Citations

e19407 Background: The purpose of this study was to evaluate the impact of a continuous improvement process aimed at reducing time to treatment on minimizing the number of days spent to complete pre-treatment visits and the associated costs for patients with non-metastatic breast cancer. Methods: System-wide initiatives were implemented in 2015 to minimize time to treatment initiation (TTI), by incorporating lean process strategies and enhanced coordination. Patient and treatment information was obtained through an IRB-approved registry for the years 2015 and 2018. Average number of days spent to complete visits, TTI, and associated patient costs including driving expenses, parking, food, childcare, and lost wages were calculated and compared between the years 2015 and 2018. Results: In 2015, the median TTI was 43.5 days and the average number of separate days spent to attend multidisciplinary visits prior to first treatment was 1.86. These were reduced to 29 days and 1.52 visits, respectively, in 2018 (p < 0.0001 for both). When evaluating treatment visits by surgical procedure, the average number of visits was reduced regardless of surgical procedure. The average number of visits was highest for patients undergoing mastectomy with reconstruction (2.34 in 2015, reduced to 1.65 in 2018, p < 0.0001). A single visit to complete treatment planning was associated with patient costs of $249 as compared with multiple trips costing $491 for 2 visits and up to $1,226 for 5 visits. Conclusions: In breast cancer patients, implementing a continuous improvement process to reduce time to treatment was associated with fewer visits required prior to treatment initiation, resulting in lower patient costs.

2524 Background: Postoperative radiosurgery (SRS) has been associated with up to 30% risk of subsequent leptomeningeal disease (LMD). We previously demonstrated that radiographic pattern of LMD (classical “sugarcoating” [cLMD] vs. nodular [nLMD]) in this setting is prognostic. The association between radiographic pattern of LMD, type of salvage treatment (tx), and neurologic death (ND) has not been well described. Methods: The records of patients (pts) with brain metastases (BM), of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. Pts with classically radiosensitive tumors or prior or planned whole brain radiotherapy (WBRT) were excluded. ND was defined as symptomatic CNS progression around the time of death without life threatening systemic symptoms or progression. Salvage radiotherapy (RT) for LMD was categorized according to use of WBRT vs. focal cranial RT. Results: The study cohort consisted of 147 pts, of which 125 had died with known cause, 107 also received LMD salvage tx, and 82 also had cranial MRI follow-up. The ND rate in the 125 pts who died with known cause was 79%; the rate in pts who underwent LMD salvage tx (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio [OR] 2.9, p = 0.04) and 2nd LMD failure after salvage tx (OR 3.9, p = 0.02) as significantly associated with ND. The ND rate was 86% for cLMD vs. 68% for nLMD pattern. WBRT was used in 95% of pts with cLMD vs. 52% of pts with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (WBRT: 67% vs. focal cranial RT: 68%, p = 0.92). Second LMD failure (vs. not) was associated with higher ND in the nLMD cohort (77% vs. 52%, p = 0.02). Of the 26 pts with nLMD who experienced 2nd LMD failure, 7 had classical 2nd LMD, of which 100% experienced ND, and 19 had nodular 2nd LMD, of which 68% experienced ND (p = 0.09). Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of neurologic death. Classical LMD pattern (vs. nodular) and 2nd LMD failure after salvage tx were significantly associated with higher risk of neurologic death. In the nodular LMD cohort, radiographic pattern of 2nd LMD may be associated with risk of subsequent neurologic death. Pts with nodular LMD treated with salvage focal cranial RT or WBRT had similar risk of neurologic death. Methods to decrease LMD and the subsequent high risk of neurologic death in this setting warrant investigation.

