Do all cardiac surgery patients benefit from antifibrinolytic therapy?

BACKGROUND: In trauma patients, the recognition of fibrinolysis phenotypes has led to a re-evaluation of the risks and benefits of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, but the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this hypothesis-generating study was to fill that gap. METHODS: Seventy-eight cardiac surgery patients were retrospectively reviewed. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (0.8%-3.0%), and hyperfibrinolytic (>3%) based on thromboelastogram. RESULTS: The population was 65 ± 10-years old, 74% male, average body mass index of 29 ± 5 kg/m2 . Fibrinolytic phenotypes were distributed as physiologic = 45% (35 of 78), hypo = 32% (25 of 78), and hyper = 23% (18 of 78). There was no obvious effect of age, gender, race, or ethnicity on this distribution; 47% received AF. For AF versus no AF, the time with chest tube was longer (4 [1] vs. 3 [1] days, p = .037), and all-cause morbidity was more prevalent (51% vs. 25%, p = .017). However, when these two groups were further stratified by phenotypes, there were within-group differences in the percentage of patients with congestive heart failure (p = .022), valve disease (p = .024), on-pump surgery (p < .0001), estimated blood loss during surgery (p = .015), transfusion requirement (p = .015), and chest tube output (p = .008), which highlight other factors along with AF that might have affected all-cause morbidity. CONCLUSION: This is the first description of the prevalence of three different fibrinolytic phenotypes and their potential influence on cardiac surgery patients. The use of AF was associated with increased morbidity, but because of the small sample size and treatment allocation bias, additional confirmatory studies are necessary. We hope these present findings open the dialog on whether it is safe to administer AFs to cardiac surgery patients who are normo- or hypofibrinolytic.

Nationwide Outcomes and Risk Factors for Reinjury After Penetrating Trauma.

BACKGROUND: Previous studies have shown that a notable portion of patients who are readmitted for reinjury after penetrating trauma present to a different hospital. The purpose of this study was to identify the risk factors for reinjury after penetrating trauma including reinjury admissions to different hospitals. METHODS: The 2010-2014 Nationwide Readmissions Database was queried for patients surviving penetrating trauma. E-codes identified patients subsequently admitted with a new diagnosis of blunt or penetrating trauma. Univariable analysis was performed using 44 injury, patient, and hospital characteristics. Multivariable logistic regression using significant variables identified risk factors for the outcomes of reinjury, different hospital readmission, and in-hospital mortality after reinjury. RESULTS: There were 443,113 patients identified. The reinjury rate was 3.5%. Patients presented to a different hospital in 30.0% of reinjuries. Self-inflicted injuries had a higher risk of reinjury (odds ratio [OR]: 2.66, P < 0.05). Readmission to a different hospital increased risk of mortality (OR: 1.62, P < 0.05). Firearm injury on index admission increased risk of mortality after reinjury (OR: 1.94, P < 0.05). CONCLUSIONS: This study represents the first national finding that one in three patients present to a different hospital for reinjury after penetrating trauma and have a higher risk of mortality due to this fragmentation of care. These findings have implications for quality and cost improvements by identifying areas to improve continuity of care and the implementation of penetrating injury prevention programs.

Chronic Lymphocytic Thyroiditis May Lower Accuracy of AUS/FLUS Cytopathology in Surgical Patients.

BACKGROUND: Chronic lymphocytic thyroiditis (CLT) increases cytologic atypia on fine-needle aspiration of thyroid nodules, and its effect on rate of malignancy in atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) thyroid nodules remains unclear. This study evaluates the effect of concomitant CLT on malignancy rates of AUS/FLUS thyroid nodules in surgical patients. METHODS: Retrospective review of 1061 patients who underwent thyroidectomy for a dominant thyroid nodule from a single institution was performed. Fine-needle aspiration was classified according to the Bethesda System for Reporting Thyroid Cytopathology. Patients with AUS/FLUS cytopathology were classified into two cohorts: AUS/FLUS with CLT and AUS/FLUS without CLT. Final pathology was reviewed, and the cohorts were further stratified into benign and malignant subgroups. When applicable, patients with gene expression classifier (GEC) testing were reviewed and the positive predictive value (PPV) was calculated. RESULTS: Of the entire surgical series, 293 (28%) patients had AUS/FLUS cytopathology with a rate of malignancy of 56% (163/293) on final pathology. Seventy-three (25%) patients had AUS/FLUS with CLT, of which 44% (n = 32) were malignant by final pathology. The remaining 75% (n = 220) had AUS/FLUS without CLT, 60% (n = 131) of which were malignant. GEC testing was performed in 36 of the AUS/FLUS with CLT patients, where of the 33 suspicious results, 17 were malignant on final pathology, yielding a PPV of 52%. CONCLUSIONS: The rate of malignancy for AUS/FLUS thyroid nodules is lower with coexisting CLT, and similar to previous studies, the PPV of GEC testing is approximately 50%. Cytologic atypia due to CLT may increase more AUS/FLUS results in thyroid nodules, which may lead to overestimation of malignancy rates in this patient population.

