bias, in which undiagnosed symptoms of cancer lead to switches in diabetes medication

Pharmacoepidemiological approaches for population-based hypothesis testing

Pharmacoepidemiology aims to study the use and both the adverse and beneficial effects of drugs and vaccines in the population after market authorization. The efficacy of drugs is assessed in experimental studies before a drug is allowed on the market in a limited and usually selected group of patients. Therefore, after market authorization the focus is on serious and adverse effects in large groups of patients in daily clinical practice. Observational drug research is needed to establish and measure these effects. Observational research faces several challenges to minimize the chance of bias, including confounding by indication, which is caused by selective prescribing of drugs to certain patient groups. A comparison between treated and untreated subjects or between different drug regimens may be biased due to uneven distribution of risk factors for the outcome of interest. Important progress has been made during the past decade in controlling confounding by design and analysis in observational studies. The increasing accessibility of large electronic health record databases has fuelled various international initiatives to analyze multiple databases across countries using common protocols and common data models. Extensive sensitivity analysis across multiple designs, databases, and analytical techniques has provided more insight into causes of variation in results across studies and increases the confidence in findings of observational studies. Transparency of observational drug research through public registration of protocols and detailed reporting of methods should improve reproducibility and thereby reliability of pharmacoepidemiological studies

CholecTriplet2021: A benchmark challenge for surgical action triplet recognition

Context-aware decision support in the operating room can foster surgical safety and efficiency by leveraging real-time feedback from surgical workflow analysis. Most existing works recognize surgical activities at a coarse-grained level, such as phases, steps or events, leaving out fine-grained interaction details about the surgical activity; yet those are needed for more helpful AI assistance in the operating room. Recognizing surgical actions as triplets of ‹instrument, verb, target› combination delivers more comprehensive details about the activities taking place in surgical videos. This paper presents CholecTriplet2021: an endoscopic vision challenge organized at MICCAI 2021 for the recognition of surgical action triplets in laparoscopic videos. The challenge granted private access to the large-scale CholecT50 dataset, which is annotated with action triplet information. In this paper, we present the challenge setup and the assessment of the state-of-the-art deep learning methods proposed by the participants during the challenge. A total of 4 baseline methods from the challenge organizers and 19 new deep learning algorithms from the competing teams are presented to recognize surgical action triplets directly from surgical videos, achieving mean average precision (mAP) ranging from 4.2% to 38.1%. This study also analyzes the significance of the results obtained by the presented approaches, performs a thorough methodological comparison between them, in-depth result analysis, and proposes a novel ensemble method for enhanced recognition. Our analysis shows that surgical workflow analysis is not yet solved, and also highlights interesting directions for future research on fine-grained surgical activity recognition which is of utmost importance for the development of AI in surgery

Beyond the Head: The Practical Work of Curating Contemporary Art

In contemporary art, the curator plays an important role in the production of artistic meaning through exhibition-making. Although sociology has tended to see this work as the exercise of tacit or embodied knowledge, curatorial knowledge and plans may be elaborated and altered by the situated actions of exhibition installation. While curators know a successful installation “when they see it,” this depends on the indexical particularities of artworks and environments which cannot be predicted in advance. In demonstrating the practical ways in which culture is mobilized in situations of object (inter)action, this paper emphasizes the “making” in artistic meaning-making