2022 Background: Studies have suggested superior outcomes for patients with cancer treated at National Cancer Institute (NCI) and academic hospitals, leading some to advocate for complex cancer care to be delivered at regional referral centers. However, growing demand at such centers may exceed their capacity to provide timely treatment, which could be detrimental to patient outcomes. We evaluated the relationship between hospital type, the average annual growth rate in patient volume (PV), and time to treatment initiation (TTI) trends. Methods: We used the National Cancer Database to identify patients undergoing initial treatment for a new diagnosis of cancer (breast, lung, prostate, colorectal, melanoma, bladder, non-Hodgkin lymphoma, renal, uterine or pancreatic) in 2007-2016. The exposure was hospital type (NCI, academic, community or integrated network). The primary outcome was TTI over time. We estimated both the average annual growth rate for PV and adjusted TTI trends by hospital type using linear mixed effects models, including a hospital type-by-time interaction and, when modeling TTI, a patient volume-by-time interaction. Results: We identified 4,218,577 patients treated at 1351 hospitals (49% at 897 community, 23% at 177 academic, 14% at 50 NCI and 14% at 227 integrated network hospitals). Over the study period, PV grew by 40% at NCI and 25% at academic hospitals, compared to 8% at community hospitals (p-value for trend both < 0.001). Meanwhile, mean TTI increased by 3.2 days at community, remained stable at academic (+0.3 days) and decreased by 4.3 days at NCI hospitals (p-value for trend both < 0.001 vs community). A higher annual PV growth rate was associated with a statistically but not clinically significant TTI increase (0.05 days for each 100 patient/year increase in the growth rate, p = 0.001). Conclusions: Patients with newly diagnosed cancer are increasingly receiving treatment at NCI and academic hospitals. While TTI at NCI and academic hospitals is longer than in the community, PV growth has been possible without delaying cancer treatment. Further study is needed to determine whether continued growth at this rate is sustainable. [Table: see text]

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

An estimated 1.4 million transgender adults live in the United States; this equates to approximately 0.6% of the U.S. population (Lane et al., 2018). Clinical focus on gender dysphoria has significantly increased over the past 30 years (MacCarthy, Reisner, Nunn, Perez-Brumer, & Operario, 2015), with burgeoning evidence from across disciplines documenting the positive outcomes associated with gender-affirming interventions. The purpose of this article is to illustrate how RNs optimize psychosocial, hormonal, and surgical gender-affirming care through performing comprehensive assessments, coordinating care, and providing education and health coaching.

Abstract Background: Non-Hodgkin lymphoma (NHL) is a malignancy of lymphocytes, and may develop in the setting of inflammation and immune dysfunction. Small scale evaluations have suggested that common genetic variation in candidate genes related to immune function may predispose to the development of NHL. Here we report a comprehensive analysis of variants within genes associated with immunity and inflammation and risk of NHL. Methods: We used ParAllele’s Immune and Inflammation panel of 9,412 single nucleotide polymorphisms (SNPs) from 1,450 immune/inflammation genes as a discovery tool in a clinic-based study of 458 NHL cases and 484 frequency matched controls seen at the Mayo Clinic from 2002–2005. The panel included 537 coding non-synonymous SNPs (nsSNPs), with the remainder of the SNPs selected as tags from HapMap (tagSNPs) to provide coverage of the candidate genes (r2 = 0.8 and minor allele frequency &gt;0.05). To assess the association of individual SNPs with risk of NHL, we calculated Odds Ratios (ORs) and 95% confidence intervals, adjusted for age and gender. The most prevalent homozygous genotype was used as the reference group, and each polymorphism was modeled individually as having a log-additive effect in the regression model. Associations between haplotypes from each gene and the risk of NHL were calculated using a score test implemented in HAPLO.SCORE. We also modeled the main effects for all independent (r2 &lt;0.25) SNPs from a gene in a multivariate logistic regression model. Results: The mean age at diagnosis was 60 years for cases and 58% were male; in controls the mean age at enrollment was 61.6 years and 55% were male. In the gene analyses, the strongest findings (p≤0.001 from multiple SNP logistic regression or haplotype analysis) were for cAMP responsive element binding protein 1 (CREB1; p=0.0004), fibrinogen alpha chain (FGA; p=0.0006), TNF receptor-associated factor 1 (TRAF1; p=0.001), dual specificity phosphatase 2 (DUSP2; p=0.001), and fibrinogen gamma chain (FGG; p=0.001). In the nsSNP analyses, the strongest findings (p≤0.01) were for integrin β3 (ITGB3) L59P (OR=0.64, 0.50–0.83), Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) H328R (OR=0.72, 0.57–0.91), transporter 2, ATP-binding cassette (TAP2) T665A (OR=1.32, 1.07–1.63), HLA-B associated transcript 2 (BAT2) V1895L (OR=0.60, 0.42–0.85), and complement component 7 (C7) T587P (OR=1.39, 1.07–1.80). Conclusions. Our results suggest that genetic variability in genes associated with antigen processing (CREB1 and TAP2), lymphocyte trafficking (B3GNT3), immune activation (TRAF1, BAT2), complement and coagulation pathways (FGA, FGG, ITGB3, C7), and MAPK signaling (DUSP2) may be important in the etiology of NHL, and should be pursued in replication studies.