Drivers of Hospital Readmission and Early Liver Transplant after Kasai Portoenterostomy.

BACKGROUND: Kasai portoenterostomy (KPE) remains the first-line operation for patients with biliary atresia (BA), but ultimately fails in up to 60% of cases. This study sought to identify factors contributing to hospital readmission and early liver transplant. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was used to identify patients with BA who underwent KPE on index admission. Patient factors, hospital characteristics, and complications of BA were compared by readmission rates and rate of liver transplant within 1 y. The results were weighted for national estimates. RESULTS: Nine hundred and sixty three patients were identified. The readmission rate within 30-d was 36% (n = 346) and within 1-y was 67% (n = 647). Only 9% (n = 90) received a liver transplant within a year. The most common complications after KPE were cholangitis in 58%, decompensated cirrhosis in 54%, and recurrent jaundice in 34%. Male patients (OR 1.5, P = 0.02) with comorbid gastrointestinal anomalies (OR 2.1, P < 0.01) from lower income households (OR 4.6, P < 0.01) and early development of cirrhosis (OR 3.0, P < 0.01) were more likely to be readmitted. Liver transplant was more common in men (OR 4.0, P < 0.01) and those from lower income households (OR 5.2, P < 0.01) with decompensated cirrhosis (OR 8.6, P < 0.01), cholangitis (OR 5.0, P < 0.01), or sepsis (OR 5.7, P < 0.01) on index admission. CONCLUSIONS: This is the first nationwide study to evaluate readmissions in patients with BA undergoing KPE. Although KPE is a lifesaving procedure, hospital readmission rates are high and complications are common. Cholangitis, early progression of cirrhosis, and infections are highly associated with readmission and failure of KPE.

Risk Factors and Clinical Outcomes Associated With Augmented Renal Clearance in Trauma Patients.

BACKGROUND: Augmented renal clearance (ARC; i.e., creatinine clearance [CLCr] ≥ 130 mL/min) has an incidence of 14%-80% in critically ill patients and has been associated with therapy failures for renally cleared drugs. However, the clinical implications of ARC are poorly defined. We hypothesize that modifiable risk factors that contribute to ARC can be identified in severely injured trauma patients and that these risk factors influence clinical outcome. METHODS: In 207 trauma intensive care unit patients, 24-h CLCr was correlated with clinical estimates of glomerular filtration rate (by Cockroft-Gault, modification of diet in renal disease, or chronic kidney disease epidemiology), and clinical outcomes (infection, venous thromboembolism [VTE], length of stay, and mortality). RESULTS: The population was 45 ± 20 y, 68% male, 77% blunt injury with injury severity score of 24 (17-30). Admission serum creatinine was 1.02 ± 0.35 mg/dL, CLCr was 154 ± 77 mL/min, VTE incidence was 15%, ARC incidence was 57%, and mortality was 11%. Clinical estimates of glomerular filtration rate by Cockroft-Gault, modification of diet in renal disease, chronic kidney disease epidemiology underestimated actual CLCr by 20%, 22%, or 15% (all P < 0.01). CLCr was higher in males and those who survived, and lower in those with hypertension, diabetes, positive cultures, receiving transfusions, or pressors (all P < 0.05). On multivariate analysis, male gender (odds ratio [OR] 2.9 [1.4-6.1]), age (OR 0.97 [0.95-0.99]), and packed red blood cells transfusion (OR 0.31 [0.15-0.66]) were the only independent predictors of ARC. CONCLUSIONS: ARC occurs in more than half of all high-risk trauma intensive care unit patients and is underestimated by standard clinical equations. ARC was not associated with increased incidence of VTE or infection but rather is associated with younger healthier males and reduced mortality. ARC seems to be a beneficial compensatory response to trauma.

