Implementing an Interdisciplinary Procedure Curriculum.

INTRODUCTION: This curriculum was designed to improve access to procedures for our internal medicine residents. METHODS: We created an interdisciplinary procedure course (IDPC) composed of two simulation sessions and a one-week procedural rotation supervised by multiple specialties including nephrology, cardiology, cardiothoracic anesthesiology, general anesthesiology, and interventional radiology. After the course, residents completed two surveys documenting the number of procedures and their level of confidence on a Likert scale (1 = very unconfident to 5 = very confident) prior to and after completing the curriculum. RESULTS: Sixteen residents participated in the course from September 2021 to June 2022. The collective number of procedures performed by these 16 residents increased from 176 to 343 after a one-week rotation. For arterial lines, the proportion of residents that reported an improvement in confidence scores was 0.44 (95% confidence interval 0.23 to 1, p-value of 0.60). The proportion of residents that had an increase in their confidence performing central lines was 0.63 (95% confidence interval 0.39 to 1, p-value of 0.23). For intubations, the proportion of residents that reported an improvement in confidence was 0.94 (95% confidence interval 0.72 to 1, p-value of 0.0006). CONCLUSION: By collaborating with multiple specialties, residents almost doubled the number of procedures performed during training and reported an increased level of confidence in procedural performance for airway intubation. We learned residents want to improve their access to procedures and described a curriculum that was easily implemented.

Research Opportunities in Stroke Prevention for Atrial Fibrillation: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Established Clinical Prediction Rules for Bleeding Had Mediocre Discrimination in Left Ventricular Assist Device Recipients.

Left ventricular assist devices (LVAD) reduce mortality in patients with end-stage heart failure, but LVAD management is frequently complicated by bleeding. Bleeding prediction post-LVAD implantation is challenging as prediction rules for hemorrhage have not been rigorously studied in this population. We aimed to validate clinical prediction rules for bleeding, derived in the atrial fibrillation and venous thromboembolism populations, in an LVAD cohort. This was a retrospective cohort study of LVAD recipients at an academic center. The primary end-point was time to gastrointestinal bleed or intracranial hemorrhage after implant; the secondary end-point was time to any major hemorrhage after hospital discharge. Four hundred and eighteen patients received an LVAD (135 HeartMate II, 125 HeartMate 3, 158 HVAD) between November 2009 and January 2019. The primary end-point occurred in 169 (40.4%) patients with C -statistics ranging 0.55-0.58 (standard deviation [SD] 0.02 for all models). The secondary end-point occurred in 167 (40.0%) patients with C -statistics ranging 0.53-0.58 (SD 0.02 for all models). Modifying the age and liver function thresholds increased the C -statistic range to 0.56-0.60 for the primary and secondary end-points. In a sensitivity analysis of HeartMate 3 patients, prediction rules performed similarly. Existing prediction rules for major bleeding had mediocre discrimination in an LVAD cohort.

D-dimer predicts venous thromboembolism in multiple myeloma: a nested case-control study.

Background: Clinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment. Objectives: We sought to determine the association between soluble P-selectin (sP-selectin) and D-dimer with VTE in MM. Methods: We identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the association after adjusting for IMPEDE VTE. Results: Each 1-point increase in IMPEDE VTE score was associated with a 27% increase in odds of VTE (odds ratio 1.27; 95% CI 1.08-1.51; c-statistic 0.61; 95% CI 0.51-0.71). There was no association between sP-selectin and VTE. Each one increase in natural log of D-dimer was associated with a 44% increase in odds of VTE, so we assigned points (ranging from -2 to +2) to D-dimer values and incorporated them into IMPEDE VTE, forming IMPEDED VTE. There was a 30% increase in odds of VTE per each 1-point increase in IMPEDED VTE (OR 1.30; 95% CI 1.12-1.52; c-statistic 0.65; 95% CI 0.55-0.75). Conclusion: Among patients with newly diagnosed MM starting chemotherapy, D-dimer was associated with increased odds of developing VTE within the subsequent 6-months. The addition of D-dimer to IMPEDE VTE-IMPEDED VTE-could improve prediction of VTE among patients with MM.

Predicting Postoperative Troponin in Patients Undergoing Elective Hip or Knee Arthroplasty: A Comparison of Five Cardiac Risk Prediction Tools.

