Benjamin Peter Geisler

• Müller, Marcel; Geisler, Benjamin P.; Shamas, Samar; Bomhard, Nikolaus v.; Hoster, Eva & Pfirrmann, Markus [Show all 7 contributors for this article] (2026). FAIR by design (TRACE): A Trusted Research Access & Collaboration Environment. BMC Medical Informatics and Decision Making. 26(1). doi: 10.1186/s12911-026-03840-3. Full text in Research Archive Show summary

  Background A tension exists between the open science imperative for data transparency through FAIR (Findable, Accessible, Interoperable, Reusable) data sharing and the stringent requirements of current data protection regulations for health data. Researchers lack efficient yet affordable tools to share sensitive data responsibly. Existing solutions are often either difficult to use, expensive, or lack features like variable-level access control and auditable and reproducible workflows. Our objective was to develop a solution that lowers the threshold for researchers to share sensitive data responsibly and that can be operated by existing institutional staff. Results TRACE (Trusted Research Access & Collaboration Environment) was designed to support several data-sharing elements highlighted in the 2025 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) statements by providing controlled and auditable workflows and supporting reproducibility at the level of data and analysis code. Its features for data governance, sharing, reproducibility and security allow institutions to manage study data access and to establish consistent, transparent standard operating procedures through granular variable selection, integrated study visualisation, and provisioning into a sealed analysis environment. TRACE provides an automated workflow for selected data-access steps that had previously relied on manual curation and ad-hoc sharing. A core feature versions datasets together with the corresponding analysis scripts, supporting reproducibility at the level of data and code; the computational environment is not captured. TRACE has supported data governance across seven clinical studies and processed 56 data access applications. Across three studies, an uncontrolled before-and-after comparison found 42.4 manual interface exports per 30 days before TRACE and 4.7 after implementation; causality cannot be inferred. Conclusions Platforms like TRACE may help shift resource-intensive, expert-dependent data governance towards automated processes. Operated by existing institutional staff, TRACE may make controlled data sharing feasible for institutions with limited resources. By automating previously manual steps, TRACE is intended to reduce the administrative burden of governed data sharing; whether it shortens the interval from data request to analysis has not been measured. TRACE is used as a training environment for preparing and using data in sharing processes.

• Yang, Freda; Geisler, Benjamin Peter; d’Ancona, Grainne; Lee, Bohee; Jackson, David J. & Bloom, Chloe I. (2026). Prevalence and cost implications of broadening asthma biologic eligibility criteria. World Allergy Organization Journal. 19(9). doi: 10.1016/j.waojou.2026.101449. Full text in Research Archive Show summary

  Rationale: Eligibility for biologic therapy in severe asthma varies internationally because government-funded schemes apply stricter criteria than pivotal trials. While relaxing eligibility thresholds may expand access, the effects on prevalence and healthcare costs remain uncertain. Objective: To quantify how alternative biologic eligibility criteria affect prevalence, clinical characteristics, and budget impact in adults with asthma. Methods: We studied adults with active asthma (2004–2021) using nationally representative primary care and hospital records. Biologic eligibility was assessed yearly using asthma severity (inhaled corticosteroid dose, additional controllers, rescue therapy) and exacerbations (oral corticosteroid prescriptions, emergency visits and hospitalisations). We assessed prevalence using United Kingdom (UK) criteria (severe asthma, ≥3 exacerbations), Global criteria (severe asthma, ≥1 or ≥2 exacerbations) and RCT criteria (moderate asthma, ≥1 or ≥2 exacerbations). Anti-IL-5/5Rα eligibility was evaluated using blood eosinophil counts. Budget impact was modelled over 5 years. Results: Among 1,306,307 asthma patients, 7.2% had severe asthma. Under UK criteria, 19,093 patients were biologic-eligible (20.4% of severe asthma; 1.5% of all asthma). Global criteria increased eligibility to 2.4% (≥2 exacerbations) to 4.3% (≥1 exacerbation), while RCT criteria expanded eligibility to 4.7% (≥2 exacerbations) and 9% (≥1 exacerbation). Among patients with eosinophil data, 38–45% met anti-IL-5/5Rα criteria. UK-eligible patients had higher prevalence of lower respiratory tract infections, pneumonia, and bronchiectasis. Five-year costs were £261 M under UK criteria, £436–767 M under Global criteria, and £878M-1.6B under RCT criteria. Conclusion: Only one-fifth of patients with severe asthma met UK biologic eligibility. Global criteria tripled eligibility and RCT criteria increased it six-fold, with substantial budget implications.

• Geisler, Benjamin P.; Holmboe, Fredrik; Starinieri, Irene & Aas, Eline (2026). Applications of Structural Expert Elicitations for Economic Evaluations: A Systematic Review Update. PharmacoEconomics (Auckland). ISSN 1170-7690. doi: 10.1007/s40273-026-01628-x. Full text in Research Archive Show summary

  Background Structured expert elicitation (SEE) has become increasingly important in health technology assessment and economic evaluations. Complementing previous work, we aimed to synthesize recent developments in published SEE applications within health economics over the past 8 years. Methods A systematic literature search was conducted in Medline and Embase databases from April 2017 to February 2026, supplemented with snowball sampling, to identify applications of SEE as part of economic evaluations. Data extraction and synthesis focused on expert selection, elicitation methods, and analytical techniques to identify commonalities and gaps. Results In total, 28 studies met the inclusion criteria. SEE applications covered diverse health interventions, from rare diseases treatments to diagnostic accuracy assessments. The number of experts recruited through purposive sampling varied from 1 to 18 clinicians per study. SEE processes remain bespoke and diverse, spanning from paper-based to software-assisted remote techniques. The studies used mainly variable and fixed interval methods (29% versus 67%) for encoding. Aggregation methods were mainly mathematical, with some studies using consensus approaches. Most studies (75%) directly incorporated pooled expert distributions into decision models. Conclusions While SEE methods vary considerably across applications, suggesting that optimal approaches have yet to emerge, there is growing recognition of their potential for informing healthcare decision-making where empirical data are scarce, particularly in rare diseases and early-stage technology assessment. Future research should prioritize standardizing best practices, validating expert predictions against subsequently available empirical data, and developing enhanced bias mitigation strategies to improve the credibility of expert-informed health economic evaluations.

• Satomi, Kazuhiro; Soejima, Kyoko; Kusano, Kengo; Myung, Jae-Eun; Tanaka, Yuji & Ryschon, Anne M. [Show all 9 contributors for this article] (2026). Cost-Effectiveness of Atrioventricular Synchronous Leadless Pacing in Patients With Atrioventricular Block　― Results and Implications From an Exploratory Analysis for Japan ―. Circulation Reports. 26. doi: 10.1253/circrep.cr-26-0090. Full text in Research Archive Show summary

  Background: Atrioventricular (AV) synchronous pacing with a transcatheter pacing system (TC-PM) is an alternative to transvenous pacemakers (TV-PM) in patients with AV block. In this study we assessed the potential cost-effectiveness of TC-PM in Japan and methodological implications for future global cost-effectiveness analyses. Methods and Results: A decision-analytic Markov model captured strategy-specific complication rates, device replacements, and health-related quality of life. Parameter inputs were derived from systematic literature search, clinical studies, and claims data. The discounted lifetime incremental cost-effectiveness ratio (ICER, in JPY per quality-adjusted life-year (QALY) gained) was evaluated against a 5 million JPY per QALY willingness-to-pay threshold. Extensive scenario and sensitivity analyses were conducted. TC-PM was associated with lower complication rates (3.8% vs. 9.8% at 36 months, hazard ratio 0.39; P<0.001) and a lifetime cost increase of JPY632,849 (JPY2,268,945 vs. JPY1,636,096). TC-PM concurrently added 0.24 (3.33 vs. 3.09) QALYs, rendering TC-PM cost-effective in the base case (ICER JPY2,640,519 per QALY gained), but not all scenarios. Long-term quality-of-life assumptions, as also evidenced by a recent Japanese government study, are an important driver of cost-effectiveness. Conclusions: AV-synchronous pacing with a TC-PM is associated with lower complication rates and some improvement in projected quality-adjusted survival that can render it a cost-effective intervention in the Japanese healthcare system as long as some of the observed short-term quality-of-life benefit is maintained.

• Geisler, Benjamin P; Vergunst, Francis & Ghosh, Arnab K (2026). Preparing for the cardiovascular risks of tropical storms amplified by climate change. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehag211. Full text in Research Archive
• Ree, Anne Hansen; Bousquet, Paula; Visnovska, Martina; Lüders, Torben; Geisler, Benjamin Peter & Wang, Shixiong [Show all 16 contributors for this article] (2026). Exploratory biomarkers for oxaliplatin-induced nivolumab responsiveness in metastatic microsatellite-stable colorectal cancer. British Journal of Cancer. ISSN 0007-0920. 134, p. 1176–1182. doi: 10.1038/s41416-026-03357-6. Full text in Research Archive Show summary

  ABackground The randomised METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with nivolumab for metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer. In a post hoc analysis, we investigated whether tumour mutations or patients’ systemic inflammation might provide insights into responsiveness to the METIMMOX regimen. Methods Patients received either oxaliplatin-based chemotherapy (control group) or alternating two cycles each of chemotherapy and nivolumab (experimental group), with progression-free survival (PFS) as the primary endpoint. Tumour biopsies were sequenced with the TruSight Oncology 500 assay. Results The median tumour mutational burden (TMB; in mutations/megabase) was 8 (range, 1–13). The experimental-arm patients with TMB ≥9 or BRAF -V600E mutation ( n  = 17) achieved median PFS of 19.8 months (95% confidence interval, 11.3–28.3), longer ( p  = 0.0090) than experimental-arm patients with TMB < 9 not BRAF -V600E ( n  = 19) and control-arm patients with either TMB and BRAF status combination ( n  = 31). With TMB ≥9 or BRAF -V600E and normal, non-inflammatory level of C-reactive protein when starting nivolumab ( n  = 11), median PFS was 35.0 months (95% confidence interval, 6.8–63.0; p  < 0.0001). Conclusions TMB, somatic BRAF status and systemic inflammation should be prospectively investigated as practical biomarkers for predicting potential responsiveness to immune checkpoint inhibitors in metastatic microsatellite-stable/mismatch repair-proficient colorectal cancer.

• Groot, Carin A. Uyl-de; Xander, Nicolas S.H.; Belleman, Tom; Burger, Emily Annika; Doeswijk, Robin & Durand-Zaleski, Isabelle [Show all 23 contributors for this article] (2026). Bridging affordability and sustainability of health innovations via novel pricing, cost-effectiveness, and reimbursement models to improve patient access: The ASCERTAIN project. Health Policy and Technology. ISSN 2211-8837. 15(2). doi: 10.1016/j.hlpt.2026.101155. Full text in Research Archive Show summary

  Objectives Disparities in access to potential innovative health technologies (pIHTs) persist across Europe due to differing healthcare budgets, pricing policies, and health technology assessment (HTA) practices. The ASCERTAIN project aims to reduce these inequalities by developing integrated pricing, cost-effectiveness, and reimbursement approaches that enhance affordability, long-term sustainability, and timely patient access. Methods The project applies a mixed-methods approach, including literature review, stakeholder surveys, interviews, and focus groups, to ensure relevance across diverse health systems. It integrates access-based pricing, value-driven HTA, and adaptable reimbursement models into a practical, open-access ACCESS2MEDS Toolbox. This includes access-based pricing frameworks, cost-effectiveness models, and budget impact and reimbursement analyses, all adaptable to country-specific conditions to reduce uncertainty and improve transparency. Tools are co-created with patients, developers, clinicians, and policymakers and will be tested and validated using three use cases representing high-impact areas of innovation: precision oncology medicines, cell and gene therapies, and next-generation sequencing tests. Results Outputs will include validated tools enabling improved evaluation of clinical benefit, cost-effectiveness, and financial sustainability, strengthening value-based decision-making across Europe. Innovative access- and outcome-based pricing strategies will support responsible innovation while encouraging fair reimbursement and improved budget control. Policy roadmaps will guide the adoption of equitable access models and support system-level implementation. Conclusions ASCERTAIN will provide a harmonized framework that balances cost control, innovation incentives, and patient-centered care. By facilitating consistent, evidence-based pricing and reimbursement decisions, the project supports fair and sustainable access to pIHTs across Europe, with continued multi-stakeholder collaboration driving its wider adoption and real-world impact.

• Bruin, Odette de; Maisonneuve, Emeline; Hurley, Eimir; Nordeng, Hedvig Marie Egeland; Bérard, Anick & Sheehy, Odile [Show all 73 contributors for this article] (2025). Adverse outcomes among pregnant women with COVID‐19 according to hospitalization status: A prospective individual participant data meta‐analysis in Europe and North America. International Journal of Gynecology & Obstetrics. ISSN 0020-7292. p. 1–10. doi: 10.1002/ijgo.70694. Full text in Research Archive Show summary

  Abstract Background Understanding the varied impact of COVID‐19 severity on pregnancy outcomes is crucial for informed clinical management and targeted interventions. Objective To evaluate the impact of COVID‐19 on pregnancy outcomes, distinguishing between pregnant women managed in primary care and those requiring hospitalization. Search Strategy Regulatory authorities actively promoted global cooperation on COVID‐19's impact during pregnancy. Data were obtained through these regulatory bodies and direct researcher communication rather than through systematic searches. Selection Criteria Data sources required secondary population‐based data to identify pregnancies with COVID‐19, along with hospitalization, diagnostic and medication codes. Eligibility for the meta‐analysis was determined through protocol evaluation and researcher consultations. Data Collection and Analysis PRISMA‐IPD and Cochrane guidelines for prospective meta‐analysis were followed. Protocols and definitions were standardized across sources, and a common R script was developed. Initially, crude and adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated to assess adverse outcomes in pregnant women with and without COVID‐19 in each data source. Estimates were stratified by trimester at infection and hospitalization status. Subsequently, data were pooled using a random‐effects meta‐analysis. Main Results Data from 10 sources across seven countries contributed to the meta‐analysis, including 86 210 pregnant women diagnosed with COVID‐19, of whom 4.4% were hospitalized. Non‐hospitalized pregnant women with COVID‐19 had no increased risks of adverse outcomes compared to pregnant women without COVID‐19. However, hospitalized women with COVID‐19 in each trimester had higher risks of cesarean section, preterm birth, and LBW compared to pregnant women without COVID‐19. Hospitalization due to COVID‐19 in the third trimester was associated with increased risk of stillbirth (aRR 5.90, 95% CI: 2.22–15.71, I 2  = 0%). First‐trimester hospitalizations due to COVID‐19 did not show heightened risks of GDM (aRR 2.08, 95% CI: 0.93–4.64, I 2  = 65%), pre‐eclampsia (aRR 1.79, 95% CI: 0.48–6.66, I 2  = 71%), or major congenital anomalies (aRR 1.30, 95% CI: 0.55–3.06, I 2  = 0%). Conclusions and Relevance COVID‐19 requiring hospitalization is associated with adverse pregnancy outcomes, emphasizing the need to prevent severe illness during pregnancy. This study also highlights the importance of international collaboration for gathering pregnancy data and shows that building global research networks is essential for responding to future health crises.