Cost-effectiveness analysis of erenumab for the preventive treatment of episodic and chronic migraine: Results from the US societal and payer perspectives.

Objectives To assess the cost-effectiveness of erenumab 140 mg ("erenumab") for the prophylactic treatment of episodic migraine and chronic migraine. Study design A hybrid Monte Carlo patient simulation and Markov cohort model was constructed to compare erenumab to no preventive treatment or onabotulinumtoxinA among adult ( ≥ 18 years) patients with episodic migraine and chronic migraine who failed prior preventive therapy from the US societal and payer perspectives. Methods Patients entered the model one at a time and were assigned to a post-treatment monthly migraine day category based on baseline monthly migraine days and treatment effect. Using monthly cycles, patients were followed for 2 years and accumulated costs and utilities associated with their post-treatment monthly migraine days. The primary outcome included the incremental cost-effectiveness ratio presented as cost per quality-adjusted life year gained. Results With an annual drug price of erenumab of $6900, treatment with erenumab in the societal perspective ranges from a dominant strategy versus no preventive treatment among chronic migraine patients to an incremental cost-effectiveness ratio of $122,167 versus no preventive treatment among episodic migraine patients. When excluding indirect costs (i.e. payer perspective), the incremental cost-effectiveness ratios are cost-effective among chronic migraine patients ($23,079 and $65,720 versus no preventive treatment and onabotulinumtoxinA, respectively), but not among episodic migraine patients ($180,012 versus no preventive treatment). Model results were sensitive to changes in monthly migraine days, health utilities, and treatment costs. Conclusion The use of erenumab may be a cost-effective approach to preventing monthly migraine days among patients with chronic migraine versus onabotulinumtoxinA and no preventive treatment in the societal and payer perspectives, but is less likely to offer good value for money for those with episodic migraine, unless lost productivity costs are considered.

Prevalence of menopausal symptoms among mid-life women: findings from electronic medical records.

BACKGROUND: To assess the prevalence of menopausal symptoms among women prescribed hormone therapy (HT) using electronic medical record data from a regional healthcare organization. METHODS: Retrospective data from the Reliant Medical Group from 1/1/2006-12/31/2011 were assessed for 102 randomly-selected patients. Study eligibility criteria included: females aged 45 to 65; prescribed oral or transdermal HT; no history of breast cancer, venous thromboembolism, stroke, gynecological cancer, or hysterectomy; continuously enrolled in the health plan for 1 year before and after the first observed HT prescription. Prevalence of menopause-related symptoms was analyzed descriptively at both the patient and visit levels. RESULTS: Mean age of patients was 54 years. The most common menopausal symptoms were: hot flushes (40%), night sweats (17%), insomnia (16%), vaginal dryness (13%), mood disorders (12%), and weight gain (12%). Among the 102 patients, 163 individual visits listing menopausal symptoms were identified, of which hot flushes (71 visits) were the most common symptom identified. CONCLUSION: Our findings provide recent data on the types of menopausal symptoms experienced by mid-life women prescribed HT. Electronic medical records may be a rich source of data for future studies of menopausal symptoms in this population.

Failure of surgical and endovascular infrainguinal and iliac procedures in the management of peripheral arterial disease using data from electronic medical records.

PURPOSE: To understand rates of procedure failure among patients undergoing revascularization for peripheral arterial disease (PAD) in clinical practice. MATERIALS AND METHODS: This retrospective analysis of patients with PAD who underwent a PAD-related procedure used claims and electronic medical record data from 2005 to 2009. Procedures were grouped by type (endovascular [ie, angioplasty with/without stent, atherectomy] or surgical [ie, bypass surgery, endarterectomy, thrombectomy]) and site (ie, iliac, infrainguinal). The study assessed antiplatelet and anticoagulant agent use; procedure failure, defined as a subsequent procedure or amputation; and predictors of time to procedure failure. RESULTS: A sample of 248 patients with PAD who underwent a PAD-related procedure was identified. The population was 59% male, had a mean age of 73 years, and had a mean follow-up of 23 months. Endovascular procedures alone were performed in 37% of patients, with the remainder receiving surgery only or surgery with an endovascular procedure, and 79% of patients had an infrainguinal intervention. Antiplatelet and anticoagulant use rates after the procedure were 90% and 25%, respectively. After their initial procedure, 20% of patients required a second procedure or amputation, with an average failure time of 228 days. Patients treated with infrainguinal procedures had a significantly higher failure rate versus those treated with iliac procedures (23% vs 8%; P = .011). In multivariate analysis, patients without anticoagulant use before the procedure were at significantly lower failure risk (P = .022). CONCLUSIONS: Repeated intervention and/or major amputation after revascularization of PAD was common. Further investigation of the factors associated with procedure failure is warranted.

