The Triage Capability of Laypersons: Retrospective Exploratory Analysis

Background: Although medical decision-making may be thought of as a task involving health professionals, many decisions, including critical health-related decisions are made by laypersons alone. Specifically, as the first step to most care episodes, it is the patient who determines whether and where to seek health care (triage). Overcautious self-assessments (ie, overtriaging) may lead to overutilization of health care facilities and overcrowded emergency departments, whereas imprudent decisions (ie, undertriaging) constitute a risk to the patient's health. Recently, patient-facing decision support systems, commonly known as symptom checkers, have been developed to assist laypersons in these decisions. Objective: The purpose of this study is to identify factors influencing laypersons' ability to self-triage and their risk averseness in self-triage decisions. Methods: We analyzed publicly available data on 91 laypersons appraising 45 short fictitious patient descriptions (case vignettes; N=4095 appraisals). Using signal detection theory and descriptive and inferential statistics, we explored whether the type of medical decision laypersons face, their confidence in their decision, and sociodemographic factors influence their triage accuracy and the type of errors they make. We distinguished between 2 decisions: whether emergency care was required (decision 1) and whether self-care was sufficient (decision 2). Results: The accuracy of detecting emergencies (decision 1) was higher (mean 82.2%, SD 5.9%) than that of deciding whether any type of medical care is required (decision 2, mean 75.9%, SD 5.25%; t>90=8.4; P89=3.7; P<.001; d=0.39). Conclusions: Our study suggests that laypersons are overcautious in deciding whether they require medical care at all, but they miss identifying a considerable portion of emergencies. Our results further indicate that women are more risk averse than men in both types of decisions. Layperson participants made most triage errors when they were certain of their own appraisal. Thus, they might not follow or even seek advice (eg, from symptom checkers) in most instances where advice would be useful

A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop.

Artemisinin-based therapies are the only effective treatment for malaria, the most devastating disease in human history. To meet the growing demand for artemisinin and make it accessible to the poorest, an inexpensive and rapidly scalable production platform is urgently needed. Here we have developed a new synthetic biology approach, combinatorial supertransformation of transplastomic recipient lines (COSTREL), and applied it to introduce the complete pathway for artemisinic acid, the precursor of artemisinin, into the high-biomass crop tobacco. We first introduced the core pathway of artemisinic acid biosynthesis into the chloroplast genome. The transplastomic plants were then combinatorially supertransformed with cassettes for all additional enzymes known to affect flux through the artemisinin pathway. By screening large populations of COSTREL lines, we isolated plants that produce more than 120 milligram artemisinic acid per kilogram biomass. Our work provides an efficient strategy for engineering complex biochemical pathways into plants and optimizing the metabolic output. DOI: http://dx.doi.org/10.7554/eLife.13664.00

Interactive Versus Static Decision Support Tools for COVID-19: Randomized Controlled Trial

Background: During the COVID-19 pandemic, medical laypersons with symptoms indicative of a COVID-19 infection commonly sought guidance on whether and where to find medical care. Numerous web-based decision support tools (DSTs) have been developed, both by public and commercial stakeholders, to assist their decision making. Though most of the DSTs’ underlying algorithms are similar and simple decision trees, their mode of presentation differs: some DSTs present a static flowchart, while others are designed as a conversational agent, guiding the user through the decision tree’s nodes step-by-step in an interactive manner. Objective: This study aims to investigate whether interactive DSTs provide greater decision support than noninteractive (ie, static) flowcharts. Methods: We developed mock interfaces for 2 DSTs (1 static, 1 interactive), mimicking patient-facing, freely available DSTs for COVID-19-related self-assessment. Their underlying algorithm was identical and based on the Centers for Disease Control and Prevention’s guidelines. We recruited adult US residents online in November 2020. Participants appraised the appropriate social and care-seeking behavior for 7 fictitious descriptions of patients (case vignettes). Participants in the experimental groups received either the static or the interactive mock DST as support, while the control group appraised the case vignettes unsupported. We determined participants’ accuracy, decision certainty (after deciding), and mental effort to measure the quality of decision support. Participants’ ratings of the DSTs’ usefulness, ease of use, trust, and future intention to use the tools served as measures to analyze differences in participants’ perception of the tools. We used ANOVAs and t tests to assess statistical significance. Results: Our survey yielded 196 responses. The mean number of correct assessments was higher in the intervention groups (interactive DST group: mean 11.71, SD 2.37; static DST group: mean 11.45, SD 2.48) than in the control group (mean 10.17, SD 2.00). Decisional certainty was significantly higher in the experimental groups (interactive DST group: mean 80.7%, SD 14.1%; static DST group: mean 80.5%, SD 15.8%) compared to the control group (mean 65.8%, SD 20.8%). The differences in these measures proved statistically significant in t tests comparing each intervention group with the control group (P<.001 for all 4 t tests). ANOVA detected no significant differences regarding mental effort between the 3 study groups. Differences between the 2 intervention groups were of small effect sizes and nonsignificant for all 3 measures of the quality of decision support and most measures of participants’ perception of the DSTs. Conclusions: When the decision space is limited, as is the case in common COVID-19 self-assessment DSTs, static flowcharts might prove as beneficial in enhancing decision quality as interactive tools. Given that static flowcharts reveal the underlying decision algorithm more transparently and require less effort to develop, they might prove more efficient in providing guidance to the public. Further research should validate our findings on different use cases, elaborate on the trade-off between transparency and convenience in DSTs, and investigate whether subgroups of users benefit more with 1 type of user interface than the other. Trial Registration: Deutsches Register Klinischer Studien DRKS00028136; https://tinyurl.com/4bcfausx (retrospectively registered