Background: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty. Methods: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular disease calculator (ASCVD), the Framingham risk score (FRS), the American College of Surgeon's National Surgical Quality Improvement Program (ACS-NSQIP) calculator, the revised cardiac risk index (RCRI), and the reconstructed RCRI (R-RCRI). Results: None of the scores predicted MINS in women. Among men, the ASCVD (C-statistic of 0.66; p=0.04), ACS-NSQIP (C-statistic of 0.69; p=0.01), and RCRI (C-statistic of 0.64; p=0.04) predicted MINS. Among all patients, spearman correlations (r s) of the risk scores with the POD2 hs-cTnI levels were 0.24, 0.20, 0.11, 0.11, and 0.08 for the ASCVD, Framingham, ACS-NSQIP, RCRI, and R-RCRI scores, respectively, with p values of <0.001, <0.001, <0.001, 0.006, and 0.025. Baseline hs-cTnI predicted MINS (C-statistics: 0.63 in women and 0.72 in men) and postoperative hs-cTnI (r s = 0.51, p=0.001). Conclusion: In elderly patients undergoing elective hip or knee arthroplasty, several of the scores modestly predicted MINS in men and correlated with POD2 hs-cTnI.

Standardization of risk prediction model reporting in cancer-associated thrombosis: Communication from the ISTH SSC subcommittee on hemostasis and malignancy.

Since the development of the Khorana score to predict risk of cancer-associated venous thromboembolism (VTE), many modified and de novo risk prediction models (RPMs) have been proposed. Comparison of the prognostic performance across models requires comprehensive reporting and standardized methods for model development, validation and evaluation. To improve the standardization of RPM reporting, the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) tool was published in 2015. To better understand the quality of reporting and development of RPMs for cancer-associated VTE, we performed a literature search of published RPMs and assessed each model using the TRIPOD checklist. Our results yielded 29 RPMs for which 30 items were evaluated. There was a non-significant (p = 0.15) improvement in reporting of the 30 items in the post-TRIPOD era (81%) versus the pre-TRIPOD era (75%). Of seven items (title, sample size, missing data handling, baseline demographics, methods and results for model performance, and supplemental resources) with the lowest reporting in the pre-TRIPOD era (<70%), there was an average improvement of 22% in the post-TRIPOD era. Only two of the 22 studies published in the post-TRIPOD era acknowledged compliance with TRIPOD. Informed by the results of this assessment, the Scientific and Standardization Committee (SSC) Subcommittee on Hemostasis & Malignancy of the International Society on Thrombosis and Hemostasis (ISTH) advocates for standardization of four key elements of RPMs for cancer-associated VTE: (1) inclusion of the TRIPOD checklist, (2) clear definition of the derivation population, with justification of sample size, (3) clear definition of predictors, and (4) external validation prior to implementation.

Different risks of hemorrhage in patients with elevated international normalized ratio from chronic liver disease versus warfarin therapy, a population-based retrospective cohort study.

BACKGROUND: Patients with chronic liver disease (CLD) often present with an elevated international normalized ratio (INR). Although elevated INR reflects a higher risk of hemorrhage among warfarin users, its clinical significance in CLD patients is less clear. OBJECTIVES: We used Veterans Health Administration data to quantify the association between INR and (non-variceal) hemorrhage in patients with CLD compared to warfarin users. METHODS: We performed a multivariate competing risk analysis to study the association between INR and hemorrhage in the two cohorts. We used an interaction term between INR and cohort (CLD/warfarin users) to test if INR had different effects on hemorrhage in the two cohorts. RESULTS: Data from 80 134 patients (14, 412 with CLD and 65, 722 taking warfarin) were analyzed. The effect of INR on the risk of hemorrhage differed between CLD patients and warfarin users (interaction P < .001). As INR increased above 1.5, the adjusted hazard ratio (aHR) for hemorrhage in CLD patients increased to 2.25 but remained fairly constant with further elevation of INR values. In contrast, the risk of hemorrhage in patients taking warfarin remained low with INR in the subtherapeutic (INR <2.0) and therapeutic ranges (INR 2.0-3.0), and increased exponentially with INR in the supratherapeutic range (aHR 1.64 with INR >3.0-3.5, and 4.70 with INR >3.5). CONCLUSIONS: The relationship between INR and risk of hemorrhage in CLD patients is different from that in warfarin users. Caution should be exercised extrapolating data from warfarin users to make clinical decisions in CLD patients.

