Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis

Background Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints. Methods We used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD. Results There was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®. Conclusions The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints. Trial registration ClinicalTrials.govNCT02597933. Registered on 8 October 2015.

Impact of the SARS-CoV-2 Epidemic on Lung Cancer Surgery in France: A Nationwide Study

Few studies have investigated the link between SARS-CoV-2 and health restrictions and its effects on the health of lung cancer (LC) patients. The aim of this study was to assess the impact of the SARS-CoV-2 epidemic on surgical activity volume, postoperative complications and in-hospital mortality (IHM) for LC resections in France. All data for adult patients who underwent pulmonary resection for LC in France in 2020, collected from the national administrative database, were compared to 2018–2019. The effect of SARS-CoV-2 on the risk of IHM and severe complications within 30 days among LC surgery patients was examined using a logistic regression analysis adjusted for age, sex, comorbidities and type of resection. There was a slight decrease in the volume of LC resections in 2020 (n = 11,634), as compared to 2018 (n = 12,153) and 2019 (n = 12,227), with a noticeable decrease in April 2020 (the peak of the first wave of epidemic in France). We found that SARS-CoV-2 (0.43% of 2020 resections) was associated with IHM and severe complications, with, respectively, a sevenfold (aOR = 7.17 (3.30–15.55)) and almost a fivefold (aOR = 4.76 (2.31–9.80)) increase in risk. Our study suggests that LC surgery is feasible even during a pandemic, provided that general guidance protocols edited by the surgical societies are respected.

Reactive Risk-Taking: Anxiety Regulation Via Approach Motivation Increases Risk-Taking Behavior

Experimental research and real-world events demonstrate a puzzling phenomenon—anxiety, which primarily inspires caution, sometimes precedes bouts of risk-taking. We conducted three studies to test whether this phenomenon is due to the regulation of anxiety via reactive approach motivation (RAM), which leaves people less sensitive to negative outcomes and thus more likely to take risks. In Study 1 ( N = 231), an achievement anxiety threat caused increased risk-taking on the Behavioral Analogue Risk Task (BART) among trait approach-motivated participants. Using electroencephalogram in Study 2 ( N = 97), an economic anxiety threat increased behavioral inhibition system-specific theta activity, a neural correlate of anxiety, which was associated with an increase in risk-taking on the BART among trait approach-motivated participants. In a preregistered Study 3 ( N = 432), we replicated the findings of Study 1. These results offer preliminary support for the reactive risk-taking hypothesis.

When are idiopathic and clonal cytopenias of unknown significance (ICUS or CCUS)?

Rapid advances in sequencing technology have led to the identification of somatic mutations that predispose a significant subset of the aging population to myeloid malignancies. Recently recognized myeloid precursor conditions include clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS). These conditions can present diagnostic challenges and produce unwarranted anxiety in some instances. While the risk of progression to myeloid malignancies is very low in CHIP, true CCUS confers an exponential increase in risk. Idiopathic cytopenia of unknown significance (IDUS) lacks the predisposing genetic mutations and has a variable course. In this review we define the early myeloid precursor conditions and their risk of progression. We present our diagnostic approach to patients with unexplained cytopenias and discuss the clinical consequences of CHIP and CCUS.