The impact of early remission on disease trajectory and patient outcomes in major depression disorder (MDD): A targeted literature review and microsimulation modeling approach based on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

BACKGROUND: While literature has suggested that the duration of a major depressive episode (MDE) may affect both symptomatic and functional outcomes in major depressive disorder (MDD), study designs are limited in their ability to isolate a causal relationship. METHODS: A targeted literature review was conducted using the MEDLINE database to assess whether there was an association between (1) shorter duration of an MDE, or (2) increased rapidity of symptom improvement, and MDD outcomes in adult patients. Given findings from the literature, we hypothesized that rapid symptom improvement could be associated with other longer-term clinical outcomes and used a previously-developed microsimulation model to test this hypothesis. The base case of the model replicated step-therapy treatment patterns, for 10,000 simulated patients, based on lines of therapy related to standard of care, observed remission rates, and observed time to relapse from the STAR*D study. In alternative scenario analyses, the step 1 remission rate was varied by +25 % and +50 % from the base case value to simulate the potential impact of improved earlier remission on disease trajectory and patient-level clinical outcomes. RESULTS: The literature review (N = 35 studies) suggests a statistically significant relationship between the duration of MDE or early symptom improvement and MDD outcomes. The microsimulation model corroborated these findings and demonstrated that increasing the rate of remission in step 1 results in patients experiencing decreased number of treatment steps, faster time to remission, decreased rate of reaching treatment-resistant depression, and delayed time to relapse. LIMITATIONS: Rates of relapse in STAR*D were deemed unreliable due to the high-loss of follow-up; rates of relapse for the MDD DTM were instead derived using parametric extrapolation methods (i.e., exponential, Weibull, log-logistic, Gaussian, log-normal, logistic). Adherence to treatment was assumed to be 100 %; however, non-adherence is expected to result in lower cumulative remission rates. CONCLUSION: Findings from the literature, coupled with quantification through a novel microsimulation model, demonstrate the potential impact of increased remission on disease trajectory and patient outcomes in MDD. While additional analyses with the model may be warranted to explore the impact of novel interventions on population health, including long-term outcomes (i.e., 5-year follow-up, lifetime follow-up), efforts by clinicians to increase remission early in the disease trajectory may improve long-term outcomes.

A systematic review of the treatment of residual below the knee venous reflux after endovenous thermal ablation of the great saphenous vein.

BACKGROUND: Great saphenous vein (GSV) antireflux procedures have evolved during the past few decades to reduce elevated venous pressure. Untreated reflux in the below knee (BK) GSV (BK-GSV) can lead to persistent venous hypertension and deterioration of the venous circulation. The purpose of the present systematic review was to study the influence of BK-GSV intervention on venous disease progression. METHODS: A search was conducted, adhering to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The PubMed and Embase databases were searched and cross-referenced. Studies were included if they had met the inclusion criterion of BK-GSV disease as a primary or secondary outcome. Two of the authors independently determined the eligibility and extracted the relevant data. RevMan, version 5.3 (Cochrane Training, London, UK), and SPSS (IBM Corp, Armonk, NY) were used for statistical computation. RESULTS: Fifteen studies that had assessed BK-GSV reflux recurrence after ablative intervention were included in our analysis. Of the 15 studies, 6 had assessed patients after above knee (AK) high ligation and stripping (HLS), 7 after AK endovenous laser ablation (AK-EVLA), and 2 after AK- and BK-EVLA (AK+BK EVLA). In total, 525 limbs had undergone HLS, 696 AK-EVLA, and 147 AK+BK EVLA. AK+BK EVLA was associated with significantly lower odds of BK-GSV reflux recurrence compared with AK-EVLA only (odds ratio [OR], 0.1857; 95% confidence interval [CI], 0.076-0.4734; P < .0001). Although the odds of recurrent BK-GSV reflux appeared to be greater for patients who had undergone AK-HLS compared with AK+BK HLS, the difference was not statistically significant (OR, 0.62; CI, 0.27-1.43; P = .69). Finally, no statistically significant difference was observed in BK-GSV reflux recurrence between patients receiving AK-EVLA and those receiving AK-HLS (OR, 0.85; 95% CI, 0.52-1.39; P = .31). CONCLUSIONS: Axial hydrostatic reflux from the groin to ankle is best controlled with AK+BK-GSV ablation. However, GSV ablation can result in saphenous nerve injury. For C4 to C6 disease, more aggressive treatment of the AK+BK-GSV is justified if the duplex ultrasound findings demonstrate groin to ankle reflux. Thermal ablation of the BK-GSV has a lower incidence of saphenous nerve injury than does BK saphenous stripping. More randomized controlled trials are needed to answer questions involving disease recurrence and the best techniques to mitigate these recurrences.