• Bruin, Odette de; Maisonneuve, Emeline; Hurley, Eimir; Nordeng, Hedvig Marie Egeland; Bérard, Anick & Sheehy, Odile [Show all 75 contributors for this article] (2025). Medications Used Among Nonhospitalized Pregnant Women With COVID‐19: A Prospective Individual Patient Data Meta‐Analysis in Europe and North America. Pharmacoepidemiology and Drug Safety. ISSN 1053-8569. 35(1). doi: 10.1002/pds.70303. Full text in Research Archive Show summary

  ABSTRACT Aim To estimate the prevalence of medication use in nonhospitalized pregnant women with COVID‐19. Methods A prospective two‐stage individual patient meta‐analysis across 10 data sources in Europe and North America studied medication use among nonhospitalized pregnant women with COVID‐19 between January 2020 and December 2022. Comparisons were made between medication use within 30 days pre‐ and post‐COVID‐19 diagnosis in this cohort and two comparator groups: pregnant women without COVID‐19 and nonpregnant women with COVID‐19. Prevalence estimates were pooled using a random‐effects model stratified by trimester. Results 50 335 nonhospitalized pregnant women with COVID‐19 were identified. The pooled prevalence of antibacterial use in the third trimester was higher post‐COVID‐19 diagnosis (6.8%, 95% confidence interval [CI] = 5.5–8.4, I 2  = 94%) compared with the same women pre‐COVID‐19 (3.9%, 95% CI = 3.1–4.9, I 2  = 89%). Overall, pregnant women with COVID‐19 had higher medication use compared to pregnant women without COVID‐19, although the CIs of the prevalence overlapped. Post‐COVID‐19, antithrombotic prevalence was 4.5% (95% CI = 1.1–16.5, I 2  = 100%) among pregnant women with COVID‐19 in the third trimester, compared to 2.1% (95% CI = 1.2–3.6, I 2  = 99%) among those without COVID‐19 in the third trimester. Compared to nonpregnant women with COVID‐19, pregnant women with COVID‐19 were less likely to be prescribed analgesics, antiprotozoals, corticosteroids, psychoanaleptics and psycholeptics, and more likely to be prescribed antithrombotics, cough and cold and nasal preparations, and drugs used in diabetes across all trimesters. High heterogeneity existed in nearly all analyses. Conclusion This international meta‐analysis reveals low medication use and country‐specific variations, enhancing insight into the management of COVID‐19 in nonhospitalized pregnant women. Higher antithrombotic use post‐COVID‐19 suggests prophylactic treatment in this population, but variation between countries emphasizes the challenges of combining multinational data.

• Pietzsch, Jan B; Geisler, Benjamin Peter; Garner, Abigail M; Ryschon, Anne M; Gray, William A & Fujihara, Masahiko [Show all 7 contributors for this article] (2025). Clinical and economic implications of focal dissection treatment following percutaneous transluminal angioplasty of the superficial femoral artery: an exploratory analysis based on the TOBA II Study. Journal of Comparative Effectiveness Research. ISSN 2042-6305. 14(1). doi: 10.57264/cer-2024-0055. Full text in Research Archive Show summary

  Aim: Percutaneous transluminal angioplasty (PTA) for peripheral artery disease (PAD) commonly leads to dissections which are associated with higher target lesion revascularization (TLR) rates. Clinical and economic consequences of dissection management in the femoropopliteal artery following PTA, and specifically the potential economic benefit of focal dissection repair using the novel Tack Endovascular System, remain unknown. Methods: A decision-analytic model was used to estimate 24-month clinical events, costs and quality-adjusted life year (QALY) gain for a Tack-supported versus status-quo PTA strategy. Patient and lesion characteristics and TLR rates were derived from the PTA cohort of the TOBA II clinical trial, an observational cohort, and literature. Cost–effectiveness was determined from a US payer and provider perspective separately for the non-severe (grade A or B), severe (grade C and higher) and the entire dissection cohort. Results: TLR rates were lower for the Tack-supported strategy compared with PTA (7.7 vs 27.4% in the non-severe, 13.9 vs 25.8% in the severe and 12.0 vs 26.3% in the entire dissection cohort). Cost and QALY differences were +$297/ + 0.0110 in the non-severe dissection cohort and -$1602/ + 0.0067 in the severe dissection cohort, resulting in an incremental cost–effectiveness ratio (ICER) of $25,622 in the non-severe cohort and dominance in the severe cohort and the entire cohort. Conclusion: Compared with a ‘status-quo’ approach, proactive focal stenting may lead to fewer reinterventions and improved quality of life. There appears to be a graded economic benefit of focal dissection treatment, being cost-effective in non-severe dissections and even cost saving in severe dissections.

• Gutmann, Andrea S.; Mandl, Maximilian M.; Rieder, Clemens; Hoechter, Dominik J.; Dietz, Konstantin & Geisler, Benjamin Peter [Show all 9 contributors for this article] (2025). Comparing supervised machine learning algorithms for the prediction of partial arterial pressure of oxygen during craniotomy. BMC Medical Informatics and Decision Making. 25(1). doi: 10.1186/s12911-025-03148-8. Full text in Research Archive Show summary

  Abstract Background and Objectives Brain tissue oxygenation is usually inferred from arterial partial pressure of oxygen (paO 2 ), which is in turn often inferred from pulse oximetry measurements or other non-invasive proxies. Our aim was to evaluate the feasibility of continuous paO 2 prediction in an intraoperative setting among neurosurgical patients undergoing craniotomies with modern machine learning methods. Methods Data from routine clinical care of lung-healthy neurosurgical patients were extracted from databases of the respective clinical systems and normalized. We used recursive feature elimination to identify relevant features for the prediction of paO 2 . Six machine learning regression algorithms (gradient boosting, k-nearest neighbors, random forest, support vector, neural network, linear model with stochastic gradient descent) and a multivariable linear regression were then tuned and fitted to the selected features. A performance matrix consisting of standard deviation of absolute errors ( σ ae ), mean absolute percentage error (MAPE), adjusted R 2 , root mean squared error (RMSE), mean absolute error (MAE) and Spearman’s ρ was finally computed based on the test set, and used to compare and rank each algorithm. Results We analyzed N  = 4,581 patients with n  = 17,821 observations. Between 5 and 22 features were selected from the analysis of the training dataset comprising 3,436 patients with 13,257 observations. The best algorithm, a regularized linear model with stochastic gradient descent, could predict paO 2 values with σ ae  = 86.4 mmHg, MAPE = 16 %, adjusted R 2  = 0.77, RMSE = 44 mmHg and Spearman’s ρ = 0.83. Further improvement was possible by calibrating the algorithm with the first measured paO 2 /FiO 2 (p/F) ratio during surgery. Conclusion PaO 2 can be predicted by perioperative routine data in neurosurgical patients even before blood gas analysis. The prediction improves further when including the first measured p/F ratio, realizing quasi-continuous paO 2 monitoring.

• Pigat, Lena; Geisler, Benjamin P; Sheikhalishahi, Seyedmostafa; Sander, Julia; Kaspar, Mathias & Schmutz, Maximilian [Show all 11 contributors for this article] (2024). Predicting Hypoxia Using Machine Learning: Systematic Review. JMIR Medical Informatics. 12. doi: 10.2196/50642. Full text in Research Archive Show summary

  Abstract Background Hypoxia is an important risk factor and indicator for the declining health of inpatients. Predicting future hypoxic events using machine learning is a prospective area of study to facilitate time-critical interventions to counter patient health deterioration. Objective This systematic review aims to summarize and compare previous efforts to predict hypoxic events in the hospital setting using machine learning with respect to their methodology, predictive performance, and assessed population. Methods A systematic literature search was performed using Web of Science, Ovid with Embase and MEDLINE, and Google Scholar. Studies that investigated hypoxia or hypoxemia of hospitalized patients using machine learning models were considered. Risk of bias was assessed using the Prediction Model Risk of Bias Assessment Tool. Results After screening, a total of 12 papers were eligible for analysis, from which 32 models were extracted. The included studies showed a variety of population, methodology, and outcome definition. Comparability was further limited due to unclear or high risk of bias for most studies (10/12, 83%). The overall predictive performance ranged from moderate to high. Based on classification metrics, deep learning models performed similar to or outperformed conventional machine learning models within the same studies. Models using only prior peripheral oxygen saturation as a clinical variable showed better performance than models based on multiple variables, with most of these studies (2/3, 67%) using a long short-term memory algorithm. Conclusions Machine learning models provide the potential to accurately predict the occurrence of hypoxic events based on retrospective data. The heterogeneity of the studies and limited generalizability of their results highlight the need for further validation studies to assess their predictive performance.

• Sheikhalishahi, Seyedmostafa; Frasch, Martin G.; Kaspar, Mathias; Zaghdoudi, Sarra; Sander, Julia & Simon, Philipp [Show all 9 contributors for this article] (2024). Predicting Successful Weaning from Mechanical Ventilation by Reduction in Positive End-expiratory Pressure Level Using Machine Learning. PLOS Digital Health. 3(3). doi: 10.1371/journal.pdig.0000478. Full text in Research Archive Show summary

  Weaning patients from mechanical ventilation (MV) is a critical and resource intensive process in the Intensive Care Unit (ICU) that impacts patient outcomes and healthcare expenses. Weaning methods vary widely among providers. Prolonged MV is associated with adverse events and higher healthcare expenses. Predicting weaning readiness is a non-trivial process in which the positive end-expiratory pressure (PEEP), a crucial component of MV, has potential to be indicative but has not yet been used as the target. We aimed to predict successful weaning from mechanical ventilation by targeting changes in the PEEP-level using a supervised machine learning model. This retrospective study included 12,153 mechanically ventilated patients from Medical Information Mart for Intensive Care (MIMIC-IV) and eICU collaborative research database (eICU-CRD). Two machine learning models (Extreme Gradient Boosting and Logistic Regression) were developed using a continuous PEEP reduction as target. The data is splitted into 80% as training set and 20% as test set. The model’s predictive performance was reported using 95% confidence interval (CI), based on evaluation metrics such as area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), F1-Score, Recall, positive predictive value (PPV), and negative predictive value (NPV). The model’s descriptive performance was reported as the variable ranking using SHAP (SHapley Additive exPlanations) algorithm. The best model achieved an AUROC of 0.84 (95% CI 0.83–0.85) and an AUPRC of 0.69 (95% CI 0.67–0.70) in predicting successful weaning based on the PEEP reduction. The model demonstrated a Recall of 0.85 (95% CI 0.84–0.86), F1-score of 0.86 (95% CI 0.85–0.87), PPV of 0.87 (95% CI 0.86–0.88), and NPV of 0.64 (95% CI 0.63–0.66). Most of the variables that SHAP algorithm ranked to be important correspond with clinical intuition, such as duration of MV, oxygen saturation (SaO 2 ), PEEP, and Glasgow Coma Score (GCS) components. This study demonstrates the potential application of machine learning in predicting successful weaning from MV based on continuous PEEP reduction. The model’s high PPV and moderate NPV suggest that it could be a useful tool to assist clinicians in making decisions regarding ventilator management.

• Hurley, Eimir; Geisler, Benjamin Peter; Lupattelli, Angela; Poblador-Plou, Beatriz; Lassalle, Régis & Jové, Jérémy [Show all 30 contributors for this article] (2024). COVID-19 and pregnancy: A European study on pre- and post-infection medication use. European Journal of Clinical Pharmacology. ISSN 0031-6970. 80, p. 707–716. doi: 10.1007/s00228-024-03639-z. Full text in Research Archive Show summary

  Purpose The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. Methods We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. Results The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1–2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. Conclusion Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes.

• Kuo, Tsung-Ting; Pham, Anh; Edelson, Maxim E; Kim, Jihoon; Chan, Jason & Gupta, Yash [Show all 62 contributors for this article] (2023). Blockchain-enabled immutable, distributed, and highly available clinical research activity logging system for federated COVID-19 data analysis from multiple institutions. JAMIA Journal of the American Medical Informatics Association. ISSN 1067-5027. 30(6), p. 1167–1178. doi: 10.1093/jamia/ocad049. Full text in Research Archive Show summary

  Abstract Objective We aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions. Materials and Methods We preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain for immutability, transparency, and high availability of research communication. We measured run-time efficiency of contract deployment, network transactions, and confirmed the accuracy of recorded logs compared to a centralized baseline solution. Results The smart contract deployment took 4.5 s on an average. The time to record an activity log on blockchain was slightly over 2 s, versus 5–9 s for baseline. For querying, each query took on an average less than 0.4 s on blockchain, versus around 2.1 s for baseline. Discussion The low deployment, recording, and querying times confirm the feasibility of our cross-cloud, blockchain-based federated data analysis system. We have yet to evaluate the system on a larger network with multiple nodes per cloud, to consider how to accommodate a surge in activities, and to investigate methods to lower querying time as the blockchain grows. Conclusion Blockchain technology can be used to support federated data analysis among multiple institutions.

