Financial toxicity part II: A practical guide to measuring and tracking long-term financial outcomes among acute care surgery patients.

ABSTRACT: Acute care surgery (ACS) patients are frequently faced with significant long-term recovery and financial implications that extend far beyond their hospitalization. While major injury and emergency general surgery (EGS) emergencies are often viewed solely as acute moments of crisis, the impact on patients can be lifelong. Financial outcomes after major injury or emergency surgery have only begun to be understood. The Healthcare Economics Committee from the American Association for the Surgery of Trauma previously published a conceptual overview of financial toxicity in ACS, highlighting the association between financial outcomes and long-term physical recovery. The aims of second-phase financial toxicity review by the Healthcare Economics Committee of the American Association for the Surgery of Trauma are to (1) understand the unique impact of financial toxicity on ACS patients; (2) delineate the current limitations surrounding measurement domains of financial toxicity in ACS; (3) explore the "when, what and how" of optimally capturing financial outcomes in ACS; and (4) delineate next steps for integration of these financial metrics in our long-term patient outcomes. As acute care surgeons, our patients' recovery is often contingent on equal parts physical, emotional, and financial recovery. The ACS community has an opportunity to impact long-term patient outcomes and well-being far beyond clinical recovery.

Estimating the clinical and budgetary impact of using angiotensin receptor neprilysin inhibitor as first line therapy in patients with HFrEF.

AIMS: Recent updates of international treatment guidelines for heart failure with reduced ejection fraction (HFrEF) differ regarding the use of angiotensin receptor neprilysin inhibitor (ARNI) as first-line treatment. The American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) 2022 guidelines gives ARNI a Class IA recommendation for HFrEF patients while the European Society of Cardiology's guidelines are less clear when ARNI could be considered as first line treatment option in de novo patients. This study aimed to model the clinical and budgetary outcomes of implementing these guidelines, comparing conservative ARNI prescription patterns with less conservative in Sweden and in the United Kingdom. METHODS AND RESULTS: A health economic model was developed to compare different treatment patterns for HFrEF. Incident cohorts were included on an annual basis and followed over 10 years. The model included treatment specific all-cause mortality and hospitalization rates, as well as drug acquisition, monitoring, and hospitalization costs. Increasing the use of ARNI could lead to about 7000-12 300 life years gained and 2600-4600 hospitalizations prevented in Sweden. These health benefits come with an additional cost of 112-195 million euros. Similar results were estimated for the United Kingdom, albeit on a larger population. CONCLUSIONS: Increasing the proportion of patients receiving ARNI instead of angiotensin converting enzyme inhibitors as first-line treatment of HFrEF will lead to a considerable number of additional life years gained and prevented hospitalizations but with additional cost in terms of health care expenditure in Sweden and in the United Kingdom.

Characteristics and quality assessment of online mentoring profile texts in academic medical mentoring.

BACKGROUND: Mentoring is important for a successful career in academic medicine. In online matching processes, profile texts are decisive for the mentor-selection. We aimed to qualitatively characterize mentoring-profile-texts, identify differences in form and content and thus elements that promote selection. METHODS: In a mixed method study first, quality of texts in 150 selected mentoring profiles was evaluated (10-point Likert scale; 1 = insufficient to 10 = very good). Second, based on a thematic and content analysis approach of profile texts, categories and subcategories were defined. We compared the presence of the assigned categories between the 25% highest ranked profiles with the 25% lowest ranked ones. Finally, additional predefined categories (hot topics) were labelled on the selected texts and their impact on student evaluation was statistically examined. RESULTS: Students rated the quality of texts with a mean of 5.89 ± 1.45. 5 main thematic categories, 21 categories and a total of 74 subcategories were identified. Ten subcategories were significantly associated with high- and four with low-rated profiles. The presence of three or more hot topics in texts significantly correlated with a positive evaluation. CONCLUSION: The introduced classification system helps to understand how mentoring profile texts are composed and which aspects are important for choosing a suited mentor.

Circulating miR-133a-3p defines a low-risk subphenotype in patients with heart failure and central sleep apnea: a decision tree machine learning approach.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes. OBJECTIVE: To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA. METHODS: The study included patients with HFrEF and CSA from the SERVE-HF trial. A three-step protocol was applied: microRNA (miRNA) screening (n = 20), technical validation (n = 60), and biological validation (n = 587). The primary outcome was either death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of heart failure, whatever occurred first. MiRNA quantification was performed in plasma samples using miRNA sequencing and RT-qPCR. RESULTS: Circulating miR-133a-3p levels were inversely associated with the primary study outcome. Nonetheless, miR-133a-3p did not improve a previously established clinical prognostic model in terms of discrimination or reclassification. A customized regression tree model constructed using the Classification and Regression Tree (CART) algorithm identified eight patient subphenotypes with specific risk patterns based on clinical and molecular characteristics. MiR-133a-3p entered the regression tree defining the group at the lowest risk; patients with log(NT-proBNP) ≤ 6 pg/mL (miR-133a-3p levels above 1.5 arbitrary units). The overall predictive capacity of suffering the event was highly stable over the follow-up (from 0.735 to 0.767). CONCLUSIONS: The combination of clinical information, circulating miRNAs, and decision tree learning allows the identification of specific risk subphenotypes in patients with HFrEF and CSA.

