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Featured researches published by Ann Brunson.


Blood | 2013

Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia.

Soames Boyle; Richard H. White; Ann Brunson; Ted Wun

Patients with immune thrombocytopenia (ITP) who relapse after an initial trial of corticosteroid treatment present a therapeutic challenge. Current guidelines recommend consideration of splenectomy, despite the known risks associated with surgery and the postsplenectomy state. To better define these risks, we identified a cohort of 9976 patients with ITP, 1762 of whom underwent splenectomy. The cumulative incidence of abdominal venous thromboembolism (AbVTE) was 1.6% compared with 1% in patients who did not undergo splenectomy; venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus) after splenectomy was 4.3% compared with 1.7% in patients who did not undergo splenectomy. There was increased risk of AbVTE early (<90 days; hazard ratio [HR] 5.4 [confidence interval (CI), 2.3-12.5]), but not late (≥90 days; HR 1.5 [CI, 0.9-2.6]) after splenectomy. There was increased risk of VTE both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on comorbidities). We conclude that ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis.


British Journal of Haematology | 2014

Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non‐Hodgkin lymphoma

Joseph M. Tuscano; Mrinal Dutia; Karen Chee; Ann Brunson; Christine Reed-Pease; Mehrdad Abedi; Jeanna Welborn; Robert T. O'Donnell

This phase II study evaluated the safety and efficacy of lenalidomide in combination with rituximab in patients with relapsed/refractory, indolent non‐Hodgkin lymphoma (NHL). Patients were treated with daily lenalidomide in 28‐d cycles and weekly rituximab for 4 weeks. Lenalidomide was continued until progression or unacceptable toxicity. Twenty‐two patients were assessed for FCGR3A polymorphisms. Thirty patients were enrolled; 27 were evaluable for response. The overall response rate (ORR) was 74% including 44% complete responses (CR); median progression‐free survival (PFS) was 12·4 months. The 13 rituximab refractory patients had an ORR of 61·5% (four CR/unconfirmed CR). The ORR was 77% in the 22 follicular lymphoma patients (nine CR/unconfirmed CR). At a median follow‐up time of 43 months, the median duration of response and time to next therapy were 15·4 and 37·4 months, respectively. Most common grade 3/4 adverse events were lymphopenia (45%), neutropenia (55%), fatigue (23%) and hyponatraemia (9%). The ORR and PFS in patients with low‐affinity FCGR3A polymorphisms (F/F and F/V) suggest that lenalidomide may improve the activity of rituximab in these patients. These data suggest that combining lenalidomide with rituximab can produce durable responses with acceptable toxicity in patients with indolent NHL.


JAMA Internal Medicine | 2013

High variation between hospitals in vena cava filter use for venous thromboembolism.

Richard H. White; Estella Marie Geraghty; Ann Brunson; Susan Murin; Ted Wun; Fred Spencer; Patrick S. Romano

BACKGROUND The extent to which vena cava filter (VCF) use varies between hospitals in the management of acute venous thromboembolism (VTE) is not clear. METHODS We conducted a retrospective observational study that compared the frequency of VCF use among California hospitals from January 1, 2006, through December 31, 2010. Using administrative hospital discharge data, we followed explicit criteria to identify nontrauma patients with acute VTE, and determined the frequency of VCF placement in each of the hospitals that admitted more than 55 VTE patients. Multivariable hierarchical regression models to predict VCF use included important clinical and demographic variables as fixed effects and hospital as a random effect. RESULTS Among the 263 hospitals included, 130 643 acute VTE hospitalizations occurred with the placement of 19 537 VCFs (14.95%). Variation in the percentage of acute VTE hospitalizations that included VCF placement was very high, from 0% to 38.96% (interquartile range, 6.23%-18.14%), with 18.49% of the observed variation due to differences among the hospitals that provided care. Significant clinical predictors of VCF use included acute bleeding at the time of admission (odds ratio, 3.4 [95% CI, 3.2-3.6]), a major operation after admission for VTE (3.4 [3.3-3.5]), presence of metastatic cancer (1.7 [1.6-1.8]), and extreme severity of illness (2.5 [2.3-2.7] vs mild). Insertion of VCFs occurred more frequently than expected in 109 hospitals and less frequently in 59. Hospital characteristics associated with VCF use included a small number of beds (odds ratio, 0.2 [95% CI, 0.2-0.4], <100 vs >400 beds), a rural location (0.4 [0.2-0.5]), and other private vs Kaiser hospitals (1.5 [1.1-2.0]). Use of VCFs varied widely even in geographically proximate areas. CONCLUSIONS The frequency of VCF use in patients with acute VTE varied widely and depended on which hospital provided the care, even after adjusting for clinical and socioeconomic factors. Further research is needed to determine whether this variation is associated with local cultural differences between hospitals or with differences in the availability of interventional radiologists or specialists, or whether it reflects the absence of high-quality evidence that VCFs are effective.


