The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians Already Decided?

Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor-positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20-0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26-0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25-1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.

An epidemiological analysis of acute flaccid paralysis and its surveillance system in Iraq, 1997-2011.

BACKGROUND: Acute flaccid paralysis surveillance (AFP) is an essential strategy of the WHO's Polio Eradication Initiative. This is the first study conducted to estimate the incidence, etiology, distribution, and surveillance performance of AFP in Iraq. METHODS: Surveillance data about the AFP cases under the age of 15 years reported from Iraq during January 1997 to December 2011 were depended in the current study. RESULTS: A total of 4974 cases of AFP were reported from Iraq during the study period, with an annual incidence of 2.5/100,000 population. Guillain-Barré syndrome represented more than half of the reported cases (N = 2611, 52.5%), followed by traumatic neuritis (N = 715, 14.4%), and other CNS infections (N = 292, 5.9%). Poliomyelitis accounted for 166 (3.3%) of cases, the last reported case being in January 2000. Surveillance performance showed that all, but two, indicators were below the required WHO recommended levels. CONCLUSIONS: AFP surveillance remains the gold standard method for poliomyelitis detection. It witnessed dramatic changes over the last two decades. This has raised people's and clinicians' awareness to the importance of promptness in notifying suspected cases and timely transportation of stool specimens to the National Poliovirus Laboratory in Baghdad, or alternatively having more than one laboratory for poliovirus detection in the country, all of which are very useful measures to increase the surveillance performance in the country.

Guillain-Barré syndrome as a cause of acute flaccid paralysis in Iraqi children: a result of 15 years of nation-wide study.

BACKGROUND: Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis (AFP) in the post-poliomyelitis eradication era. This is the first study done to identify the epidemiology, clinical features, and outcome of GBS in Iraqi children over 15 years. METHODS: The surveillance database about AFP cases < 15 years reported during January 1997-December 2011 was used. RESULTS: GBS represented 52.5% of AFP cases, with an incidence of 1.33 case/100,000 population < 15 years/year. There was a higher incidence in the Southern provinces, age group 1-4 years, males, and outside the capital city of province, with no significant seasonal variations (p = .22). Survival probability after the 1 year of onset for those with respiratory muscle involvement was .76 (95% CI: .60-.86), versus .97 (95% Cl: .96-.98) for those who did not develop it (p < .001); and .97 (95% CI: .96-.98) for those living inside the capital city, versus .94 (.93-.95) for those living outside (p = .001). Cumulative incidence of residual paralysis for patients living inside the capital city was .21 (95% CI: .18-.24), versus .27 (95% CI: .25-.29) for those living outside (p < .001). CONCLUSIONS: The incidence, age and gender distribution, and seasonality of GBS among Iraqi children is similar to those reported from other previous studies. It is the most important cause of AFP, especially in those between the age of 1 to 4 years living in rural areas.

Cancer Treatment Data in Central Cancer Registries: When Are Supplemental Data Needed?

Background: We evaluated treatment concordance between the Colorado All Payer Claims Database (APCD) and the Colorado Central Cancer Registry (CCCR) to explore whether APCDs can augment registry data. We compare treatment concordance for breast cancer, an extensively studied site with an inpatient reporting source and select leukemias that are often diagnosed outpatient. Methods: We analyzed concordance by cancer type and treatment, patient demographics, reporting source, and health insurance, calculating the sensitivity, specificity, positive predictive values (PPV) and Kappa statistics. We estimated an adjusted logistic regression model to assess whether the APCD statistically significantly reports additional cancer-directed treatments. Results: Among women with breast cancer, 14% had chemotherapy treatments that were absent from the CCCR. Missing treatments were more common among women younger than age 50 (15%) and patients aged 75 and older (19%), rural residents (17%), and when the reporting source was outpatient (22%). Similar and more pronounced patterns for people with leukemia were observed. Concordance for oral treatments was lower for each cancer. Sensitivity and PPVs were high, with moderate Kappa statistics. The APCD was 5.3 percentage points less likely to identify additional treatments for breast cancer patients and 10 percentage points more likely to identify additional treatments when the reporting source was an outpatient facility. Conclusion: A robust data infrastructure is needed to investigate research questions that require population-level analyses, particularly for questions seeking to reduce health inequity and comparisons across payers, including Medicare Advantage and fee-for-service. APCD data are a step toward creating an infrastructure for cancer, particularly for patients who reside in rural areas and/or receive care from outpatient centers.

Synthetic cannabinoid-associated coagulopathy secondary to long-acting anticoagulant rodenticides: Observational case series and management recommendations.