The burden of undertreatment and non-treatment among patients with non-valvular atrial fibrillation and elevated stroke risk: a systematic review.

OBJECTIVE: Global treatment guidelines recommend treatment with oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and an elevated stroke risk. However, not all patients with NVAF and an elevated stroke risk receive guideline-recommended therapy. A literature review and synthesis of observational studies were undertaken to identify the body of evidence on untreated and undertreated NVAF and the association with clinical and economic outcomes. METHODS: An extensive search (1/2010-4/2020) of MEDLINE, the Cochrane Library, conference proceedings, and health technology assessments (HTAs) was conducted. Studies must have evaluated rates of nontreatment or undertreatment in NVAF. Nontreatment was defined as absence of OACs (but with possible antiplatelet treatment), while undertreatment was defined as treatment with only antiplatelet agents. RESULTS: Sixteen studies met our inclusion criteria. Rates of nontreatment for patients with elevated stroke risk ranged from 2.0-51.1%, while rates of undertreatment ranged from 10.0-45.1%. The clinical benefits of anticoagulation were reported in the evaluated studies with reductions in stroke and mortality outcomes observed among patients treated with anticoagulants compared to untreated or undertreated patients. Adverse events associated with all bleeding types (i.e. hemorrhagic stroke, major bleeding or gastrointestinal hemorrhaging) were found to be higher for warfarin patients compared to untreated patients in real-world practice. Healthcare resource utilization was found to be lower among patients highly-adherent to warfarin compared to untreated patients. CONCLUSIONS: Rates of nontreatment and undertreatment among NVAF patients remain high and are associated with preventable cardiovascular events and death. Strategies to increase rates of treatment may improve clinical outcomes.

Applying State-of-the-Art Survival Extrapolation Techniques to the Evaluation of CAR-T Therapies: Evidence from a Systematic Literature Review.

INTRODUCTION: Traditional statistical techniques for extrapolating short-term survival data for anticancer therapies assume the same mortality rate for noncured and "cured" patients, which is appropriate for projecting survival of non-curative therapies but may lead to an underestimation of the treatment effectiveness for potentially curative therapies. Our objective was to ascertain research trends in survival extrapolation techniques used to project the survival benefits of chimeric antigen receptor T cell (CAR-T) therapies. METHODS: A global systematic literature search produced a review of survival analyses of CAR-T therapies, published between January 1, 2015 and December 14, 2020, based on publications sourced from MEDLINE, scientific conferences, and health technology assessment agencies. Trends in survival extrapolation techniques used, and the rationale for selecting advanced techniques, are discussed. RESULTS: Twenty publications were included, the majority of which (65%, N = 13) accounted for curative intent of CAR-T therapies through the use of advanced extrapolation techniques, i.e., mixture cure models [MCMs] (N = 10) or spline-based models (N = 3). The authors' rationale for using the MCM approach included (a) better statistical fits to the observed Kaplan-Meier curves (KMs) and (b) visual inspection of the KMs indicated that a proportion of patients experienced long-term remission and survival which is not inherently captured in standard parametric distributions. DISCUSSION: Our findings suggest that an advanced extrapolation technique should be considered in base case survival analyses of CAR-T therapies when extrapolating short-term survival data to long-term horizons extending beyond the clinical trial duration. CONCLUSION: Advanced extrapolation techniques allow researchers to account for the proportion of patients with an observed plateau in survival from clinical trial data; by only using standard-partitioned modeling, researchers may risk underestimating the survival benefits for the subset of patients with long-term remission. Sensitivity analysis with an alternative advanced extrapolation technique should be implemented and re-assessment using clinical trial extension data and/or real-world data should be conducted as longer-term data become available.