Clinical Genitourinary Cancer | 2012

Epidemiologic Trends in Renal Cell Carcinoma in the Cytokine and Post-Cytokine Eras: A Registry Analysis of 28,252 Patients

Derek Shek; Benjamin Tomlinson; Monica Brown; Ann Brunson; Chong Xian Pan; Primo N. Lara

UNLABELLED Advances in the targeted treatment of renal cell cancer (RCC) have shown improvements in survival in clinical trials and have largely replaced cytokine therapies as the standard of care. However it is unclear if these advances have translated to the general RCC population. We present a retrospective study of a large clinical cancer registry that demonstrates statistically significant improvements in survival in cancer patients, but the causes of this improvement are difficult to determine because of many confounders. BACKGROUND Before 2004, advanced renal cell cancer (RCC) therapy consisted primarily of cytokines such as interferon and/or interleukin-2. Subsequently, randomized trials of targeted therapies have shown a survival benefit, leading to the approval of several new agents since 2004. Whether the survival benefit seen in highly selected patients accrued to these trials has already translated to the general RCC patient population is unclear. To explore this, a large RCC patient registry was evaluated for changes in outcome between the cytokine (1998-2003) and post-cytokine (2004-2007) eras. METHODS Data from the California Cancer Registry (CCR), a population-based cancer surveillance system, was used to retrospectively analyze 28,252 patients with RCC diagnosed between 1998 and 2007. Inter-era differences in clinical variables-including year of diagnosis, histologic characteristics, age, sex, race, stage, nephrectomy status, overall survival (OS), and cause-specific survival (CSS)-were assessed. Univariate and multivariate Cox models were used. RESULTS Crude 3-year OS (68.2% vs. 74.6%; 2P < .001) and CSS (78.1% vs. 82.3%; 2P < .001) were significantly higher in the post-cytokine era. In multivariate analysis, the 3 strongest predictors for improved survival were localized disease (hazard ratio [HR], 18.1; 95% confidence interval [CI], 16.6-19.6), nephrectomy (HR, 2.87; 95% CI, 2.68-3.08), and clear cell histologic type (HR, 1.33; 95% CI, 1.22-1.44). CONCLUSIONS In this analysis of a large RCC registry, there was an apparent increase in crude OS and CSS in the post-cytokine era compared with the cytokine era. Insufficient follow-up time in the post-cytokine era and a higher proportion of localized disease in that era confound the possibility of benefit derived from targeted therapies. Longer follow-up for patients treated in the post-cytokine era is necessary for a more robust comparison of long-term OS.


Circulation | 2016

Outcomes After Vena Cava Filter Use in Noncancer Patients With Acute Venous Thromboembolism