• Olds, Peter K.; Musinguzi, Nicholas; Geisler, Benjamin Peter & Haberer, Jessica E. (2023). Evaluating disparities by social determinants in hospital admission decisions for patients with COVID-19 quaternary hospital early in the pandemic. Medicine. ISSN 0025-7974. 102(10). doi: 10.1097/md.0000000000033178. Full text in Research Archive Show summary

  The COVID-19 pandemic has highlighted significant disparities in hospital outcomes when focusing on social determinants of health. Better understanding the drivers of these disparities is not only critical for COVID-19 care but also to ensure equitable treatment more generally. In this paper, we look at how hospital admission patterns, both to the medical ward and the intensive care unit (ICU), may have differed by race, ethnicity, and social determinants of health. We conducted a retrospective chart review of all patients who presented to the Emergency Department of a large quaternary hospital between March 8 and June 3, 2020. We built logistic regression models to analyze how race, ethnicity, area deprivation index, English as a primary language, homelessness, and illicit substance use impacted the likelihood of admission while controlling for disease severity and timing of admission in relation to the start of data collection. We had 1302 recorded Emergency Department visits of patients diagnosed with SARS-CoV-2. White, Hispanic, and African American patients made up 39.2%, 37.5%, and 10.4% of the population respectively. Primary language was recorded as English for 41.2% and non-English for 30% of patients. Among the social determinants of health assessed, we found that illicit drug use significantly increased the likelihood for admission to the medical ward (odds ratio 4.4, confidence interval 1.1–17.1, P  = .04), and that having a language other than English as a primary language significantly increased the likelihood of ICU admission (odds ratio 2.6, confidence interval 1.2–5.7, P  = .02). Illicit drug use was associated with an increased likelihood of medical ward admission, potentially due to clinician concerns for complicated withdrawal or blood-stream infections from intravenous drug use. The increased likelihood of ICU admission associated with a primary language other than English may have been driven by communication difficulties or differences in disease severity that our model did not detect. Further work is required to better understand drivers of disparities in hospital COVID-19 care.

• Olds, Peter K.; Musinguzi, Nicholas; Geisler, Benjamin Peter; Sarin, Pankaj & Haberer, Jessica E. (2023). Evaluating disparities in code status designation among patients admitted with COVID-19 at a quaternary care center early in the pandemic. Medicine. ISSN 0025-7974. 102(30). doi: 10.1097/md.0000000000034447. Full text in Research Archive Show summary

  The COVID-19 pandemic has highlighted disparities in outcomes by social determinants to health. It is unclear how much end-of-life discussions and a patient’s decision about code status (“do not resuscitate,” do not resuscitate, or “comfort measures only,” [CMO] orders) might contribute to in hospital disparities in care, especially given know racial inequities in end-of-life care. Here, we looked at factors associated with code status orders at the end of hospitalization for patients with COVID-19. We conducted a retrospective chart review of all patients who presented to the Emergency Department of a large quaternary hospital between 8 March and 3 June 2020. We used logistic regression modeling to quantify the degree to which social determinants of health, including race, ethnicity, area deprivation index (ADI), English as a primary language, homelessness, and illicit substance use might impact the likelihood of a particular code status at the end-of a patient’s hospitalization, while controlling for disease severity. Among social determinants to health, only white race (odds ratio [OR] 2.0; P = .03) and higher ADI (OR 1.2; P = .03) were associated with having a do not resuscitate or a CMO order. Additionally, we found that patients with white race (OR 2.9; P = .02) were more likely to carry a CMO order. Patient race and ADI were associated with different code status orders at the end of hospitalization. Differences in code status might have contributed to disparities in COVID-19 outcomes early in the pandemic, though further investigations are warranted.

• Geisler, Benjamin Peter; Cao, Khoa N.; Ryschon, Anne M.; Alavi, Karim; Komen, Niels & Pietzsch, Jan B. (2023). Cost associated with diverting ostomy after rectal cancer surgery: a transnational analysis. Surgical Endoscopy. ISSN 0930-2794. 37(10), p. 7759–7766. doi: 10.1007/s00464-023-10300-w. Full text in Research Archive Show summary

  Background: Diverting ileostomy and colostomy after total mesorectal excision reduces the risk of complications related to anastomotic leakages but is associated with a reduction in health-related quality of life and long-term economic consequences that are unknown. Our objective was to estimate the lifetime costs of stoma placement after rectal cancer resection in the U.S., England, and Germany. Methods: Input parameters were derived from quasi-systematic literature searches. Decision-analytic models with survival from colorectal cancer-adjusted life tables and country-specific stoma reversal proportions were created for the three countries to calculate lifetime costs. Main cost items were stoma maintenance costs and reimbursement for reversal procedures. Discounting was applied according to respective national guidelines. Sensitivity analysis was conducted to explore the impact of parameter uncertainty onto the results. Results: The cohort starting ages and median survival were 63 and 11.5 years for the U.S., 69 years and 8.5 years for England, and 71 and 6.5 years for Germany. Lifetime discounted stoma-related costs were $26,311, £9512, and €10,021, respectively. All three models were most sensitive to the proportion of ostomy reversal, age at baseline, and discount rate applied. Conclusion: Conservative model-based projections suggest that stoma care leads to significant long-term costs. Efforts to reduce the number of patients who need to undergo a diverting ostomy could result in meaningful cost savings.

• Wendt, Ralph; Fenves, Andrew Z. & Geisler, Benjamin Peter (2023). Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone. JAMA Network Open. 6(10). doi: 10.1001/jamanetworkopen.2023.40313. Full text in Research Archive Show summary

  Importance Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated. Objective To evaluate the efficacy and safety of urea for the treatment of SIADH. Evidence Review A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay. Findings Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized. Conclusions and Relevance In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.

• Heyne, Thomas; Negishi, Kay; Choi, Daniel; Saud, Ahad Al; Marinacci, Lucas & Smithedajkul, Patrick [Show all 15 contributors for this article] (2023). Handheld Lung Ultrasound to Detect COVID-19 Pneumonia in Inpatients: A Prospective Cohort Study. POCUS Journal. 8(2), p. 175–183. doi: 10.24908/pocus.v8i2.16484. Full text in Research Archive Show summary

  Background: Chest imaging, including chest X-ray (CXR) and computed tomography (CT), can be a helpful adjunct to nucleic acid test (NAT) in the diagnosis and management of Coronavirus Disease 2019 (COVID-19). Lung point of care ultrasound (POCUS), particularly with handheld devices, is an imaging alternative that is rapid, highly portable, and more accessible in low-resource settings. A standardized POCUS scanning protocol has been proposed to assess the severity of COVID-19 pneumonia, but it has not been sufficiently validated to assess diagnostic accuracy for COVID-19 pneumonia.  Purpose: To assess the diagnostic performance of a standardized lung POCUS protocol using a handheld POCUS device to detect patients with either a positive NAT or a COVID-19-typical pattern on CT scan.  Methods: Adult inpatients with confirmed or suspected COVID-19 and a recent CT were recruited from April to July 2020. Twelve lung zones were scanned with a handheld POCUS machine. Images were reviewed independently by blinded experts and scored according to the proposed protocol. Patients were divided into low, intermediate, and high suspicion based on their POCUS score.  Results: Of 79 subjects, 26.6% had a positive NAT and 31.6% had a typical CT pattern. The receiver operator curve for POCUS had an area under the curve (AUC) of 0.787 for positive NAT and 0.820 for a typical CT. Using a two-point cutoff system, POCUS had a sensitivity of 0.90 and 1.00 compared to NAT and typical CT pattern, respectively, at the lower cutoff; it had a specificity of 0.90 and 0.89 compared to NAT and typical CT pattern at the higher cutoff, respectively.  Conclusions: The proposed lung POCUS protocol with a handheld device showed reasonable diagnostic performance to detect inpatients with a positive NAT or typical CT pattern for COVID-19. Particularly in low-resource settings, POCUS with handheld devices may serve as a helpful adjunct for persons under investigation for COVID-19 pneumonia.

• Tchétché, Didier; Gennes, Coline Dubois de; Cormerais, Quentin; Geisler, Benjamin Peter; Dutot, Camille & Wilquin-Bequet, Fanny [Show all 9 contributors for this article] (2023). Cost-effectiveness of transcatheter aortic valve implantation in patients at low surgical risk in France: a model-based analysis of the Evolut LR trial. European Journal of Health Economics. ISSN 1618-7598. doi: 10.1007/s10198-023-01590-x. Full text in Research Archive
• Pietzsch, Jan B.; Geisler, Benjamin Peter; Iken, Annabelle R.; Wijck, Iris P. S. van; Holewijn, Suzanne & Reijnen, Michel M. P. J. (2022). Cost-Effectiveness of Urea Excipient-Based Drug-Coated Balloons for Chronic Limb-Threatening Ischemia from Femoropopliteal Disease in the Netherlands and Germany. Cardiovascular and Interventional Radiology. ISSN 0174-1551. 45(3), p. 298–305. doi: 10.1007/s00270-021-03050-6. Full text in Research Archive Show summary

  Purpose: Drug-coated balloons (DCBs) for femoropopliteal peripheral artery disease have been shown to be clinically superior and cost-effective compared to conventional percutaneous transluminal angioplasty (PTA). However, few studies enrolled patients with chronic limb-threatening ischemia (CLTI). Our objective was to study the cost-effectiveness of endovascular treatment with versus without DCB in CLTI patient populations in the Netherlands and Germany. Material and methods: Target lesion revascularization (TLR) and major amputation rates were obtained from the CLTI subgroup of the IN.PACT Global study. Rates for "status quo" treatment involving PTA with primary or bailout stenting were derived from systematic literature search. Costs and cost-effectiveness were calculated using a decision-analytic Markov model considering, in the base case, a 2-year horizon, and strategy-specific quality-adjusted life year (QALY) gains calculated from survival and health state-specific utilities. A willingness-to-pay threshold of €50,000/QALY was assumed, and extensive sensitivity analyses were performed. Results: Model-projected 24-month probabilities of TLR were 26.2% and 32.8% for treatment with and without DCB, and probabilities for amputation were 2.8% and 11.9%, respectively. DCB added 0.017 QALYs while saving €1,030 in the Dutch setting and €513 in the German setting, respectively. DCB was found dominant or cost-effective across a wide range of assumptions. Conclusion: Urea excipient drug-coated balloon therapy for treating CLTI from femoropopliteal artery disease is associated with improved patient outcomes and expected overall cost savings to payers in the Dutch and German healthcare systems, rendering it a cost-effective and likely dominant treatment strategy.

• Du, Shangming; Mansmann, Ulrich; Geisler, Benjamin Peter; Li, Yingxia & Hornung, Roman (2022). A Diagnostic Model for Kawasaki Disease Based on Immune Cell Characterization From Blood Samples. Frontiers in Pediatrics. 9. doi: 10.3389/fped.2021.769937. Full text in Research Archive Show summary

  Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. However, distinguishing KD from febrile infections early in the disease course remains difficult. Our goal was to estimate the immune cell composition in KD patients and febrile controls (FC), and to develop a tool for KD diagnosis. Methods: We used a machine-learning algorithm, CIBERSORT, to estimate the proportions of 22 immune cell types based on blood samples from children with KD and FC. Using these immune cell compositions, a diagnostic score for predicting KD was then constructed based on LASSO regression for binary outcomes. Results: In the training set ( n = 496), a model was fit which consisted of eight types of immune cells. The area under the curve (AUC) values for diagnosing KD in a held-out test set ( n = 212) and an external validation set ( n = 36) were 0.80 and 0.77, respectively. The most common cell types in KD blood samples were monocytes, neutrophils, CD4 + -naïve and CD8 + T cells, and M0 macrophages. The diagnostic score was highly correlated to genes that had been previously reported as associated with KD, such as interleukins and chemokine receptors, and enriched in reported pathways, such as IL-6/JAK/STAT3 and TNFα signaling pathways. Conclusion: Altogether, the diagnostic score for predicting KD could potentially serve as a biomarker. Prospective studies could evaluate how incorporating the diagnostic score into a clinical algorithm would improve diagnostic accuracy further.

• Pietzsch, Jan B.; Geisler, Benjamin Peter; Manda, Bharati; Misra, Sanjay; Lyden, Sean P. & Pflederer, Timothy A. [Show all 7 contributors for this article] (2022). IN.PACT AV Access Trial: Economic Evaluation of Drug-Coated Balloon Treatment for Dysfunctional Arteriovenous Fistulae Based on 12-Month Clinical Outcomes. Journal of Vascular and Interventional Radiology. ISSN 1051-0443. 33(8), p. 895–902. doi: 10.1016/j.jvir.2022.04.014. Full text in Research Archive Show summary

  Purpose: To study, from a U.S. payer's perspective, the economic consequences of drug-coated balloon (DCB) versus standard percutaneous transluminal angioplasty (PTA) use for the treatment of stenotic lesions in dysfunctional hemodialysis arteriovenous fistulae. Materials and methods: Cost differences between DCBs and PTA at year 1 and beyond were calculated via 2 methods. The first approach used the mean absolute number of trial-observed access circuit reinterventions through 12 months (0.65 ± 1.05 vs 1.05 ± 1.18 events per patient for DCBs and PTA, respectively) and projected treatment outcomes to 3 years. The second approach was based on the trial-observed access circuit primary patency rates at 12 months (53.8% vs 32.4%) and calculated the cost difference on the basis of previously published Medicare cost for patients who maintained or did not maintain primary patency. Assumptions regarding DCB device prices were tested in sensitivity analyses, and the numbers needed to treat were calculated. Results: Using the absolute number of access circuit reinterventions approach, the DCB strategy resulted in an estimated per-patient savings of $1,632 at 1 year and $4,263 at 3 years before considering the DCB device cost. The access circuit primary patency approach was associated with a per-patient cost savings of $2,152 at 1 year and $3,894 at 2.5 years of follow-up. At the theoretical DCB device reimbursement of $1,800, savings were $1,680 and $2,049 at 2.5 and 3 years, respectively. The one-year NNT of DCB compared to PTA was 2.48. Conclusions: Endovascular therapy for arteriovenous access stenosis with the IN.PACT AV DCB can be expected to be cost-saving if longer follow-up data confirm its clinical effectiveness.

