Rates of Strokes in Californians with Sickle Cell Disease in the Post-STOP Era.

Neurovascular complications, including strokes and transient ischemic attacks (TIAs), are common and cause significant morbidity in individuals with sickle cell disease (SCD). The STOP trial (1998) established chronic transfusions as the standard of care for children with SCD at high risk for stroke. Using statewide emergency department and hospitalization data from the California Department of Health Care Access and Innovation (1991-2019), we determined the cumulative incidence and rates for primary and recurrent strokes and TIAs in people with SCD pre- and post-STOP. For the 7,636 patients included in our SCD cohort, cumulative incidence for first ischemic stroke was 2.1% (95% CI: 1.8%, 2.4%) by age 20 years and 13.5% (95% CI: 12.3%, 14.7%) by age 60 years. Cumulative incidence for first intracranial hemorrhage (ICH) was 0.5% (95% CI: 0.4%, 0.7%) by age 20 years and 6.8% (95%CI: 5.9%, 7.7%) by age 60 years. Ischemic stroke rates increased in children (age <18 years, 234.9 vs 165.1 per 100,000PY, P=0.012) and adults (ages 31-50 years, 431.1 vs 303.2 per 100,000PY, P=0.031) in 2010-2019, compared to the preceding decade. There was an increase in rates of ICH in ages 18-30 and TIA in children <18 years from 2010-2019 when compared to the prior decade. Risk factors for stroke and TIA included increasing age, hypertension, and hyperlipidemia. These findings underscore the need for prevention of strokes in adults with SCD and suggest an emphasis on the management of modifiable cerebrovascular risk factors that have been demonstrated to be effective in the general population.

Late endocrine diseases in survivors of adolescent and young adult cancer in California: a population-based study.

BACKGROUND: Cancer survivors have increased risk of endocrine complications, but there is a lack of information on the occurrence of specific endocrinopathies at the population-level. METHODS: We used data from the California Cancer Registry (2006-2018) linked to statewide hospitalisation, emergency department, and ambulatory surgery databases. We estimated the cumulative incidence of and factors associated with endocrinopathies among adolescents and young adults (AYA, 15-39 years) who survived ≥2 years after diagnosis. RESULTS: Among 59,343 AYAs, 10-year cumulative incidence was highest for diabetes (4.7%), hypothyroidism (4.6%), other thyroid (2.2%) and parathyroid disorders (1.6%). Hypothyroidism was most common in Hodgkin lymphoma, leukaemia, breast, and cervical cancer survivors, while diabetes was highest among survivors of leukaemias, non-Hodgkin lymphoma, colorectal, cervical, and breast cancer. In multivariable models, factors associated with increased hazard of endocrinopathies were treatment, advanced stage, public insurance, residence in low/middle socioeconomic neighbourhoods, older age, and non-Hispanic Black or Hispanic race/ethnicity. Haematopoietic cell transplant was associated with most endocrinopathies, while chemotherapy was associated with a higher hazard of ovarian dysfunction and hypothyroidism. CONCLUSIONS: We observed a high burden of endocrinopathies among AYA cancer survivors, which varied by treatment and social factors. Evidence-based survivorship guidelines are needed for surveillance of these diseases.

Utilization of allogeneic hematopoietic stem cell transplantation among patients with newly diagnosed acute myeloid leukemia in California: a population-based linked dataset study.