Inferring Hypotheses on Functional Relationships of Genes: Analysis of the Arabidopsis thaliana Subtilase Gene Family

The gene family of subtilisin-like serine proteases (subtilases) in Arabidopsis thaliana comprises 56 members, divided into six distinct subfamilies. Whereas the members of five subfamilies are similar to pyrolysins, two genes share stronger similarity to animal kexins. Mutant screens confirmed 144 T-DNA insertion lines with knockouts for 55 out of the 56 subtilases. Apart from SDD1, none of the confirmed homozygous mutants revealed any obvious visible phenotypic alteration during growth under standard conditions. Apart from this specific case, forward genetics gave us no hints about the function of the individual 54 non-characterized subtilase genes. Therefore, the main objective of our work was to overcome the shortcomings of the forward genetic approach and to infer alternative experimental approaches by using an integrative bioinformatics and biological approach. Computational analyses based on transcriptional co-expression and co-response pattern revealed at least two expression networks, suggesting that functional redundancy may exist among subtilases with limited similarity. Furthermore, two hubs were identified, which may be involved in signalling or may represent higher-order regulatory factors involved in responses to environmental cues. A particular enrichment of co-regulated genes with metabolic functions was observed for four subtilases possibly representing late responsive elements of environmental stress. The kexin homologs show stronger associations with genes of transcriptional regulation context. Based on the analyses presented here and in accordance with previously characterized subtilases, we propose three main functions of subtilases: involvement in (i) control of development, (ii) protein turnover, and (iii) action as downstream components of signalling cascades. Supplemental material is available in the Plant Subtilase Database (PSDB) (http://csbdb.mpimp-golm.mpg.de/psdb.html), as well as from the CSB.DB (http://csbdb.mpimp-golm.mpg.de)

Ranking ligand affinity for the DNA minor groove by experiment and simulation

The structural and thermodynamic basis for the strength and selectivity of the interactions of minor-groove binders (MGBs) with DNA is not fully understood. In 2003 we reported the first example of a thiazole containing MGB that bound in a phase shifted pattern that spanned 6 base-pairs rather than the usual 4 (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and molecular dynamics, we have established that the flanking bases around the central 4 being read by the ligand have subtle effects on recognition. We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences

Determinants of Laypersons’ Trust in Medical Decision Aids: Randomized Controlled Trial

Background: Symptom checker apps are patient-facing decision support systems aimed at providing advice to laypersons on whether, where, and how to seek health care (disposition advice). Such advice can improve laypersons' self-assessment and ultimately improve medical outcomes. Past research has mainly focused on the accuracy of symptom checker apps' suggestions. To support decision-making, such apps need to provide not only accurate but also trustworthy advice. To date, only few studies have addressed the question of the extent to which laypersons trust symptom checker app advice or the factors that moderate their trust. Studies on general decision support systems have shown that framing automated systems (anthropomorphic or emphasizing expertise), for example, by using icons symbolizing artificial intelligence (AI), affects users' trust. Objective: This study aims to identify the factors influencing laypersons' trust in the advice provided by symptom checker apps. Primarily, we investigated whether designs using anthropomorphic framing or framing the app as an AI increases users' trust compared with no such framing. Methods: Through a web-based survey, we recruited 494 US residents with no professional medical training. The participants had to first appraise the urgency of a fictitious patient description (case vignette). Subsequently, a decision aid (mock symptom checker app) provided disposition advice contradicting the participants' appraisal, and they had to subsequently reappraise the vignette. Participants were randomized into 3 groups: 2 experimental groups using visual framing (anthropomorphic, 160/494, 32.4%, vs AI, 161/494, 32.6%) and a neutral group without such framing (173/494, 35%). Results: Most participants (384/494, 77.7%) followed the decision aid's advice, regardless of its urgency level. Neither anthropomorphic framing (odds ratio 1.120, 95% CI 0.664-1.897) nor framing as AI (odds ratio 0.942, 95% CI 0.565-1.570) increased behavioral or subjective trust (P=.99) compared with the no-frame condition. Even participants who were extremely certain in their own decisions (ie, 100% certain) commonly changed it in favor of the symptom checker's advice (19/34, 56%). Propensity to trust and eHealth literacy were associated with increased subjective trust in the symptom checker (propensity to trust b=0.25; eHealth literacy b=0.2), whereas sociodemographic variables showed no such link with either subjective or behavioral trust. Conclusions: Contrary to our expectation, neither the anthropomorphic framing nor the emphasis on AI increased trust in symptom checker advice compared with that of a neutral control condition. However, independent of the interface, most participants trusted the mock app's advice, even when they were very certain of their own assessment. Thus, the question arises as to whether laypersons use such symptom checkers as substitutes rather than as aids in their own decision-making. With trust in symptom checkers already high at baseline, the benefit of symptom checkers depends on interface designs that enable users to adequately calibrate their trust levels during usage