• Abid, Muhammad Hasan; Lucier, David J.; Hidrue, Michael K. & Geisler, Benjamin P. (2022). The Effect of Standardized Hospitalist Information Cards on the Patient Experience: a Quasi-Experimental Prospective Cohort Study. Journal of General Internal Medicine (JGIM). ISSN 0884-8734. 37(15), p. 3931–3936. doi: 10.1007/s11606-022-07674-3. Full text in Research Archive Show summary

  Abstract Background Communication with clinicians is an important component of a hospitalized patient’s experience. Objective To test the impact of standardized hospitalist information cards on the patient experience. Design Quasi-experimental study in a U.S. tertiary-care center. Participants All-comer medicine inpatients. Interventions Standardized hospitalist information cards containing name and information on a hospitalist’s role and availability vs. usual care. Main Measures Patients’ rating of the overall communication as excellent (“top-box” score); qualitative feedback summarized via inductive coding. Key Results Five hundred sixty-six surveys from 418 patients were collected for analysis. In a multivariate regression model, standardized hospitalist information cards significantly improved the odds of a “top-box” score on overall communication (odds ratio: 2.32; 95% confidence intervals: 1.07–5.06). Other statistically significant covariates were patient age (0.98, 0.97–0.99), hospitalist role (physician vs. advanced practice provider, 0.56; 0.38–0.81), and hospitalist-patient gender combination (female-female vs. male-male, 2.14; 1.35–3.40). Eighty-seven percent of patients found the standardized hospitalist information cards useful, the perceived most useful information being how to contact the hospitalist and knowing their schedule. Conclusions Hospitalized patients’ experience of their communication with hospitalists may be improved by using standardized hospitalist information cards. Younger patients cared for by a team with an advanced practice provider, as well as female patients paired with female providers, were more likely to be satisfied with the overall communication. Assessing the impact of information cards should be studied in other settings to confirm generalizability.

• Nowatzke, Joseph; Guedeney, Paul; Palaskas, Nicholas; Lehmann, Lorenz; Ederhy, Stephane & Zhu, Han [Show all 91 contributors for this article] (2022). Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis: Report from an international registry. European Journal of Cancer. ISSN 0959-8049. 177, p. 197–205. doi: 10.1016/j.ejca.2022.07.018. Full text in Research Archive Show summary

  Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis. Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram. Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057). Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis.

• Ghosh, Arnab K.; Demetres, Michelle R.; Geisler, Benjamin Peter; Ssebyala, Shakirah N.; Yang, Tianyi & Shapiro, Martin F. [Show all 8 contributors for this article] (2022). Impact of Hurricanes and Associated Extreme Weather Events on Cardiovascular Health: A Scoping Review. Environmental Health Perspectives. ISSN 0091-6765. 130(11), p. 116003-1–116003-12. doi: https:/pmc.ncbi.nlm.nih.gov/articles/PMC9710380/pdf/ehp11252.pdf. Full text in Research Archive Show summary

  Background: The frequency and destructiveness of hurricanes and related extreme weather events (e.g., cyclones, severe storms) have been increasing due to climate change. A growing body of evidence suggests that victims of hurricanes have increased incidence of cardiovascular disease (CVD), likely due to increased stressors around time of the hurricane and in their aftermath. Objectives: The objective was to systematically examine the evidence of the association between hurricanes (and related extreme weather events) and adverse CVD outcomes with the goal of understanding the gaps in the literature. Methods: A comprehensive literature search of population-level and cohort studies focused on CVD outcomes (i.e., myocardial infarction, stroke, and heart failure) related to hurricanes, cyclones, and severe storms was performed in the following databases from inception to December 2021: Ovid MEDLINE, Ovid EMBASE, Web of Science, and The Cochrane Library. Studies retrieved were then screened for eligibility against predefined inclusion/exclusion criteria. Studies were then qualitatively synthesized based on the time frame of the CVD outcomes studied and special populations that were studied. Gaps in the literature were identified based on this synthesis. Results: Of the 1,103 citations identified, 48 met our overall inclusion criteria. We identified articles describing the relationship between CVD and extreme weather, primarily hurricanes, based on data from the United States (42), Taiwan (3), Japan (2), and France (1). Outcomes included CVD and myocardial infarction-related hospitalizations (30 studies) and CVVD-related mortality (7 studies). Most studies used a retrospective study design, including one case-control study, 39 cohort studies, and 4 time-series studies. Discussion: Although we identified a number of papers that reported evaluations of extreme weather events and short-term adverse CVD outcomes, there were important gaps in the literature. These gaps included a) a lack of rigorous long-term evaluation of hurricane exposure, b) lack of investigation of hurricane exposure on vulnerable populations regarding issues related to environmental justice, c) absence of research on the exposure of multiple hurricanes on populations, and d) absence of an exploration of mechanisms leading to worsened CVD outcomes. Future research should attempt to fill these gaps, thus providing an important evidence base for future disaster-related policy.

• O’neil, Jessica C; Geisler, Benjamin Peter; Rusinak, Donna; Bassett, Ingrid V; Triant, Virginia A & Mckenzie, Rachael [Show all 8 contributors for this article] (2022). Discharge to post–acute care and other predictors of prolonged length of stay during the initial COVID-19 surge: a single site analysis. International Journal for Quality in Health Care. ISSN 1353-4505. 35(1). doi: 10.1093/intqhc/mzac098. Full text in Research Archive Show summary

  Abstract Background During the initial surge of coronavirus disease 2019 (COVID-19), health-care utilization fluctuated dramatically, straining acute hospital capacity across the USA and potentially contributing to excess mortality. Methods This was an observational retrospective study of patients with COVID-19 admitted to a large US urban academic medical center during a 12-week COVID-19 surge in the Spring of 2020. We describe patterns in length of stay (LOS) over time. Our outcome of interest was prolonged LOS (PLOS), which we defined as 7 or more days. We performed univariate analyses of patient characteristics, clinical outcomes and discharge disposition to evaluate the association of each variable with PLOS and developed a final multivariate model via backward elimination, wherein all variables with a P-value above 0.05 were eliminated in a stepwise fashion. Results The cohort included 1366 patients, of whom 13% died and 29% were readmitted within 30 days. The LOS (mean: 12.6) fell over time (P &lt; 0.0001). Predictors of PLOS included discharge to a post–acute care (PAC) facility (odds ratio [OR]: 11.9, 95% confidence interval [CI] 2.6–54.0), uninsured status (OR 3.2, CI 1.1–9.1) and requiring intensive care and intubation (OR 18.4, CI 11.5–29.6). Patients had a higher readmission rate if discharged to PAC facilities (40%) or home with home health agency (HHA) services (38%) as compared to patients discharged home without HHA services (26%) (P &lt; 0.0001). Conclusion Patients hospitalized with COVID-19 during a US COVID-19 surge had a PLOS and high readmission rate. Lack of insurance, an intensive care unit stay and a decision to discharge to a PAC facility were associated with a PLOS. Efforts to decrease LOS and optimize hospital capacity during COVID-19 surges may benefit from focusing on increasing PAC and HHA capacity and resources.

• Pietzsch, Jan B; Geisler, Benjamin P; Daniels, Matthew J; Busca, Rachele M; Tarantini, Giuseppe & Søndergaard, Lars [Show all 7 contributors for this article] (2021). An assessment of annual procedure volumes and therapy adoption of transcatheter closure of patent foramen ovale in four European countries. European Stroke Journal. ISSN 2396-9873. 6(1), p. 72–80. doi: 10.1177/2396987320939804. Full text in Research Archive Show summary

  Abstract Introduction Patent foramen ovale closure reduces recurrence of cryptogenic ischaemic stroke compared to anti-platelet therapy. Our goal was to determine procedure volumes and closure utilisation as a proportion of candidates in four large European countries. Patients and methods National statistics were obtained for Germany, England, France, and Italy for the last available five years (2014–2018). Eligibility was aligned to the enrolment criteria of pivotal trials and current consensus documents. Stroke and transient ischaemic attack incidences were obtained from epidemiological registries and claims data. The eligible candidate pool for analysis included current year candidates plus untreated patients from the prior two years. Absolute strokes avoided assumed the hazard ratio for ischaemic stroke recurrence from a recent meta-analysis. Results In 2018, closure incidence rates were 5.64, 0.53, 2.94 and 5.26 per 100,000 in Germany, England, France and Italy, respectively. This reflects five-year increases of 128% in Germany, 462% in France and 36% in Italy (p &lt; 0.05 for all), and a decline of 37% in England. The proportions of treated patients versus candidates for the combined stroke and transient ischaemic attack pool were 55%, 30%, 80%, and 6%, respectively. Discussion Patent foramen ovale closure volumes increased after the 2017 announcement of positive trial results but still differ substantially across large European countries. If all closure candidates in 2018 with prior ischaemic stroke were treated, the resulting absolute reduction of recurrent ischaemic strokes, compared to anti-platelet therapy alone, would be between 782 and 2295 across the four countries over five years. Conclusion Many eligible patients at risk for a recurrent cryptogenic event might remain untreated due to regional practice variations.

• Geisler, Benjamin P.; Zahabi, Lara; Lang, Adam Edward; Eastwood, Naomi; Tennant, Elaine & Lukic, Ljiljana [Show all 20 contributors for this article] (2021). Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review. Systematic Reviews. 10(1). doi: 10.1186/s13643-021-01693-7. Full text in Research Archive Show summary

  Abstract Background Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. Methods This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. Discussion The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. Trial registration PROSPERO 2020 CRD42020175648

• Roseleur, Jacqueline; Gonzalez-Chica, David A.; Bernardo, Carla O.; Geisler, Benjamin Peter; Karnon, Jonathan & Stocks, Nigel P. (2021). Blood pressure control in Australian general practice: analysis using general practice records of 1.2 million patients from the MedicineInsight database. Journal of Hypertension. ISSN 0263-6352. 39(6), p. 1134–1142. doi: 10.1097/hjh.0000000000002785. Full text in Research Archive Show summary

  Introduction: Hypertension is mostly managed in primary care. This study investigated the prevalence of diagnosed hypertension in Australian general practice and whether hypertension control is influenced by sociodemographic characteristics, duration since diagnosis or prescription of antihypertensive medications. Methods: Cross-sectional study using a large national database of electronic medical records of patients attending general practice in 2017 (MedicineInsight). Results: Of 1.2 million ‘regular’ patients (one or more consultations per year in every year from 2015 to 2017), 39.8% had a diagnosis of hypertension (95% confidence interval 38.7–40.9). Of these, 85.3% had their blood pressure (BP) recorded in 2017, and 54.9% (95% confidence interval 54.2–55.5) had controlled hypertension (<140/90 mmHg). BP control was lower in females (54.1%) compared with males (55.7%) and in the oldest age group (52.0%), with no differences by socioeconomic status. Hypertension control was lower among ‘regular’ patients recently diagnosed (6–12 months = 48.6% controlled) relative to those more than 12 months since diagnosis (1–2 years = 53.6%; 3–5 years 55.5%; >5 years = 55.0%). Among recently diagnosed ‘regular’ patients, 59.2% had no record of being prescribed antihypertensive therapy in the last 6 months of the study, of which 44.3% had controlled hypertension. For those diagnosed more than 5 years ago, 37.4% had no record of being prescribed antihypertensive patients, and 56% had normal BP levels. Conclusion: Although the prevalence of hypertension varied by socidemographics, there were no differences in BP assessment or control by socioeconomic status. Hypertension control remains a challenge in primary care, and electronic medical records provide an opportunity to assess hypertension management.

• Ghosh, Arnab K.; Geisler, Benjamin Peter & Ibrahim, Said (2021). Racial/ethnic and socioeconomic variations in hospital length of stay. Medicine. ISSN 0025-7974. 100(20). doi: 10.1097/md.0000000000025976. Full text in Research Archive Show summary

  Abstract Disparities by race/ethnicity and socioeconomic status (SES) exist in rehospitalization rates and inpatient mortality rates. Few studies have examined how length of stay (LOS, a measure of hospital efficiency/quality) differs by race/ethnicity and SES. This study's objective was to determine whether differences in risk-adjusted LOS exist by race/ethnicity and SES Using a retrospective cohort of 1,432,683 medical and surgical discharges, we compared risk-adjusted LOS, in days, by race/ ethnicity and SES (median household income by patient ZIP code in quartiles), using generalized linear models controlling for demographic and clinical factors, and differences between hospitals and between diagnoses. White patients were on average older than both Black and Hispanic patients, had more chronic conditions, and had a higher inpatient mortality risk. In adjusted analyses, Black patients had a significantly longer LOS than White patients (0.25-day difference when discharged to home and 0.23-day difference when discharged to non-home destinations, both P<.001); there was no difference between Hispanic and White patients. Wealthier patients had a shorter LOS than poorer patients (0.16-day difference when discharged to home and 0.06-day difference when discharged to nonhome destinations, both P<.001). These differences by race/ethnicity reversed for Medicaid patients. Disparities in LOS exist based on a patient's race/ethnicity and SES. Black and poorer patients, but not Hispanic patients, have longer LOS compared to White and wealthier patients. In aggregate, these differences may be related to trust and implicit bias and have implications for use of LOS as a quality metric. Future research should examine the drivers of these disparities.

• Hoechter, Dominik Johannes; Becker-Pennrich, Andrea Sabine; Geisler, Benjamin Peter; Zwissler, Bernhard; Irlbeck, Michael & Ramanathan, Kollengode [Show all 12 contributors for this article] (2021). Letter to the editor regarding Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Critical Care. ISSN 1364-8535. 25(1), p. 285–285. doi: 10.1186/s13054-021-03702-6. Full text in Research Archive
• Asukai, Yumi; Briggs, Andrew; Garrison, Louis P.; Geisler, Benjamin Peter; Neumann, Peter J. & Ollendorf, Daniel A. (2021). Principles of Economic Evaluation in a Pandemic Setting: An Expert Panel Discussion on Value Assessment During the Coronavirus Disease 2019 Pandemic. PharmacoEconomics (Auckland). ISSN 1170-7690. 39(11), p. 1201–1208. doi: 10.1007/s40273-021-01088-5. Full text in Research Archive Show summary

  As the coronavirus disease 2019 (COVID-19) pandemic continues to generate significant morbidity and mortality as well as economic and societal impacts, the landscape of potential treatments has slowly begun to broaden. In the case of a novel disease with widespread consequences, society is more likely to place significant value on interventions that reduce the outsized economic burden of COVID-19. Treatments for severe disease will have a different value profile to that of large-scale vaccines because of their application in targeted and potentially small subsets of those with symptomatic disease vs broad deployment as a preventative measure. Where vaccines reduce transmissibility of COVID-19, use of therapeutics will target symptoms, up to and including death for infected individuals. This paper describes discussions from a virtual expert panel that met to attempt a consensus on how existing principles of economic evaluation should be applied to therapeutics that emerge in a pandemic setting, with specific focus on severe hospitalised cases of COVID-19. The panel concluded that the core principles of economic evaluation do not need to be drastically overhauled to meet the challenges of a pandemic, but that there are several additional elements of value such as equity, disease severity, insurance value, and scientific and family spillover effects that should be considered when presenting results to decision makers. The panel also highlighted the persistent challenges on how society should value novel therapies, such as the appropriate cost-effectiveness threshold to apply, which are particularly salient during a pandemic.

