Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians.

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.

Judging One's Own or Another Person's Responsibility in Interactions With Automation.

OBJECTIVE: We explore users' and observers' subjective assessments of human and automation capabilities and human causal responsibility for outcomes. BACKGROUND: In intelligent systems and advanced automation, human responsibility for outcomes becomes equivocal, as do subjective perceptions of responsibility. In particular, actors who actively work with a system may perceive responsibility differently from observers. METHOD: In a laboratory experiment with pairs of participants, one participant (the "actor") performed a decision task, aided by an automated system, and the other (the "observer") passively observed the actor. We compared the perceptions of responsibility between the two roles when interacting with two systems with different capabilities. RESULTS: Actors' behavior matched the theoretical predictions, and actors and observers assessed the system and human capabilities and the comparative human responsibility similarly. However, actors tended to relate adverse outcomes more to system characteristics than to their own limitations, whereas the observers insufficiently considered system capabilities when evaluating the actors' comparative responsibility. CONCLUSION: When intelligent systems greatly exceed human capabilities, users may correctly feel they contribute little to system performance. They may interfere more than necessary, impairing the overall performance. Outside observers, such as managers, may overweigh users' contribution to outcomes, holding users responsible for adverse outcomes when they rightly trusted the system. APPLICATION: Presenting users of intelligent systems and others with performance measures and the comparative human responsibility may help them calibrate subjective assessments of performance, reducing users' and outside observers' biases and attribution errors.

Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry.

OBJECTIVE: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions. METHODS: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy. RESULTS: Among the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity (D LCO) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and D LCO was slow and did not differ significantly between patients with or without antifibrotic therapy. CONCLUSIONS: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and D LCO.

The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry.

BACKGROUND: Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry. METHODS: Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George's Respiratory Questionnaire (SGRQ) were used. RESULTS: Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DLCO% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DLCO % predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DLCO. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations. CONCLUSIONS: QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality.

The Triad of Risk-Related Behaviors (TriRB): A Three-Dimensional Model of Cyber Risk Taking.

OBJECTIVE: We identify three risk-related behaviors in coping with cyber threats-the exposure to risk a person chooses, use of security features, and responses to security indications. The combinations of behaviors that users choose determine how well they cope with threats and the severity of adverse events they experience. BACKGROUND: End users' coping with risks is a major factor in cybersecurity. This behavior results from a combination of risk-related behaviors rather than from a single risk-taking tendency. METHOD: In two experiments, participants played a Tetris-like game, attempting to maximize their gains, while exogenous occasional attacks could diminish earnings. An alerting system provided indications about possible attacks, and participants could take protective actions to limit the losses from attacks. RESULTS: Variables such as the costs of protective actions, reliability of the alerting system, and attack severity affected the three behaviors differently. Also, users dynamically adjusted each of the three risk-related behaviors after gaining experience with the system. CONCLUSION: The results demonstrate that users' risk taking is the complex combination of three behaviors rather than the expression of a general risk-taking tendency. The use of security features, exposure to risk, and responses to security indications reflect long-term strategy, short-term tactical decisions, and immediate maneuvering in coping with risks in dynamic environments. APPLICATION: The results have implications for the analysis of cybersecurity-related decisions and actions as well as for the evaluation and design of systems and targeted interventions in other domains.

Optimality is both elusive and necessary.

Optimality of any decision, including perceptual decisions, depends on the criteria used to evaluate outcomes and on the assumptions about available alternatives and information. In research settings, these are often difficult to define, and therefore, claims about optimality are equivocal. However, optimality is important in applied settings when evaluating, for example, the detection of abnormalities in medical images.

Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry.