Warfarin Dosing in Patients With CYP2C9*5 Variant Alleles.

Pharmacogenetic dosing improves the accuracy of warfarin dosing, but current pharmacogenetic dosing algorithms are less accurate in populations of African ancestry. The cytochrome P450 2C9*5 (CYP2C9*5) allele is found almost exclusively in populations of African ancestry, and in vitro studies suggest CYP2C9*5 is associated with reduced clearance of warfarin. The clinical relevance of this single-nucleotide variation (SNV) (formerly SNP) is uncertain. In this multicentered study of 2,298 patients (49% female, 35% Black) taking warfarin, we quantified the association between the CYP2C9*5 allele and warfarin requirements. The CYP2C9*5 SNV was present in 2.3% of Black and 0.07% of White patients. Without taking CYP2C9*5 into account, pharmacogenetic algorithms that include other SNVs overestimated the warfarin dose by 30% (95% confidence interval (19-40%), P < 0.001), an average of 1.87 mg/day (SD 1.64) in heterozygotes (P < 0.001). Noncarriers required a slightly (0.23 mg/day, SD 2.09) higher than predicted dose. Genotyping for CYP2C9*5 corrected the potential overdose and halved overall dosing error in heterozygotes. Patients carrying CYP2C9*5 require a clinically relevant reduction in warfarin dose. Given the potential to improve the accuracy and safety of warfarin dosing in populations of African ancestry, we have incorporated this SNV into a nonprofit website to assist warfarin initiation (www.WarfarinDosing.org).

Evaluation of the Khorana score for prediction of venous thromboembolism in patients with multiple myeloma.

BACKGROUND: Guidelines recommend thromboprophylaxis for patients with multiple myeloma (MM) at high risk for venous thromboembolism (VTE). However, the optimal risk prediction model for VTE in MM remains unclear. Khorana et al developed a VTE risk score (Khorana score) in ambulatory cancer patients receiving chemotherapy. We aimed to evaluate the predictive ability of the Khorana score in patients with MM. METHODS: We identified patients with MM within the Veterans Affairs health care system between 2006 and 2013. The Khorana score was calculated before treatment initiation. Using logistic regression, the relationship between risk group and VTE was assessed at 3 and 6 months. We tested model discrimination using the concordance statistic. RESULTS: In the cohort of 2870 patients with MM, there were 1328 at low risk (0 points), 1521 at intermediate risk (1-2 points), and 21 at high risk (≥3 points) for VTE by the Khorana score. The 6-month cumulative incidence of VTE was 5.1% (95% confidence interval [CI], 4.0%-6.4%) in low risk, 3.9% (95% CI, 3.0%-5.0%) in intermediate risk, 4.8% (95% CI, 0.3%-20.2%) in high risk. The Khorana score did not strongly discriminate between patients who did and did not develop VTEs at 3 or 6 months (concordance statistic, 0.58; 95% CI, 0.54-0.63; and 0.53, 95% CI, 0.50-0.57, respectively. CONCLUSIONS: In conclusion, in this cohort of 2870 patients with MM, the Khorana score did not predict VTE. Our study supports the need to use myeloma-specific risk models to predict VTE risk in patients with MM.

Improving Follow-up Attendance for Discharged Emergency Care Patients Using Automated Phone System to Self-schedule: A Randomized Controlled Trial.