Computed tomography assessment of pelvic bone density: Associations with age and pelvic fracture in motor vehicle crashes.

Motor vehicle crash (MVC) occupants routinely get a computed tomography (CT) scan to screen for internal injury, and this CT can be leveraged to opportunistically derive bone mineral density (BMD). This study aimed to develop and validate a method to measure pelvic BMD in CT scans without a phantom, and examine associations of pelvic BMD with age and pelvic fracture incidence in seriously injured MVC occupants from the Crash Injury Research and Engineering Network (CIREN) study. A phantom-less muscle-fat calibration technique to measure pelvic BMD was validated using 45 quantitative CT scans with a bone calibration phantom. The technique was then used to measure pelvic BMD from CT scans of 252 CIREN occupants (ages 16+) in frontal MVCs who had sustained either abdominal or pelvic injury. Pelvic BMD was analyzed in relation to age and pelvic fracture incidence. In the validation set, phantom-based calibration vs. phantom-less muscle-fat calibration yielded similar BMD values at the anterior superior iliac spine (ASIS; R2 = 0.95, p < 0.001) and iliac crest (R2 = 0.90, p < 0.001). Pelvic BMD was measured in 150 female and 102 male CIREN occupants aged 16-89, and 25% of these occupants sustained pelvic fracture. BMD at the ASIS and iliac crest declined with age (p < 0.001). For instance, iliac crest BMD decreased an average of 25 mg/cm3 per decade of age. The rate of iliac crest BMD decline was 7.6 mg/cm3 more per decade of age in occupants with pelvic fracture compared to those not sustaining pelvic fracture. Findings suggest pelvic BMD may be a contributing risk factor for pelvic fracture in MVCs.

The cost-effectiveness of NT-proBNP for assessment of suspected acute heart failure in the emergency department.

AIMS: When relying on clinical assessment alone, an estimated 22% of acute heart failure (AHF) patients are missed, so clinical guidelines recommend the use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF diagnosis. Since publication of these guidelines, there has been poor uptake of NT-proBNP testing in part due to concerns over excessive false positive referrals resulting from the low specificity of a single 'rule-out' threshold of <300 pg/mL. Low specificity can be mitigated by the addition of age-specific 'rule-in' NT-proBNP thresholds. METHODS AND RESULTS: A theoretical hybrid decision tree/semi-Markov model was developed, combining global trial and audit data to evaluate the cost-effectiveness of NT-proBNP testing using age-specific rule-in/rule-out (RI/RO) thresholds, compared with NT-proBNP RO only and with clinical decision alone (CDA). Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained and incremental net health benefit. In the base case, using UK-specific inputs, NT-proBNP RI/RO was associated with both greater QALYs and lower costs than CDA. At a willingness-to-pay threshold of £20 000/QALY, NT-proBNP RO was also cost-effective compared with CDA [incremental cost-effectiveness ratio (ICER) of £8322/QALY], but not cost-effective vs. RI/RO (ICER of £64 518/QALY). Overall, NT-proBNP RI/RO was the most cost-effective strategy. Sensitivity and scenario analyses were undertaken; the conclusions were not impacted by plausible variations in parameters, and similar conclusions were obtained for the Netherlands and Spain. CONCLUSIONS: An NT-proBNP strategy that combines an RO threshold with age-specific RI thresholds provides a cost-effective alternative to the currently recommended NT-proBNP RO only strategy, achieving greater diagnostic specificity with minimal reduction in sensitivity and thus reducing unnecessary echocardiograms and hospital admissions.

Real-time pulmonary artery pressure monitoring in heart failure patients: an updated cost-effectiveness analysis.