BACKGROUND: The INSIGHTS-IPF registry provides one of the largest data sets of clinical data and self-reported patient related outcomes including health related quality of life (QoL) on patients with idiopathic pulmonary fibrosis (IPF). We aimed to describe associations of various QoL instruments between each other and with patient characteristics at baseline. METHODS: Six hundred twenty-three IPF patients with available QoL data (St George's Respiratory Questionnaire SGRQ, UCSD Shortness-of-Breath Questionnaire SoB, EuroQol visual analogue scale and index EQ-5D, Well-being Index WHO-5) were analysed. Mean age was 69.6 ± 8.7 years, 77% were males, mean disease duration 2.0 ± 3.3 years, FVC pred was 67.5 ± 17.8%, DLCO pred 35.6 ± 17%. RESULTS: Mean points were SGRQ total 48.3, UCSD SoB 47.8, EQ-5D VAS 66.8, and WHO-5 13.9. These instruments had a high or very high correlation (exception WHO-5 to EQ-5D VAS with moderate correlation). On bivariate analysis, QoL by SGRQ total was statistically significantly associated with clinical symptoms (NYHA; p < 0.001), number of comorbidities (p < 0.05), hospitalisation rate (p < 0.01) and disease severity (as measured by GAP score, CPI, FVC and 6-min walk test; p < 0.05 each). Multivariate analyses showed a significant association between QoL (by SGRQ total) and IPF duration, FVC, age, NYHA class and indication for long-term oxygen treatment. CONCLUSIONS: Overall, IPF patients under real-life conditions have lower QoL compared to those in clinical studies. There is a meaningful relationship between QoL and various patient characteristics. TRIAL REGISTRATION: The INSIGHTS-IPF registry is registered at Clinicaltrials.gov ( NCT01695408 ).

The Intricacies of User Adjustments of Alerting Thresholds.

OBJECTIVE: We address the question of necessary conditions for users to adjust system settings, such as alarm thresholds, correctly. BACKGROUND: When designing systems, we need to decide which system functions users should control. Giving control to users empowers them, but users must have the relevant information and the ability to adjust settings correctly for their control to be beneficial. METHOD: Using the example of adjusting an alerting threshold, we analyze the conditions for when users can and when they cannot possibly adjust threshold settings adequately. RESULTS: We identify two obstacles that limit users' ability to adjust thresholds adequately: (a) the difficulty of determining the correct threshold settings, especially because of users' strong response to false positive indications, and (b) the difficulty of collecting the information necessary for setting the threshold. CONCLUSION: Users often cannot identify the optimal settings for a system, so it is unlikely that they choose adequate system settings. APPLICATION: System designers must consider the difficulties users face and analyze them explicitly when deciding on user involvement in processes.

Physician adherence to the dyslipidemia guidelines is as challenging an issue as patient adherence.

BACKGROUND: A wide therapeutic gap exists between evidence-based guidelines and their practice in the primary care, which is primarily attributed to physician and patient adherence. OBJECTIVE: This study aims to differentiate physician and patient adherence to dyslipidemia secondary prevention guidelines and various factors affecting it. METHODS: A post hoc analysis of data collected by a prospective cluster randomized trial with 7041 patients diagnosed with clinical atherosclerosis requiring secondary prevention of dyslipidemia and 127 primary care physicians over an 18-month period. Adherence was measured by physicians' and patients' actions taken according to the guidelines and correlated using multivariate logistic regressions. RESULTS: Physician adherence was 36.9% for lipid profile screening, 27.6% for pharmacotherapy up-titration and 21.0% for pharmacotherapy initiation. Physician adherence was positively correlated with frequent patient visits [odds ratios (OR = 1.304)], having more dyslipidemic patients (OR = 1.304) and treating immigrants (OR = 1.268). Patient adherence was 83.8%, 71.9% and 62.6% for medication up-titration, lipid profile screening and pharmacotherapy initiation, respectively. Patient adherence was affected by attending clinics with many dyslipidemic patients (OR = 1.542), being older (OR = 1.271) and being treated by a male physician (OR = 0.870). CONCLUSIONS: We learn from this study that (i) physician non-adherence was a major cause for the failure to follow guidelines, (ii) pharmacotherapy initiation was the most challenging issue to tackle and (iii) greater adherence occurred mainly in high volume conditions (patients and visits). Practical implications are designated focus on metabolic condition prevention in primary care by cardiologists or primary care clinics specializing in metabolic conditions and the need to facilitate more frequent follow-up visits.