BACKGROUND: Automated phone appointment reminders have improved adherence with follow-up appointments in a variety of hospital settings, but have mixed results in patients discharged from the emergency department (ED). Increasing adherence to follow-up care has been a priority in the ED to improve patient outcomes and reduce unnecessary future visits. METHODS: We conducted a prospective randomized open, blinded end-point (PROBE) trial of 278 adult patients discharged from the ED and referred to a provider for follow-up care. Participants in the intervention arm received a self-scheduling text or phone message that automatically connected them to their referral provider to schedule a follow-up appointment and sent them appointment reminders. Those in the control arm received standard-of-care written instructions to contact listed referral providers. The primary outcome was time to appointment. The secondary outcome was time to return visit to the ED. RESULTS: The automated reminders increased the cumulative incidence of keeping the referral appointment after ED discharge (p < 0.001, Gray's test). Of participants randomized to the automated phone intervention, 49.3% (n = 74) kept their follow-up appointment versus 23.4% (n = 30) in the control arm, with a hazard ratio (HR) and 95% confidence interval (CI) over the duration of the study period of 2.4 (1.6 to 3.7; p < 0.001). In a sensitivity analysis using 30 days of follow-up data, 42.0% (n = 63) of participants randomized to the phone intervention kept their follow-up versus 21.1% (n = 27) in the control arm, with a HR (95% CI) of 2.2 (1.4 to 3.5; p < 0.001). There was no difference in ED revisits between the intervention and control group within 120 days postdischarge. CONCLUSIONS: An automated self-scheduling phone system significantly improved follow-up adherence after ED discharge, but did not decrease ED revisits.

Predictors of long-term opioid use and opioid use disorder among construction workers: Analysis of claims data.

BACKGROUND: Construction workers have high rates of work-related musculoskeletal disorders, which lead to frequent opioid use and opioid use disorder (OUD). This paper quantified the incidence of opioid use and OUD among construction workers with and without musculoskeletal disorders. METHODS: We conducted a retrospective study using union health claims from January 2015 to June 2018 from 19,909 construction workers. Claims for diagnoses of chronic musculoskeletal disorders, acute musculoskeletal injuries, musculoskeletal surgery, and other conditions were linked to new opioid prescriptions. We examined the effects of high doses (≥50 morphine mg equivalents per day), large supply (more than 7 days per fill), long-term opioid use (60 or more days supplied within a calendar quarter), and musculoskeletal disorders, on the odds of a future OUD. RESULTS: There were high rates (42.8% per year) of chronic musculoskeletal disorders among workers, of whom 24.1% received new opioid prescriptions and 6.3% received long-term opioid prescriptions per year. Workers receiving opioids for chronic musculoskeletal disorders had the highest odds of future OUD: 4.71 (95% confidence interval 3.09-7.37); workers prescribed long-term opioids in any calendar quarter had a nearly 10-fold odds of developing an OUD. CONCLUSIONS: Among construction workers, opioids initiated for musculoskeletal pain were strongly associated with incident long-term opioid use and OUD. Musculoskeletal pain from physically demanding work is likely one driver of the opioid epidemic in occupations like construction. Prevention of work injuries and alternative pain management are needed for workers at risk for musculoskeletal injuries.

Venous thromboembolism in multiple myeloma is associated with increased mortality.

BACKGROUND: In multiple myeloma, venous thromboembolism (VTE) is common, and treatments for myeloma, such as lenalidomide, increase the risk of thrombosis while improving survival. The association between VTE and survival is not well known. OBJECTIVES: To determine the association between VTE and survival in multiple myeloma (MM) while adjusting for known confounders that affect risk of thrombosis and survival, including patient characteristics and treatment in a retrospective cohort of US veterans. PATIENTS/METHODS: A cohort of patients with newly diagnosed MM treated within Veterans Health Administration between September 1, 1999, and June 30, 2014, was created to assess the association between VTE and mortality using Cox proportional hazards regression modeling while accounting for known prognostic factors and treatments. RESULTS: The cohort comprised 4446 patients with myeloma, including 2837 patients diagnosed after lenalidomide approval in July 2006. VTE occurred in 327 (7.4%) patients within 1 year and occurred at a median of 77 days (interquartile range, 37-153) after starting therapy for MM. In all patients, VTE was associated with increased mortality at 6 months (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.18-2.37). Patients in the post-lenalidomide cohort with VTE had an increased mortality at both 6 months (aHR, 2.31; 95% CI, 1.52-3.51) and 12 months (aHR, 1.66; 95% CI, 1.19-2.33) after treatment initiation. DISCUSSION: This study shows that VTE during the first 6-12 months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed.

Quality of anticoagulation with warfarin in rural Chhattisgarh, India.

