Publications by authors named "Julia Braun"

90 Publications

Effect of a factor-based coagulation management on blood product use after major burn injury: A retrospective cohort study.

Burns 2021 Aug 21. Epub 2021 Aug 21.

Department of Plastic Surgery and Hand Surgery, Burn Center, University and University Hospital Zurich, Switzerland; Department of Plastic Surgery and Hand Surgery, Cantonal Hospital Aarau, Aarau, Switzerland. Electronic address:

Background: Transfusion of allogenic blood products was shown to be associated with more adverse events and a higher mortality in severely burned patients. This study investigated the impact of a goal-directed and factor-based coagulation algorithm on blood product use and clinical outcomes in severely burned patients.

Methods: This retrospective cohort study included adult patients admitted to the burn center of the University Hospital Zurich with major burn injuries compromising 20-80% of total body surface area. We compared two 3-year periods, one before the introduction of a goal-directed coagulation and transfusion algorithm (period 1: 2009-2011) and one after (period 2: 2016-2018). We applied linear and logistic regression models adjusted for confounders.

Results: We analyzed 36 patients (27.8% female) versus 42 patients (14.3% female) in period 1 and 2, respectively. Comorbidities and burn types were comparable between both collectives. Treatment according to the coagulation algorithm resulted in an overall reduction of 33 units of red blood cells (95% CI -52.8 to -12.9, p = 0.002), 9 units fresh frozen plasma (95% CI -14.7 to -2.6, p = 0.006) and 1.4g fibrinogen (95% CI -2.2 to -0.5, p = 0.001) per patient. We observed less infections (61.8% vs. 41.5%, p = 0.11) and a reduced mortality (38.9% vs. 26.8%, p = 0.33) during the algorithm treated period, although not significant.

Conclusion: Treatment of severely burned patients with a goal-directed coagulation algorithm reduced blood product use and resulted in target-oriented administration of coagulation factors to improve outcomes.
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http://dx.doi.org/10.1016/j.burns.2021.08.015DOI Listing
August 2021

Voice alerting as a medical alarm modality for next-generation patient monitoring: a randomised international multicentre trial.

Br J Anaesth 2021 Nov 26;127(5):769-777. Epub 2021 Aug 26.

Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Background: Acoustic alarms in medical devices are vital for patient safety. State-of-the-art patient monitoring alarms are indistinguishable and contribute to alarm fatigue. There are two promising new sound modalities for vital sign alarms. Auditory icons convey alarms as brief metaphorical sounds, and voice alerts transmit information using a clear-spoken language. We compared how reliably healthcare professionals identified alarms using these two modalities.

Methods: This investigator-initiated computer-based multicentre simulation study included 28 anaesthesia providers who were asked to identify vital sign alarms in randomised order, once with voice alerts and once with auditory icons. We further assessed time to decision, diagnostic confidence, and perceived helpfulness. We analysed the results using mixed models, adjusted for possible confounders.

Results: We assessed 14 alarms for each modality, resulting in 392 comparisons across all participants. Compared with auditory icons, healthcare providers had 58 times higher odds of correctly identifying alarms using voice alerts (odds ratio 58.0; 95% confidence interval [CI]: 25.1-133.6; P<0.001), made their decisions about 14 s faster (coefficient -13.9; 95% CI: -15.8 to -12.1 s; P<0.001), perceived higher diagnostic confidence (100% [392 of 392] vs 43% [169 of 392; P<0.001]), and rated voice alerts as more helpful (odds ratio 138.2; 95% CI: 64.9-294.1; P<0.001). The participants were able to identify significantly higher proportions of alarms with voice alerts (98.5%; P<0.001) and auditory icons (54.1%; P<0.001) compared with state-of-the-art alarms (17.9%).

Conclusions: Voice alerts were superior to auditory icons, and both were superior to current state-of-the-art auditory alarms. These findings demonstrate the potential that voice alerts hold for patient monitoring.
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http://dx.doi.org/10.1016/j.bja.2021.07.015DOI Listing
November 2021

Personalising add-on treatment with inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a benefit-harm modelling study.

Lancet Digit Health 2021 10 24;3(10):e644-e653. Epub 2021 Aug 24.

Department of Epidemiology, Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland. Electronic address:

Background: Since the benefit-harm balance of adding inhaled corticosteroids to long-acting β-agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles.

Methods: Analyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderate-to-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care.

Findings: Adding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54-83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40-91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per μL, patients with a BEC of 150 cells per μL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32-95% in those aged 40-79 years and 41-93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per μL or more at 52-86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%.

Interpretation: The net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids.

Funding: None.
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http://dx.doi.org/10.1016/S2589-7500(21)00130-8DOI Listing
October 2021

Nationwide implementation of the self-management program "Living well with COPD": Process and effectiveness evaluation using a mixed-methods approach.

Patient Educ Couns 2021 Jun 18. Epub 2021 Jun 18.

Epidemiology, Biostatistics und Prevention Institute, University of Zurich, Zurich, Switzerland. Electronic address:

Objective: To evaluate the nationwide implementation of the "Living well with COPD" program by the Swiss Lung Association in various cantons in Switzerland.

Methods: For the process evaluation, we used qualitative (interview, focus group) and quantitative (questionnaires, documentation analysis) methods to assess the implementation outcomes reach, dose, fidelity and acceptability. For the effectiveness, we performed a pre-post analysis of patient data collected at baseline and program end (after 14 months).

Results: Seven Cantonal Lung Associations implemented the program into their services according to plan, conducted it 13 times and included 122 COPD patients. Patients' attendance rate was 81% and coaches' fidelity to protocol 94%. Acceptance and satisfaction of all involved persons was high. Integration of the coaches' additional workload, uncertainties regarding roles and responsibilities and sustainable reimbursement were major challenges. Patients significantly improved in COPD specific quality of life and increased exercise capacity with on average 3.2 more repetitions in the 1-minute sit-to-stand test.

Conclusion: The program was successfully implemented throughout Switzerland with high acceptability and positive association with patients' quality of life.

Practice Implications: Our findings support the broader multiplication throughout Switzerland and serves the international community since it is one of the first nationwide implementations beyond study settings.
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http://dx.doi.org/10.1016/j.pec.2021.06.018DOI Listing
June 2021

Interleukin-6 Is an Early Plasma Marker of Severe Postoperative Complications in Thoracic Surgery: Exploratory Results From a Substudy of a Randomized Controlled Multicenter Trial.

Anesth Analg 2021 Jun 16. Epub 2021 Jun 16.

Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.

Background: Postoperative complications in surgery are a significant burden, not only for the patients but also economically. While several predicting factors have already been identified, it is still not well known if increased levels of inflammatory markers in the immediate perioperative phase correlate with a higher incidence of postoperative complications. This study aimed to evaluate which patient characteristics and intraoperative parameters correlate with increased plasma values of monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) of thoracic surgery patients. A second goal was to explore whether MCP-1 and IL-6 are associated with the incidence of postoperative complications. We hypothesized that there is a positive association between inflammatory markers and the occurrence of complications within 6 months after surgery.