Adherence by primary care physicians to guidelines for the clinical management of dyslipidemia.

BACKGROUND: There is a wide treatment gap between evidence-based guidelines and their implementation in primary care. OBJECTIVE: To evaluate the extent to which physicians "literally" follow guidelines for secondary prevention of dyslipidemia and the extent to which they practice "substitute" therapeutic measures. METHODS: We performed a post hoc analysis of data collected in a prospective cluster randomized trial. The participants were 130 primary care physicians treating 7745 patients requiring secondary prevention of dyslipidemia. The outcome measure was physician literal adherence or substitute adherence. We used logistic regressions to evaluate the effect of various clinical situations on literal and substitute adherence. RESULTS: Literal adherence was modest for ordering a lipoprotein profile (35.1%) and for pharmacotherapy initiations (26.0%), but rather poor for drug up-titrations (16.1%) and for referrals for specialist consultation (3.8%). In contrast, many physicians opted for substitute adherence for up-titrations (75.9%) and referrals for consultation (78.7%). Physicians tended to follow the guidelines literally in simple clinical situations (such as the need for lipid screening) but to use substitute measures in more complex cases (when dose up-titration or metabolic consultation was required). Most substitute actions were less intense than the actions recommended by the guidelines. CONCLUSIONS: Physicians often do not blindly follow guidelines, but rather evaluate their adequacy for a particular patient and adjust the treatment according to their assessment. We suggest that clinical management be evaluated in a broader sense than strict guideline adherence, which may underestimate physicians' efforts.

Patient monitoring as a predictor of blood culture results in a tertiary neonatal intensive care unit.

We present a mesoergonomic approach to the early detection of neonatal sepsis, analyzing clinical data for 4999 patients from a neo-natal intensive care unit to predict positive culture results. The Apgar score at birth predicted positive results. For neonates with poor and intermediate Apgar scores, culture results for monitored infants were more likely to be positive than those for unmonitored infants. Thus, the medical staff tended to monitor infants who eventually had a greater chance for positive test results. A cost-effectiveness analysis indicated that for infants with high Apgar scores, the physician should decide whether to obtain a blood culture, based on the patient's characteristics. For infants with lower Apgar scores, it may be advisable to obtain a blood culture whenever one decides to monitor a neonate. The study demonstrates that staff decisions regarding a patient can serve as input for further clinical decision-making.

Impact of prolonged duration of different types of renal replacement therapies on serum levels of endothelin-1 and pulmonary function tests.

INTRODUCTION: This study was carried out to investigate the impact of duration of different renal replacement therapies such as hemodialysis and continuous ambulatory peritoneal dialysis on potential overproduction of endothelin-1 (ET-1) and pulmonary function tests in these patients. MATERIALS AND METHODS: The study included 26 patients (14 males, mean age 54.9±16.2 years) with end stage renal diseases (ESRD) receiving regular hemodialysis (HD) and 23 patients (10 males, mean age 55.8±15.8 years) with ESRD treated with continuous ambulatory peritoneal dialysis (CAPD). The spirometry values were recorded before the onset of HD and prior to emptying the peritoneal cavity in CAPD patients and ET-1 was measured using the enzyme immunoassay (EIA) methodology. Two groups of patients (groups 1 and 2) were further divided into subgroups (group A and group B). Groups A (1-A and 2-A) included patients treated with any type of renal replacement therapy (RRT) (HD or CAPD) less than 5 years, and groups B (1-B and 2-B) included patients treated with any type of RRT (HD or CAPD) longer than 5 years. RESULTS: Patients treated with HD or CAPD for more than five years were found to have significantly higher serum levels of ET-1 (HD = 41.49±21.28 vs. 185.13±73.67, p<0.01; PD = 51.24±32.11 vs. 139.53±42.42, p<0.01, respectively). Values of most pulmonary function parameters differed significantly between groups treated longer or shorter than 5 years: FVC (HD = 108.4±13.34 vs. 80.82±11.26, p<0.01; CAPD = 97.20±18.99 vs. 73.25±10.73, p<0.01, respectively), FEV1 (HD = 108.33±15.8 vs. 76.73±4.9, p<0.01; CAPD = 100.67±18.31 vs. 66.75±6.25, p<0.01, respectively). CONCLUSIONS: Prolonged duration of any type of renal replacement therapy is associated with higher serum levels of ET-1 and with lower pulmonary function tests in ESRD patients.