Synthetic cannabinoids have become increasingly popular drugs of abuse due to low cost and inability to detect these substances on routine drug screenings. In the United States, incidence of synthetic cannabinoid contamination with long-acting anticoagulant rodenticides (LAARs) resulting in coagulopathy and bleeding complications has been described.We sought to describe the natural history, management approach, and outcomes of bleeding secondary to synthetic cannabinoid-associated LAAR toxicity in an observational case series of patients evaluated at an urban academic medical system.We conducted an observational study of patients with suspected exposure to LAAR-contaminated synthetic cannabinoids and associated bleeding treated within the Johns Hopkins Health System.In this 16 subject cohort, hematuria was the most common bleeding symptom at presentation. The majority of the cohort (75%) had international normalized ratio (INR) > 9.6 at presentation. Of the 13 patients with brodifacoum testing, 12/13 (92%) were positive. Twelve patients (75%) had at least 1 INR value below 2 within 24 hours of the first INR measurement. Of this cohort, 1/16 (6%) died in hospital. The median length of hospital stay was 4 days, (interquartile range = 3-6). The average cost of pharmacological treatment for coagulopathy during inpatient hospitalization was $5300 (range, $2241-$8086).In patients presenting with unexplained coagulopathy it is important for emergency department providers to consider LAAR intoxication and consider formal testing for brodifacoum to assist with treatment planning. Use of a standardized management algorithm including intravenous/oral vitamin K, judicious use of blood products and close laboratory monitoring is essential to optimizing outcomes.

Vitamin D status in acute myocardial infarction: a case-control study.

BACKGROUND: The association of vitamin D deficiency with coronary artery disease (CAD) is controversial. This study seeks the association between vitamin D deficiency and acute myocardial infarction (MI) in Iraq. PATIENTS AND METHODS: A total of 104 patients with acute MI and 104 healthy controls were studied throughout 2015. Their demographic, cardiovascular risk factors, and clinical characteristics were recorded. Serum vitamin D measurement was carried out for all patients. RESULTS: Vitamin D was more deficient in cases than controls; the number of cases was 60 (57.7%) and 53 (51%), respectively. However, a statistically significant difference (P=0.6) was not obtained. In the patient group, type 2 diabetes mellitus showed a strong association with vitamin D deficiency; there were 31 (81.6%) diabetic patients and 29 (43.9%) nondiabetic patients (P<0.001). CONCLUSION: No statistical association between vitamin D deficiency and acute MI was found. Nevertheless, a strong association between vitamin D deficiency and acute MI with type 2 diabetes mellitus was seen.

Germline mutations in the alternative pathway of complement predispose to HELLP syndrome.

BACKGROUND: HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is a severe variant of hypertensive disorders of pregnancy affecting approximately 1% of all pregnancies, and has significant maternal and fetal morbidity. Previously, we showed that upregulation of the alternative pathway of complement (APC) plays a role in HELLP syndrome. We hypothesize that HELLP syndrome follows a 2-hit disease model similar to atypical hemolytic uremic syndrome (aHUS), requiring both genetic susceptibility and an environmental risk factor. Our objective was to perform a comparative analysis of the frequency of APC activation and germline mutations in affected women and to create a predictive model for identifying HELLP syndrome. METHODS: Pregnant women with HELLP syndrome, and healthy controls after 23 weeks of gestation were recruited, along with aHUS and thrombotic thrombocytopenic purpura participants. We performed a functional assay, the mHam, and targeted genetic sequencing in all groups. RESULTS: Significantly more participants with rare germline mutations in APC genes were present in the HELLP cohort compared with controls (46% versus 8%, P = 0.01). In addition, significantly more HELLP participants were positive for the mHam when compared with controls (62% versus 16%, P = 0.009). Testing positive for both a germline mutation and the mHam was highly predictive for the diagnosis of HELLP syndrome. CONCLUSION: HELLP syndrome is characterized by both activation of the APC and frequent germline mutations in APC genes. Similar to aHUS, treatment via complement inhibition to mitigate maternal and fetal morbidity and mortality may be possible. FUNDING: National Heart Lung and Blood Institute grants T32HL007525 and R01HL133113.

21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile.