Acute myeloid leukemia (AML) often requires allogeneic hematopoietic cell transplantation (alloHCT) for cure, but historically alloHCT has been strikingly underutilized. Reasons for this remain uncertain at the population level. We examined alloHCT utilization over time and explored associations between demographic/healthcare factors and use of alloHCT by age group (AYA 15-39y, adult 40-64y, older adult 65-79y) using a linked dataset merging the Center for International Blood and Marrow Transplant Research, California Cancer Registry, and California Patient Discharge Database. Eligibility included patients newly diagnosed with AML in California between 2001-2016 who received induction therapy and had no prior HCT. Multivariable Fine-Gray regression analyses were fitted separately across age groups. Among 7,925 patients with AML, alloHCT utilization increased over time across all age groups; however, in the most recent time period studied (2011-2016), utilization within 2 years of diagnosis remained lowest in older adults (13%) relative to adults (41%) and AYAs (49%). Factors statistically significantly associated with lower alloHCT utilization: (1) AYAs: female sex, lower neighborhood socioeconomic status (nSES), uninsured or Indian Health Services (IHS) coverage; (2) adults: older age, male sex, non-Hispanic Black or Asian race and ethnicity, unmarried, lower nSES, uninsured or covered by Medicaid, Medicare, or IHS, higher comorbidity, and living 100+ miles from a transplant center; and (3) older adults: older age, Asian race, and unmarried. In conclusion, using a population-based linked dataset, we demonstrate that utilization of alloHCT among older patients newly diagnosed with AML remains low in California, and factors associated with utilization vary by age group.

Pregnancy outcomes in women with sickle cell disease in California.

Adverse pregnancy outcomes occur frequently in women with sickle cell disease (SCD) across the globe. In the United States, Black women experience disproportionately worse maternal health outcomes than all other racial groups. To better understand how social determinants of health impact SCD maternal morbidity, we used California's Department of Health Care Access and Information data (1991-2019) to estimate the cumulative incidence of pregnancy outcomes in Black women with and without SCD-adjusted for age, insurance status, and Distressed Community Index (DCI) scores. Black pregnant women with SCD were more likely to deliver at a younger age, use government insurance, and live in at-risk or distressed neighborhoods, compared to those without SCD. They also experienced higher stillbirths (26.8, 95% confidence interval [CI]: 17.5-36.1 vs. 12.4 [CI: 12.1-12.7], per 1000 births) and inpatient maternal mortality (344.5 [CI: 337.6-682.2] vs. 6.1 [CI: 2.3-8.4], per 100 000 live births). Multivariate logistic regression models showed Black pregnant women with SCD had significantly higher odds ratios (OR) for sepsis (OR 14.89, CI: 10.81, 20.52), venous thromboembolism (OR 13.60, CI: 9.16, 20.20), and postpartum hemorrhage (OR 2.25, CI 1.79-2.82), with peak onset in the second trimester, third trimester, and six weeks postpartum, respectively. Despite adjusting for sociodemographic factors, Black women with SCD still experienced significantly worse pregnancy outcomes than those without SCD. We need additional studies to determine if early introduction to reproductive health education, continuation of SCD-modifying therapies during pregnancy, and increasing access to multidisciplinary perinatal care can reduce morbidity in pregnant women with SCD.

Splenectomy and the incidence of venous thromboembolism and sepsis in patients with autoimmune hemolytic anemia.

INTRODUCTION: The impact of splenectomy on venous thrombosis (VTE), abdominal thrombosis (abVTE) and sepsis in autoimmune hemolytic anemia (AIHA) is unclear. METHODS: Using the California Discharge Dataset 1991-2014, 4756 AIHA patients were identified. Cumulative incidences (CI) of VTE, abVTE, and sepsis were determined in patients with and without splenectomy. Using propensity score matching adjusted for competing risk of death, the association between VTE, abVTE and sepsis with splenectomy was determined. RESULTS: In those without splenectomy, the CIs of VTE, abVTE, and sepsis were 1.4%, 0.2%, and 4.3% respectively, compared to 4.4%, 3.0% and 6.7% with splenectomy. Splenectomy was associated with increased risk for VTE in immediate (HR 2.66, CI 1.36-5.23) and late (HR 3.29, CI 2.10-5.16) post-operative periods. AbVTE was increased in immediate post-operative period (HR 34.11, CI 4.93-236.11). Sepsis was only increased in late post-operative period (HR 2.20, CI 1.75-2.77). In multivariate models, older age, having >1 comorbidity and having VTE, abVTE, and sepsis were associated with increased mortality. Splenectomy was not associated with increased mortality. DISCUSSION: Splenectomy in AIHA was associated with significant early thrombotic risk and long-term morbidity. Future research should evaluate the role of splenectomy in AIHA patients, and potential long-term thrombotic and antibiotic prophylaxis.