• O'Neil, Jessica C.; Geisler, Benjamin P.; Rusinak, Donna; Bassett, Ingrid V.; Triant, Virginia A. & McKenzie, Rachael [Show all 8 contributors for this article] (2021). Case management in a COVID‐19 surge: A single‐institution study of disposition and access to post‐acute care. Journal of The American Geriatrics Society. ISSN 0002-8614. 70(2), p. 372–375. doi: 10.1111/jgs.17595. Full text in Research Archive
• Geisler, Benjamin Peter; Kingsley, Thomas C.; Izmirly, Peter M.; Costedoat-Chalumeau, Nathalie & Roswell, Robert O. (2020). Hydroxychloroquine Toxicity: Concurrent Complete Heart Block and Severe Left Ventricular Systolic Dysfunction. A Clinical Image. Journal of clinical rheumatology. ISSN 1076-1608. 27(8S), p. S657–S658. doi: 10.1097/rhu.0000000000001647. Full text in Research Archive
• Pietzsch, Jan Benjamin; Richter, Ann-Kathrin; Randerath, Winfried; Steffen, Armin; Liu, Shan & Geisler, Benjamin P. [Show all 8 contributors for this article] (2019). Clinical and Economic Benefits of Upper Airway Stimulation for Obstructive Sleep Apnea in a European Setting. Respiration. ISSN 0025-7931. 98(1), p. 38–47. doi: 10.1159/000497101. Full text in Research Archive Show summary

  Background: Upper airway stimulation (UAS) is a treatment approach for patients with moderate-to-severe obstructive sleep apnea who cannot adhere to continuous positive airway pressure therapy. Objective: The objective was to evaluate added patient benefit and cost-effectiveness of UAS in the German health care system. Methods: We used a decision-analytic Markov model to project major adverse cardiovascular or cerebrovascular events (myocardial infarction [MI] or stroke), motor vehicle collision (MVC), mortality, quality-adjusted life years (QALYs), and costs. The assumed reduction in the apnea-hypopnea index with UAS compared to no treatment is based on German real-world data. Other input data were derived from the literature, public statistics, and multivariate regression. Cost-effectiveness was evaluated in Euros per QALY gained, both discounted at 3%. Results: UAS was projected to reduce event risks (10-year relative risk for stroke, MI, cardiovascular death, and MVC: 0.76, 0.64, 0.65, and 0.34, respectively), and to increase survival by 1.27 years. While the UAS strategy incurred an additional 1.02 QALYs within the patient lifetime, there were also additional costs of EUR 45,196, resulting in an incremental cost-effectiveness ratio of EUR 44,446 per QALY gained. -Conclusions: In the present model-based analysis, UAS therapy provides meaningful benefit to patient-relevant endpoints and is a cost-effective therapy in the German setting.

• Geisler, Benjamin Peter; Jilg, N.; Patton, R.G. & Pietzsch, J.B. (2019). Model to evaluate the impact of hospital-based interventions targeting false-positive blood cultures on economic and clinical outcomes. Journal of Hospital Infection. ISSN 0195-6701. 102(4), p. 438–444. doi: 10.1016/j.jhin.2019.03.012. Full text in Research Archive Show summary

  Background: Blood culture contamination (BCC) increases length of stay (LOS) and leads to unnecessary antimicrobial therapy and/or hospital-acquired conditions (HACs). Aim: To quantify the magnitude of additional LOS, costs to hospitals and society, and harm to patients attributable to BCC. Methods: A retrospective matched survival analysis was performed involving hospitalized patients with septicaemia-compatible symptoms. BCC costs, HACs and potential savings were calculated based on the primary LOS data, a modified Delphi process and published sources. The cost analysis compared standard care with interventions for reducing BCC, and estimated annual economic and clinical consequences for a typical hospital and for the USA as a whole. Findings: Patients with BCC experienced a mean increase in LOS of 2.35 days (P=0.0076). Avoiding BCC would decrease costs by $6463 [$4818 from inpatient care (53% of which was from reduced LOS) and 26% from reduced antibiotic use]. Annually, in a typical 250- to 400-bed hospital, employing phlebotomists would save $1.3 million and prevent 24 HACs (including two cases of Clostridium difficile infection); based on clinical efficacy evidence, use of the studied initial specimen diversion device (ISDD) would save $1.9 million and prevent 34 HACs (including three cases of C. difficile infection). In the USA, the respective strategies would prevent 69,300 and 102,900 HACs (including 6000 and 8900 cases of C. difficile infection) and save $5 and $7.5 billion. Conclusion: Costs and clinical burdens associated with false-positive cultures are substantial and can be reduced by available interventions, including phlebotomists and use of ISDD.

• Upadhyay, Vivek A.; Geisler, Benjamin Peter; Sun, Lova; Uhl, Lynne; Kaufman, Richard M. & Stowell, Christopher [Show all 8 contributors for this article] (2019). Utilizing a PLASMIC score‐based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative. British Journal of Haematology. ISSN 0007-1048. 186(3), p. 490–498. doi: 10.1111/bjh.15932. Full text in Research Archive Show summary

  Summary The PLASMIC score is a recently described clinical scoring algorithm that rapidly assesses the probability of severe ADAMTS 13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency among patients presenting with microangiopathic haemolytic anaemia. Using a large multi‐institutional cohort, we explored whether an approach utilizing the PLASMIC score to risk‐stratify patients with suspected immune thrombotic thrombocytopenic purpura ( iTTP ) could lead to significant cost savings. Our consortium consists of institutions with an unrestricted approach to ADAMTS 13 testing (Group A) and those that require pre‐approval by the transfusion medicine service (Group B). Institutions in Group A tested more patients than those in Group B ( P  < 0·001) but did not identify more cases of iTTP ( P  = 0·29) or have lower iTTP ‐related mortality ( P  = 0·84). Decision tree cost analysis showed that applying a PLASMIC score‐based strategy to screen patients for ADAMTS 13 testing in Group A would have reduced costs by approximately 27% over the 12‐year period of our study compared to the current approach. Savings were primarily driven by a reduction in unnecessary therapeutic plasma exchanges, but lower utilization of ADAMTS 13 testing and subspecialty consultations also contributed. Our data indicate that using the PLASMIC score to guide ADAMTS 13 testing and the management of patients with suspected iTTP could be associated with significant cost savings.

• Geisler, Benjamin Peter; Jørgensen, Troels H.; Thyregod, Hans Gustav H.; Pietzsch, Jan Benjamin & Søndergaard, Lars (2019). Cost-effectiveness of transcatheter versus surgical aortic valve replacement in patients at lower surgical risk: results from the NOTION trial. EuroIntervention. ISSN 1774-024X. 15(11), p. e959–e967. doi: 10.4244/eij-d-18-00847. Full text in Research Archive Show summary

  Aims: The aim of this study was to estimate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients at lower surgical risk. Methods and results: Discounted costs from a societal perspective and effectiveness as quality-adjusted life years (QALYs) were projected to lifetime via a decision-analytic model calibrated to 60-month data from the NOTION trial. The base case assumed a scenario in which any mortality benefit would gradually fade out over time, with other scenarios explored in sensitivity analyses. The incremental cost-effectiveness ratio (ICER) was compared to the country-specific willingness-to-pay (WTP) threshold of 1.13 million Danish kroner (DKK). The base case ICER was DKK 696,264/QALY (around €72,100/QALY via purchasing parity adjustment). Variation in long-term mortality beyond five years led to limited variation of incremental costs (DKK 64,200 to 64,600), but a more pronounced variation in incremental QALYs (0.07 to 0.19 QALYs for most conservative and optimistic assumptions, compared to base case of 0.09 QALYs). All resulting ICERs (range DKK 334,200 to DKK 904,100 per QALY gained) were below the WTP threshold. Conclusions: TAVI in a cohort of primarily low surgical risk patients was found to be a cost-effective treatment strategy in the Danish healthcare system. Cost-effectiveness analyses in other settings are warranted as are registries given the sensitivity of the model to long-term mortality.

• Kaul, Viren; Bhan, Rohit; Stewart, Nancy H.; Behrens, Deanna M.; Gutman, Amy & Dangayach, Neha [Show all 8 contributors for this article] (2019). Study Comparing Traditional Versus Alternative Metrics to Measure the Impact of the Critical Care Medicine Literature. Critical Care Explorations. 1(8). doi: 10.1097/cce.0000000000000028. Full text in Research Archive Show summary

  Our objective was to evaluate the association between traditional metrics such as Impact Factor and Eigenfactor with respect to alternative metrics. The Altmetric Attention Score for the top nine pulmonary and critical care journals was compared with Impact Factor, Eigenfactor, and citations over two time periods (2007–2011 and 2012–2016). There was a significant increase in the Altmetric Attention Score (52 from 2007 to 2011 vs 1,061 from 2012 to 2016; p < 0.001) but no significant differences in Total Citations, Impact Factor, or Eigenfactor. There was a strong positive correlation between citations and Altmetric Attention Score, negative correlations between Eigenfactor and Altmetric Attention Score for most journals, and no clear association between Impact Factor and Altmetric Attention Score. Over time, the digital reach of traditional publications has increased significantly, while no significant increase was noted for the traditional metrics. These findings likely reflect discussions of articles online that are not captured by traditional metrics and hence their impact on the community at large.

• Rush, Barret; Tyler, Patrick D.; Stone, David J.; Geisler, Benjamin Peter; Walley, Keith R. & Celi, Leo Anthony (2018). Outcomes of Ventilated Patients With Sepsis Who Undergo Interhospital Transfer: A Nationwide Linked Analysis. Critical Care Medicine. ISSN 0090-3493. 46(1), p. e81–e86. doi: 10.1097/ccm.0000000000002777. Full text in Research Archive Show summary

  Objectives: The outcomes of critically ill patients who undergo interhospital transfer are not well understood. Physicians assume that patients who undergo interhospital transfer will receive more advanced care that may translate into decreased morbidity or mortality relative to a similar patient who is not transferred. However, there is little empirical evidence to support this assumption. We examined country-level U.S. data from the Nationwide Readmissions Database to examine whether, in mechanically ventilated patients with sepsis, interhospital transfer is associated with a mortality benefit. Design: Retrospective data analysis using complex survey design regression methods with propensity score matching. Setting: The Nationwide Readmissions Database contains information about hospital admissions from 22 States, accounting for roughly half of U.S. hospitalizations; the database contains linkage numbers so that admissions and transfers for the same patient can be linked across 1 year of follow-up. Patients: From the 2013 Nationwide Readmission Database Sample, 14,325,172 hospital admissions were analyzed. There were 61,493 patients with sepsis and on mechanical ventilation. Of these, 1,630 patients (2.7%) were transferred during their hospitalization. A propensity-matched cohort of 1,630 patients who did not undergo interhospital transfer was identified. Interventions: None. Measurements and Main Results: The exposure of interest was interhospital transfer to an acute care facility. The primary outcome was hospital mortality; the secondary outcome was hospital length of stay. The propensity score included age, gender, insurance coverage, do not resuscitate status, use of renal replacement therapy, presence of shock, and Elixhauser comorbidities index. After propensity matching, interhospital transfer was not associated with a difference in in-hospital mortality (12.3% interhospital transfer vs 12.7% non–interhospital transfer; p = 0.74). However, interhospital transfer was associated with a longer total hospital length of stay (12.8 d interquartile range, 7.7–21.6 for interhospital transfer vs 9.1 d interquartile range, 5.1–17.0 for non–interhospital transfer; p < 0.01). Conclusions: Patients with sepsis requiring mechanical ventilation who underwent interhospital transfer did not have improved outcomes compared with a cohort with matched characteristics who were not transferred. The study raises questions about the risk-benefit profile of interhospital transfer as an intervention.

• Tyler, Patrick D.; Stone, David J.; Geisler, Benjamin Peter; McLennan, Stuart; Celi, Leo Anthony & Rush, Barret (2018). Racial and Geographic Disparities in Interhospital ICU Transfers. Critical Care Medicine. ISSN 0090-3493. 46(1), p. e76–e80. doi: 10.1097/ccm.0000000000002776. Full text in Research Archive Show summary

  Objectives: Interhospital transfer, a common intervention, may be subject to healthcare disparities. In mechanically ventilated patients with sepsis, we hypothesize that disparities not disease related would be found between patients who were and were not transferred. Design: Retrospective cohort study. Setting: Nationwide Inpatient Sample, 2006–2012. Patients: Patients over 18 years old with a primary diagnosis of sepsis who underwent mechanical ventilation. Interventions: None. Measurements and Main Results: We obtained age, gender, length of stay, race, insurance coverage, do not resuscitate status, and Elixhauser comorbidities. The outcome used was interhospital transfer from a small- or medium-sized hospital to a larger acute care hospital. Of 55,208,382 hospitalizations, 46,406 patients met inclusion criteria. In the multivariate model, patients were less likely to be transferred if the following were present: older age (odds ratio, 0.98; 95% CI, 0.978–0.982), black race (odds ratio, 0.79; 95% CI, 0.70–0.89), Hispanic race (odds ratio, 0.79; 95% CI, 0.69–0.90), South region hospital (odds ratio, 0.79; 95% CI, 0.72–0.88), teaching hospital (odds ratio, 0.31; 95% CI, 0.28–0.33), and do not resuscitate status (odds ratio, 0.19; 95% CI, 0.15–0.25). Conclusions: In mechanically ventilated patients with sepsis, we found significant disparities in race and geographic location not explained by medical diagnoses or illness severity.