Methods: This is a substudy of a recent randomized controlled trial, which defined the effect of desflurane versus propofol anesthesia on morbidity and mortality in patients undergoing thoracic surgery. MCP-1 and IL-6 were determined in plasma obtained before and 30 minutes after 1-lung ventilation, 6 hours after surgery, and on postoperative days 1 and 2. Complications were recorded for 6 months. Mixed linear models were used to examine factors associated with MCP-1 and IL-6 levels. Logistic regression models and receiver operating characteristic curves were used to determine the association between MCP-1 and IL-6 and postoperative complications.

Results: In the original study, 460 patients were included, MCP-1 and IL-6 levels were determined in 428 patients. MCP-1 was positively associated with the duration of surgery (P = .016), whereas IL-6 levels increased with both the length (P < .001) and invasiveness of lung surgery (thoracoscopic wedge resection or lobectomy versus open lobectomy, P = .005; thoracoscopic wedge resection or lobectomy versus pneumonectomy, P = .021). In an exploratory approach, elevated IL-6 plasma peaks were associated with the occurrence of severe complications defined as Clavien-Dindo score grade ≥IVa during the postoperative phase up to 6 months after thoracic surgery (P = .006).

Conclusions: In summary, this substudy reveals factors, which correlate with high MCP-1 and IL-6 values. Moreover, higher IL-6 seems to be associated with postoperative severe complications. Perioperative IL-6 monitoring might be helpful for risk estimation in the perioperative setting of patients after lung surgery.
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http://dx.doi.org/10.1213/ANE.0000000000005639DOI Listing
June 2021

Criterion validity of the ActiGraph and activPAL in classifying posture and motion in office-based workers: A cross-sectional laboratory study.

PLoS One 2021 2;16(6):e0252659. Epub 2021 Jun 2.

Division of Occupational and Environmental Medicine, Epidemiology, Biostatistics and Prevention Institute, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Background: The ActiGraph and activPAL monitors are the most frequently used thigh-worn devices to measure motion and posture, but the criterion validity to measure sitting, standing and postural transfer in the office setting is not known. Research question: To examine the criterion validity of the ActiGraph and activPAL activity monitors in repeatedly measuring a variety of different postures and motion in the office setting.

Methods: Twenty office workers from the University of Zurich wore an ActiGraph and activPAL during two identical laboratory experiments lasting approximately 60 minutes each, within a maximum of 7 days. The experimental setting consisted of a standard computer office workstation with an electrically powered height-adjustable desk, a swivel chair without arm rests, a standard chair, a footrest, and a bookcase. The protocol consisted of 24 pre-defined tasks mimicking sitting, standing, stepping, and postural transitions around the workplace. All tasks were supervised and observed by the same experimenter.

Results: In repeated measurements (40 individual experiments), the percentages of correctly classified tasks for the ActiGraph and activPAL were, respectively, 100% vs. 85% for sitting, 87% vs. 100% for standing, and 100% vs. 73% for postural transitions. Both monitors correctly identified all stepping tasks. The activPAL misclassified sitting with legs outstretched, and sitting with both feet placed beneath the chair, as standing ~25-70% and 45% of the time, respectively. The ActiGraph misclassified standing with the right foot on a footrest as sitting in 65% of events.

Conclusions: The ActiGraph appears to be slightly more sensitive than the activPAL with respect to the measurement of sitting and postural transitions of short duration, whereas the activPAL seems to be slightly more accurate in capturing standing postures. This knowledge will help guide researchers to choose the best suitable monitor for their research setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252659PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171934PMC
June 2021

Are we prepared for the future? A mixed-method study on quality management in decentralized family medicine teaching.

Med Educ Online 2021 Dec;26(1):1923114

Institute for General Practice and Interprofessional Health Care, Tübingen University Hospital, Tübingen, Germany.

In Germany, two-week clinical clerkships in university-associated general practices have existed since 2002. Approximately 10,000 medical students participate in these decentral clerkships each year. Empirical information on quality management strategies in decentral learning environments is sparse. This nationwide study aims to describe the current quality management efforts of German family medicine departments in response to negative events. A nationwide three-part mixed methods study on the quality management of family medicine clerkships was conducted. First, individuals from n = 37 family medicine departments involved in the organization of family medicine clerkships were interviewed. Interview transcripts were analyzed with qualitative content analysis. Second, a questionnaire on quality management of decentralized learning environments based on the categories of the analysis was developed and sent to the departments. Three negative event cases in family medicine clerkships were included in the questionnaire. Third, interview and survey data were integrated based on respondents' process descriptions of how each department handled the cases. Of the 37 contacted departments, n = 12 (32%) performed an interview. Major categories of negative events included problems in the student-teacher interaction, didactical challenges, and problematic student behavior. Twenty departments answered at least one questionnaire (54%). Most respondents indicated that their department conducts quality management in decentralized teaching. Negative events in decentral family medicine clerkships occurred at a rate of 66.4 to 179.5 events per 10.000 Students per semester. The mixed-method analysis showed that departments are conscious about quality management issues in decentral learning environments but adhere to heterogeneous local standards. Negative events occur regularly in decentral learning environments. Local quality management processes exist but lack national harmonization. Further outcome-based research is needed to explore the effectiveness and feasibility of quality management strategies. This will become increasingly relevant with an expected upscaled family medicine content.
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http://dx.doi.org/10.1080/10872981.2021.1923114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118471PMC
December 2021

Does diet map with mortality? Ecological association of dietary patterns with chronic disease mortality and its spatial dependence in Switzerland.

Br J Nutr 2021 May 11:1-13. Epub 2021 May 11.

Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

We investigated the associations between dietary patterns and chronic disease mortality in Switzerland using an ecological design and explored their spatial dependence, i.e. the tendency of near locations to present more similar and distant locations to present more different values than randomly expected. Data of the National Nutrition Survey menuCH (n 2057) were used to compute hypothesis- (Alternate Healthy Eating Index (AHEI)) and data-driven dietary patterns. District-level standardised mortality ratios (SMR) were calculated using the Swiss Federal Statistical Office mortality data and linked to dietary data geographically. Quasipoisson regression models were fitted to investigate the associations between dietary patterns and chronic disease mortality; Moran's I statistics were used to explore spatial dependence. Compared with the first, the fifth AHEI quintile (highest diet quality) was associated with district-level SMR of 0·95 (95 % CI 0·93, 0·97) for CVD, 0·91 (95 % CI 0·88, 0·95) for ischaemic heart disease (IHD), 0·97 (95 % CI 0·95, 0·99) for stroke, 0·99 (95 % CI 0·98, 1·00) for all-cancer, 0·98 (95 % CI 0·96, 0·99) for colorectal cancer and 0·93 (95 % CI 0·89, 0·96) for diabetes. The Swiss traditional and Western-like patterns were associated with significantly higher district-level SMR for CVD, IHD, stroke and diabetes (ranging from 1·02 to 1·08) compared with the Prudent pattern. Significant global and local spatial dependence was identified, with similar results across hypothesis- and data-driven dietary patterns. Our study suggests that dietary patterns partly contribute to the explanation of geographic disparities in chronic disease mortality in Switzerland. Further analyses including spatial components in regression models would allow identifying regions where nutritional interventions are particularly needed.
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http://dx.doi.org/10.1017/S0007114521001525DOI Listing
May 2021

Avatar-based patient monitoring in critical anaesthesia events: a randomised high-fidelity simulation study.