Background & objectives: In most of rural India, warfarin is the only oral anticoagulant available. Among patients taking warfarin, there is a strong association between poor control of the international normalized ratio (INR) and adverse events. This study was aimed to quantify INR control in a secondary healthcare system in rural Chhattisgarh, India. Methods: The INR data were retrospectively obtained from all patients taking warfarin during 2014-2016 at a secondary healthcare system in rural Chhattisgarh, India. Patients attending the clinic had their INR checked at the hospital laboratory and their warfarin dose adjusted by a physician on the same day. The time in therapeutic range (TTR) was calculated for patients who had at least two INR visits. Results: The 249 patients had 2839 INR visits. Their median age was 46 yr, and the median body mass index was 17.7 kg/m[2]. They lived a median distance of 78 km (2-3 h of travel) from the hospital. The median INR was 1.7 for a target INR of 2.0-3.0 (n=221) and 2.1 for a target of 2.5-3.5 (n=28). The median TTR was 13.0 per cent, and INR was subtherapeutic 66.0 per cent of the time. Distance from the hospital was not correlated with TTR. Interpretation & conclusions: INR values were subtherapeutic two-thirds of the time, and TTR values were poor regardless of distance from the health centre. Future studies should be done to identify interventions to improve INR control.

Statins Reduce Mortality in Multiple Myeloma: A Population-Based US Study.

BACKGROUND: We studied the effect of statins on mortality in a nationally representative sample of patients with multiple myeloma, and explored the benefit of statins in a subgroup of patients treated with novel agents. METHODS: Patients diagnosed with multiple myeloma between 2007 and 2013 were identified in the SEER-Medicare database using International Classification of Diseases (ICD)-03 codes. ICD-9 and Healthcare Common Procedure Coding System codes were used to identify comorbidities and treatments. We assessed the association of statins with mortality in patients with multiple myeloma using multivariate Cox proportional hazards regression analysis. For subanalysis, we used the same statistical technique to investigate the effect of statins on mortality in myeloma patients treated with novel agents. RESULTS: A total of 5922 patients were diagnosed with multiple myeloma within the study period. Use of statins was associated with 21% reduction in risk of death (adjusted hazard ratio [aHR] 0.79; 95% confidence interval [CI] 0.74-0.84) among all patients with multiple myeloma. Among the patents treated with novel agents (n = 3603), statins reduced mortality by 10% (aHR = 0.90, 95% CI 0.83-0.98). CONCLUSIONS: Use of statins is likely associated with lower mortality in patients with multiple myeloma.

Inverse Probability of Treatment Weighting (Propensity Score) using the Military Health System Data Repository and National Death Index.

When randomized controlled trials are not feasible, retrospective studies using big data provide an efficient and cost-effective alternative, though they are at risk for treatment selection bias. Treatment selection bias occurs in a non-randomized study when treatment selection is based on pre-treatment characteristics that are also associated with the outcome. These pre-treatment characteristics, or confounders, can influence evaluation of a treatment's effect on the outcome. Propensity scores minimize this bias by balancing the known confounders between treatment groups. There are a few approaches to performing propensity score analyses, including stratifying by the propensity score, propensity matching, and inverse probability of treatment weighting (IPTW). Described here is the use of IPTW to balance baseline comorbidities in a cohort of patients within the US Military Health System Data Repository (MDR). The MDR is a relatively optimal data source, as it provides a contained cohort in which nearly complete information on inpatient and outpatient services is available for eligible beneficiaries. Outlined below is the use of the MDR supplemented with information from the national death index to provide robust mortality data. Also provided are suggestions for using administrative data. Finally, the protocol shares an SAS code for using IPTW to balance known confounders and plot the cumulative incidence function for the outcome of interest.

Maximal dose-response of vitamin-K2 (menaquinone-4) on undercarboxylated osteocalcin in women with osteoporosis.