An end-to-end automated platform process for high-throughput engineering of next-generation multi-specific antibody therapeutics.

Next-generation multi-specific antibody therapeutics (MSATs) are engineered to combine several functional activities into one molecule to provide higher efficacy compared to conventional, mono-specific antibody therapeutics. However, highly engineered MSATs frequently display poor yields and less favorable drug-like properties (DLPs), which can adversely affect their development. Systematic screening of a large panel of MSAT variants in very high throughput (HT) is thus critical to identify potent molecule candidates with good yield and DLPs early in the discovery process. Here we report on the establishment of a novel, format-agnostic platform process for the fast generation and multiparametric screening of tens of thousands of MSAT variants. To this end, we have introduced full automation across the entire value chain for MSAT engineering. Specifically, we have automated the in-silico design of very large MSAT panels such that it reflects precisely the wet-lab processes for MSAT DNA library generation. This includes mass saturation mutagenesis or bulk modular cloning technologies while, concomitantly, enabling library deconvolution approaches using HT Sanger DNA sequencing. These DNA workflows are tightly linked to fully automated downstream processes for compartmentalized mammalian cell transfection expression, and screening of multiple parameters. All sub-processes are seamlessly integrated with tailored workflow supporting bioinformatics. As described here, we used this platform to perform multifactor optimization of a next-generation bispecific, cross-over dual variable domain-Ig (CODV-Ig). Screening of more than 25,000 individual protein variants in mono- and bispecific format led to the identification of CODV-Ig variants with over 1,000-fold increased potency and significantly optimized production titers, demonstrating the power and versatility of the platform.

Recommendations for Face Coverings While Exercising During the COVID-19 Pandemic.

In an effort to reduce transmission and number of infections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) virus, governments and official bodies around the world have produced guidelines on the use of face masks and face coverings. While there is a growing body of recommendations for healthcare professionals and the wider population to use facial protection in "enclosed spaces" where minimal distancing from other individuals is not possible, there is a dearth of clear guidelines for individuals undertaking exercise and sporting activity. The present viewpoint aims to propose recommendations for face coverings while exercising during the COVID-19 pandemic that consider physical distancing, the environment, the density of active cases associated with the specific sports activity, and the practical use of face coverings in order to reduce potential viral transmission. Recommendations are provided on the basis of very limited available evidence in conjunction with the extensive collective clinical experience of the authors and acknowledging the need to consider the likelihood of the presence of the SARS-CoV-2 in the general population. We recommend that face coverings should be used in any environment considered to be of a high or moderate transmission risk, where tolerated and after individual risk assessment. In addition, as national caseloads fluctuate, individual sporting bodies should consider up to date guidance on the use of face coverings during sport and exercise, alongside other preventative measures.

Factors affecting physicians compliance with enrollment suggestions into a clinical reminders intervention.

Clinical reminders can promote adherence with evidence-based clinical guidelines, but they may also have unintended consequences such as alert fatigue, false alarms and increased workload, which cause clinicians to ignore them. The described clinical reminder system identifies patients eligible for primary prevention of cardiovascular diseases and lets the physician to choose which patients will be included in the reminders intervention. We analyzed data of 87,165 visits of 35,699 patients and evaluated factors which may affect clinicians' decision to enroll patients to the intervention. The physicians included most of the patients suggested for inclusion (85.7%). Yet, they skipped the enrollment suggestion in 62.6% of the visits. Patients with a cardiovascular disease, dyslipidemia, diabetes, or hypertension were more likely to be included in the intervention, while older patients were less likely to be included. Insights regarding the usability of clinical reminders are discussed.