What are the chances? How descriptions of probability affect risky decisions

<p>People make different decisions when they know the odds of an event occurring, (e.g. told 10% chance of an earthquake that year) than when they draw on only their own experience (e.g. living in a city with, on average, one earthquake every 10 years). It may be that when we make decisions based on our past experience (decisions from experience) we are more likely to choose a risky option when it can lead to the biggest win and avoid it when it can lead to the biggest loss, this effect is called the Extreme-Outcome rule. Across three Experiments we tested the Extreme-Outcome rule by having participants make repeated choices between either safe or risky options which had the same expected value. In each experiment, we varied the magnitude of the reinforcer’s participants could win in both an Experience condition and a condition that had both description and experience information. In Experiment 1 where we had two reinforcer sizes (small and large) we found an Extreme-Outcome effect in the Experience condition, but not the Description-Experience condition. In Experiment 2 we tested a prediction of the Extreme-Outcome rule that participants would be sensitive to the best and worst outcome by adding another reinforcer size (reinforcers were small, medium and large) and therefore on some trials neither alternative included an extreme outcome. We also removed zero as a potential outcome to investigate whether zero aversion might be driving the effect of reinforcer magnitude in the Experience condition. We did not find response patterns consistent with an Extreme-Outcome rule in the Experience condition. Instead, participants were least risk seeking when the reinforcer was small, but there was no difference in levels of risk seeking between the medium and large reinforcer trials. In other words, there was an effect of the low-extreme outcome but not the high-extreme outcome. Like Experiment 1, in the Description-Experience condition risk preference was not influenced by reinforcer size, but the absolute levels were higher. To investigate whether this increase in risk preference was due to removing the zero, in Experiment 3 we manipulated whether zero was present or absent. When zero was absent, risk preference was not influenced by the size of the reinforcer in the Description-Experience condition, but there was an effect of the low-extreme outcome when zero was present. We also found an effect of the low extreme outcome in the Experience condition regardless of whether zero was present or absent. Overall, these findings suggest the Extreme-Outcome rule needs to be modified to take into account the effect of the low extreme but not the high extreme outcome.</p>

What are the chances? How descriptions of probability affect risky decisions

<p>People make different decisions when they know the odds of an event occurring, (e.g. told 10% chance of an earthquake that year) than when they draw on only their own experience (e.g. living in a city with, on average, one earthquake every 10 years). It may be that when we make decisions based on our past experience (decisions from experience) we are more likely to choose a risky option when it can lead to the biggest win and avoid it when it can lead to the biggest loss, this effect is called the Extreme-Outcome rule. Across three Experiments we tested the Extreme-Outcome rule by having participants make repeated choices between either safe or risky options which had the same expected value. In each experiment, we varied the magnitude of the reinforcer’s participants could win in both an Experience condition and a condition that had both description and experience information. In Experiment 1 where we had two reinforcer sizes (small and large) we found an Extreme-Outcome effect in the Experience condition, but not the Description-Experience condition. In Experiment 2 we tested a prediction of the Extreme-Outcome rule that participants would be sensitive to the best and worst outcome by adding another reinforcer size (reinforcers were small, medium and large) and therefore on some trials neither alternative included an extreme outcome. We also removed zero as a potential outcome to investigate whether zero aversion might be driving the effect of reinforcer magnitude in the Experience condition. We did not find response patterns consistent with an Extreme-Outcome rule in the Experience condition. Instead, participants were least risk seeking when the reinforcer was small, but there was no difference in levels of risk seeking between the medium and large reinforcer trials. In other words, there was an effect of the low-extreme outcome but not the high-extreme outcome. Like Experiment 1, in the Description-Experience condition risk preference was not influenced by reinforcer size, but the absolute levels were higher. To investigate whether this increase in risk preference was due to removing the zero, in Experiment 3 we manipulated whether zero was present or absent. When zero was absent, risk preference was not influenced by the size of the reinforcer in the Description-Experience condition, but there was an effect of the low-extreme outcome when zero was present. We also found an effect of the low extreme outcome in the Experience condition regardless of whether zero was present or absent. Overall, these findings suggest the Extreme-Outcome rule needs to be modified to take into account the effect of the low extreme but not the high extreme outcome.</p>

Confirmation Bias and Auditor Risk Assessments: Archival Evidence

Judgment and decision making research suggests that auditors’ judgments are negatively affected by the use of heuristics. However, there is little research investigating whether such biases survive the quality control processes that regulators and audit firms implement to mitigate them. We investigate this by identifying a setting where one such bias – confirmation bias – is likely to manifest. Consistent with confirmation bias influencing observable audit outcomes, we find that auditors with previous experience auditing a client with a history of low risk followed by an increase in risk do not adequately respond to the higher level of risk. This effect is mitigated when the risk increase is likely large enough to violate auditors’ reasonableness constraint and when the client is highly visible or has strong external monitors. Our study complements prior experimental research by providing archival evidence that auditors’ use of heuristics has a significant effect on auditor judgments.