PURPOSE: The 21-gene Recurrence Score (RS) assay is used to predict disease recurrence and benefit of chemotherapy in estrogen receptor-positive, lymph node-negative early-stage breast cancer (EBC). Our study is the first analysis of trends and differences in the use of the RS assay and its impact on recommending chemotherapy in a population-based data set. METHODS: Patients with EBC diagnosed from 2004 to 2012 and included in the National Cancer Data Base were analyzed. Multivariate logistic regression analysis was used to estimate the covariates associated with use of the test and its impact on chemotherapy decisions. RESULTS: The RS assay was ordered for 54.0% of the 143,032 identified patients. Of all the variables, RS assay had the strongest association with recommendation for chemotherapy, with an adjusted odds ratio (AOR) of 83 for high assay scores. When indicated, test use was significantly associated with younger age, white race, academic centers, private insurance, and pT2/pN0(i+) grade 2 to 3 disease. Black patients (AOR, 1.31; 95% CI, 1.20 to 1.43) and those treated in community facilities (AOR, 1.49; 95% CI, 1.35 to 1.63) were more likely to be tested outside the National Comprehensive Cancer Network guidelines. Black patients (AOR, 1.51; 95% CI, 1.31 to 1.69) and those with high tumor grade (AOR, 30.76; 95% CI, 26.48 to 35.73) had significantly higher assay scores. Younger black patients (AOR, 1.33; 95% CI, 1.16 to 1.54) were more likely to receive chemotherapy despite low assay scores. CONCLUSION: The RS assay significantly influences clinicians' recommendations for chemotherapy in patients with EBC. Black patients tended to have higher assay scores, which may reflect use patterns or less favorable tumor biology for estrogen receptor-positive disease. There are significant differences in use and clinical implications of the test on the basis of race, insurance, and type of facility.

Predictors of overall survival in human papillomavirus-associated oropharyngeal cancer using the National Cancer Data Base.

OBJECTIVES: This study identifies clinical characteristics associated with HPV-positive oropharynx squamous cell carcinoma (OPSCC) and evaluates predictors of overall survival (OS) in HPV-positive patients undergoing definitive treatment within the National Cancer Data Base (NCDB). MATERIAL AND METHODS: The NCDB was queried for patients ⩾18years old with OPSCC and known HPV status who underwent definitive treatment: surgery, radiation (RT), chemotherapy-RT (CRT), surgery+RT, surgery+CRT (S-CRT). Cox proportional hazards model was used for multivariate analysis (MVA) to evaluate predictors of OS by HPV status. RESULTS: 3952 patients were included: 2454 (62%) were HPV-positive. Median follow up was 23.7months (range, 1.0-54.5). Unadjusted 2-year OS rates for HPV-positive vs. negative were 93.1% vs. 77.8% (p<0.001) with an adjusted hazard ratio of 0.44 (95% CI, 0.36-0.53; p<0.001). MVA identified multimodality treatment including CRT (HR, 0.42; p=0.024) and S-RT (HR, 0.30; p=0.024), but not S-CRT (HR, 0.51; p=0.086), as predictors for improved OS in HPV-positive stage III-IVB disease. Multimodality treatment including S-CRT was associated with longer OS in HPV-negative OPSCC. Nodal stage was poorly associated with OS in HPV-positive cancers. The presence of positive margins and/or extracapsular extension was associated with worse OS in HPV-negative (HR, 2.11; p=0.008) but not HPV positive OPSCC (HR, 1.61; p=0.154). CONCLUSION: The established demographic and clinical features of HPV-positive OPSCC were corroborated in the NCDB. Population analysis suggests that AJCC staging is poorly associated with OS in HPV-positive cancer, and traditional high-risk features may be less impactful. Bimodality therapy appears beneficial in HPV-positive HNSCC.

Central Nervous System Complications and Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival. PATIENTS AND METHODS: This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. RESULTS: Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04). CONCLUSION: The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes.

Epidemiological analysis of measles and evaluation of measles surveillance system performance in Iraq, 2005-2010.

OBJECTIVES: The objectives of this study were to identify the risk factors for measles and low vaccination rates, to evaluate the performance of surveillance, and to calculate vaccine effectiveness and failure in Iraq for the years 2005 to 2010. METHODS: Logistic regression was used on measles surveillance data from Iraq obtained during the period 1 January 2005 to 31 December 2010; adjusted odds ratios were calculated. The performance of surveillance was evaluated according to World Health Organization (WHO) guidelines. RESULTS: Of 18,746 suspected cases, a measles diagnosis was made for 81.4%. Children aged 1-5 years were the most affected (>48%). The odds of measles were significantly higher in the central and southern provinces than in the northern provinces. Those vaccinated with at least one dose of measles-containing vaccine had a 3.7-times lower risk of contracting measles than those who were not vaccinated. Lower odds of vaccination were noted for adults aged 18 years and older and those living in central and southern provinces, as well as those living outside the capital city of a province. Three WHO performance indicators were lower than the recommended cut-off levels. A vaccine failure rate of 66.1% and effectiveness of 90.03% were estimated. CONCLUSIONS: Measles continues to be an important cause of morbidity in Iraq. Improvements in vaccine coverage, proper vaccine handling, and prompt reporting of suspected cases are all necessary to eliminate measles from Iraq.