• Faucett, Scott C.; Geisler, Benjamin Peter; Chahla, Jorge; Krych, Aaron J.; Kurzweil, Peter R. & Garner, Abigail M. [Show all 9 contributors for this article] (2018). Meniscus Root Repair vs Meniscectomy or Nonoperative Management to Prevent Knee Osteoarthritis After Medial Meniscus Root Tears: Clinical and Economic Effectiveness. American Journal of Sports Medicine. ISSN 0363-5465. 47(3), p. 762–769. doi: 10.1177/0363546518755754. Full text in Research Archive Show summary

  Background: Medial meniscus root tears are a common knee injury and can lead to accelerated osteoarthritis, which might ultimately result in a total knee replacement. Purpose: To compare meniscus repair, meniscectomy, and nonoperative treatment approaches among middle-aged patients in terms of osteoarthritis development, total knee replacement rates (clinical effectiveness), and cost-effectiveness. Study Design: Meta-analysis and cost-effectiveness analysis. Methods: A systematic literature search was conducted. Progression to osteoarthritis was pooled and meta-analyzed. A Markov model projected strategy-specific costs and disutilities in a cohort of 55-year-old patients presenting with a meniscus root tear without osteoarthritis at baseline. Failure rates of repair and meniscectomy procedures and disutilities associated with osteoarthritis, total knee replacement, and revision total knee replacement were accounted for. Utilities, costs, and event rates were based on literature and public databases. Analyses considered a time frame between 5 years and lifetime and explored the effects of parameter uncertainty. Results: Over 10 years, meniscus repair, meniscectomy, and nonoperative treatment led to 53.0%, 99.3%, and 95.1% rates of osteoarthritis and 33.5%, 51.5%, and 45.5% rates of total knee replacement, respectively. Meta-analysis confirmed lower osteoarthritis and total knee replacement rates for meniscus repair versus meniscectomy and nonoperative treatment. Discounted 10-year costs were $22,590 for meniscus repair, as opposed to $31,528 and $25,006 for meniscectomy and nonoperative treatment, respectively; projected quality-adjusted life years were 6.892, 6.533, and 6.693, respectively, yielding meniscus repair to be an economically dominant strategy. Repair was either cost-effective or dominant when compared with meniscectomy and nonoperative treatment across a broad range of assumptions starting from 5 years after surgery. Conclusion: Repair of medial meniscus root tears, as compared with total meniscectomy and nonsurgical treatment, leads to less osteoarthritis and is a cost-saving intervention. While small confirmatory randomized clinical head-to-head trials are warranted, the presented evidence seems to point relatively clearly toward adopting meniscus repair as the preferred initial intervention for medial meniscus root tears.

• Faucett, Scott C.; Geisler, Benjamin Peter; Chahla, Jorge; Krych, Aaron J.; LaPrade, Robert F. & Pietzsch, Jan B. (2018). Should Surgical Repair Be Recommended Over Nonoperative Management for Medial Meniscus Root Tears? Response. American Journal of Sports Medicine. ISSN 0363-5465. 46(9), p. NP44–NP45. doi: 10.1177/0363546518783956. Full text in Research Archive
• Pietzsch, Jan B.; Busca, Rachele; Rott, Christina; Geisler, Benjamin P.; Weber, Simon A. & Slebos, Dirk-Jan [Show all 8 contributors for this article] (2018). Adoption Patterns of Bronchoscopic Lung Volume Reduction Procedures in Germany and Predicted Procedure Volumes for Other European Countries. Respiration. ISSN 0025-7931. 97(1), p. 34–41. doi: 10.1159/000491677. Full text in Research Archive Show summary

  Background: Bronchoscopic lung volume reduction (BLVR) using valves and coils has been approved for use since 2003 and 2010, respectively. Objective(s): To study adoption patterns of BLVR in an early-adopting country, and to estimate potential treatment volumes in other European countries. Methods: Therapy- and age-specific volumes for endobronchial valve and coil procedures were obtained from German federal statistics for 2007-2016. Therapy-specific and total BLVR procedure volumes and growth were computed, and patterns in treatment age and device utilization analyzed. Patient volumes for other European countries were predicted using mean German patient volumes of the last 3 data years and age-specific population and emphysema incidences. Results: Over the study period, annual BLVR procedure volumes grew from 91 to 2,053 (+2,256%), reaching a peak of 2,556 procedures in 2013. Coil procedures constituted 36% of the total volume in 2016. Treatment age was stable over time, with highest procedure counts in age group 60-64 years for valves and 65-69 years for coils. A limited increase in device use per procedure was observed. For -Germany, 1,655 newly treated BLVR patients were estimated per year, approximating about 5% of the annual newly diagnosed severe emphysema cases. Predicted volume estimates for other European countries ranged from 1 for Liechtenstein to 1,226 for France. Conclusions: Analysis of -German procedure data show pronounced BLVR therapy uptake in the early years of adoption, with the more recently introduced coil therapy used in about one-third of patients. Estimated patient volumes to date constitute only a small fraction of the severe emphysema population.

• Feller-Kopman, David; Liu, Shan; Geisler, Benjamin Peter; DeCamp, Malcolm M. & Pietzsch, Jan B. (2017). Cost-Effectiveness of a Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer. Journal of Thoracic Oncology. ISSN 1556-0864. 12(8), p. 1223–1232. doi: 10.1016/j.jtho.2017.04.030. Full text in Research Archive Show summary

  Introduction: The use of a bronchial genomic classifier has been shown to improve the diagnostic accuracy of bronchoscopy for suspected lung cancer by identifying patients who may be more suitable for radiographic surveillance as opposed to invasive procedures. Our objective was to assess the cost-effectiveness of bronchoscopy plus a genomic classifier versus bronchoscopy alone in the diagnostic work-up of patients at intermediate risk for lung cancer. Methods: A decision-analytic Markov model was developed to project the costs and effects of two competing strategies by using test performance from the Airway Epithelial Gene Expression in the Diagnosis of Lung Cancer-1 and Airway Epithelial Gene Expression in the Diagnosis of Lung Cancer-2 studies. The diagnostic accuracy of noninvasive and invasive follow-up, as well as associated adverse event rates, were derived from published literature. Procedure costs were based on claims data and 2016 inpatient and outpatient reimbursement amounts. The model projected the number of invasive follow-up procedures, 2-year costs and quality-adjusted life-years (QALYs) by strategy, and resulting incremental cost-effectiveness ratio discounted at 3% per annum. Results: Use of the genomic classifier reduced invasive procedures by 28% at 1 month and 18% at 2 years, respectively. Total costs and QALY gain were similar with classifier use ($27,221 versus $27,183 and 1.512 versus 1.509, respectively), resulting in an incremental cost-effectiveness ratio of $15,052 per QALY. Conclusions: Our analysis suggests that the use of a genomic classifier is associated with meaningful reductions in invasive procedures at about equal costs and is therefore a high-value strategy in the diagnostic work-up of patients at intermediate risk of lung cancer.

• Geisler, Benjamin Peter; Ji, Yisi D. & Peacock, Zachary S. (2017). Value in Oral and Maxillofacial Surgery: A Systematic Review of Economic Analyses. Journal of oral and maxillofacial surgery. ISSN 0278-2391. 75(11), p. 2287–2303. doi: 10.1016/j.joms.2017.05.007. Full text in Research Archive Show summary

  Purpose: The purpose of this study is to describe the state of economic analyses in the field of oral and maxillofacial surgery (OMS). Materials and methods: A systematic search of published literature up to 2016 was performed. The inclusion criteria were as follows: English-language articles on economic analyses pertaining to OMS including anesthesia and pain management; dentoalveolar surgery; orthognathic, cleft, and/or obstructive sleep apnea treatment; pathology; reconstruction; temporomandibular disorders; trauma; and other. The exclusion criteria were as follows: opinion or perspective articles, studies unrelated to OMS, nonhuman research, and implant-related studies. Cost-effectiveness analyses (CEAs), cost-utility analyses, and cost-minimization analyses (CMAs) were evaluated with the original Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist or a modified CHEERS checklist. Results: The search yielded 798 articles, 77 of which met the inclusion criteria (published from 1980 to 2016, 48 from the United States). There were an increasing number of studies over time (P for trend < .01). There were 7 economic studies on anesthesia and pain management (9.1%); 16 studies on dentoalveolar surgery (20.7%); 15 studies on orthognathic, cleft, and/or obstructive sleep apnea treatment (19.4%); 1 study on pathology (1.3%); 6 studies on reconstruction (7.8%); no studies on temporomandibular joint disorders and/or facial pain (0%); 20 studies on trauma (25.9%); and 12 studies categorized as other (15.5%). CEAs made up 11.7% of studies, and CMAs comprised 58.4%. Of the 9 CEAs, 55.6% were published in 2010 or later. Of the 45 CMAs, 88.6% were published in 2000 or later and 61.4% in 2010 or later. CEAs met 56.0% (range, 29.2 to 87.5%) of the CHEERS criteria, whereas CMA studies met 45.1% (range, 23.9 to 76.1%) of the modified CHEERS criteria. Only 1 study succeeded in estimating costs and health outcomes (value) of an OMS procedure. Conclusions: There is an increasing trend in the number of economic studies in the field of OMS. More high-quality economic evaluations are needed to demonstrate the value of OMS procedures. To determine value, future studies should compare both costs and health-related outcomes.

• Feller-Kopman, David; Liu, Shan; Geisler, Benjamin Peter; DeCamp, Malcolm M. & Pietzsch, Jan B. (2017). Response to Lee et al. Journal of Thoracic Oncology. ISSN 1556-0864. 12(9), p. e152–e153. doi: 10.1016/j.jtho.2017.07.002. Full text in Research Archive
• Pietzsch, Jan B.; Geisler, Benjamin Peter & Ikeno, Fumiaki (2017). Cost-effectiveness of orbital atherectomy compared to rotational atherectomy in treating patients with severely calcified coronary artery lesions in Japan. Cardiovascular Intervention and Therapeutics (CVIT). ISSN 1868-4300. 33(4), p. 328–336. doi: 10.1007/s12928-017-0488-3. Full text in Research Archive Show summary

  Compared to rotational atherectomy (RA), orbital atherectomy (OA) has been shown to decrease procedure failure and reintervention rates in the treatment of severely calcified coronary artery lesions. Our objective was to explore the cost-effectiveness of OA compared to RA in the Japanese healthcare system. A decision-analytic model calculated reintervention rates and consequent total 1-year costs. Effectiveness inputs were therapy-specific target lesion revascularization (TLR) rates and all-cause mortality, pooled from clinical studies. Index and reintervention costs were determined based on claims data analysis of n = 33,628 subjects treated in 2014-2016. We computed incremental cost-effectiveness in Japanese Yen (JPY) per life year (LY) gained based on differences in 1-year cost and projected long-term survival, assuming OA device cost between JPY 350,000 and ​JPY 550,000. OA was found to be associated with improved clinical outcomes (12-month TLR rate 5.0 vs. 15.7%) and projected survival gain (8.34 vs. 8.16 LYs (+0.17), based on 1-year mortality of 5.5 vs. 6.8%). Total 1-year costs were lower for device cost of JPY 430,000 or less, and reached a maximum ICER of JPY 753,445 per LY at the highest assumed device cost, making OA dominant or cost-effective across the tested range, at ICERs substantially below the willingness-to-pay threshold. In conclusion, orbital atherectomy for the treatment of severely calcified coronary artery lesions, compared to rotational atherectomy, is a cost-effective treatment approach in the Japanese healthcare system due to improved clinical performance.

• Pietzsch, Jan B.; Geisler, Benjamin Peter & Ikeno, Fumiaki (2017). Correction to: Cost-effectiveness of orbital atherectomy compared to rotational atherectomy in treating patients with severely calcified coronary artery lesions in Japan. Cardiovascular Intervention and Therapeutics (CVIT). ISSN 1868-4300. 33(4), p. 337–337. doi: 10.1007/s12928-017-0492-7. Full text in Research Archive
• Geisler, Benjamin P. (2016). Cardiovascular Benefits of the Mediterranean Diet Are Driven by Stroke Reduction and Possibly by Decreased Atrial Fibrillation Incidence. American Journal of Medicine. ISSN 0002-9343. 129(1), p. 11–11. doi: 10.1016/j.amjmed.2015.04.046. Full text in Research Archive
• Heffron, Sean P.; Alviar, Carlos L.; Towe, Christopher; Geisler, Benjamin Peter; Axel, Leon & Galloway, Aubrey C. [Show all 7 contributors for this article] (2016). Dyspnea and Chest Pain in a Young Woman Caused by a Giant Pericardial Lymphohemangioma: Diagnosis and Treatment. Canadian Journal of Cardiology. ISSN 0828-282X. 32(10), p. 1260.e23–1260.e25. doi: 10.1016/j.cjca.2015.12.001. Full text in Research Archive Show summary

  We describe a 21-year-old woman who presented with chest pain and dyspnea on exertion and who was found to have a large pericardial mass. Multimodality imaging was instrumental in narrowing the differential diagnosis and planning surgical treatment, which included coronary artery bypass and right-sided heart reconstruction. The final pathologic diagnosis was lymphohemangioma; to our knowledge, this was the largest cardiac/pericardial vascular tumor ever to be reported in the literature.

• Katsanos, Konstantinos; Geisler, Benjamin P; Garner, Abigail M; Zayed, Hany; Cleveland, Trevor & Pietzsch, Jan B (2016). Economic analysis of endovascular drug-eluting treatments for femoropopliteal artery disease in the UK. BMJ Open. 6(5). doi: 10.1136/bmjopen-2016-011245. Full text in Research Archive Show summary

  Objectives To estimate the clinical and economic impact of drug-eluting endovascular treatment strategies for femoropopliteal artery disease compared with current standard of care. Design Systematic literature search to pool target lesion revascularisations (TLR). Model-based per-patient cost impact and quasi-cost-effectiveness projection over 24 months based on pooled TLRs and current reimbursement. Setting The UK's National Health Service (NHS). Participants Patients presenting with symptomatic femoropopliteal disease eligible for endovascular treatment. Interventions Current National Institute for Health and Care Excellence (NICE) guideline-recommended treatment with percutaneous transluminal balloon angioplasty (PTA) and bailout bare metal stenting (BMS) versus primary BMS placement, or drug-coated balloon (DCB), or drug-eluting stent (DES) treatment. Primary and secondary outcome measures 24-month per-patient cost impact to NHS (primary outcome). Secondary outcomes: pooled 24-month TLR rates; numbers needed to treat (NNTs); cost per TLR avoided and estimated incremental cost-effectiveness ratio (ICER) in £ per quality-adjusted life year (QALY). Results N=28 studies were identified, reporting on 5167 femoropopliteal lesions. Over 24 months, DCB, DES and BMS reduced TLRs of de novo lesions from 36.2% to 17.6%, 19.4% and 26.9%, respectively, at an increased cost of £43, £44 and £112. NNTs to avoid 1 TLR in 24 months were 5.4, 6.0 and 10.8, resulting in cost per TLR avoided of £231, £264 and £1204. DCB was estimated to add 0.011 QALYs, DES 0.010 QALYs and BMS 0.005 QALYs, resulting in estimated ICERs of £3983, £4534 and £20 719 per QALY gained. A subset analysis revealed more favourable clinical and economic outcomes for a 3.5 µg/mm 2 DCB with urea excipient, compared with the rest of DCBs. A modest reduction of 10% in DCB and DES prices made drug-eluting treatments dominant. Conclusions Widespread adoption of drug-eluting endovascular therapies for femoropopliteal disease would add meaningful clinical benefit at reasonable additional costs to the NHS. Based on currently available data, DCBs offer the highest clinical and economic value.