AIMS: Previous cost-effectiveness analysis suggests that CardioMEMS is cost-effective compared with usual care for patients with persistent New York Heart Association class III symptoms and at least one heart failure (HF) hospitalization within 12 months. The aim of the paper is to perform an update of the cost-effectiveness analysis of CardioMEMS using the most recent data from the published literature. METHODS AND RESULTS: A Microsoft Excel Markov model from a previous UK cost-effectiveness study of CardioMEMS was updated using the clinical effectiveness of pulmonary artery pressure (PAP)-guided treatment derived from the pivotal trials. The model included the device costs (and the implantation procedure and related complications), costs of remote monitoring, costs of HF-related hospitalizations, and costs of usual care. Quality-adjusted life years (QALYs) were estimated based on utilities from pivotal trials and published literature. Cost-effectiveness results were estimated as incremental cost per QALY gained of CardioMEMS compared with usual care. Scenario analyses were also performed using data from real-world studies that showed a significant decrease in HF-related hospitalizations. In the base case analysis over a time horizon of 10 years, PAP-guided HF therapy increased cost compared with usual care by £6337 (i.e. from £22 770 in usual care to £29 107 in PAP-guided HF therapy) and the QALYs per patient for usual care and PAP-guided patients were 2.62 and 2.94, respectively, reflecting an increase of 0.32 QALYs with PAP-guided treatment. The resultant incremental cost-effectiveness ratio (ICER), the ratio between incremental costs and the QALYs, is estimated at £19 761/QALY. Scenario analyses suggest that the ICER for CardioMEMS can range from being dominant to £27 910/QALY. Probabilistic sensitivity analyses suggested that PAP-guided HF therapy has 81.9% probability of being cost-effective at a threshold of £30 000/QALY. CONCLUSIONS: Our model suggests that CardioMEMS is likely to be cost-effective in the United Kingdom, at the currently considered thresholds of £20 000-30 000/QALY.

Younger Patients with Colon Cancer are More Likely to Experience Financial Toxicity Than Older Patients.

BACKGROUND: The incidence of young-onset colon cancer is increasing. This study investigated the extent to which financial hardships associated with colon cancer care are associated with patient age. METHODS: A consecutive sample of patients with non-metastatic colon cancer who underwent resection at a comprehensive cancer center between 2017 and 2019 were retrospectively enrolled from a clinical database. Patients with one or more of the following events associated with their colon cancer care were categorized as having experienced financial toxicity: two or more bills sent to collections, application for a payment plan, settlement, bankruptcy, or enrollment in a financial assistance program. RESULTS: Of 764 patients identified, 157 (21 %) experienced financial toxicity. In a univariable analysis, financial toxicity was significantly associated with younger age, female sex, nonpartnered marital status, and median income by ZIP code area (p < 0.05). A multivariable analysis showed that with each 10-year decrease in patient age, the odds of financial toxicity increased by 30 % (odds ratio [OR], 1.30; 95 % confidence interval [CI], 1.14-1.48). With each $50,000 decrease in median income by ZIP code area, the odds of financial toxicity increased by 35 % (OR, 1.35; 95 % CI, 1.05-1.74). CONCLUSIONS: Younger patients with colon cancer are at greater risk for financial toxicity than older patients. As this population continues to grow, so will the need for timely and effective financial support mechanisms.

Wearable technology and the cardiovascular system: the future of patient assessment.

The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.

National Institutes of Health funding among vascular surgeons is rare.

BACKGROUND: The National Institutes of Health (NIH) is an essential source of funding for vascular surgeons conducting research. NIH funding is frequently used to benchmark institutional and individual research productivity, help determine eligibility for academic promotion, and as a measure of scientific quality. We sought to appraise the current scope of NIH funding to vascular surgeons by appraising the characteristics of NIH-funded investigators and projects. In addition, we also sought to determine whether funded grants addressed recent Society for Vascular Surgery (SVS) research priorities. METHODS: In April 2022, we queried the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database for active projects. We only included projects that had a vascular surgeon as a principal investigator. Grant characteristics were extracted from the NIH Research Portfolio Online Reporting Tools Expenditures and Results database. Principal investigator demographics and academic background information were identified by searching institution profiles. RESULTS: There were 55 active NIH awards given to 41 vascular surgeons. Only 1% (41/4037) of all vascular surgeons in the United States receive NIH funding. Funded vascular surgeons are an average of 16.3 years out of training; 37% (n = 15) are women. The majority of awards (58%; n = 32) were R01 grants. Among the active NIH-funded projects, 75% (n = 41) are basic or translational research projects, and 25% (n = 14) are clinical or health services research projects. Abdominal aortic aneurysm and peripheral arterial disease are the most commonly funded disease areas and together accounted for 54% (n = 30) of projects. Three SVS research priorities are not addressed by any of the current NIH-funded projects. CONCLUSIONS: NIH funding of vascular surgeons is rare and predominantly consists of basic or translational science projects focused on abdominal aortic aneurysm and peripheral arterial disease research. Women are well-represented among funded vascular surgeons. Although the majority of SVS research priorities receive NIH funding, three SVS research priorities are yet to be addressed by NIH-funded projects. Future efforts should focus on increasing the number of vascular surgeons receiving NIH grants and ensuring all SVS research priorities receive NIH funding.