Abstract Background: Most reports of the causes of extreme leukocytosis (i.e., total white blood count (WBC) &gt;50 × 109/L) have included relatively small numbers of cases or data from the era prior to FDA approval of filgrastim (recombinant G-CSF; February 1991), sargramostim (GM-CSF; March 1991), and pegfilgrastim (G-CSF conjugated to polyethylene glycol; January 2002). The contribution of myeloid growth factors to extreme leukocytosis in contemporary medical practice is unclear. Methods: We evaluated the medical records of all patients with extreme leukocytosis evaluated in the clinical laboratory of the University of Missouri-Columbia (UMC) Medical Center during the years 2000 to 2007. We collected complete blood count data, information on the etiology of the leukocytosis, demographic factors, and clinical complications. Results: We identified 371 unique patients who had at least one WBC &gt;50 × 109/L during this 8-year period (43.7% females; median age 56 (range 0–92)). Review of the primary cause of the leukocytosis in each case revealed that, while the various subtypes of leukemia (n=165, 44.5% of cases) and leukemoid reactions to general medical disorders (n=155, 41.8%) still represent the most common etiologies of extreme WBC elevation, growth factor-associated leukocytosis (GFL) is common, accounting for 13.7% (n=51) of patients. Among the subset of patients with GFL, the median peak WBC count was 60.8 × 109/L (range, 50–114.7); 51% were female, and the median age was 52 years (range 0–85). The median absolute WBC differential was as follows: neutrophils 40.8 × 109/L, granulocytes 55.7, bands 7.1, lymphocytes 2.4, monocytes 1.3, eosinophils 0, and basophils 0. Most (84%) of the patients receiving growth factors were being treated for cancer, the most common being non-Hodgkin lymphoma (NHL, 19.6%), Hodgkin lymphoma (HL, 11.8%), breast cancer (9.8%), ovarian cancer (5.9%), melanoma (5.9%), and endometrial cancer (5.9%). The non-malignant diagnoses (n = 8) included autoimmune neutropenia, bruton’s agammagloblinemia with pneumonia, leukopenia of undefined etiology, preterm neutropenia/sepsis (n = 4), and neutropenia associated with HIV. 70.6% of patients with GFL were receiving filgrastim, 29.4% pegfilgrastim, and 0% sargramostim. 0% of patients were undergoing conditioning for stem cell transplant. While myeloid growth factors are generally well tolerated, extreme leukocytosis is concerning because it may be associated with serious adverse events such as spontaneous splenic rupture, leukostasis/hyperviscosity, and hemorrhage. Other diagnoses continue to be important contributors to extreme leukocytosis. Of the 165 patients with leukemia, 43% were diagnosed with CLL, 15.8% CML, 15.2% AML, 13.3% ALL, 3.6% CMML, 3.6% BCR/ABL-negative myeloproliferative disorders, and 3.6% NHL. Other diagnoses included plasma cell leukemia, undifferentiated leukemia, and an undefined lymphoproliferative disease with macroglobulinemia variant. The causes of non-clonal leukocytosis (leukemoid reactions) could be divided into four broad categories: infection (n=109, 70.3%), reaction to hemorrhage (n=15, 9.7%), paraneoplastic (n=11, 7.1%), and other miscellaneous causes (20, 12.9%). The most common infections causing extreme leukocytosis include sepsis (59, 54.1%), pneumonia (19, 17.4%), and Clostridium difficile-associated colitis (5, 4.6%). Paraneoplastic causes of leukocytosis were diverse and associated neoplasms included cancer of unknown primary (n = 2), cholangiocarcinoma, extranodal marginal zone B-cell lymphoma, HL, SCLC, NSCLC, lymphoplasmacytic lymphoma, melanoma, peripheral T-cell lymphoma, and squamous cell carcinoma of the penis. Conclusion: In the current era, extreme leukocytosis is often iatrogenic and associated with filgrastim or pegfilgrastim usage. WBC counts should be routinely monitored in patients receiving pegfilgrastim or filgrastim and the medication discontinued with evolving leukocytosis.