Br J Anaesth 2021 May 8;126(5):1046-1054. Epub 2021 Apr 8.

Institute of Anaesthesiology, University and University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Failures in situation awareness cause two-thirds of anaesthesia complications. Avatar-based patient monitoring may promote situation awareness in critical situations.

Methods: We conducted a prospective, randomised, high-fidelity simulation study powered for non-inferiority. We used video analysis to grade anaesthesia teams managing three 10 min emergency scenarios using three randomly assigned monitoring modalities: only conventional, only avatar, and split-screen showing both modalities side by side. The primary outcome was time to performance of critical tasks. Secondary outcomes were time to verbalisation of vital sign deviations and the correct cause of the emergency, perceived workload, and usability. We used mixed Cox and linear regression models adjusted for various potential confounders. The non-inferiority margin was 10%, or hazard ratio (HR) 0.9.

Results: We analysed 52 teams performing 154 simulations. For performance of critical tasks during a scenario, split-screen was non-inferior to conventional (HR=1.13; 95% confidence interval [CI], 0.96-1.33; not significant in test for superiority); the result for avatar was inconclusive (HR=0.98; 95% CI, 0.83-1.15). Avatar was associated with a higher probability for verbalisation of the cause of the emergency (HR=1.78; 95% CI, 1.13-2.81; P=0.012). We found no evidence for a monitor effect on perceived workload. Perceived usability was lower for avatar (coefficient=-23.0; 95% CI, -27.2 to -18.8; P<0.0001) and split-screen (-6.7; 95% CI, -10.9 to -2.4; P=0.002) compared with conventional.

Conclusions: This study showed non-inferiority of split-screen compared with conventional monitoring for performance of critical tasks during anaesthesia crisis situations. The patient avatar improved verbalisation of the correct cause of the emergency. These results should be interpreted considering participants' minimal avatar but extensive conventional monitoring experience.
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http://dx.doi.org/10.1016/j.bja.2021.01.015DOI Listing
May 2021

Effects of an Animated Blood Clot Technology (Visual Clot) on the Decision-Making of Users Inexperienced in Viscoelastic Testing: Multicenter Trial.

J Med Internet Res 2021 05 3;23(5):e27124. Epub 2021 May 3.

Institute of Anesthesiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: Viscoelastic test-guided coagulation management has become increasingly important in assessing hemostasis. We developed Visual Clot, an animated, 3D blood clot that illustrates raw rotational thromboelastometry (ROTEM) parameters in a user-centered and situation awareness-oriented method.

Objective: This study aimed to evaluate the applicability of Visual Clot by examining its effects on users that are novices in viscoelastic-guided resuscitation.

Methods: We conducted an investigator-initiated, international, multicenter study between September 16, 2020, and October 6, 2020, in 5 tertiary care hospitals in central Europe. We randomly recruited medical students and inexperienced resident physicians without significant prior exposure to viscoelastic testing. The 7 participants per center managed 9 different ROTEM outputs twice, once as standard ROTEM tracings and once as the corresponding Visual Clot. We randomly presented the 18 viscoelastic cases and asked the participants for their therapeutic decisions. We assessed the performance, diagnostic confidence, and perceived workload in managing the tasks using mixed statistical models and adjusted for possible confounding factors.

Results: Analyzing a total of 630 results, we found that the participants solved more cases correctly (odds ratio [OR] 33.66, 95% CI 21.13-53.64; P<.001), exhibited more diagnostic confidence (OR 206.2, 95% CI 93.5-454.75; P<.001), and perceived less workload (coefficient -41.63; 95% CI -43.91 to -39.36; P<.001) using Visual Clot compared to using standard ROTEM tracings.

Conclusions: This study emphasizes the practical benefit of presenting viscoelastic test results in a user-centered way. Visual Clot may allow inexperienced users to be involved in the decision-making process to treat bleeding-associated coagulopathy. The increased diagnostic confidence, diagnostic certainty, reduced workload, and positive user feedback associated with this visualization may promote the further adoption of viscoelastic methods in diverse health care settings.
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http://dx.doi.org/10.2196/27124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129883PMC
May 2021

Physicians' perceptions regarding acute bleeding management: an international mixed qualitative quantitative study.

BMC Anesthesiol 2021 02 10;21(1):43. Epub 2021 Feb 10.

Institute of Anesthesiology, University of Zurich and University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Background: Acute bleeding is an omnipresent challenge for all physicians. Uncontrolled hemorrhage is the most common preventable cause of death after trauma worldwide. In different surgical disciplines, hemorrhage represents an independent risk factor for increased postoperative morbimortality, directly affecting patients' outcomes. This study asked anesthesiologists about their personal perceived challenges when treating bleeding patients.

Methods: This investigator-initiated, prospective, international, dual-center, mixed qualitative and quantitative study interrogated anesthesiologists about what they found easy and what difficult in treating acutely bleeding patients. Following the template approach for qualitative research, we identified major and minor topics through free inductive coding and word count. In a second step, we derived ten statements from the participants' answers. Using a field survey, we then asked the participants to rate their level of agreement with the derived statements. We analyzed the answers using one sample Wilcoxon test and the Mann-Whitney test.

Results: We included a total of 84 physicians in the qualitative interrogations and a different group of 42 anesthesiologists in the quantitative part. We identified 11 major topics and 19 associated subtopics. The main topics and the degree of agreement (here as agree or strongly agree) were as follows: "Complexity of the topic" (52.4% agreed to find the topic complex), "Cognitive aids" (92.9% agreed to find them helpful), "Time management" (64.3% agreed to feeling time pressure), "Human factors" (95.2% agreed that human factors are essential), "Resources" (95.2% agreed that resources are essential), "Experience" and "Low frequency of cases" (57.1% agreed to lack practice), "Diagnostic methods" (31.0% agreed that the interpretation of test results is difficult), "Anticoagulation" (85.7% agreed to it being difficult), "Treatment" (81.0% agreed to knowing the first therapeutic steps), and "Nothing".

Conclusions: Anesthesiologists in two large tertiary care facilities in different parts of the world found coagulation management, especially in anticoagulated patients, complex. We identified the delayed diagnostic test results and their interpretation as challenges. Resources, treatment protocols and human factors such as team communication were perceived to facilitate management. Future studies should explore the challenges in smaller hospitals and other parts of the world and test new technologies addressing the identified difficulties.
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http://dx.doi.org/10.1186/s12871-021-01269-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874660PMC
February 2021

Coronavirus-induced coagulopathy during the course of disease.

PLoS One 2020 17;15(12):e0243409. Epub 2020 Dec 17.

Institute of Anesthesiology, University and University Hospital Zurich, Zurich, Switzerland.