Low concentrations of serum vitamin K accompany high concentrations of undercarboxylated osteocalcin (ucOC) and osteoporotic fractures. Although vitamin K2 (MK-4) is approved as a therapeutic agent for the treatment of osteoporosis in some countries, the dose-response is unknown. The objective of this study was to assess the improvement in carboxylation of osteocalcin (OC) in response to escalating doses of MK-4 supplementation. A nine-week, open-labeled, prospective cohort study was conducted in 29 postmenopausal women who suffered hip or vertebral compression fractures. Participants took low-dose MK-4 (0.5 mg) for 3 weeks (until the second visit), then medium-dose MK-4 (5 mg) for 3 weeks (until the third visit), then high-dose MK-4 (45 mg) for 3 weeks. The mean ± SD age of the participants was 69 ± 9 years. MK-4 dose (p < 0.0001), but neither age nor other relevant medications (e.g. bisphosphonates) correlated with improvement in %ucOC. As compared to baseline concentrations (geometric mean ± SD) of 16.8 ± 2.4, 0.5 mg supplementation halved %ucOC to 8.7 ± 2.2 (p < 0.0001) and the 5-mg dose halved %ucOC again (to 3.9 ± 2.2; p = 0.0002 compared to 0.5-mg dose). However, compared to 5 mg/day, there was no additional benefit of 45 mg/day (%ucOC 4.6; p = NS vs. 5-mg dose). MK-4 supplementation resulted in borderline increases in γ-carboxylated osteocalcin (glaOC; p = 0.07). There were no major side effects of MK-4 supplementation. In postmenopausal women with osteoporotic fractures, supplementation with either 5 or 45 mg/day of MK-4 reduces ucOC to concentrations typical of healthy, pre-menopausal women.

Lung transplant outcomes are influenced by severity of neutropenia and granulocyte colony-stimulating factor treatment.

Although neutropenia is a common complication after lung transplant, its relationship with recipient outcomes remains understudied. We evaluated a retrospective cohort of 228 adult lung transplant recipients between 2008 and 2013 to assess the association of neutropenia and granulocyte colony-stimulating factor (GCSF) treatment with outcomes. Neutropenia was categorized as mild (absolute neutrophil count 1000-1499), moderate (500-999), or severe (<500) and as a time-varying continuous variable. Associations with survival, acute rejection, and chronic lung allograft dysfunction (CLAD) were assessed with the use of Cox proportional hazards regression. GCSF therapy impact on survival, CLAD, and acute rejection development was analyzed by propensity score matching. Of 228 patients, 101 (42.1%) developed neutropenia. Recipients with severe neutropenia had higher mortality rates than those of recipients with no (adjusted hazard ratio [aHR] 2.97, 95% confidence interval [CI] 1.05-8.41, P = .040), mild (aHR 14.508, 95% CI 1.58-13.34, P = .018), or moderate (aHR 3.27, 95% CI 0.89-12.01, P = .074) neutropenia. Surprisingly, GCSF treatment was associated with a higher risk for CLAD in mildly neutropenic patients (aHR 3.49, 95% CI 0.93-13.04, P = .063), although it did decrease death risk in severely neutropenic patients (aHR 0.24, 95% CI 0.07-0.88, P = .031). Taken together, our data point to an important relationship between neutropenia severity and GCSF treatment in lung transplant outcomes.

Splanchnic vein thrombosis predicts worse survival in patients with advanced pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a thrombogenic malignancy with nearly half of venous thrombotic events occurring in the splanchnic circulation. The effect of splanchnic vein thrombosis on mortality in pancreatic cancer is unknown. We studied the effect of splanchnic vein thrombosis on mortality in veterans with advanced pancreatic adenocarcinoma, and explored the association of anticoagulant therapy on mortality and hemorrhage. METHODS: Using International Classification of Diseases (ICD) codes, we identified eligible patients and outcomes in the Veterans Health Administration database. Using Cox proportional hazards regression, we analyzed the association between splanchnic vein thrombosis and mortality among patients with advanced pancreatic cancer. We used propensity score inverse probability-of-treatment weighting to balance the groups who did and did not receive anticoagulation. To understand the role of anticoagulant therapy, we used Cox proportional hazards regression to analyze mortality and competing risk analysis to assess the risk of hemorrhage. RESULTS: Of the patients with advanced pancreatic cancer (N = 6164), 122 developed splanchnic vein thrombosis. Splanchnic vein thrombosis was associated with a two-fold increase in mortality, aHR 2.02, 95% CI 1.65-2.47. The finding held true after restricting the analysis to patients undergoing treatment for pancreatic cancer, and after adjusting for immortal time bias by a 30-day landmark analysis. Anticoagulant therapy did not affect mortality (aHR 0.99, 95% CI 0.65-1.51), and increased the risk of hemorrhage (aHR 2.7, 95% CI 1.02-7.07). CONCLUSION: Splanchnic vein thrombosis predicts worse survival in patients with advanced pancreatic adenocarcinoma. Anticoagulant therapy may not mitigate this increased mortality, and increases the risk of hemorrhage.