Impact of insurance type and timing of Medicaid enrollment on survival among adolescents and young adults with cancer.

BACKGROUND: Adolescents and young adults (AYAs) with public or no insurance experience later stage at diagnosis and worse overall survival compared with those with private insurance. However, prior studies have not distinguished the survival impact of continuous Medicaid coverage prior to diagnosis compared with gaining Medicaid coverage at diagnosis. METHODS: We linked a cohort of AYAs aged 15-39 who were diagnosed with 13 common cancers from 2005 to 2014 in the California Cancer Registry with California Medicaid enrollment files to ascertain Medicaid enrollment, with other insurance determined from registry data. We used Cox proportional hazards regression to evaluate the impact of insurance on survival, adjusting for clinical and demographic characteristics. RESULTS: Among 62 218 AYAs, over 65% had private/military insurance, 10% received Medicaid at diagnosis, 13.2% had continuous Medicaid, 4.1% had discontinuous Medicaid, 1.7% had other public insurance, 3% were uninsured, and 2.6% had unknown insurance. Compared with those with private/military insurance, individuals with Medicaid insurance had significantly worse survival regardless of when coverage began (received Medicaid at diagnosis: hazard ratio [95% confidence interval]: 1.51 [1.42-1.61]; continuously Medicaid insured: 1.42 [1.33-1.52]; discontinuous Medicaid: 1.64 [1.49, 1.80]). Analyses of those with Medicaid insurance only demonstrated slightly worse cancer-specific survival among those with discontinuous Medicaid or enrollment at diagnosis compared with those with continuous enrollment, but results were not significant stratified by cancer site. CONCLUSIONS AND RELEVANCE: AYAs with Medicaid insurance experience worse cancer-specific survival compared with those with private/military insurance, yet continuous enrollment demonstrates slight survival improvements, providing potential opportunities for future policy intervention.

Cancer specific survival in patients with sickle cell disease.

Sickle cell disease (SCD) patients have a higher incidence of certain cancers, but no studies have determined the impact of cancer on survival among SCD patients. SCD patients (n = 6423), identified from state-wide hospitalisation data, were linked to the California Cancer Registry (1988-2014). Multivariable Cox proportional hazards regression was used to examine survival. Among SCD patients, a cancer diagnosis was associated with a 3-fold increased hazard of death. Compared to matched cancer patients without SCD, SCD was associated with worse overall survival, but not cancer-specific survival, suggesting that SCD cancer patients should be treated with similar therapeutic intent.

The Epidemiology of Cancer-Associated Venous Thromboembolism: An Update.

The incidence of venous thromboembolism (VTE) is known to be higher in patients with malignancy as compared with the general population. It is important to understand and review the epidemiology of VTE in cancer patients because it has implications regarding treatment and prognosis. Multiple studies have shown that cancer patients who develop VTE are at higher risk for mortality. This article will focus on an update regarding the epidemiology of cancer-associated thrombosis (CT). The authors will describe factors associated with CT risk including cancer type and stage at the time of diagnosis, race and ethnicity, and cancer-directed therapy. In addition, recurrent thrombosis and the effect of thromboembolism on survival in cancer patients will also be addressed.

High incidence of venous thromboembolism recurrence in patients with sickle cell disease.