Richard H. White; Ann Brunson; Patrick S. Romano; Zhongmin Li; Ted Wun

Background— Evidence that vena cava filters (VCFs) are beneficial is limited. Methods and Results— We retrospectively analyzed all noncancer patients admitted to nonfederal California hospitals for acute venous thromboembolism from 2005 to 2010. Analysis was stratified by the presence/absence of a contraindication to anticoagulation (active bleeding, major surgery). Outcomes were death within 30 or 90 days of admission and the 1-year incidence of recurrent venous thromboembolism manifested as pulmonary embolism or deep vein thrombosis. Propensity score methods were used to account for observed systematic differences in baseline characteristics between patients treated and those not treated with a VCF. Among 80 697 patients with no contraindication to anticoagulation, VCF use (n=7762, 9.6%) did not significantly reduce the 30-day risk of death (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.98–1.28). Among 3017 patients with active bleeding, VCF use (n=1095, 36.3%) reduced the 30-day risk of death by 32% (HR, 0.68; 95% CI, 0.52–0.88) and the 90-day risk by 27% (HR, 0.73; 95% CI, 0.59–0.90). VCF use (n=489, 33.8%) did not reduce mortality among 1445 patients who underwent major surgery (HR, 1.1; 95% CI, 0.71–1.77). In all subgroups, filter use did not reduce the risk of subsequent pulmonary embolism. However, the risk of subsequent deep vein thrombosis increased by 50% among VCF patients with no contraindication (HR, 1.53; 95% CI, 1.34–1.74) and by 135% among VCF patients with active bleeding (HR, 2.35; 95% CI, 1.56–3.52). Conclusions— VCF use significantly reduced the short-term risk of death only among patients with acute venous thromboembolism who had a contraindication to anticoagulation because of active bleeding. These results support the findings of a randomized clinical trial and current guidelines that recommend VCF use only in patients who cannot receive anticoagulation treatment.


Lung Cancer | 2014

Predictors of survival for younger patients less than 50 years of age with non-small cell lung cancer (NSCLC): A California Cancer Registry analysis

Matthew S. Lara; Ann Brunson; Ted Wun; Ben Kent Tomlinson; Lihong Qi; Rosemary D. Cress; David R. Gandara; Karen Kelly

BACKGROUND Non-small cell lung cancer (NSCLC) is uncommonly diagnosed in patients younger than 50 years of age. We analyzed the California Cancer Registry (CCR) to describe epidemiologic characteristics and outcomes in this patient subset and to identify factors prognostic for cause-specific survival (CSS). METHODS Patients diagnosed with NSCLC between 1/1/98 through 12/31/09 and reported to the (CCR) as of October 2011 were included. The primary outcome measure was CSS. Cox regression models were used to evaluate predictors of CSS in young patients with NSCLC, adjusted for potential confounders. Interaction analysis was performed between age groups (<50 vs. ≥50) and specific demographic and tumor covariates. RESULTS We identified 132,671 lung cancer cases, of which 114,451 (86.3%) had NSCLC. Of these, 6389 (5.6%) were<50 years of age (median, 46 years). The most common histology was adenocarcinoma (3697, 57.9%). Most patients had stage III (1522, 23.8%) or IV (3655, 57.2%) disease. Fewer young patients were diagnosed in recent years (n, % of total NSCLC population of that era): 1998-2001 (2355, 6.0), 2002-2005 (2182, 5.7), and 2006-2009 (1852, 5.0), P<0.001. Multivariate analysis showed that age <50 years was an independent predictor of improved CSS (HR 0.827, P<0.001). Significant predictors of better CSS in patients <50 years included female sex, Asian or Hispanic ethnicity, lower stage, later year of diagnosis, and higher socioeconomic status, among others. Adenocarcinoma histology was not associated with improved CSS in this patient subset (HR 0.987, P=0.78). Interaction analysis revealed that Hispanic race and bronchioloalveolar histology had differential CSS outcomes dependent on age group. CONCLUSIONS This large registry study found that age <50 years is an independent predictor of improved CSS. Variables prognostic for CSS differed somewhat from those in older patients.


Circulation | 2016

Outcomes After Vena Cava Filter Use in Noncancer Patients With Acute Venous Thromboembolism A Population-Based Study