Background: A significant proportion of patients with coronavirus disease 19 (COVID-19) suffer from excessive coagulation activation and coagulopathy which is associated with an increased risk of venous and arterial thromboembolism and adverse outcome. Our study investigates coagulation markers and the incidence of thromboembolic events in COVID-19 patients receiving recommended anticoagulation strategies.

Methods: In a retrospective single-center analysis at the University Hospital Zurich, Switzerland, we investigated 31 adult COVID-19 patients between April 6th and May 13th, 2020 and with at least one laboratory assessment of the coagulation markers prothrombin time/Quick, thrombin time, fibrinogen and D-dimers. For antithrombotic prophylaxis low-molecular-weight-heparin or unfractionated heparin was administered and two patients with heparin-induced thrombocytopenia received argatroban.

Results: We analyzed 31 patients (68% male, mean age 60± SD 15 years). 22 (71%) of these required intensive care unit treatment, 5 (16%) were hospitalized in a ward, and 4 (13%) were outpatients. Mean fibrinogen levels were markedly elevated to 6.4± SD 1.8g/l, with a peak in the third week of the disease and no significant decrease over time. D-dimers were elevated to a mean value of 5.1±4.4mg/l with peak levels of 6.8±5.3mg/l in the fourth week of disease, and a subsequent decrease. Platelet count (308±136G/l) and PT/Quick (85±22%) showed no significant changes over time. Sensitivity analyses for patients treated in the ICU showed that D-dimer levels were higher in this group. The results of other sensitivity analyses were comparable. Thromboembolic events were diagnosed in 4 (13%) patients and 5 (16%) patients died during the observation period.

Conclusion: We find coagulation alterations in COVID-19 patients indicating significant hypercoagulability. These alterations are visible despite antithrombotic treatment, and peak around week 3-4 of the disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243409PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745968PMC
December 2020

Degree of regional variation and effects of health insurance-related factors on the utilization of 24 diverse healthcare services - a cross-sectional study.

BMC Health Serv Res 2020 Nov 27;20(1):1091. Epub 2020 Nov 27.

Department of Epidemiology, Epidemiology, Biostatistics & Prevention Institute, University of Zurich, Hirschengraben 84, 8001, Zurich, Switzerland.

Background: Regional variation in healthcare utilization could reflect unequal access to care, which may lead to detrimental consequences to quality of care and costs. The aims of this study were to a) describe the degree of regional variation in utilization of 24 diverse healthcare services in eligible populations in Switzerland, and b) identify potential drivers, especially health insurance-related factors, and explore the consistency of their effects across the services.

Methods: We conducted a cross-sectional study using health insurance claims data for the year of 2014. The studied 24 healthcare services were predominantly outpatient services, ranging from screening to secondary prevention. For each service, a target population was identified based on applicable clinical recommendations, and outcome variable was the use of the service. Possible influencing factors included patients' socio-demographics, health insurance-related and clinical characteristics. For each service, we performed a comprehensive methodological approach including small area variation analysis, spatial autocorrelation analysis, and multilevel multivariable modelling using 106 mobilité spaciale regions as the higher level. We further calculated the median odds ratio in model residuals to assess the unexplained regional variation.

Results: Unadjusted utilization rates varied considerably across the 24 healthcare services, ranging from 3.5% (osteoporosis screening) to 76.1% (recommended thyroid disease screening sequence). The effects of health insurance-related characteristics were mostly consistent. A higher annual deductible level was mostly associated with lower utilization. Supplementary insurance, supplementary hospital insurance and having chosen a managed care model were associated with higher utilization of most services. Managed care models showed a tendency towards more recommended care. After adjusting for multiple influencing factors, the unexplained regional variation was generally small across the 24 services, with all MORs below 1.5.

Conclusions: The observed utilization rates seemed suboptimal for many of the selected services. For all of them, the unexplained regional variation was relatively small. Our findings confirmed the importance and consistency of effects of health insurance-related factors, indicating that healthcare utilization might be further optimized through adjustment of insurance scheme designs. Our comprehensive approach aids in the identification of regional variation and influencing factors of healthcare services use in Switzerland as well as comparable settings worldwide.
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http://dx.doi.org/10.1186/s12913-020-05930-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694910PMC
November 2020

Self-Monitoring App Preferences for Sun Protection: Discrete Choice Experiment Survey Analysis.

J Med Internet Res 2020 11 27;22(11):e18889. Epub 2020 Nov 27.

Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland.

Background: The availability and use of health apps continues to increase, revolutionizing the way mobile health interventions are delivered. Apps are increasingly used to prevent disease, improve well-being, and promote healthy behavior. On a similar rise is the incidence of skin cancers. Much of the underlying risk can be prevented through behavior change and adequate sun protection. Self-monitoring apps have the potential to facilitate prevention by measuring risk (eg, sun intensity) and encouraging protective behavior (eg, seeking shade).

Objective: Our aim was to assess health care consumer preferences for sun protection with a self-monitoring app that tracks the duration and intensity of sun exposure and provides feedback on when and how to protect the skin.

Methods: We conducted an unlabeled discrete choice experiment with 8 unique choice tasks, in which participants chose among 2 app alternatives, consisting of 5 preidentified 2-level attributes (self-monitoring method, privacy control, data sharing with health care provides, reminder customizability, and costs) that were the result of a multistep and multistakeholder qualitative approach. Participant preferences, and thus, the relative importance of attributes and their levels were estimated using conditional logit modeling. Analyses consisted of 200 usable surveys, yielding 3196 observations.

Results: Our respondents strongly preferred automatic over manually operated self-monitoring (odds ratio [OR] 2.37, 95% CI 2.06-2.72) and no cost over a single payment of 3 Swiss francs (OR 1.72, 95% CI 1.49-1.99). They also preferred having over not having the option of sharing their data with a health care provider of their choice (OR 1.66, 95% CI 1.40-1.97), repeated over single user consents, whenever app data are shared with commercial thirds (OR 1.57, 95% CI 1.31-1.88), and customizable over noncustomizable reminders (OR 1.30, 95% CI 1.09-1.54). While most participants favored thorough privacy infrastructures, the attribute of privacy control was a relatively weak driver of app choice. The attribute of self-monitoring method significantly interacted with gender and perceived personal usefulness of health apps, suggesting that female gender and lower perceived usefulness are associated with relatively weaker preferences for automatic self-monitoring.

Conclusions: Based on the preferences of our respondents, we found that the utility of a self-monitoring sun protection app can be increased if the app is simple and adjustable; requires minimal effort, time, or expense; and has an interoperable design and thorough privacy infrastructure. Similar features might be desirable for preventive health apps in other areas, paving the way for future discrete choice experiments. Nonetheless, to fully understand these preference dynamics, further qualitative or mixed method research on mobile self-monitoring-based sun protection and broader preventive mobile self-monitoring is required.

International Registered Report Identifier (irrid): RR2-10.2196/16087.
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http://dx.doi.org/10.2196/18889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732707PMC
November 2020

Seroprevalence and immunity of SARS-CoV-2 infection in children and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study.