Recommendations for return to sport during the SARS-CoV-2 pandemic.

In this viewpoint we make specific recommendations that can assist and make the return to sport/exercise as safe as possible for all those impacted - from the recreational athlete to the elite athlete. We acknowledge that there are varying rules and regulations around the world, not to mention the varying philosophies and numerous schools of thought as it relates to return to sport/exercise and we have been cognisant of this in our recommendations. Despite the varying rules and circumstances around the world, we believe it is essential to provide some helpful and consistent guidance for return to training and sport for sport and exercise physicians around the world at this most difficult time. The present viewpoint provides practical and medical recommendations on the resumption to sport process.

Defining and measuring physicians' responses to clinical reminders.

Decision-support systems, and specifically rule-based clinical reminders, are becoming common in medical practice. Despite their potential to improve clinical outcomes, physicians do not always use information from these systems. Concepts from the cognitive engineering literature on users' responses to warning systems may help to define physicians' responses to reminders. Based on this literature, we suggest an exhaustive set of possible responses to clinical reminders, consisting of four responses named "Compliance", "Reliance", "Spillover" and "Reactance". We suggest statistical measures to estimate these responses and empirically demonstrate them on data from a large-scale clinical reminder system for secondary prevention of cardiovascular diseases. There was evidence for Compliance, probably since the physicians found the reminders informative, but not for Reliance, in line with the notion that Compliance and Reliance are two distinct types of trust in information from decision-support systems. Our research supports the notion that CDSS can promote closing the treatment gap and improve physicians' adherence to guidelines.

Effects of Trust, Self-Confidence, and Feedback on the Use of Decision Automation.

Operators often fail to rely sufficiently on alarm systems. This results in a joint human-machine (JHM) sensitivity below the one of the alarm system. The 'confidence vs. trust hypothesis' assumes the use of the system depends on the weighting of both values. In case of higher confidence, the task is performed manually, if trust is higher, the user relies on the system. Thus, insufficient reliance may be due to operators' overconfidence in their own abilities and/or insufficient trust in the decision automation, but could be mitigated by providing feedback. That was investigated within a signal detection task, supported by a system with either higher sensitivity (HSS) or lower sensitivity (LSS) than the human, while being provided with feedback or not. We expected disuse of the LSS and insufficiently reliance on the HSS, in the condition without feedback. The feedback was expected to increase reliance on the HSS through an increase in trust and/or decreases in confidence, and thus, improve performance. Hypotheses were partly supported. Confidence in manual performance was similar to trust in the HSS even though humans' sensitivity was significantly lower than systems' sensitivity. While confidence had not effect on reliance or JHM sensitivity, trust was found to be positively related with both. We found disuse of the HSS, that could be improved through feedback, increasing also trust and JHM sensitivity. However, contrary to 'confidence vs. trust' expectations, participants were also found to make use of the LSS. This misuse could not be reduced by feedback. Results indicate the use of feedback being beneficial for the overall performance (with HSS only). Findings do not support the idea that misuse or disuse of the system may result from comparison of confidence and trust. We suppose it may rather be the product of users' wrong strategy of function allocation, based on the underlying idea of team work in combination with missing assignment of responsibility. We discuss this alternative explanation.

Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018.

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to the definition, clinical classification and initial diagnosis of PH. While the European guidelines provide a detailed clinical classification and a structured approach for diagnostic testing, their application in routine care may be challenging, particularly given the changing phenotype of PH patients who are nowadays often elderly and may present with multiple potential causes of PH, as well as comorbid conditions. Specifically, the working group addresses the thoroughness of diagnostic testing, and the roles of echocardiography, exercise testing, and genetic testing in diagnosing PH. Furthermore, challenges in the diagnostic work-up of patients with various causes of PH including "PAH with comorbidities", CTEPH and coexisting conditions are highlighted, and a modified diagnostic algorithm is provided. The detailed results and recommendations of the working group on definition, clinical classification and initial diagnosis of PH, which were last updated in the spring of 2018, are summarized in this article.