Richard H. White; Ann Brunson; Patrick S. Romano; Zhongmin Li; Ted Wun

Background— Evidence that vena cava filters (VCFs) are beneficial is limited. Methods and Results— We retrospectively analyzed all noncancer patients admitted to nonfederal California hospitals for acute venous thromboembolism from 2005 to 2010. Analysis was stratified by the presence/absence of a contraindication to anticoagulation (active bleeding, major surgery). Outcomes were death within 30 or 90 days of admission and the 1-year incidence of recurrent venous thromboembolism manifested as pulmonary embolism or deep vein thrombosis. Propensity score methods were used to account for observed systematic differences in baseline characteristics between patients treated and those not treated with a VCF. Among 80 697 patients with no contraindication to anticoagulation, VCF use (n=7762, 9.6%) did not significantly reduce the 30-day risk of death (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.98–1.28). Among 3017 patients with active bleeding, VCF use (n=1095, 36.3%) reduced the 30-day risk of death by 32% (HR, 0.68; 95% CI, 0.52–0.88) and the 90-day risk by 27% (HR, 0.73; 95% CI, 0.59–0.90). VCF use (n=489, 33.8%) did not reduce mortality among 1445 patients who underwent major surgery (HR, 1.1; 95% CI, 0.71–1.77). In all subgroups, filter use did not reduce the risk of subsequent pulmonary embolism. However, the risk of subsequent deep vein thrombosis increased by 50% among VCF patients with no contraindication (HR, 1.53; 95% CI, 1.34–1.74) and by 135% among VCF patients with active bleeding (HR, 2.35; 95% CI, 1.56–3.52). Conclusions— VCF use significantly reduced the short-term risk of death only among patients with acute venous thromboembolism who had a contraindication to anticoagulation because of active bleeding. These results support the findings of a randomized clinical trial and current guidelines that recommend VCF use only in patients who cannot receive anticoagulation treatment.


Annals of Vascular Surgery | 2015

Racial Disparities in Outcomes of Endovascular Procedures for Peripheral Arterial Disease: An Evaluation of California Hospitals, 2005–2009

Melissa N. Loja; Ann Brunson; Chin Shang Li; John G. Carson; Richard H. White; Patrick S. Romano; Nasim Hedayati

BACKGROUND Racial/ethnic disparities in treatment outcomes of peripheral arterial disease (PAD) are well documented. Compared with non-Hispanic (NH) whites, blacks and Hispanics are more likely to undergo amputation and less likely to undergo bypass surgery for limb salvage. Endovascular procedures are being increasingly performed as first line of therapy for PAD. In this study, we examined the outcomes of endovascular PAD treatments based on race/ethnicity in a contemporary large population-based study. METHODS We used Patient Discharge Data from Californias Office of Statewide Health Planning and Development to identify all patients over the age of 35 who underwent a lower extremity arterial intervention from 2005 to 2009. A look-back period of 5 years was used to exclude all patients with prior lower extremity arterial revascularization procedures or major amputation. Cox proportional hazards regression was used to compare amputation-free survival and time to death within 365 days. Logistic regression was used for comparison of 1-month myocardial infarction, 1-month major amputation, 1-month all-cause mortality, 12-month major amputation, 12-month reintervention, and 12-month all-cause mortality rates among NH white, black, and Hispanic patients. These analyses were adjusted for age, gender, insurance status, severity of PAD, comorbidities, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. RESULTS Between 2005 and 2009, a total of 41,507 individuals underwent PAD interventions, 25,635 (61.7%) of whom underwent endovascular procedures. There were 17,433 (68%) NH whites, 4,417 (17.2%) Hispanics, 1,979 (7.7%) blacks, 1,163 (4.5%) Asian/Native Hawaiians, and 643 (2.5%) others in this group. There was a statistically significant difference in the amputation-free survival within 365 days among the NH white, Hispanic, and black groups (P < 0.0001); the hazard ratio for amputation within 365 days was 1.69 in Hispanics (95% confidence interval [CI] 1.51-1.90, P < 0.0001) and 1.68 in blacks (95% CI 1.44-1.96, P < 0.001) compared with NH whites following endovascular procedures after adjusting for age, gender, insurance status, comorbidities, severity of PAD, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. After adjusting for the aforementioned confounders, the first reintervention within 12 months was also significantly associated with race/ethnicity (P = 0.002). Odds ratio for reintervention was 1.17 in blacks (95% CI 1.06-1.30, P = 0.002) and 1.084 in Hispanics (95% CI 1.00-1.16, P = 0.04) compared with NH whites. CONCLUSIONS In this contemporary large population-based study, we demonstrated that even among matched cohorts Hispanics and blacks have worse amputation-free survival than NH whites following endovascular therapy. Our study also found that Hispanics and blacks are more likely to undergo lower extremity arterial reinterventions than NH whites. Further research is crucial in understanding if higher reintervention rates in Hispanics and blacks are because of more severe disease and/or poor access to proper follow-up care and optimal medical management.