Comparative Effectiveness Research for CAR-T Therapies in Multiple Myeloma: Appropriate Comparisons Require Careful Considerations of Data Sources and Patient Populations.

BACKGROUND AND OBJECTIVE: Registrational trials for ciltacabtagene autoleucel [cilta-cel]) and idecabtagene vicleucel [ide-cel] chimeric antigen receptor T-cell (CAR-T) therapies were single-arm studies conducted with relapse refractory multiple myeloma (MM) patients who were triple-class-exposed (TCE) or triple-class-refractory (TCR). It is critical for researchers conducting comparative effectiveness research (CER) to carefully consider the most appropriate data sources and comparable patient populations. The aim of this study was to identify potential data sources and populations for comparing to single-arm CAR-T trials CARTITUDE-1 (cilta-cel) and KarMMa (ide-cel). METHODS: A 2-part global systematic literature search produced a review of (1) clinical trials of National Comprehensive Cancer Network (NCCN) guideline preferred regimens in previously treated MM, and (2) real-world data cohorts of TCE or TCR populations, published between 1/1/2015 and 12/10/2020, with sample sizes of > 50 patients and reporting survival-related outcomes. Implications on CER and accepted best practices are discussed. RESULTS: Nine clinical trials of NCCN preferred regimens were identified along with five real-world data-based publications. No clinical trials evaluated patients with TCE or TCR MM. Among the real-world data-based publications, two evaluated patients exclusively with TCR MM, two analyzed a mixed population of patients with TCE or TCR MM, and one publication assessed patients exclusively with TCE MM. Real-world data treatment patterns were heterogeneous. CONCLUSION: Current NCCN preferred regimens were not specifically studied in TCE or TCR MM patients, although some studies do include a proportion of these types of patients. Therefore, appropriate matching of populations using either real-world data or patient level clinical trial data is critical to putting trials of novel CAR-Ts (i.e., CARTITUDE-1 or KarMMa) into appropriate comparative context.

The IMPact of untReated nOn-Valvular atrial fibrillation on short-tErm clinical and economic outcomes in the US Medicare population: the IMPROVE-AF model.

BACKGROUND: Despite treatment guidelines recommending the use of oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and moderate to high risk of stroke (CHA2DS2-VASc score ≥1), many patients remain untreated. A study conducted among Medicare beneficiaries with AF and a CHA2DS2-VASc score of ≥2 found that 51% of patients were not prescribed an OAC despite being eligible for treatment. When left untreated, NVAF poses an enormous burden to society, as stroke events are estimated to cost the US healthcare system about $34 billion each year in both direct medical costs and indirect productivity losses. This research explored the short-term clinical implications and budget impact (BI) of increasing OAC use among Medicare beneficiaries with NVAF. METHODS: A decision-analytic model was developed from the payer and societal perspectives to estimate the impact of increasing treatment rates among Medicare-eligible NVAF patients with a moderate-to-high risk of stroke over 1 year. Results of the model compared (1) a base case scenario using literature-derived rates of OAC use, and (2) a hypothetical scenario assuming an absolute 5% increase in overall OAC use. Clinical outcomes included the incremental annual number of ischemic stroke, hemorrhagic stroke, and gastrointestinal bleeding events, and stroke-related deaths. Economic outcomes included incremental annual and per-member per-month (PMPM) direct medical costs for the payer perspective and the incremental sum of annual direct medical and indirect costs from productivity loss and caregiver burden for the societal perspective. RESULTS: In total, 1.95 million Medicare patients with NVAF were estimated to be treated with OACs in the base case (3.8% of beneficiaries). In the hypothetical scenario analysis, nearly 200,000 more patients were treated resulting in 3,705 fewer ischemic strokes, 14 fewer gastrointestinal bleeds, 141 more hemorrhagic strokes, and 175 fewer deaths. The total incremental BI was $399.16 million ($0.65 PMPM) from the payer perspective and $377.10 million from the societal perspective due to indirect cost savings ($22.06 million). CONCLUSION: Our findings suggest that increased overall OAC use has a positive clinical benefit on the annual number of ischemic stroke events and deaths avoided in the Medicare population, while maintaining a modest increase in the overall BI to the Medicare system.