Int J Public Health 2020 Dec 15;65(9):1549-1557. Epub 2020 Oct 15.

Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Hirschengraben 84, 8001, Zurich, Switzerland.

Objectives: This longitudinal cohort study aims to assess the extent and patterns of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in school-attending children, and their parents and school personnel. It will examine risk factors for infection, the relationship between seropositivity and symptoms, and temporal persistence of antibodies.

Methods: The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children aged 5-16 years, attending primary and secondary schools, and their parents and school personnel are invited. Venous blood and saliva samples are collected for serological testing in June/July 2020, in October/November 2020, and in March/April 2021. Bi-monthly questionnaires will cover SARS-CoV-2 symptoms and tests, health, preventive behavior, and lifestyle information. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological tests in the analyses and complex sampling structure, i.e., clustering within classes and schools.

Results And Conclusions: This unique school-based study will allow describing temporal trends of immunity, evaluate effects of preventive measures and will inform goal-oriented policy decisions during subsequent outbreaks. Trial registration ClinicalTrials.gov Identifier: NCT04448717, registered June 26, 2020. https://clinicaltrials.gov/ct2/show/NCT04448717 .
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http://dx.doi.org/10.1007/s00038-020-01495-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561232PMC
December 2020

In out-of-hospital cardiac arrest, is the positioning of victims by bystanders adequate for CPR? A cohort study.

BMJ Open 2020 09 23;10(9):e037676. Epub 2020 Sep 23.

University Hospital Zurich, Institute of Anesthesiology, University of Zurich Faculty of Medicine, Zurich, Switzerland

Objectives: Outcome from out-of-hospital cardiac arrest (OHCA) highly depends on bystander cardiopulmonary resuscitation (CPR) with high-quality chest compressions (CCs). Precondition is a supine position of the victim on a firm surface. Until now, no study has systematically analysed whether bystanders of OHCA apply appropriate positions to victims and whether the position is associated with a particular outcome.

Design: Prospective observational cohort study.

Setting: Metropolitan emergency medical services (EMS) serving a population of 400 000; dispatcher-assisted CPR was implemented. We obtained information from the first EMS vehicle arriving on scene and matched this with data from semi-structured interviews with witnesses of the arrest.

Participants: Bystanders of all OHCAs occurring during a 12-month period (July 2006-July 2007). From 201 eligible missions, 200 missions were fully reported by EMS. Data from 138 bystander interviews were included.

Primary And Secondary Outcome Measures: Proportion of positions suitable for effective CCs; related survival with favourable neurological outcome at 3 months.

Results: Positioning of victims at EMS arrival was 'supine on firm surface' in 64 cases (32.0%), 'recovery position (RP)' in 37 cases (18.5%) and other positions unsuitable for CCs in 99 cases (49.5%). Survival with favourable outcome at 3 months was 17.2% when 'supine position' had been applied, 13.5% with 'RP' and 6.1% with 'other positions unsuitable for CCs'; a statistically significant association could not be shown (p=0.740, Fisher's exact test). However, after 'effective CCs' favourable outcome at 3 months was 32.0% compared with 5.3% if no actions were taken. The OR was 5.87 (p=0.02).

Conclusion: In OHCA, two-thirds of all victims were found in positions not suitable for effective CCs. This was associated with inferior outcomes. A substantial proportion of the victims was placed in RP. More attention should be paid to the correct positioning of victims in OHCA. This applies to CPR training for laypersons and dispatcher-assisted CPR.
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http://dx.doi.org/10.1136/bmjopen-2020-037676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513596PMC
September 2020

Choices of Therapeutic Strategies for Colorectal Liver Metastases Among Expert Liver Surgeons: A Throw of the Dice?

Ann Surg 2020 11;272(5):715-722

Department of Radiology, University Hospital Zurich, Zurich, Switzerland.

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe.

Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients.

Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers.

Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries.

Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.
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http://dx.doi.org/10.1097/SLA.0000000000004331DOI Listing
November 2020

Validation of the Raw National Aeronautics and Space Administration Task Load Index (NASA-TLX) Questionnaire to Assess Perceived Workload in Patient Monitoring Tasks: Pooled Analysis Study Using Mixed Models.

J Med Internet Res 2020 09 7;22(9):e19472. Epub 2020 Sep 7.

Department of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.

Background: Patient monitoring is indispensable in any operating room to follow the patient's current health state based on measured physiological parameters. Reducing workload helps to free cognitive resources and thus influences human performance, which ultimately improves the quality of care. Among the many methods available to assess perceived workload, the National Aeronautics and Space Administration Task Load Index (NASA-TLX) provides the most widely accepted tool. However, only few studies have investigated the validity of the NASA-TLX in the health care sector.

Objective: This study aimed to validate a modified version of the raw NASA-TLX in patient monitoring tasks by investigating its correspondence with expected lower and higher workload situations and its robustness against nonworkload-related covariates. This defines criterion validity.

Methods: In this pooled analysis, we evaluated raw NASA-TLX scores collected after performing patient monitoring tasks in four different investigator-initiated, computer-based, prospective, multicenter studies. All of them were conducted in three hospitals with a high standard of care in central Europe. In these already published studies, we compared conventional patient monitoring with two newly developed situation awareness-oriented monitoring technologies called Visual Patient and Visual Clot. The participants were resident and staff anesthesia and intensive care physicians, and nurse anesthetists with completed specialization qualification. We analyzed the raw NASA-TLX scores by fitting mixed linear regression models and univariate models with different covariates.

Results: We assessed a total of 1160 raw NASA-TLX questionnaires after performing specific patient monitoring tasks. Good test performance and higher self-rated diagnostic confidence correlated significantly with lower raw NASA-TLX scores and the subscores (all P<.001). Staff physicians rated significantly lower workload scores than residents (P=.001), whereas nurse anesthetists did not show any difference in the same comparison (P=.83). Standardized distraction resulted in higher rated total raw NASA-TLX scores (P<.001) and subscores. There was no gender difference regarding perceived workload (P=.26). The new visualization technologies Visual Patient and Visual Clot resulted in significantly lower total raw NASA-TLX scores and all subscores, including high self-rated performance, when compared with conventional monitoring (all P<.001).

Conclusions: This study validated a modified raw NASA-TLX questionnaire for patient monitoring tasks. The scores obtained correctly represented the assumed influences of the examined covariates on the perceived workload. We reported high criterion validity. The NASA-TLX questionnaire appears to be a reliable tool for measuring subjective workload. Further research should focus on its applicability in a clinical setting.
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http://dx.doi.org/10.2196/19472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506540PMC
September 2020

Predictors of long-term employment among patients with cystic fibrosis undergoing lung transplantation.

Swiss Med Wkly 2020 Jul 13;150:w20286. Epub 2020 Jul 13.

University of Zurich, Switzerland.

Aims Of The Study: Lung transplantation is an established therapy in selected patients with advanced cystic fibrosis lung disease. Resumption of employment after lung transplantation is generally supported. In Switzerland, there are no data on long-term employment in people with cystic fibrosis undergoing lung transplantation.