Abstract Background: Inhibitors of HMG-CoA reductase (“statins”) are effective in reducing the risk of cardiovascular disease. Preclinical data from rodents suggested that they may increase the incidence of some cancers, including lymphoma. However, monitoring of randomized trials in humans have generally found decreased cancer risks, and these findings have been supported by a growing number of observational studies, including three recent reports of a protective association in NHL. The suggested anti-carcinogenic mechanisms for statins include their impact on inflammatory (including a shift from a Th1 to Th2 profile) and angiogenesis pathways, as well as the induction of apoptosis by modulation of signaling pathways, all of which are of biologic relevance in NHL. Methods: We evaluated the history of statin use and risk of NHL in a clinic-based study of 243 newly diagnosed NHL cases and 499 frequency matched controls enrolled at the Mayo Clinic from 2002-2005. Risk factor data were collected using self-administered questionnaires, and included history of use of cholesterol lowering drugs two or more years before diagnosis (for cases) or enrollment (for controls); specific drug names were not available. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusting for age, gender, and residence. NHL subtypes were centrally reviewed, and subtype-specific risks were estimated using polychotomous logistic regression. Results. The mean age at diagnosis was 59.5 years for cases and 55% were men; among controls, the mean age at enrollment was 61.8 years and 54% were men. Twenty-one percent of the cases reported ever using statins compared to 30% of the controls, supporting a lower risk of NHL for ever users (OR=0.69; 95% CI 0.47–1.00). The lowest risk was seen for the longest users; i.e., compared to never users, person who had 10 or more years of use had the greatest reduction in risk (OR=0.52; 95% CI 0.24–1.10). A history of high cholesterol was also inversely associated with risk of NHL (OR=0.72; 95% CI 0.55–0.93). However, the association for the type of treatment for cholesterol lowering varied. Those who were medically treated had inverse association with risk of NHL (OR=0.63; 95% CI 0.46–0.86), while the no treatment and dietary change only groups were found to have no association with risk. The reduction in NHL risk with medical treatment was specific to statin use, as the use of other cholesterol lowering drugs was not associated with risk (OR=1.13; 95% CI 0.50–2.57). These results were not confounded by education, family history of NHL, body mass index, cigarette smoking or alcohol use. In subtype analysis, the inverse association was seen for diffuse large B-cell lymphoma (OR=0.27; 95% CI 0.08–0.90), but not for CLL/SLL or follicular NHL. Conclusions. Statin use was associated with a lower risk of developing NHL, particular diffuse large B-Cell lymphoma.

Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P <0.05 for each). Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.