Noor Al-Hammadi

Disparities in Ovarian Cancer Care Quality and Survival According to Race and Socioeconomic Status

BACKGROUND The relationship between racial and socioeconomic status (SES) disparities and the quality of epithelial ovarian cancer care and survival outcome are unclear. METHODS A population-based analysis of National Cancer Data Base (NCDB) records for invasive primary epithelial ovarian cancer diagnosed in the period from 1998 to 2002 was done using data from patients classified as white or black. Adherence to National Comprehensive Cancer Network (NCCN) guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy. The main outcome measures were differences in adherence to NCCN guidelines and overall survival according to race and SES and were analyzed using binomial logistic regression and multilevel survival analysis. RESULTS A total of 47 160 patients (white = 43 995; black = 3165) were identified. Non-NCCN-guideline-adherent care was an independent predictor of inferior overall survival (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.38 to 1.47). Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio [OR] = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19 to 1.49). After controlling for disease and treatment-related variables, independent racial and SES predictors of survival were black race (HR = 1.29, 95% CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household income less than

Ovarian cancer in the United States: Contemporary patterns of care associated with improved survival

35 000 (HR = 1.06, 95% CI = 1.02 to 1.11). CONCLUSIONS These data highlight statistically and clinically significant disparities in the quality of ovarian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters. Increased efforts are needed to more precisely define the patient, provider, health-care system, and societal factors leading to these observed disparities and guide targeted interventions.

“Dementia-friendly Hospitals: Care not Crisis”

BACKGROUND Ovarian cancer (OC) requires complex multidisciplinary care with wide variations in outcome. We sought to determine the impact of institutional and process of care factors on overall survival (OS) and delivery of guideline care nationally. METHODS This was a retrospective cohort study of primary OC diagnosed from 1998 to 2007 using the National Cancer Data Base (NCDB) capturing 80% of all U.S. cases. Patient- (demographics, comorbidities, stage/grade), process of care (adherence to guidelines) and institutional- (facility type, case volume) factors were evaluated. Primary outcomes were OS and delivery of guideline therapy. Multivariable logistic regression and Cox proportional hazards models were used for analysis. RESULTS We analyzed 96,802 consecutive cases. Five-year OS was 84%, 66.3%, 32% and 15.7% for stages I, II, III and IV, respectively. The annual mean facility case volumes varied by cancer center type (range: 5.7 to 26.7), with 25% of cases spread over 65% of centers--all treating fewer than 8 cases. Overall, 56% of cases received non-guideline care. Low facility case volume and higher comorbidity index independently predicted non-guideline care; high volume centers were less likely to deliver non-guideline care (OR: 0.44, 95% CI: 0.41-0.47). Delivery of non-guideline care (OR: 1.4, 95% CI: 1.36-1.44), and higher facility case volume (OR: 0.91, 95% CI: 0.86-0.96) were both independent predictors of OS. CONCLUSIONS Delivery of guideline care and facility case volume are important drivers of overall survival. Most cancer centers treat very few women with OC. National efforts should focus on improved access to centers with expertise in OC and ensuring delivery of guideline care.

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial

BackgroundApproximately 3.2 million hospital stays annually involve a person with dementia, leading to higher costs, longer lengths of stay, and poorer outcomes. Older adults with dementia are vulnerable when hospitals are unable to meet their special needs. MethodsWe developed, implemented, and evaluated a training program for 540 individuals at 4 community hospitals. Pretest, posttest, and a 120-day delayed posttest were performed to assess knowledge, confidence, and practice parameters. ResultsThe mean age of the sample was 46 years; 83% were White, 90% were female, and 60% were nurses. Upon completion, there were significant gains (Ps <0.001) in knowledge and confidence in recognizing, assessing, and managing dementia. Attendees reported gains in communication skills and strategies to improve the hospital environment, patient safety, and behavioral management. At 120 days, 3 of 4 hospitals demonstrated maintenance of confidence. In the hospital that demonstrated lower knowledge and confidence scores, the sample was older and had more nurses and more years in practice. ConclusionsWe demonstrate the feasibility of training hospital staff about dementia and its impact on patient outcomes. At baseline, there was low knowledge and confidence in the ability to care for dementia patients. Training had an immediate impact on knowledge, confidence, and attitudes with lasting impact in 3 of 4 hospitals. We identified targets for intervention and the need for ongoing training and administrative reinforcement to sustain behavioral change. Community resources, such as local chapters of the Alzheimer Association, may be key community partners in improving care outcomes for hospitalized persons with dementia.

Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Importance Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. Objective To determine whether genotype-guided dosing improves the safety of warfarin initiation. Design, Setting, and Patients The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. Main Outcomes and Measures The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Results Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0.05-1.15), 56 vs 77 for INR of 4 or greater (RR, 0.71; 95% CI, 0.51-0.99), 33 vs 38 for venous thromboembolism (RR, 0.85; 95% CI, 0.54-1.34), and there were no deaths. Conclusions and Relevance Among patients undergoing elective hip or knee arthroplasty and treated with perioperative warfarin, genotype-guided warfarin dosing, compared with clinically guided dosing, reduced the combined risk of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Further research is needed to determine the cost-effectiveness of personalized warfarin dosing. Trial Registration clinicaltrials.gov Identifier: NCT01006733

Concomitant chemotherapy and radiation for the treatment of advanced-stage endometrial cancer

Background: Cognitive fluctuations are spontaneous alterations in cognition, attention, and arousal. Fluctuations are a core feature of dementia with Lewy bodies, but the impact of fluctuations in healthy brain aging and Alzheimer disease (AD) are unknown. Methods: Research participants (n = 511, age 78.1 ± 8 years, education 14.9 ± 3 years) enrolled in a longitudinal study of memory and aging at the Washington University Alzheimer Disease Research Center were assessed for the presence and severity of dementia with the Clinical Dementia Rating (CDR) and a neuropsychological test battery. Informant assessments of fluctuations with the Mayo Fluctuations Questionnaire and daytime level of alertness with the Mayo Sleep Questionnaire were completed. Results: After controlling for age and alertness level, participants with cognitive fluctuations (3 or 4 individual symptoms) were 4.6 times more likely to have dementia (95% confidence interval: 2.05, 10.40). Participants who presented with disorganized, illogical thinking were 7.8 times more likely to be rated CDR >0. The risk of being rated CDR 0.5 among those with fluctuations was 13.4 times higher than among those without fluctuations. The risk of being rated CDR 1 increased 34-fold among participants with fluctuations. Compared with participants without fluctuations, the presence of cognitive fluctuations corresponds to a decrease in performance across individual neuropsychological tests as well as composite scores. Conclusions: Cognitive fluctuations occur in Alzheimer disease and, when present, significantly affect both clinical rating of dementia severity and neuropsychological performance. Assessment of fluctuations should be considered in the evaluation of patients for cognitive disorders.

Clinical Presentation, Progression, and Outcome of Patients With Clonal B-Cell Counts of Less Than 5 × 109/L, 5 to 10 × 109/L, and More Than 10 × 109/L and Chronic Lymphocytic Leukemia Immunophenotype

INTRODUCTION Ccombination chemotherapy and radiation therapy is used for adjuvant treatment of stage III-IV endometrial cancer. The goal of this study was to review the treatment duration, toxicity, and survival for patients treated with concomitant chemotherapy and radiation. METHODS Women with stage III-IV endometrial cancer treated with concurrent chemotherapy and radiation between 2006 and 2013 were included. Toxicities were classified per CTCAE v3.0 and RTOG/EORTC late radiation morbidity scoring. Descriptive statistics were used to quantify treatment and toxicities. Kaplan-Meier method was used to estimate survival. RESULTS Fifty-one patients met our inclusion criteria. Median age was 60 (range 33-85). Thirty-six patients (70.6%) had endometrioid histology, 13 patients (25.5%) had serous, clear cell, or mixed histology, and 2 women (3.9%) had carcinosarcoma. Forty-eight patients had stage III disease and three patients were stage IVB. Mean treatment duration was 107 ± 19 days. Forty-two patients received all planned chemotherapy, and 16 patients required a dose reduction. Thirty-four patients (66.7%) experienced grade 3-4 toxicities, the majority of which were hematologic. There were no deaths related to therapy. Eighty-six percent of patients received leukocyte growth factors, and 25% of patients received a blood transfusion. Seven late grade 3-4 complications occurred: four gastrointestinal and two genitourinary, and one patient had ongoing neuropathy. Median progression-free survival was 42.8 months (range 4.4-81.5 months) and median overall survival was 44.9 months (range 5.1-82.6 months). Three-year overall survival was 80%. CONCLUSION Concomitant chemotherapy and radiation is an adequately tolerated treatment modality that allows for shorter treatment duration.