HLA-A*03:01 is associated with increased risk of fever, chills, and more severe reaction to Pfizer-BioNTech COVID-19 vaccination

COVID-19 vaccines are safe and highly effective, but some individuals experience unpleasant reactions to vaccination. As the majority of adults in the US have received a COVID-19 vaccine this year, there is an unprecedented opportunity to study the genetics of reactions to vaccination via surveys of individuals who are already part of genetic research studies. Here, we have queried 17,440 participants in the Helix DNA Discovery Project and Healthy Nevada Project about their reactions to COVID-19 vaccination. Our GWAS identifies an association between severe vaccine side effects and HLA-A*03:01. This association was statistically significant only for those who received the Pfizer-BioNTech vaccine (BNT162b2; p=4.70E-11), but showed a trending association in those who received the Moderna vaccine (mRNA-1273; p=0.005) despite similar sample sizes for study. In Pfizer-BioNTech recipients, HLA-A*03:01 was associated with a two-fold increase in risk of severe vaccine side effects. The effect was consistent across ages, sexes, and whether the person had previously had a COVID-19 infection. The reactions experienced by HLA-A*03:01 carriers were driven by associations with chills, fever, fatigue, and in general feeling unwell.

Inflammation-Based Scores as a Common Tool for Prognostic Assessment in Heart Failure or Cancer

Background: Inflammation-based scores are widely tested in cancer and have been evaluated in cardiovascular diseases including heart failure.Objectives: We investigated the impact of established inflammation-based scores on disease severity and survival in patients with stable heart failure with reduced ejection fraction (HFrEF) paralleling results to an intra-institutional cohort of treatment naïve cancer patients.Methods: HFrEF and cancer patients were prospectively enrolled. The neutrophil-to-lymphocyte-ratio (NLR), the monocyte-to-lymphocyte-ratio (MLR), the platelet-to-lymphocyte-ratio (PLR), and the prognostic nutritional index (PNI) at index day were calculated. Association of scores with disease severity and impact on overall survival was determined. Interaction analysis was performed for the different populations.Results: Between 2011 and 2017, a total of 818 patients (443 HFrEF and 375 cancer patients) were enrolled. In HFrEF, there was a strong association between all scores and disease severity reflected by NT-proBNP and NYHA class (p ≤ 0.001 for all). In oncologic patients, association with tumor stage was significant for the PNI only (p = 0.035). In both disease entities, all scores were associated with all-cause mortality (p ≤ 0.014 for all scores). Kaplan–Meier analysis confirmed the discriminatory power of all scores in the HFrEF and the oncologic study population, respectively (log-rank p ≤ 0.026 for all scores). A significant interaction with disease (HFrEF vs. cancer) was observed for PNI (pinteraction = 0.013) or PLR (pinteraction = 0.005), respectively, with higher increase in risk per inflammatory score increment for HFrEF.Conclusion: In crude models, the inflammatory scores NLR, MLR, PLR, and PNI are associated with severity of disease in HFrEF and with survival in HFrEF similarly to cancer patients. For PNI and PLR, the association with increase in risk per increment was even stronger in HFrEF than in malignant disease.

Personality characteristics and the decision to hire

As the policy debate on entrepreneurship increasingly centers on firm growth in terms of job creation, it is important to understand whether the personality of entrepreneurs drives the first hiring in their firms. Using the German Socio-Economic Panel (SOEP), we analyze to what extent personality traits influence the probability of becoming an employer. The results indicate that personality matters. Risk tolerance unfolds the strongest influence on hiring, shortening the time until entrepreneurs hire their first employee; the effect size of a one-standard-deviation increase in risk tolerance is similar to that of having a university degree. Moreover, individuals who are more open to experience, more conscientious, and more trustful are more likely to hire upon establishing their business.