Acute Kidney Injury Risk in Patients Treated with Vancomycin Combined with Meropenem or Cefepime.

Background: No previous studies have determined the incidence of acute kidney injury (AKI) in trauma patients treated with vancomycin + meropenem (VM) versus vancomycin + cefepime (VC). The purpose of this study was to fill this gap. Methods: A series of 99 patients admitted to an American College of Surgeons-verified level 1 trauma center over a two-year period who received VC or VM for >48 hours were reviewed retrospectively. Exclusion criteria were existing renal dysfunction or on renal replacement therapy. The primary outcome was AKI as defined by a rise in serum creatinine (SCr) to 1.5 times baseline. Multi-variable analysis was performed to control for factors associated with AKI (age, obesity, gender, length of stay [LOS], nephrotoxic agent(s), and baseline SCr), with significance defined as p < 0.05. Results: The study population was 50 ± 19 years old, 76% male, with a median LOS of 21 [range 15-39] days, and baseline SCr of 0.9 ± 0.2 mg/dL. Antibiotics, diabetes mellitus, and Injury Severity Score were independent predictors of AKI (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4-12; OR 9.3; 95% CI 1-27; OR 1.2; 95% CI 1.023-1.985, respectively). The incidence of AKI was higher with VM than VC (10/26 [38%] versus 14/73 [19.1%]; p = 0.049). Conclusions: The renal toxicity of vancomycin is potentiated by meropenem relative to cefepime in trauma patients. We recommend caution when initiating vancomycin combination therapy, particularly with meropenem.

Geodemographic analysis of pediatric firearm injuries in Miami, FL.

PURPOSE: Firearm injuries (GSW) are a growing public health concern and leading cause of morbidity and mortality among children, yet predictors of injury remain understudied. This study examines the correlates of pediatric GSW within our county. METHODS: We retrospectively queried an urban Level 1 trauma center registry for pediatric (0-18 years) GSW from September 2013 to January 2019, examining demographic, clinical, and injury information. We used a geographic information system to map GSW rates and perform spatial and spatiotemporal cluster analysis to identify zip code "hot spots." RESULTS: 393 cases were identified. The cohort was 877% male, 87% African American, 10% Hispanic, and 22% Caucasian/Other. Injuries were 92% violence-related and 4% accidental, with 63% occurring outside school hours. Mortality was 12%, with 53% of deaths occurring in the resuscitation unit. Zip-level GSW rates ranged from 0 to 9 (per 1000 < 18 years) by incident address and 0-6 by home address. Statistically significant hot spots were in predominantly underserved African American and Hispanic neighborhoods. CONCLUSIONS: Geodemographic analysis of pediatric GSW injuries can be utilized to identify at-risk neighborhoods. This methodology is applicable to other metropolitan areas where targeted interventions can reduce the burden of gun violence among children. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: Level III.

The Key to Combat Readiness Is a Strong Military-Civilian Partnership.

INTRODUCTION: In peacetime, it is challenging for Army Forward Resuscitative Surgical Teams (FRST) to maintain combat readiness as trauma represents <0.5% of military hospital admissions and not all team members have daily clinical responsibilities. Military surgeon clinical experience has been described, but no data exist for other members of the FRST. We test the hypothesis that the clinical experience of non-physician FRST members varies between active duty (AD) and Army reservists (AR). METHODS: Over a 3-year period, all FRSTs were surveyed at one civilian center. RESULTS: Six hundred and thirteen FRST soldiers were provided surveys and 609 responded (99.3%), including 499 (81.9%) non-physicians and 110 (18.1%) physicians/physician assistants. The non-physician group included 69% male with an average age of 34 ± 11 years and consisted of 224 AR (45%) and 275 AD (55%). Rank ranged from Private to Colonel with officers accounting for 41%. For AD vs. AR, combat experience was similar: 50% vs. 52% had ≥1 combat deployment, 52% vs. 60% peri-deployment patient load was trauma-related, and 31% vs. 32% had ≥40 patient contacts during most recent deployment (all P > .15). However, medical experience differed for AD and AR: 18% vs. 29% had >15 years of experience in practice and 4% vs. 17% spent >50% of their time treating critically injured patients (all P < .001). These differences persisted across all specialties, including perioperative nurses, certified registered nurse anesthetists, operating room (OR) techs, critical-care nurses, emergency room (ER) nurses, licensed practical nurse (LPN), and combat medics. CONCLUSIONS: This is the first study of clinical practice patterns in AD vs. AR, non-physician members of Army FRSTs. In concordance with previous studies of military surgeons, FRST non-physicians seem to be lacking clinical experience as well. To maintain readiness and to provide optimal care for our injured warriors, the entire FRST, not just individuals, should embed within civilian centers.