• Cohen, Jesse N.; Coppock, Alexander; Ghosh, Arnab K. & Geisler, Benjamin Peter (2015). Do Insurers Compete on the Federal Health Insurance Exchange? F1000 Research. 4. doi: 10.12688/f1000research.6039.1. Full text in Research Archive Show summary

  Background : On the U.S. Federal Health Insurance Exchange established by the Affordable Care Act, states with fewer insurers have higher insurance premiums than states with more insurers. This expected feature of a competitive market has not been studied within states, however. We tested the hypothesis that insurance premiums decrease in more competitive geographic rating areas within states in the U.S.A. Methodology/principle findings : This cross-sectional study utilized publicly available premiums from the Federal Health Insurance Exchange website, www.healthcare.gov. Univariate and multivariate analyses were used to model premiums based on the number of insurers in geographic rating areas. The relationship between premiums and the number of insurers competing in a geographic rating area was also calculated for each unique insurance plan offered on the exchange. The data set and statistical code used for this research is linked in the publication. We found that there was an unexpected, marginally positive relationship between average monthly premiums and the number of insurers in a geographic rating area (+$5.71 in monthly premiums per additional insurer, p<0.001). We also found that identical plans tend to be offered with marginally higher premiums in rating areas with more insurers (+$3.18 in monthly premiums per additional insurer, p=0.002), contrary to the relationship we expected from a competitive marketplace. The principle limitation of the study is that this unexpected relationship, which suggests a lack of competitiveness of this early market, could be due to unobserved confounding factors that influence pricing in more competitive rating areas. Conclusion : On the Federal Health Insurance Exchange, the price of insurance is higher in more competitive rating areas within states. This may be explained by lack of competition in this early stage market.

• Geisler, Benjamin Peter; Raad, Roy A; Esaian, Diana; Sharon, Elad & Schwartz, David R (2015). Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome. Journal for ImmunoTherapy of Cancer (JITC). 3(1). doi: 10.1186/s40425-015-0048-2. Full text in Research Archive Show summary

  Although animal studies have shown that the immunomodulator ipilimumab causes inflammation of the myocardium, clinically significant myocarditis has been observed only infrequently. We report a case of suspected acute coronary syndrome without a culprit lesion on cardiac angiography and takotsubo cardiomyopathy (TC)-like appearance on echocardiography in a patient with metastatic melanoma who received four standard doses of ipilimumab. Apical ballooning, hyperdynamic basal wall motion, systolic anterior motion of the mitral valve, and associated severe left ventricular outflow tract obstruction were present. Restaging with positron emission tomography-computed tomography done soon after discharge incidentally revealed increased fludeoxyglucose uptake in the apex. This case illustrates that a TC-like syndrome might be caused by autoimmune myocarditis after ipilimumab treatment although this was not biopsy-confirmed. Post-marketing surveillance should capture cardiac events occurring in patients treated with ipilimumab to better document and clarify a relationship to the drug, and biopsies should be considered. Physicians utilizing this novel agent should be aware of the potential for immune-related adverse events.

• Pietzsch, Jan B.; Geisler, Benjamin P.; Garner, Abigail M.; Zeller, Thomas & Jaff, Michael R. (2014). Economic analysis of endovascular interventions for femoropopliteal arterial disease: A systematic review and budget impact model for the United States and Germany. Catheterization and cardiovascular interventions. ISSN 1522-1946. 84(4), p. 546–554. doi: 10.1002/ccd.25536. Full text in Research Archive Show summary

  Objectives To study the economic impact on payers and providers of the four main endovascular strategies for the treatment of infrainguinal peripheral artery disease. Background Bare metal stents (BMS), drug‐eluting stents (DES), and drug‐coated balloons (DCB) are associated with lower target lesion revascularization (TLR) probabilities than percutaneous transluminal angioplasty (PTA), but the economic impact is unknown. Methods In December 2012, PubMed and Embase were systematically searched for studies with TLR as an endpoint. The 24‐month probability of TLR for each treatment was weighted by sample size. A decision‐analytic Markov model was used to assess the budget impact from payers' and facility‐providers' perspectives of the four index procedure strategies (BMS, DES, DCB, and PTA). Base cases were developed for U.S. Medicare and the German statutory sickness fund perspectives using current 2013 reimbursement rates. Results Thirteen studies with 2,406 subjects were included. The reported probability of TLR in the identified studies varied widely, particularly following treatment with PTA or BMS. The pooled 24‐month probabilities were 14.3%, 19.3%, 28.1%, and 40.3% for DCB, DES, BMS, and PTA, respectively. The drug‐eluting strategies had a lower projected budget impact over 24 months compared to BMS and PTA in both the U.S. Medicare (DCB: $10,214; DES: $12,904; uncoated balloons $13,114; BMS $13,802) and German public health care systems (DCB €3,619; DES €3,632; BMS €4,026; PTA €4,290). Conclusions DCB and DES, compared to BMS and PTA, are associated with lower probabilities of target lesion revascularization and cost savings for U.S. and German payers. © 2014 Wiley Periodicals, Inc.

• Geisler, Benjamin Peter & Ghosh, Arnab (2014). Gabapentin Treatment for Alcohol Dependence. JAMA Internal Medicine. ISSN 2168-6106. 174(7), p. 1201–1201. doi: 10.1001/jamainternmed.2014.1618. Full text in Research Archive
• Pietzsch, J.B.; Geisler, Benjamin Peter & Esler, M.D. (2014). Estimated Added Benefit Of Catheter-Based Renal Denervation For Moderate Treatment-Resistant Hypertension: Impact Of Age And Cardiovascular Risk Factors. Value in Health. ISSN 1098-3015. 17(7). doi: 10.1016/j.jval.2014.08.1354. Full text in Research Archive
• Neumann, Anja; Mostardt, Sarah; Biermann, Janine; Gelbrich, Götz; Goehler, Alexander & Geisler, Benjamin Peter [Show all 11 contributors for this article] (2014). Cost-effectiveness and cost-utility of a structured collaborative disease management in the Interdisciplinary Network for Heart Failure (INH) study. Clinical Research in Cardiology. ISSN 1861-0684. 104(4), p. 304–309. doi: 10.1007/s00392-014-0781-4. Full text in Research Archive Show summary

  Background: Non-pharmacological treatment programmes are being developed, in which specialised nurses take care of heart failure (HF) patients. Such disease management programmes might increase survival and quality of life in HF patients, but evidence on their cost-effectiveness remains limited. Methods and results: A prospective economic evaluation piggy-backed onto the randomised controlled Interdisciplinary Network for Heart Failure (INH) Study weighted costs of the intervention HeartNetCare -HF™ (HNC) regarding effectiveness, mortality and quality-adjusted life years (QALYs). To consider uncertainty sensitivity analyses were performed. Compared to usual care (UC), HNC revealed 8,284 <euro> per death avoided within the 6 month study follow-up period. The cost-utility analysis showed additional costs of 49,335 <euro> per QALY. Conclusion: Although HNC did not reduce short-term re-admission rates of HF patients hospitalised for cardiac decompensation within the first 180 days after discharge, HNC might reduce mortality and increase quality of life in these patients at reasonable costs. Therefore, long-term HNC-effects deserve further evaluation.

• Zonies, David; Maier, Ronald V.; Civil, Ian; Eid, Anas; Geisler, Benjamin Peter & Guerrero, Alejandro [Show all 7 contributors for this article] (2012). Trauma and Burn Education: A Global Survey. World Journal of Surgery. ISSN 0364-2313. 36(3), p. 548–555. doi: 10.1007/s00268-011-1419-6. Full text in Research Archive Show summary

  Abstract Background The World Health Assembly recently adopted a resolution to urge improved competency in the provision of injury care through medical education. This survey sought to investigate trauma education experience and competency among final year medical students worldwide. Methods An Internet survey was distributed to medical students and conducted from March 2008 to January 2009. Demographic data and questions pertaining to both instruction and attainment of specific skills in burn and trauma care were assessed. Results There were 776 responses from final year medical students in 77 countries, with at least 10 countries from each economic stratum. Over 93% of final year students reported receiving some form of trauma or burn training, with 79% reporting a minimum compulsory requirement. Students received theoretical instruction without practical exposure. Few felt prepared to undertake basic procedures, such as laceration repair (19%), vascular access (8%), or endotracheal intubation (21%). Over 99% agreed that trauma education should be mandatory, but only half felt prepared to provide basic care. Those from low income and low middle income countries felt better prepared to provide trauma care than students from high middle and high income countries. Conclusions Trauma education and experience varies among medical students in different countries. Many critical concepts are not formally taught and practical experience with many basic procedures is often lacking. The present study confirms that the trauma care training received by medical students needs to be strengthened in countries at all economic levels.

• Geisler, Benjamin Peter; Egan, Brent M.; Cohen, Joshua T.; Garner, Abigail M.; Akehurst, Ronald L. & Esler, Murray D. [Show all 7 contributors for this article] (2012). Cost-Effectiveness and Clinical Effectiveness of Catheter-Based Renal Denervation for Resistant Hypertension. Journal of the American College of Cardiology. ISSN 0735-1097. 60(14), p. 1271–1277. doi: 10.1016/j.jacc.2012.07.029. Full text in Research Archive Show summary

  Objectives: The purpose of this study was to assess cost-effectiveness and long-term clinical benefits of renal denervation in resistant hypertensive patients. Background: Resistant hypertension affects 12% of hypertensive persons. In the Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation (RDN) lowered systolic blood pressure by 32 ± 23 mm Hg from 178 ± 18 mm Hg at baseline. Methods: A state-transition model was used to predict the effect of RDN and standard of care on 10-year and lifetime probabilities of stroke, myocardial infarction, all coronary heart disease, heart failure, end-stage renal disease, and median survival. We adopted a societal perspective and estimated an incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life-year, both discounted at 3% per year. Robustness and uncertainty were evaluated using deterministic and probabilistic sensitivity analyses. Results: Renal denervation substantially reduced event probabilities (10-year/lifetime relative risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81). Median survival was 18.4 years for RDN versus 17.1 years for standard of care. The discounted lifetime incremental cost-effectiveness ratio was $3,071 per quality-adjusted life-year. Findings were relatively insensitive to variations in input parameters except for systolic blood pressure reduction, baseline systolic blood pressure, and effect duration. The 95% credible interval for incremental cost-effectiveness ratio was cost-saving to $31,460 per quality-adjusted life-year. Conclusions: The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.

• Goehler, Alexander; Geisler, Benjamin Peter; Manne, Jennifer M.; Jahn, Beate; Conrads-Frank, Annette & Schnell-Inderst, Petra [Show all 8 contributors for this article] (2011). Decision-Analytic Models to Simulate Health Outcomes and Costs in Heart Failure. PharmacoEconomics (Auckland). ISSN 1170-7690. 29(9), p. 753–769. doi: 10.2165/11585990-000000000-00000. Full text in Research Archive Show summary

  Chronic heart failure (CHF) is a critical public health issue with increasing effect on the healthcare budgets of developed countries. Various decision-analytic modelling approaches exist to estimate the cost effectiveness of health technologies for CHF. We sought to systematically identify these models and describe their structures. We performed a systematic literature review in MEDLINE/PreMEDLINE, EMBASE, EconLit and the Cost-Effectiveness Analysis Registry using a combination of search terms for CHF and decision-analytic models. The inclusion criterion required 'use of a mathematical model evaluating both costs and health consequences for CHF management strategies'. Studies that were only economic evaluations alongside a clinical trial or that were purely descriptive studies were excluded. We identified 34 modelling studies investigating different interventions including screening (n = 1), diagnostics (n = 1), pharmaceuticals (n = 15), devices (n = 13), disease management programmes (n = 3) and cardiac transplantation (n = 1) in CHF. The identified models primarily focused on middle-aged to elderly patients with stable but progressed heart failure with systolic left ventricular dysfunction. Modelling approaches varied substantially and included 27 Markov models, three discrete-event simulation models and four mathematical equation sets models; 19 studies reported QALYs. Three models were externally validated. In addition to a detailed description of study characteristics, the model structure and output, the manuscript also contains a synthesis and critical appraisal for each of the modelling approaches. Well designed decision models are available for the evaluation of different CHF health technologies. Most models depend on New York Heart Association (NYHA) classes or number of hospitalizations as proxy for disease severity and progression. As the diagnostics and biomarkers evolve, there is the hope for better intermediate endpoints for modelling disease progression as those that are currently in use all have limitations.

• Geisler, Benjamin Peter (2011). Perspectives on “Early Dialogue” between a Manufacturer and Health Technology Assessment Agencies. Value in Health. ISSN 1098-3015. 14(4), p. 607–607. doi: 10.1016/j.jval.2011.01.003. Full text in Research Archive
• Venkatesh, Arjun K.; Ross, Joseph S.; Geisler, Benjamin Peter; Chambers, Jennifer J. Gibson; Baugh, Christopher W. & Bohan, J. Stephen [Show all 7 contributors for this article] (2011). Use of Observation Care in US Emergency Departments, 2001 to 2008. PLOS ONE. 6(9). doi: 10.1371/journal.pone.0024326. Full text in Research Archive Show summary

  Background: Observation care is a core component of emergency care delivery, yet, the prevalence of emergency department (ED) observation units (OUs) and use of observation care after ED visits is unknown. Our objective was to describe the 1) prevalence of OUs in United States (US) hospitals, 2) clinical conditions most frequently evaluated with observation, and 3) patient and hospital characteristics associated with use of observation. Methods: Retrospective analysis of the proportion of hospitals with dedicated OUs and patient disposition after ED visit (discharge, inpatient admission or observation evaluation) using the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 to 2008. NHAMCS is an annual, national probability sample of ED visits to US hospitals conducted by the Center for Disease Control and Prevention. Logistic regression was used to assess hospital-level predictors of OU presence and polytomous logistic regression was used for patient-level predictors of visit disposition, each adjusted for multi-level sampling data. OU analysis was limited to 2007-2008. Results: In 2007-2008, 34.1% of all EDs had a dedicated OU, of which 56.1% were under ED administrative control (EDOU). Between 2001 and 2008, ED visits resulting in a disposition to observation increased from 642,000 (0.60% of ED visits) to 2,318,000 (1.87%, p<.05). Chest pain was the most common reason for ED visit resulting in observation and the most common observation discharge diagnosis (19.1% and 17.1% of observation evaluations, respectively). In hospital-level adjusted analysis, hospital ownership status (non-profit or government), non-teaching status, and longer ED length of visit (>3.6 h) were predictive of OU presence. After patient-level adjustment, EDOU presence was associated with increased disposition to observation (OR 2.19). Conclusions: One-third of US hospitals have dedicated OUs and observation care is increasingly used for a range of clinical conditions. Further research is warranted to understand the quality, cost and efficiency of observation care.