Characteristics of Users and Nonusers of Symptom Checkers in Germany: Cross-Sectional Survey Study

Background: Previous studies have revealed that users of symptom checkers (SCs, apps that support self-diagnosis and self-triage) are predominantly female, are younger than average, and have higher levels of formal education. Little data are available for Germany, and no study has so far compared usage patterns with people's awareness of SCs and the perception of usefulness. Objective: We explored the sociodemographic and individual characteristics that are associated with the awareness, usage, and perceived usefulness of SCs in the German population. Methods: We conducted a cross-sectional online survey among 1084 German residents in July 2022 regarding personal characteristics and people's awareness and usage of SCs. Using random sampling from a commercial panel, we collected participant responses stratified by gender, state of residence, income, and age to reflect the German population. We analyzed the collected data exploratively. Results: Of all respondents, 16.3% (177/1084) were aware of SCs and 6.5% (71/1084) had used them before. Those aware of SCs were younger (mean 38.8, SD 14.6 years, vs mean 48.3, SD 15.7 years), were more often female (107/177, 60.5%, vs 453/907, 49.9%), and had higher formal education levels (eg, 72/177, 40.7%, vs 238/907, 26.2%, with a university/college degree) than those unaware. The same observation applied to users compared to nonusers. It disappeared, however, when comparing users to nonusers who were aware of SCs. Among users, 40.8% (29/71) considered these tools useful. Those considering them useful reported higher self-efficacy (mean 4.21, SD 0.66, vs mean 3.63, SD 0.81, on a scale of 1-5) and a higher net household income (mean EUR 2591.63, SD EUR 1103.96 [mean US $2798.96, SD US$1192.28], vs mean EUR 1626.60, SD EUR 649.05 [mean US $1756.73, SD US$700.97]) than those who considered them not useful. More women considered SCs unhelpful (13/44, 29.5%) compared to men (4/26, 15.4%). Conclusions: Concurring with studies from other countries, our findings show associations between sociodemographic characteristics and SC usage in a German sample: users were on average younger, of higher socioeconomic status, and more commonly female compared to nonusers. However, usage cannot be explained by sociodemographic differences alone. It rather seems that sociodemographics explain who is or is not aware of the technology, but those who are aware of SCs are equally likely to use them, independently of sociodemographic differences. Although in some groups (eg, people with anxiety disorder), more participants reported to know and use SCs, they tended to perceive them as less useful. In other groups (eg, male participants), fewer respondents were aware of SCs, but those who used them perceived them to be more useful. Thus, SCs should be designed to fit specific user needs, and strategies should be developed to help reach individuals who could benefit but are not aware of SCs yet

Metabolic Profiling of Heathland Plants in the Diet of Sheep

Little is known about how plant biochemistry influences the grazing behaviour of animals grazing heterogeneous vegetation communities. Furthermore, most biochemical profiles of grassland species are restricted to major nutritional characteristics. Recent developments in analytical techniques have made possible the detailed analysis of minor components, which can potentially affect animal feeding preferences, performance and health. Gas chromatography/time of flight mass spectroscopy (GC/TOF-MS) coupled with automated library annotation is ideally suited to the acquisition of detailed metabolite profiles of plant extracts (Wagner et al., 2003) and can be applied to other matrices such as blood and faeces. In this study GC/TOF-MS was used to identify metabolites within heathland plants, and to investigate which of these metabolites were present and absent within plasma and faeces from sheep consuming mixtures of these plants