Early stroke post–heart transplant is associated with decreased survival in children

OBJECTIVES The flow cytometric evaluation of peripheral lymphocytosis has led to a dramatic increase in the diagnosis of early stage chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL). Few studies exist to better delineate the natural history and differences between MBL and CLL. METHODS Applying the recently updated B-lymphocyte threshold of 5 × 10(9) B lymphocytes/L for the diagnosis of CLL, we evaluated the differences in initial presentation, disease progression, time to treatment (TTT), and 10-year overall survival rates between patients with less than 5 × 10 × 10(9)/L, 5 to 10 × 10(9)/L, and more than 10 × 10(9)/L B cells. These clinical/treatment parameters were also compared among the MBL, 5 to 10 CLL Rai stage 0, and more than 10 CLL Rai stage 0 groups. RESULTS In total, 310 patients were included, with 67 in the less than 5, 75 in the 5 to 10, and 168 in the more than 10 B-cell groups. Statistically significant differences were seen when comparing the 5 to 10 and more than 10 B-cell groups regarding anemia (P = .021 for median hemoglobin; P = .028 for anemia <11 g/dL), platelet count (P = .041 for median platelet count), splenomegaly (P = .013), initial management plan (P = .012 for observation; P = .0021 for treatment with chemotherapy), and TTT (P = .0033). No statistically significant difference was seen among the MBL, 5 to 10, and more than 10 CLL Rai stage 0 groups regarding TTT and 10-year overall survival. CONCLUSIONS Findings suggest that patients with B-cell counts of 5 to 10 × 10(9)/L behave clinically more similar to patients with B-cell counts of less than 5 × 10(9)/L.

Hugh Barber Outstanding Abstract AwardDisparities in epithelial ovarian cancer according to race and socioeconomic status: Adherence to National Comprehensive Cancer Network (NCCN) guidelines and survival outcome, a study of 47,160 patients from the National Cancer Data Base

BACKGROUND Major neurologic events (MNEs) after heart transplantation (HTx) and their effect on survival have not been well described in children. In this study we aimed to characterize early MNEs (stroke, isolated seizures not from stroke and posterior reversible leukoencephalopathy [PRES] within 1 year after primary pediatric HTx) and evaluate their impact on 1-year post-HTx survival. We hypothesized that early an MNE after HTx is associated with decreased 1-year patient survival. METHODS We performed a pediatric, single-center, retrospective analysis of 345 consecutive patients aged 0 to 22 years who underwent primary HTx during the period from November 1, 1994 to October 31, 2015. Characteristics were compared between patients with and without early MNEs. RESULTS Nineteen percent (65 of 345) of patients had an MNE within 1 year after HTx (median 9 days, interquartile range [IQR] 4 to 23 days). Freedom from early MNE was 97%, 85% and 80% at 1, 6 and 12 months, respectively. Of the total 65 events, stroke comprised 55.4% (n = 36), isolated seizure 29.2% (n = 19) and PRES 15.4% (n = 10). With multiple logistic regression, previous neurologic disease, infection requiring intravenous antibiotic therapy and post-operative drug-treated hypertension were found to be significant risk factors for early MNEs. Stroke (hazard ratio 4.1, IQR 2.3 to 7.6, p < 0.0001), but not seizures and PRES, was associated with decreased 1-year patient survival. CONCLUSIONS Major neurologic events are common after pediatric HTx and usually occur within the first few weeks. Early stroke was associated with decreased 1-year survival. Potentially modifiable factors, including prior neurologic event, drug-treated hypertension and infection, were associated with increased risk of developing early MNEs.