PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Non-response for health-related quality of life outcomes in ICU patients: A systematic review of the reporting in randomised trials

Background

Health-related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of patients without responses or not surviving to HRQoL follow-up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data in intensive care trials and describe how these data and deaths were handled statistically.

Methods

We conducted a systematic review and meta-analysis following a published protocol. We searched PubMed, EMBASE, CINAHL and Cochrane Library for RCTs involving adult ICU patients reporting HRQoL as an outcome and excluded RCTs unobtainable in full text. We performed risk of bias assessment independently and in duplicate.

Results

We included 196 outcomes from 88 RCTs published in the years 2002–2022; the numbers of patients alive and eligible to respond HRQoL were reported in 76% of trials. At follow-up, median 27% (interquartile range 14%–39%) of patients had died, and median 20% (9%–38%) of survivors did not respond across outcomes. Analyses of 80% of outcomes were restricted to complete cases only. The handling of non-survivors in analyses were reported for 46% of outcomes, with 26% of all outcomes reported as including non-survivors (using the value zero or the worst possible score).

Conclusion

For HRQoL outcomes in ICU trials, we found that mortality at time of follow-up was high and non-response among survivors frequent. The reporting and statistical handling of these issues were insufficient, which may have biased results.     

Heritable Genome Editing in a Global Context: National and International Policy Challenges

A central problem for the international governance of heritable germline gene editing is that there are important differences in attitudes and values as well as ethical and health care considerations around the world. These differences are reflected in a complicated and diverse regulatory landscape. Several publications have discussed whether reproductive uses would be legally permissible in individual countries and whether clinical applications could emerge in the context of regulatory gaps and gray areas. Systematic comparative studies that explore issues related to the governance of this technology from different national and international perspectives are needed to address the lack of knowledge in this area. In this research report, we contribute to filling this gap by presenting views of stakeholders in the United Kingdom on challenges to the governance of heritable genome editing. We present findings from a multistakeholder study conducted in the United Kingdom between October 2016 and January 2018 and funded by the Wellcome Trust. This research included interviews, literature analysis, and a workshop. We involved leading U.K. scientists, in vitro fertilization clinicians, and representatives from regulatory bodies, patient organizations, and other civil societal organizations, as well as fertility companies. Part one of this article explores stakeholder perceptions of possible global developments in heritable genome editing and associated risks and governance challenges. Part two presents a range of policy options that were generated during the workshop in relation to the challenges discussed in part one.     

Point of Care Ultrasound Use by Associate Providers for Differentiating Abscess Versus Cellulitis Skin and Soft Tissue Infection in the Emergency Department

BackgroundSkin and soft tissue infections (SSTIs) are a common complaint in the ambulatory setting and pose a significant burden on the health care system.ObjectivesWe sought to determine the accuracy of ultrasound for detecting soft tissue abscesses by emergency medicine associate providers (APs).MethodsThis was a prospective observational study of adult patients with suspected SSTI in the emergency department of a rural tertiary care academic medical center. The AP performed and interpreted point-of-care ultrasound (POCUS) of the suspected infected area. Ultrasound images and interpretation were reviewed by the attending emergency physician with either rejection or agreement of the image interpretation, diagnosis, and management. If incision and drainage was performed, presence or absence of purulent drainage was recorded.ResultsSixty-four patients with suspected SSTI were enrolled: 29 had POCUS-proven abscesses and 33 had cellulitis; 2 were excluded. AP clinical evaluation alone for identifying abscess revealed sensitivity of 92.3 (74.9–99.1), specificity of 67.7 (49.5–82.6), positive predictive value of 68.6 (57.0–78.2), and negative predictive value of 92.0 (81.4–100). The use of POCUS by APs in addition to clinical examination demonstrated sensitivity of 96.2 (80.4–99.9), specificity of 93.9 (79.8–99.3), positive predictive value of 92.6 (76.5–98.0), and negative predictive value of 96.9 (81.9–99.5). p values were <0.05 for test characteristics. Ultrasound results changed SSTI management decisions in 10 of 62 (16.1%) patients, with the most common change being a new incision and drainage or needle aspiration. Agreement of the POCUS interpretation between APs and attending physicians was 96.8% with a κ of 0.94 (0.85–1.00).ConclusionWith modest training, APs can successfully use POCUS to identify abscesses in patients in the emergency department with SSTIs. POCUS increases the ability to rule in the diagnosis and changes management in a clinically relevant number of patients with SSTIs.