Methods: In a single-centre, cross-sectional study at a Swiss university hospital, clinical data from lung transplant recipients with cystic fibrosis, covering the transplantation period from January 1996 to December 2016, were analysed retrospectively. The potential influence of pre-lung transplantation factors (age, sex, lung function, body mass index, six-minute walk test distance, lung transplantation wait list time, paid employment on the wait list, education, relationship status, housing situation) and post-lung transplantation factors (chronic allograft dysfunction [CLAD], dialysis, cancer diagnosis [except skin cancer]) on paid employment and work percentage after lung transplantation were investigated using mixed logistic and linear regression models. Descriptive analyses of paid employment were performed for various periods after lung transplantation (<1, 1–3, 3–5, 5–10, >10 years). Data are reported as odds ratios (ORs) or coefficients (β) with their 95% confidence intervals (CIs).

Results: Eighty-four subjects (46.4% female) with a mean ± SD age of 29.9 ± 8.4 years were included in the study. Mean wait time for lung transplantation was 42.7 ± 40.2 weeks. The number (percentage) of subjects employed <1 year, 1–3 years, 3–5 years, 5–10 years and >10 years after lung transplantation was n = 23 (28%), n = 51 (65%), n = 44 (75%), n = 30 (68%) and n = 21 (75%), respectively. In mixed logistic regression models, pre-lung transplantation paid employment (OR 24.03, 95% CI 6.08 to 164.39, p <0.0001), academic education (OR 7.81, 95% CI 1.66 to 48.66, p = 0.01) and time post lung transplantation (on log scale, OR 5.81, 95% CI 3.15 to 12.78, p <0.0001) were the main factors influencing post-lung transplantation paid employment status. In mixed linear regression models, pre-lung transplantation paid employment (β = 21.40, 95% CI 10.98 to 31.81, p = 0.00014), academic education (β = 12.54, 95% CI 0.48 to 24.55, p = 0.05) and time post lung transplantation (on log scale, β = 8.96, 95% CI 6.17 to 11.82, p <0.0001) were the main factors influencing work percentage post lung transplantation. No evidence for an influence of clinical factors such as CLAD, cancer or dialysis on post-lung transplantation employment and work percentage was found.

Conclusion: Pre-transplant employment is the dominant factor influencing lung transplantation employment in people with cystic fibrosis. People with cystic fibrosis undergoing lung transplantation should be encouraged to work for as long as their health status permits. Professional reintegration after successful lung transplantation should be supported by a multi-disciplinary lung transplant team.
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http://dx.doi.org/10.4414/smw.2020.20286DOI Listing
July 2020

Anesthesia and Circulating Tumor Cells in Primary Breast Cancer Patients: A Randomized Controlled Trial.

Anesthesiology 2020 09;133(3):548-558

From the Institute of Anesthesiology, University Hospital of Zurich and University of Zurich, Zurich, Switzerland (F.H., M.S., B.B.-S.) the Epidemiology, Biostatistics and Prevention Institute, Department of Public and Global Health (F.H.) the Epidemiology, Biostatistics and Prevention Institute, Department of Epidemiology (J.B., M.A.P.) the Institute of Physiology and Zurich Center for Integrative Human Physiology (B.R.Z., M.S., B.B.-S.) the Cytometry Facility (C.D., C.E.), University of Zurich, Zurich, Switzerland the Department of Gynecology, University Hospital of Zurich, Zurich, Switzerland (K.J.D., D.F.) the Institute of Anesthesiology, Hirslanden Clinic Zurich, Zurich, Switzerland (U.R., M.S.) the Faculty of Medicine, University of Basel, Basel, Switzerland (M.S.) the Department of Surgery (C.T.) the Clinical Trial Unit (B.P.), Breast Center Zurich, Zurich, Switzerland the Department of Anesthesiology, University of Illinois College of Medicine at Chicago, Chicago, Illinois (B.B.-S.).

Background: The effect of anesthetic drugs on cancer outcomes remains unclear. This trial aimed to assess postoperative circulating tumor cell counts-an independent prognostic factor for breast cancer-to determine how anesthesia may indirectly affect prognosis. It was hypothesized that patients receiving sevoflurane would have higher postoperative tumor cell counts.

Methods: The parallel, randomized controlled trial was conducted in two centers in Switzerland. Patients aged 18 to 85 yr without metastases and scheduled for primary breast cancer surgery were eligible. The patients were randomly assigned to either sevoflurane or propofol anesthesia. The patients and outcome assessors were blinded. The primary outcome was circulating tumor cell counts over time, assessed at three time points postoperatively (0, 48, and 72 h) by the CellSearch assay. Secondary outcomes included maximal circulating tumor cells value, positivity (cutoff: at least 1 and at least 5 tumor cells/7.5 ml blood), and the association between natural killer cell activity and tumor cell counts. This trial was registered with ClinicalTrials.gov (NCT02005770).

Results: Between March 2014 and April 2018, 210 participants were enrolled, assigned to sevoflurane (n = 107) or propofol (n = 103) anesthesia, and eventually included in the analysis. Anesthesia type did not affect circulating tumor cell counts over time (median circulating tumor cell count [interquartile range]; for propofol: 1 [0 to 4] at 0 h, 1 [0 to 2] at 48 h, and 0 [0 to 1] at 72 h; and for sevoflurane: 1 [0 to 4] at 0 h, 0 [0 to 2] at 48 h, and 1 [0 to 2] at 72 h; rate ratio, 1.27 [95% CI, 0.95 to 1.71]; P = 0.103) or positivity. In one secondary analysis, administrating sevoflurane led to a significant increase in maximal tumor cell counts postoperatively. There was no association between natural killer cell activity and circulating tumor cell counts.

Conclusions: In this randomized controlled trial investigating the effect of anesthesia on an independent prognostic factor for breast cancer, there was no difference between sevoflurane and propofol with respect to circulating tumor cell counts over time.
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http://dx.doi.org/10.1097/ALN.0000000000003409DOI Listing
September 2020

Agreement between trainees and supervisors on first-year entrustable professional activities for anaesthesia training.

Br J Anaesth 2020 07 16;125(1):98-103. Epub 2020 May 16.

Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Entrustable professional activities (EPAs) are commonly developed by senior clinicians and education experts. However, if postgraduate training is conceptualised as an educational alliance, the perspective of trainees should be included. This raises the question as to whether the views of trainees and supervisors on entrustability of specific EPAs differ, which we aimed to explore.

Methods: A working group, including all stakeholders, selected and drafted 16 EPAs with the potential for unsupervised practice within the first year of training. For each EPA, first-year trainees, advanced trainees, and supervisors decided whether it should be possible to attain trust for unsupervised practice by the end of the first year of anaesthesiology training (i.e. whether the respective EPA qualified as a 'first-year EPA').

Results: We surveyed 23 first-year trainees, 47 advanced trainees, and 51 supervisors (overall response rate: 68%). All groups fully agreed upon seven EPAs as 'first-year EPAs' and on four EPAs that should not be entrusted within the first year. For all five remaining EPAs, a significantly higher proportion of first-year trainees thought these should be entrusted as first-year EPAs compared with advanced trainees and supervisors. We found no differences between advanced trainees and supervisors.