Previous reports show increased incidence of venous thromboembolism [VTE, deep-vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients. The incidence, time course, and risk factors for VTE recurrence have been less well described. We determined the cumulative incidence of first VTE recurrence and bleeding in a cohort of SCD patients with incident VTE. Risk factors for recurrence and bleeding were also determined using multivariable Cox regression models, adjusting for gender, race/ethnicity, era of incident VTE, location and hospitalization-associated status of incident VTE, and SCD-related complications. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Among 877 SCD patients with an incident VTE, the 1-year and 5-year cumulative incidence of recurrence was 13.2% (95% CI 11.0%-15.5%) and 24.1% (95% CI 21.2%-27.1%). Risk factors for VTE recurrence included more severe SCD (HR = 2.41; CI: 1.67-3.47), lower extremity DVT as the incident event (HR = 1.64; CI: 1.17-2.30), and pneumonia/acute chest syndrome (HR = 1.68; CI: 1.15-2.45). The cumulative incidence of bleeding was 4.9% (CI 3.5%-6.4%) at 6 months and 7.9% (CI: 6.2%-9.8%) at 1 year. More severe SCD (HR = 1.61; CI: 1.11-2.35) was associated with bleeding. The high incidence of VTE recurrence in patients with SCD suggests that extended anticoagulation may be indicated; however, this must be weighed against a relatively high risk of bleeding. Prospective, randomized studies of anticoagulation in SCD patients with VTE are needed.

Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

BACKGROUND: To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). METHODS: Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). RESULTS: Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. CONCLUSIONS: The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society.

Sociodemographic disparities in the occurrence of medical conditions among adolescent and young adult Hodgkin lymphoma survivors.

PURPOSE: Hodgkin lymphoma (HL) survivors experience high risks of second cancers and cardiovascular disease, but no studies have considered whether the occurrence of these and other medical conditions differ by sociodemographic factors in adolescent and young adult (AYA) survivors. METHODS: Data for 5,085 patients aged 15-39 when diagnosed with HL during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to hospitalization data. We examined the impact of race/ethnicity, neighborhood socioeconomic status (SES), and health insurance on the occurrence of medical conditions (≥ 2 years after diagnosis) and the impact of medical conditions on survival using multivariable Cox proportional hazards regression. RESULTS: Twenty-six percent of AYAs experienced at least one medical condition and 15% had ≥ 2 medical conditions after treatment for HL. In multivariable analyses, Black HL survivors had a higher likelihood (vs. non-Hispanic Whites) of endocrine [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.05-1.78] and circulatory system diseases (HR = 1.58, CI 1.17-2.14); Hispanics had a higher likelihood of endocrine diseases [HR = 1.24 (1.04-1.48)]. AYAs with public or no insurance (vs. private/military) had higher likelihood of circulatory system diseases, respiratory system diseases, chronic kidney disease/renal failure, liver disease, and endocrine diseases. AYAs residing in low SES neighborhoods (vs. high) had higher likelihood of respiratory system and endocrine diseases. AYAs with these medical conditions or second cancers had an over twofold increased risk of death. CONCLUSION: Strategies to improve health care utilization for surveillance and secondary prevention among AYA HL survivors at increased risk of medical conditions may improve outcomes.

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

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.

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

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.

Early mortality and complications in hospitalized adult Californians with acute myeloid leukaemia.

Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment (N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type. Early mortality decreased over time (25·3%, 1999-2000; 16·8%, 2011-2012) across all age groups, but was higher in older patients (6·9%, 15-39, 11·4%, 40-54, 18·6% 55-65, and 35·8%, >65 years). Major bleeding [Odds ratio (OR) 1·5, 95% confidence interval (CI) 1·3-1·9], liver failure (OR 1·9, 95% CI 1·1-3·1), renal failure (OR 2·4, 95% CI 2·0-2·9), respiratory failure (OR 7·6, 95% CI 6·2-9·3) and cardiac arrest (OR 15·8, 95% CI 8·7-28·6) were associated with early mortality. Higher early mortality was also associated with single marital status, low neighbourhood socioeconomic status, lack of health insurance and comorbidities. Treatment at National Cancer Institute-designated cancer centres was associated with lower early mortality (OR 0·5, 95% CI 0·4-0·6). In conclusion, organ dysfunction, hospital type and sociodemographic factors impact early mortality. Further studies should investigate how differences in healthcare delivery affect early mortality.

Determinants of Survival for Adolescents and Young Adults with Urothelial Bladder Cancer: Results from the California Cancer Registry.