British Journal of Haematology | 2017

Increased incidence of VTE in sickle cell disease patients: Risk factors, recurrence and impact on mortality

Ann Brunson; Amy Q. Lei; Aaron S. Rosenberg; Richard H. White; Theresa H.M. Keegan; Ted Wun

Previous reports show increased incidence of venous thromboembolism [VTE, deep‐vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients but did not account for frequency of hospitalization. We determined the incidence of VTE in a SCD cohort versus matched controls. For SCD patients, risk factors for incident VTE, recurrence and the impact on mortality were also determined. Among 6237 patients with SCD, 696 patients (11·2%) developed incident‐VTE: 358 (51·6%) had PE (±DVT); 179 (25·7%) had lower‐extremity DVT only and 158 (22·7%) had upper‐extremity DVT. By 40 years of age, the cumulative incidence of VTE was 17·1% for severe SCD patients (hospitalized ≥3 times a year) versus 8·0% for the matched asthma controls. Amongst SCD patients, women (Hazard ratio [HR] = 1·22; 95% confidence interval [CI]: 1·05–1·43) and those with severe disease (HR = 2·86; 95% CI: 2·42–3·37) had an increased risk of VTE. Five‐year recurrence was 36·8% in patients with severe SCD. VTE was associated with increased risk of death (HR = 2·88, 95% CI: 2·35–3·52). In this population‐based study, the incidence of VTE was higher in SCD patients than matched controls and was associated with increased mortality. The high incidence of recurrent VTE in patients with severe SCD suggests that extended anticoagulation may be indicated.


Annals of Vascular Surgery | 2016

Amputation Risk in Patients with Diabetes Mellitus and Peripheral Artery Disease Using Statewide Data.

Misty D. Humphries; Ann Brunson; Nasim Hedayati; Patrick S. Romano; Joy Melnkow

BACKGROUND Conflicting data exist regarding changes in amputation rates in patients with ulcers because of diabetes mellitus (DM) and peripheral artery disease (PAD). This study focuses on how population-based amputation rates are changing in the current treatment era. METHODS Using the California Office of Statewide Health Planning and Development Patient Discharge database, all patients who underwent major nontraumatic lower extremity (LE) amputation in 2005 through 2011 were identified. Age-adjusted population-based amputation risk was determined by year. Gender and age trends in amputation risk were estimated separately for diabetes-related amputations and PAD-related amputations, treating all California residents as the population at risk. RESULTS From 2005 to 2011, 32,025 qualifying amputations were performed in California. Of these, 11,896 were DM-associated (n = 1,095), PAD-associated (n = 4,335), or associated with both conditions (n = 6,466). PAD-associated amputation rates and combined PAD/DM-associated amputation rates have changed little since 2009 after decreasing substantially over the prior 5 years, but DM-associated amputation rates have continuously increased since 2005. California residents older than the age of 80 years had the most dramatic decrease in PAD-associated amputation rates from 2005 to 2011 (i.e., from 317 to 175 per million Californians). Men with PAD/DM had amputation rate 1.5 times higher than those of patients with PAD alone and 5 times higher than rates of DM patients. In women the difference between patient with PAD and PAD/DM was not seen; however, these rates were 2.5 times higher than patients with DM alone. CONCLUSIONS Preventable amputations associated with high-risk diseases are no longer decreasing despite continuing advances in care and education. Octogenarians with PAD represent the highest risk group for amputation, but DM-associated amputations have increased since 2005. Further research to understand treatment pathways for patient with LE wounds may shed light on pathways for amputation prevention in the future.

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Ted Wun

University of California

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Gwendolyn Ho

University of California

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Qian Li

University of California

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Brian A. Jonas

University of California

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Chin Shang Li

University of California

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