Conclusions: The views of first-year trainees, advanced trainees, and supervisors showed high agreement. Differing views of young trainees disappeared after the first year. This finding provides a fruitful basis to involve trainees in negotiations of autonomy.
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http://dx.doi.org/10.1016/j.bja.2020.04.009DOI Listing
July 2020

Comparing Classroom Instruction to Individual Instruction as an Approach to Teach Avatar-Based Patient Monitoring With Visual Patient: Simulation Study.

JMIR Med Educ 2020 Apr 23;6(1):e17922. Epub 2020 Apr 23.

University Hospital Zurich, Zurich, Switzerland.

Background: Visual Patient is an avatar-based alternative to standard patient monitor displays that significantly improves the perception of vital signs. Implementation of this technology in larger organizations would require it to be teachable by brief class instruction to large groups of professionals. Therefore, our study aimed to investigate the efficacy of such a large-scale introduction to Visual Patient.

Objective: In this study, we aimed to compare 2 different educational methods, one-on-one instruction and class instruction, for training anesthesia providers in avatar-based patient monitoring.

Methods: We presented 42 anesthesia providers with 30 minutes of class instruction on Visual Patient (class instruction group). We further selected a historical sample of 16 participants from a previous study who each received individual instruction (individual instruction group). After the instruction, the participants were shown monitors with either conventional displays or Visual Patient displays and were asked to interpret vital signs. In the class instruction group, the participants were shown scenarios for either 3 or 10 seconds, and the numbers of correct perceptions with each technology were compared. Then, the teaching efficacy of the class instruction was compared with that of the individual instruction in the historical sample by 2-way mixed analysis of variance and mixed regression.

Results: In the class instruction group, when participants were presented with the 3-second scenario, there was a statistically significant median increase in the number of perceived vital signs when the participants were shown the Visual Patient compared to when they were shown the conventional display (3 vital signs, P<.001; effect size -0.55). No significant difference was found for the 10-second scenarios. There was a statistically significant interaction between the teaching intervention and display technology in the number of perceived vital signs (P=.04; partial η=.076). The mixed logistic regression model for correct vital sign perception yielded an odds ratio (OR) of 1.88 (95% CI 1.41-2.52; P<.001) for individual instruction compared to class instruction as well as an OR of 3.03 (95% CI 2.50-3.70; P<.001) for the Visual Patient compared to conventional monitoring.

Conclusions: Although individual instruction on Visual Patient is slightly more effective, class instruction is a viable teaching method; thus, large-scale introduction of health care providers to this novel technology is feasible.
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http://dx.doi.org/10.2196/17922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206517PMC
April 2020

Exploring geographic variation of and influencing factors for utilization of four diabetes management measures in Swiss population using claims data.

BMJ Open Diabetes Res Care 2020 02;8(1)

Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

Introduction: Four strongly recommended diabetes management measures are biannual glycated hemoglobin (HbA1c) testing, annual eye examination, kidney function examination, and low-density lipoprotein (LDL) testing in patients below 75 years. We aimed to describe regional variation in the utilization of the four measures across small regions in Switzerland and to explore potential influencing factors.

Research Design And Methods: We conducted a cross-sectional study of adult patients with drug-treated diabetes in 2014 using claims data. Four binary outcomes represented adherence to the recommendations. Possible influencing factors included sociodemographics, health insurance preferences, and clinical characteristics. We performed multilevel modeling with Medstat regions as the higher level. We calculated the median odds ratio (MOR) and checked spatial autocorrelation in region level residuals using Moran's I statistic. When significant, we further conducted spatial multilevel modeling.

Results: Of 49 198 patients with diabetes (33 957 below 75 years), 69.6% had biannual HbA1c testing, 44.3% each had annual eye examination and kidney function examination, and 55.5% of the patients below 75 years had annual LDL testing. The effects of health insurance preferences were substantial and consistent. Having any supplementary insurance (ORs across measures were between 1.08 and 1.28), having supplementary hospital care insurance (1.08-1.30), having chosen a lower deductible level (eg, SFr2500 compared with SFr300: 0.57-0.69), and having chosen a managed care model (1.04-1.17) were positively associated with recommendations adherence. The MORs (1.27-1.33) showed only moderate unexplained variation, and we observed inconsistent spatial patterns of unexplained variation across the four measures.

Conclusion: Our findings indicate that the uptake of strongly recommended measures in diabetes management could possibly be optimized by providing further incentives to patients and care providers through insurance scheme design. The absence of marked regional variation implies limited potential for improvement by targeted regional intervention, while provider-specific promotion may be more impactful.
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http://dx.doi.org/10.1136/bmjdrc-2019-001059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039601PMC
February 2020

Quorum Regulation via Nested Antagonistic Feedback Circuits Mediated by the Receptors CD28 and CTLA-4 Confers Robustness to T Cell Population Dynamics.

Immunity 2020 02 11;52(2):313-327.e7. Epub 2020 Feb 11.

Institute for Immunodeficiency, Medical Center and Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany. Electronic address:

T cell responses upon infection display a remarkably reproducible pattern of expansion, contraction, and memory formation. If the robustness of this pattern builds entirely on signals derived from other cell types or if activated T cells themselves contribute to the orchestration of these population dynamics-akin to bacterial quorum regulation-is unclear. Here, we examined this question using time-lapse microscopy, genetic perturbation, bioinformatic predictions, and mathematical modeling. We found that ICAM-1-mediated cell clustering enabled CD8 T cells to collectively regulate the balance between proliferation and apoptosis. Mechanistically, T cell expressed CD80 and CD86 interacted with the receptors CD28 and CTLA-4 on neighboring T cells; these interactions fed two nested antagonistic feedback circuits that regulated interleukin 2 production in a manner dependent on T cell density as confirmed by in vivo modulation of this network. Thus, CD8 T cell-population-intrinsic mechanisms regulate cellular behavior, thereby promoting robustness of population dynamics.
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http://dx.doi.org/10.1016/j.immuni.2020.01.018DOI Listing
February 2020

Impact of a goal-directed factor-based coagulation management on thromboembolic events following major trauma.

Scand J Trauma Resusc Emerg Med 2019 Dec 30;27(1):117. Epub 2019 Dec 30.

Institute of Anaesthesiology, Cantonal Hospital Winterthur, Brauerstrasse 15, 8400, Winterthur, Switzerland.

Background: A factor-based coagulation management following major trauma is recommended as standard of care by the European Trauma Treatment Guidelines. However, concerns about the thromboembolic risk of this approach are still prevalent. Our study therefore aims to assess if such a haemostatic management is associated with an increased risk for thromboembolic events.

Methods: In this retrospective observational study carried out at the University Hospital Zurich we compared two three-year periods before (period 1: 2005-2007) and after (period 2: 2012-2014) implementation of a factor-based coagulation algorithm. We included all adult patients following major trauma primarily admitted to the University Hospital Zurich. Thromboembolic events were defined as a new in-hospital appearance of any peripheral thrombosis, arterial embolism, pulmonary embolism, stroke or myocardial infarction. A logistic regression was performed to investigate the association of thromboembolic events with possible confounders such as age, sex, specific Abbreviated Injury Scale (AIS) subgroups, allogeneic blood products, and the coagulation management.