PURPOSE: Bladder cancer is a common malignancy often diagnosed in older adults. Previous studies have reported racial/ethnic disparities in bladder cancer survival outcomes but have not focused on younger patients. We identified whether factors influencing cause specific survival in adolescents and young adults (ages 15 to 39) differed from older adults, and defined prognostic factors specifically in adolescents and young adults using the California Cancer Registry. MATERIALS AND METHODS: Patients diagnosed with bladder cancer between 1988 through 2012 were included in the study. The primary outcome measure was cause specific survival. A multivariable Cox proportional hazards regression model was used to evaluate predictors of cause specific survival in patients of all ages and in adolescents/young adults. Interactions of age and other variables between younger and older adult patients were assessed. RESULTS: Of 104,974 patients with bladder cancer we identified 1,688 adolescent and young adult patients (1.6%). Compared to older patients these patients had a 58% reduced risk of bladder cancer death (HR 0.42, p <0.001). Significant age interactions were identified involving race/ethnicity and histology. Among adolescents and young adults, nonHispanic African-American patients with low socioeconomic status had poor cause specific (HR 7.1, p <0.001) and overall (HR 5.02, p <0.001) survival. CONCLUSIONS: Racial/ethnic and socioeconomic disparities exist in adolescent and young adult patients with bladder cancer in California. Further studies are warranted to identify the underlying causes in order to overcome these disparities.

Amputation trends for patients with lower extremity ulcers due to diabetes and peripheral artery disease using statewide data.

OBJECTIVE: This study reports all-payer amputation rates using state-based administrative claims data for high-risk patients with lower extremity (LE) ulcers and concomitant peripheral artery disease (PAD), diabetes mellitus (DM), or combination PAD/DM. In addition, we characterize patient factors that affect amputation-free survival. We also attempted to create a measure of a patient's ability to manage chronic diseases or to access appropriate outpatient care for ulcer management by accounting for hospital and emergency department (ED) visits in the preceding 60 days to determine how this also affects amputation-free survival. METHODS: Patients admitted to nonfederal hospitals, seen in an ED, or treated in an eligible ambulatory surgery center within California from 2005 through 2013 with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a disease-specific LE ulcer were identified in the California Office of Statewide Health Planning and Development database. All subsequent hospital, ED, and ambulatory surgery center visits and procedures are captured to identify whether a patient underwent major amputation. Yearly amputation rates were determined to analyze trends. Amputation-free survival for the PAD, DM, and PAD/DM groups was determined. Cox modeling was used to evaluate the effect of patient characteristics. RESULTS: There were 219,547 patients identified with an incident LE ulcer throughout the state. Of these, 131,731 were DM associated, 36,193 were PAD associated, and 51,623 were associated with both PAD and DM. From 2005 to 2013, the number of patients with LE ulcers who required inpatient admission, presented to the ED, or had outpatient procedures was stable. However, there was a statistically significant increase in overall disease-associated amputation rates from 5.1 in 2005 to 13.5 in 2013 (P < .001). Patients with PAD/DM had the greatest increase in amputation rates from 10 per 100 patients with LE ulcers in 2005 to 28 per 100 patients in 2013 (P < .001). Despite that patients with PAD/DM were 8 years younger than patients with PAD only, they had similar amputation-free survival. Within all age groups, men had worse amputation-free survival than women did. Race did not predict amputation-free survival, but having multiple prior ED or hospital admissions was a significant predictor of worse amputation-free survival. CONCLUSIONS: Potentially preventable amputations associated with high-risk diseases are increasing among patients who require inpatient hospital admission, present to the ED, or require outpatient interventional treatment. This trend is most notable among patients with a combination of PAD and DM. Patients with repeated hospitalizations before admission for the LE ulcer had the highest risk of amputation.

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

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.

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

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.

Racial disparities in outcomes of endovascular procedures for peripheral arterial disease: an evaluation of California hospitals, 2005-2009.

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 California's 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.

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

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.