Do Research Groups Align on an Intervention's Value? Concordance of Cost-Effectiveness Findings Between the Institute for Clinical and Economic Review and Other Health System Stakeholders.

The Institute for Clinical and Economic Review (ICER) employs fixed cost-effectiveness (CE) thresholds that guide their appraisal of an intervention's long-term economic value. Given ICER's rising influence in the healthcare field, we undertook an assessment of the concordance of ICER's CE findings to the published CE findings from other research groups (i.e., "non-ICER" researchers including life science manufacturers, academics, and government institutions). Disease areas and pharmaceutical interventions for comparison were determined based on ICER evaluations conducted from 1 January 2015 to 31 December 2017. A targeted literature search was conducted for non-ICER CE publications using PubMed. Studies had to be conducted from the US setting, include the same disease characteristics (e.g., disease severity; treatment history), incorporate the same pharmaceutical interventions and comparison groups, and present incremental costs per quality-adjusted life-year (QALY) gained from the healthcare sector or payer perspective. Discordance was measured as the proportion of unique interventions that would have had more favorable valuations (i.e., low, intermediate, high value-for-money) if the CE findings from other research groups had been used for decision making instead of ICER's findings. More favorable valuations were defined as transitioning from low value (as determined by ICER) to intermediate or high value (as determined by other researchers) and from intermediate value (as determined by ICER) to high value (as determined by other researchers). Among the 13 non-ICER studies meeting inclusion criteria, six disease areas and 14 interventions were assessed. Of the 14 interventions, a more favorable valuation would have been recommended for ten therapies if the CE ratios from other research groups had been used for decision making instead of ICER's findings, representing a 71.4% (10/14) discordance rate. Moreover, these discrepancies were found in each of the evaluated disease areas, with the largest number of discordant valuations found in rheumatoid arthritis (five out of six interventions were discordant) followed by one valuation each in multiple sclerosis (one out of three), non-small cell lung cancer (one out of two), multiple myeloma (one out of one), high cholesterol (one out of one), and congestive heart failure (one out of one). Our findings indicate high discordance when comparing ICER's appraisals to the CE findings of non-ICER researchers. To understand the value of new interventions, the totality of evidence on the CE of an intervention-including results from ICER and non-ICER modeling efforts-should be considered when making coverage and reimbursement decisions.

Cost-utility analyses of targeted immunomodulators in rheumatoid arthritis: systematic review.

Aims: Cost-utility (CU) modeling is a common technique used to determine whether new treatments represent good value for money. As with any modeling exercise, findings are a direct result of methodology choices, which may vary widely. Several targeted immuno-modulators have been launched in recent years to treat moderate-to-severe rheumatoid arthritis (RA) which have been evaluated using CU methods. Our objectives were to identify common and innovative modeling choices in moderate-to-severe RA and to highlight their implications for future models in RA.Materials and methods: A systematic literature search was conducted to identify CU models in moderate-to-severe RA published from January 2013 to June 2019. Studies must have included an active comparator and used quality-adjusted life-years (QALYs) as the common measure of effectiveness. Modeling methods were characterized by stakeholder perspective, simulation type, mapping between parameters, and data sources.Results: Thirty-one published modeling studies were reviewed spanning 13 countries and 9 drugs, with common methodological choices and innovations observed among them. Over the evaluated time period, we observed common methods and assumptions that are becoming more prominent in the RA CU modeling landscape, including patient-level simulations, two-stage models combining trial results and real-world evidence, real-world treatment durations, long-term health consequences, and Health Assessment Questionnaire (HAQ)-related hospitalization costs. Models that consider the societal perspective are increasingly being developed as well.Limitations: This review did not consider studies that did not report QALYs as a utility measure, models published only as conference abstracts, or cost-consequence models that did not report an incremental CU ratio.Conclusions: CU modeling for RA increasingly reflects real-world conditions and patient experiences which are anticipated to provide better information in the assessment of health technologies. Future CU models in RA should consider applying the observed advances in modeling choices to optimize their CU predictions and simulation of real-world outcomes.