Financial toxicity after trauma and acute care surgery: From understanding to action.

ABSTRACT: Gains in inpatient survival over the last five decades have shifted the burden of major injuries and surgical emergencies from the acute phase to their long-term sequelae. More attention has been placed on evaluation and optimization of long-term physical and mental health; however, the impact of major injuries and surgical emergencies on long-term financial well-being remains a critical blind spot for clinicians and researchers. The concept of financial toxicity encompasses both the objective financial consequences of illness and medical care as well as patients' subjective financial concerns. In this review, representatives of the Healthcare Economics Committee from the American Association for the Surgery of Trauma (1) provide a conceptual overview of financial toxicity after trauma or emergency surgery, (2) outline what is known regarding long-term economic outcomes among trauma and emergency surgery patients, (3) explore the bidirectional relationship between financial toxicity and long-term physical and mental health outcomes, (4) highlight policies and programs that may mitigate financial toxicity, and (5) identify the current knowledge gaps and critical next steps for clinicians and researchers engaged in this work.

A peptide-centric quantitative proteomics dataset for the phenotypic assessment of Alzheimer's disease.

Alzheimer's disease (AD) is a looming public health disaster with limited interventions. Alzheimer's is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain tissue was preserved postmortem by rapid autopsy. Samples from four brain regions were processed and analyzed by data-independent acquisition LC-MS/MS. Here we present a high-quality quantitative dataset at the peptide and protein level for each brain region. Multiple internal and external control strategies were included in this experiment to ensure data quality. All data are deposited in the ProteomeXchange repositories and available from each step of our processing.

MRI Assessment of Extramural Venous Invasion Before and After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer and Its Association with Disease-Free and Overall Survival.

BACKGROUND: Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival. METHODS: Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival. RESULTS: EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04-0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02-0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (p = 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival. CONCLUSIONS: Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear.

Systematic Assessment of Protein C-Termini Mutated in Human Disorders.

All proteins have a carboxyl terminus, and we previously summarized eight mutations in binding and trafficking sequence determinants in the C-terminus that, when disrupted, cause human diseases. These sequence elements for binding and trafficking sites, as well as post-translational modifications (PTMs), are called minimotifs or short linear motifs. We wanted to determine how frequently mutations in minimotifs in the C-terminus cause disease. We searched specifically for PTMs because mutation of a modified amino acid almost always changes the chemistry of the side chain and can be interpreted as loss-of-function. We analyzed data from ClinVar for disease variants, Minimotif Miner and the C-terminome for PTMs, and RefSeq for protein sequences, yielding 20 such potential disease-causing variants. After additional screening, they include six with a previously reported PTM disruption mechanism and nine with new hypotheses for mutated minimotifs in C-termini that may cause disease. These mutations were generally for different genes, with four different PTM types and several different diseases. Our study helps to identify new molecular mechanisms for nine separate variants that cause disease, and this type of analysis could be extended as databases grow and to binding and trafficking motifs. We conclude that mutated motifs in C-termini are an infrequent cause of disease.

The COST of liver disease: The Cirrhosis Outcomes Score in Trauma Study.

BACKGROUND: Cirrhosis in trauma patients is an indicator of poor prognosis, but current trauma injury grading systems do not take into account liver dysfunction as a risk factor. Our objective was to construct a simple clinical mortality prediction model in cirrhotic trauma patients: Cirrhosis Outcomes Score in Trauma (COST). METHODS: Trauma patients with pre-existing cirrhosis or liver dysfunction who were admitted to our ACS Level I trauma center between 2013 and 2021 were reviewed. Patients with significant acute liver trauma (AAST Grade ≥ 3) or those that developed acute liver dysfunction while admitted were excluded. Demographics as well as ISS, MELD, complications, and mortality were evaluated. COST was defined as the sum of age, ISS, and MELD. Univariate and multivariable analysis was used to determine independent predictors of mortality. The area under the receiver operating curve (AUROC) was calculated to assess the ability of COST to predict mortality. RESULTS: A total of 318 patients were analyzed of which the majority were males 214 (67.3%) who suffered blunt trauma 305 (95.9%). Mortality at 30-days, 60-days, and 90-days was 20.4%, 23.6%, and 25.5%, respectively. COST was associated with inpatient, 30-day, and 90-day mortality on regression analyses and the AUROC for COST predicting mortality at these respective time points was 0.810, 0.801, and 0.813. CONCLUSION: Current trauma injury grading systems do not take into account liver dysfunction as a risk factor. COST is highly predictive of mortality in cirrhotic trauma patients. The simplicity of the score makes it useful in guiding clinical care and in optimizing goals of care discussions. Future studies to validate this prediction model are required prior to clinical use.