Results: Out of 1138 patients, 772 met the inclusion criteria: 344 patients in period 1 and 428 patients in period 2. Thromboembolic events were present in 25 patients (7.3%) of period 1 and in 42 patients (9.8%) of period 2 (raw OR 1.39, 95% CI 0.83 to 2.33, p = 0.21). Only AIS extremities (adjusted OR 1.26, 95% CI 1.05 to 1.52, p = 0.015) and exposure to allogeneic blood products (adjusted OR 2.39, 95% CI 1.33 to 4.30, p = 0.004) were independently associated with thromboembolic events in the logistic regression, but the factor-based coagulation management was not (adjusted OR 1.60, 95% CI 0.90-2.86, p = 0.11).

Conclusion: There is no evidence that a goal-directed, factor-based coagulation management is associated with an increased risk for thromboembolic events following major trauma.
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http://dx.doi.org/10.1186/s13049-019-0697-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937999PMC
December 2019

Clinical practice of pre-hospital analgesia: An observational study of 20,978 missions in Switzerland.

Am J Emerg Med 2020 11 18;38(11):2318-2323. Epub 2019 Nov 18.

Institute of Anesthesiology, University and University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Pain is a frequent problem faced by emergency medical services (EMS) in pre-hospital settings. This large observational study aims to assess the prevalence of sufficiently provided analgesia and to analyze the efficacy of different analgesics. Moreover, we evaluated if quality of analgesia changed with an emergency physician on scene or depended on paramedics' gender.

Methods: This is a retrospective analysis of all pre-hospital medical charts from adults and adolescents treated by the municipal EMS Schutz & Rettung Zürich over a period of 4 years from 2013 to 2016. Inclusion criteria were age ≥16 years, initial GCS > 13, NACA score ≥I and ≤V, an initial numeric rating scale (NRS) ≥ I and a documented NRS at hospital admission. 20,978 out of 142,484 missions fulfilled the inclusion criteria and therefore underwent further investigation. Descriptive, univariate and multivariate analyses were applied.

Results: Initial NRS on scene was on average 5.2 ± 3.0. Mean NRS reduction after treatment was 2.2 ± 2.5 leading to a NRS at hospital admission of 3.0 ± 1.9. This resulted in sufficient analgesia for 77% of included patients. Among analgesics, the highest odds ratio for sufficient analgesia was observed for ketamine (OR 4.7, 95%CI 2.2-10.4, p < 0.001) followed by fentanyl (OR 1.4, 95%CI 1.1-1.7, p = 0.004). Female paramedics provided better analgesia (OR 1.2, 95%CI 1.1-1.2; p < 0.001). Patient's sex had no influence on analgesia. In patients with a NACA score > 2, the presence of an emergency physician on scene improved the quality of analgesia significantly.

Conclusions: Pre-hospital analgesia is mostly adequate, especially when done with ketamine or fentanyl. Female paramedics provided better analgesia and in selected patients, an emergency physician on scene improved quality of analgesia in critical patients.
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http://dx.doi.org/10.1016/j.ajem.2019.10.033DOI Listing
November 2020

Impact of rivaroxaban plasma concentration on perioperative red blood cell loss.

Transfusion 2020 01 4;60(1):197-205. Epub 2019 Nov 4.

Division of Hematology, University and University Hospital Zurich, Zurich, Switzerland.

Background: This study investigates the impact of preoperative calculated rivaroxaban (RXA) plasma concentration on perioperative red blood cell (RBC) loss.

Study Design And Methods: In this retrospective single-center study, we identified patients with RXA intake according to a preoperative determination of RXA levels within 96 hours before surgery. RXA plasma concentration at the beginning of surgery was then calculated from the last RXA intake using a single-compartment pharmacokinetic model with four categories of RXA concentration (≤20, 21-50, 51-100, and >100 μg/L). Patients were classified into surgery with high (≥500 mL) or low (<500 mL) expected blood loss. Perioperative bleeding was determined by calculating RBC loss.

Results: We analyzed 308 surgical interventions in 298 patients during the period from January 2012 to July 2018. Among patients undergoing surgery with low expected blood loss, RBC loss varied from 164 mL (standard deviation [SD], 189) to 302 mL (SD, 397) (p = 0.66), and no association of calculated RXA concentration with RBC loss was observed. In patients undergoing surgery with high expected blood loss, we found a significant correlation of calculated RXA concentration with RBC loss (Pearson's correlation coefficient, 0.29; p = 0.002). RBC loss increased with rising RXA concentration from 575 mL (SD, 365) at RXA concentration of 20 μg/L or less up to 1400 mL (SD, 1300) at RXA concentration greater than 100 μg/L. RXA concentration greater than 100 μg/L was associated with a significant increase of in RBC loss of 840 mL (95% confidence interval, 360-1300; p < 0.001). Transfusion of RBC and fresh frozen plasma units tended to increase in patients with RXA concentrations greater than 100 μg/L. The proportion of patients treated with prothrombin complex concentrate and coagulation factor XIII concentrate increased significantly with higher RXA concentrations.

Conclusion: Only in surgery with high expected blood loss, a calculated RXA concentration of greater than 100 μg/L was associated with a significant increase of perioperative RBC loss.
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http://dx.doi.org/10.1111/trf.15560DOI Listing
January 2020

Effects of the antifungal agent ciclopirox in HPV-positive cancer cells: Repression of viral E6/E7 oncogene expression and induction of senescence and apoptosis.

Int J Cancer 2020 01 31;146(2):461-474. Epub 2019 Oct 31.

Molecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), Heidelberg, Germany.

The malignant growth of human papillomavirus (HPV)-positive cancer cells is dependent on the continuous expression of the viral E6/E7 oncogenes. Here, we examined the effects of iron deprivation on the phenotype of HPV-positive cervical cancer cells. We found that iron chelators, such as the topical antifungal agent ciclopirox (CPX), strongly repress HPV E6/E7 oncogene expression, both at the transcript and protein level. CPX efficiently blocks the proliferation of HPV-positive cancer cells by inducing cellular senescence. Although active mTOR signaling is considered to be critical for the cellular senescence response towards a variety of prosenescent agents, CPX-induced senescence occurs under conditions of severely impaired mTOR signaling. Prolonged CPX treatment leads to p53-independent Caspase-3/7 activation and induction of apoptosis. CPX also eliminates HPV-positive cancer cells under hypoxic conditions through induction of apoptosis. Taken together, these results show that iron deprivation exerts profound antiviral and antiproliferative effects in HPV-positive cancer cells and suggest that iron chelators, such as CPX, possess therapeutic potential as HPV-inhibitory, prosenescent and proapoptotic agents in both normoxic and hypoxic environments.
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http://dx.doi.org/10.1002/ijc.32709DOI Listing
January 2020
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