• Patterson, Danielle; Geisler, Benjamin Peter & Morse, Abraham (2011). Determining Health-Related Quality of Life and Health State Utility Values of Urinary Incontinence in Women. Female pelvic medicine and reconstructive surgery. ISSN 2151-8378. 17(6), p. 305–307. doi: 10.1097/spv.0b013e31823c040. Full text in Research Archive Show summary

  Objectives: : Health-related quality-of-life estimates currently available for urinary incontinence have largely been derived from population-based studies without physician confirmation of diagnosis. The purpose of this study was to compare the health state utility values for urinary incontinence in women derived from EQ-5D questionnaires and visual analog scale (VAS) with the economic gold standard method, the Standard Gamble (SG) interview. Methods: : Subjects were approached for study participation after a diagnosis of stress or urge urinary incontinence was made by the attending urogynecologist. Twenty-eight patients completed the Sandvik Severity Index (SSI), EQ-5D, and VAS. They then participated in the SG conversation. Results: : The median utility (interquartile range) for stress incontinence varied based on the methods: EQ-5D, 0.83 (0.23); VAS, 0.85 (0.15); and SG, 1.00 (0.01). There was a statistically significant difference between the SG assessment and the other 2 methods of assessing utility values, the EQ-5D and VAS in women with urodynamically demonstrated stress urinary incontinence (P = 0.0003 and P < 0.0001, respectively). In the combined group of women with urodynamically proven stress, urge, and mixed urinary incontinence, there was also a statistically significant difference between the SG and the generic methods of assessing utility values, the EQ-5D and VAS (P < 0.0001). Mean SSI scores were similar in women with stress incontinence (6.6 [23.5]) and in the combined group (7.9 [3.8]). Conclusions: : Previous studies may have underestimated the health-related quality of life of urinary incontinence.

• Geisler, Benjamin Peter (2010). Health State Survey-Derived Utilities in Cost-Utility Analysis—A Call to Action. Value in Health. ISSN 1098-3015. 13(2), p. 159–159. doi: 10.1111/j.1524-4733.2009.00665.x. Full text in Research Archive
• Geisler, Benjamin Peter; Ross, Joseph S.; Schuur, Jeremiah D. & Pallin, Daniel J. (2010). Estimates of Electronic Medical Records in U.S. Emergency Departments. PLOS ONE. 5(2). doi: 10.1371/journal.pone.0009274. Full text in Research Archive Show summary

  Background: Policymakers advocate universal electronic medical records (EMRs) and propose incentives for "meaningful use" of EMRs. Though emergency departments (EDs) are particularly sensitive to the benefits and unintended consequences of EMR adoption, surveillance has been limited. We analyze data from a nationally representative sample of US EDs to ascertain the adoption of various EMR functionalities. Methodology/principal findings: We analyzed data from the National Hospital Ambulatory Medical Care Survey, after pooling data from 2005 and 2006, reporting proportions with 95% confidence intervals (95% CI). In addition to reporting adoption of various EMR functionalities, we used logistic regression to ascertain patient and hospital characteristics predicting "meaningful use," defined as a "basic" system (managing demographic information, computerized provider order entry, and lab and imaging results). We found that 46% (95% CI 39-53%) of US EDs reported having adopted EMRs. Computerized provider order entry was present in 21% (95% CI 16-27%), and only 15% (95% CI 10-20%) had warnings for drug interactions or contraindications. The "basic" definition of "meaningful use" was met by 17% (95% CI 13-21%) of EDs. Rural EDs were substantially less likely to have a "basic" EMR system than urban EDs (odds ratio 0.19, 95% CI 0.06-0.57, p = 0.003), and Midwestern (odds ratio 0.37, 95% CI 0.16-0.84, p = 0.018) and Southern (odds ratio 0.47, 95% CI 0.26-0.84, p = 0.011) EDs were substantially less likely than Northeastern EDs to have a "basic" system. Conclusions/significance: EMRs are becoming more prevalent in US EDs, though only a minority use EMRs in a "meaningful" way, no matter how "meaningful" is defined. Rural EDs are less likely to have an EMR than metropolitan EDs, and Midwestern and Southern EDs are less likely to have an EMR than Northeastern EDs. We discuss the nuances of how to define "meaningful use," and the importance of considering not only adoption, but also full implementation and consequences.

• Geisler, Benjamin Peter (2010). Treating anemia in heart failure patients: a review of erythropoiesis-stimulating agents. Expert Opinion on Biological Therapy. ISSN 1471-2598. 10(8), p. 1209–1216. doi: 10.1517/14712598.2010.500282. Full text in Research Archive Show summary

  Importance of the field: Prevalence of chronic heart failure (CHF) is increasing, and despite improvements in the past decade the prognosis in terms of mortality and health-related quality of life remains poor. Anemia is often found concomitantly in CHF patients. Areas covered in this review: Erythropoiesis-stimulating agents (ESAs) are a new treatment option for these anemic CHF patients, promising to decrease mortality and hospitalizations, and increase health-related quality of life. What the reader will gain: CHF epidemiology is briefly discussed. Currently available clinical efficacy and safety data are critically appraised. Health care utilization by CHF patients, particularly hospitalizations, are reviewed in order predict cost-effectiveness of ESAs. Take home messages: The efficacy for the most pertinent endpoints has not been proven by a pivotal trial or a meta-analysis free of bias, and there might be increased cardiovascular events and cancer incidence rates above a currently unknown target value or with multiple doses. However, subgroups should be identified in which ESAs might prove to be more efficacious and as safe as usual care and either cost-saving or cost-effective. Nevertheless, depending on the subgroup, the budget effect for payors might be dramatic due to the large number of CHF patients.

• Geisler, Benjamin Peter; Widerberg, K.F.; Berghöfer, A. & Willich, S.N. (2010). Leadership in health care: developing a post-merger strategy for Europe's largest university hospital. Journal of Health Organisation and Management. ISSN 1477-7266. 24(3), p. 258–276. doi: 10.1108/14777261011054608. Full text in Research Archive Show summary

  Purpose This paper's aim is to identify existing and developing new concepts of organization, management, and leadership at a large European university hospital; and to evaluate whether mixed qualitative‐quantitative methods with both internal and external input can provide helpful views of the possible future of large health care providers. Design/methodology/approach Using the Delphi method in semi‐structured, semi‐quantitative interviews, with managers and employees as experts, the authors performed a vertical and a horizontal internal analysis. In addition, input from innovative faculties in other countries was obtained through structured power questions. These two sources were used to create three final scenarios, which evaluated using traditional strategic planning methods. Findings There is found a collaboration scenario in which faculty and hospital are separated; a split scenario which divides the organization into three independent hospitals; and a corporation scenario in which corporate activities are bundled in three separate entities. Practical implications In complex mergers of knowledge‐driven organizations, the employees of the own organization (in addition to external consultants) might be tapped as a knowledge resource to successful future business models. Originality/value The paper uses a real world consulting case to present a new set of methods for strategic planning in large health care provider organizations.

• Göhler, Alexander; Geisler, Benjamin Peter; Manne, Jennifer M.; Kosiborod, Mikhail; Zhang, Zefeng & Weintraub, William S. [Show all 10 contributors for this article] (2009). Utility Estimates for Decision–Analytic Modeling in Chronic Heart Failure—Health States Based on New York Heart Association Classes and Number of Rehospitalizations. Value in Health. ISSN 1098-3015. 12(1), p. 185–187. doi: 10.1111/j.1524-4733.2008.00425.x. Full text in Research Archive Show summary

  Objectives: For economic evaluations of chronic heart failure (CHF) management strategies, utilities are not currently available for disease proxies commonly used in Markov models. Our objective was to estimate utilities for New York Heart Association (NYHA) classification and number of cardiovascular rehospitalizations. Methods: EuroQol 5D data from the Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study trial were used to estimate utilities as a function of NYHA classification and number of cardiovascular rehospitalizations. Results: In multivariate regression analyses adjusted for age (60 years), female sex and absence of further comorbidities, utilities for NYHA classes I-IV were 0.90, 0.83, 0.74, and 0.60 (P-value < 0.001 for trend). For cardiovascular rehospitalizations 0, 1, 2 and >or=3, the associated utilities were 0.88, 0.85, 0.84, and 0.82 (P-value < 0.001 for trend). Conclusions: NYHA class and number of cardiovascular rehospitalizations are established proxies for CHF progression and can be linked to utilities when used as health states in a Markov model. NYHA class should be used when feasible.

• Geisler, Benjamin Peter; Siebert, Uwe; Gazelle, G. Scott; Cohen, David J. & Göhler, Alexander (2009). Deterministic Sensitivity Analysis for First-Order Monte Carlo Simulations: A Technical Note. Value in Health. ISSN 1098-3015. 12(1), p. 96–97. doi: 10.1111/j.1524-4733.2008.00411.x. Full text in Research Archive Show summary

  Objectives: Monte Carlo microsimulations have gained increasing popularity in decision-analytic modeling because they can incorporate discrete events. Although deterministic sensitivity analyses are essential for interpretation of results, it remains difficult to combine these alongside Monte Carlo simulations in standard modeling packages without enormous time investment. Our purpose was to facilitate one-way deterministic sensitivity analysis of TreeAge Markov state-transition models requiring first-order Monte Carlo simulations. Methods and results: Using TreeAge Pro Suite 2007 and Microsoft Visual Basic for EXCEL, we constructed a generic script that enables one to perform automated deterministic one-way sensitivity analyses in EXCEL employing microsimulation models. In addition, we constructed a generic EXCEL-worksheet that allows for use of the script with little programming knowledge. Conclusions: Linking TreeAge Pro Suite 2007 and Visual Basic enables the performance of deterministic sensitivity analyses of first-order Monte Carlo simulations. There are other potentially interesting applications for automated analysis.

• Geisler, Benjamin Peter & Levin-Scherz, Jeffrey K. (2009). Additional Factors That Could Improve Cost-Effectiveness of Pharmacogenetic-Guided Dosing in Warfarin Therapy. Annals of Internal Medicine. ISSN 0003-4819. 151(1), p. 71–71. doi: 10.7326/0003-4819-151-1-200907070-00016. Full text in Research Archive
• Geisler, Benjamin Peter; Dam, R M van; Gazelle, G S & Goehler, A (2009). Risk of bias in meta-analysis on erythropoietin-stimulating agents in heart failure. Heart. ISSN 1355-6037. 95(15), p. 1278–1279. doi: 10.1136/hrt.2009.172163. Full text in Research Archive
• Göhler, Alexander; Conrads‐Frank, Annette; Worrell, Stewart S.; Geisler, Benjamin Peter; Halpern, Elkan F. & Dietz, Rainer [Show all 9 contributors for this article] (2008). Decision‐analytic evaluation of the clinical effectiveness and cost‐effectiveness of management programmes in chronic heart failure. European Journal of Heart Failure. ISSN 1388-9842. 10(10), p. 1026–1032. doi: 10.1016/j.ejheart.2008.07.018. Full text in Research Archive Show summary

  Abstract Background and aims: While management programmes (MPs) for chronic heart failure (CHF) are clinically effective, their cost‐effectiveness remains uncertain. Thus, this study sought to determine the cost‐effectiveness of MPs. Methods and results: We developed a Markov model to estimate life expectancy, quality‐adjusted life expectancy, lifetime costs, and the incremental cost‐effectiveness of MPs as compared to standard care. Standard care was defined by the EuroHeart Failure Survey for Germany, MP efficacy was derived from our recent meta‐analysis and cost estimates were based on the German healthcare system. For a population with a mean age 67 years (35% female) at onset of CHF, our model predicted an average quality‐adjusted life expectancy of 2.64 years for standard care and 2.83 years for MP. MP yielded additional lifetime costs of €1700 resulting in an incremental cost‐utility ratio (ICUR) of €8900 (95% CI: dominant to 177,100) per quality‐adjusted life year (QALY) gained. Sensitivity analyses demonstrated that the ICUR was sensitive to age and sex. Conclusion: MPs increase life expectancy in patients with CHF by an average of 84 days and increase lifetime cost of care by approximately €1700. MPs improve outcomes in a cost‐effective manner, although they are not cost‐saving on a lifetime horizon.

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• Geisler, Benjamin Peter; Greenwald, Jeffrey L. & Tran, Kathy May (2026). 50 Studies Every Hospitalist Should Know. Oxford University Press. ISBN 9780190937157. 408 p. doi: 10.1093/med/9780190937126.001.0001. Full text in Research Archive Show summary

  This volume in the “50 Studies Every Doctor Should Know” series explores the 50 most important studies relevant for hospital medicine. By reviewing and critically analyzing published evidence, this book highlights the role of hospitalists in navigating diagnostic challenges, developing treatment options, and prioritizing patient safety. Beyond clinical considerations of subspecialties of internal medicine and other relevant fields, the volume also addresses hospital systems and operations and administrative pressures that hospitalists face in their practice. The 50 studies included in this book were chosen to equip hospitalists in understanding the underpinnings of hospital-based clinical practice and applying that evidence to an individual patient’s care. Each chapter focuses upon a single study, beginning with a quote about the primary study’s relevance. It then describes the study in detail, including high-yield flow charts, tables, and bullet points of important results and findings. The chapter authors then critically appraise the study by noting limitations, referencing other relevant studies, and listing pertinent guidelines. The final section of each chapter is a clinical case in which the study is applied to a relevant hospital-based scenario, in which evidence-based knowledge is applied to make a medical decision. This book is a valuable resource for hospital-based clinicians, helping trainees and established hospitalists alike learn not just about the 50 individual studies but also how to critically appraise new evidence.

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