scholarly journals All-Cause and Inhibitor-Related Mortality in Non-Severe Hemophilia Α Patients in the United States

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 902-902 ◽  
Author(s):  
Ming Y. Lim ◽  
Dunlei Cheng ◽  
Christine L. Kempton ◽  
Nigel S. Key
Keyword(s):  
United States ◽  
At Risk ◽  
Mortality Rate ◽  
Hemophilia A ◽  
The United States ◽  
Severe Hemophilia ◽  
All Cause Mortality ◽  
Related Mortality ◽  
Observation Period

Introduction: The majority of published studies evaluating inhibitors have focused mainly on patients with severe hemophilia A. In non-severe hemophilia A (NSHA) patients, the development of inhibitors can have a profound clinical impact, with major bleeding complications similar to that of patients with severe or acquired hemophilia. Yet, epidemiological data on inhibitors in NSHA patients, specifically mortality, is scarce and currently limited to the European and Australian cohort [Eckhardt CL, et al. J Thromb Haemost. 2015 Jul;13(7):1217-251]. Objectives: To determine the all-cause and inhibitor-related mortality in NSHA patients in the United States using the ATHNdataset Methods: Subjects and study design The ATHNdataset is a 'limited dataset' as defined under the United States Health Insurance Portability and Accountability Act (HIPAA) to be free of protected health information, with data collection by more than 130 hemophilia treatment centers (HTC) across the United States. It includes patients with congenital bleeding disorders in the United States who have authorized the sharing of their demographic and clinical information for research. Data collection and definitions The ATHNdataset was queried on December 31, 2018 to extract the following information on NSHA patients: Patient demographics, inhibitor status, date of death, and primary cause of death. The presence of inhibitors was defined as: (i) ≥ 2 positive Bethesda inhibitor assay titers of ≥ 1.0 BU/mL; or (ii) a decrease in plasma FVIII coagulant activity (FVIII:C) to at least 50% of baseline activity and/or spontaneous bleeding symptoms in patients with inhibitor titers between 0.6 and 1.0 BU/mL. Patients who had a negative inhibitor history or have never been tested for FVIII inhibitors were classified as negative for inhibitors. Statistical analyses The person-year mortality rate was calculated as the ratio of the number of deaths to the number of person-years at risk, presented as rates per 1000 person-years. Person-years at risk was calculated for each patient as the time between the start of the observation period (January 1, 2010 or date of birth for patients who are born later) and the end of the observation period (date of death, loss-to follow-up or December 31, 2018). Patients who were deceased or lost to follow-up before January 1, 2010 were not included in the analysis. Inhibitor person-years at risk for inhibitor patients was calculated from January 1, 2010 if the first positive inhibitor test occurred prior to January 1, 2010 or from the date of the first positive inhibitor test that occurred during the observation period until the end of the observation period. Inhibitor-related death was attributed to all patients who had a positive inhibitor history. Mortality rates were compared between inhibitor and non-inhibitor patients using z- test. Results: Between 1/1/2010 and 12/31/2018, the ATHNdataset included 6,606 NSHA patients who were born between 1920 and 2018. Patients were observed for a total of 56,064 person-years. 85.57% (n = 5,653) of these patients were observed for the full nine years. The average follow-up time per patient was almost 8.5 years. Inhibitors developed in 171 (2.59%) NSHA patients. The median age for inhibitor development was 13 years (IQR, 6 - 37 years) and the mean age was 22 years. Demographics characteristics of the patients are listed in Table 1. All-cause mortality At the end of follow-up, there was a total of 136 deaths in the NSHA population, occurring at a median age of 63 years (IQR, 51 - 75 years). The overall all-cause mortality rate was 2.43 per 1,000 person-years (95% CI: 2.02 - 2.83). The most common primary cause of death was cancer (n=27, 19.9%) (Table 2). Inhibitor-related mortality Three deaths were associated with inhibitors. Inhibitor-related mortality rate was 2.40 per 1,000 person-years, whereas among the never inhibitor group, the mortality rate was 2.44 per 1,000 person-years (p = 0.790). Mortality risk ratio between inhibitor and never inhibitor was 0.98 (95% CI: 0.31 - 3.08). Conclusion: In NSHA patients, the development of inhibitors occurred at a relatively early age and was not associated with increased mortality. Disclosures Kempton: Novo Nordisk: Research Funding; Octapharma: Honoraria; Genentech: Honoraria; Spark Therapeutics: Honoraria. Key:Uniqure BV: Research Funding.

Breast Cancer in Women with Cystic Disease of the Breast

1965 ◽  
Vol 51 (4) ◽  
pp. 227-236
Author(s):  
Umberto Veronesi ◽  
Giorgio Pizzocaro ◽  
Aldo Vittorio Bono
Keyword(s):  
Breast Cancer ◽  
United States ◽  
At Risk ◽  
National Cancer Institute ◽  
Metropolitan Areas ◽  
The United States ◽  
Contralateral Breast ◽  
Cystic Disease

From 1937 to 1960, 1051 women with cystic disease of the breast were hospitalized at the National Cancer Institute of Milan; 1008 of them were followed for a period ranging from 1 to 26 years, with an average of 8.5 years. All cases were histologically proved. Twenty-one of the patients developed a cancer of the breast; 16 in the breast with the cystic disease, 5 in the contralateral breast. In 667 cases the disease was histologically classified as «simple cystic disease »; 12 of these cases had a breast cancer. In 384 cases the disease was classififed as «hyperplastic cystic disease»; 9 of these developed a cancer of the breast. The follow-up of the 1008 cases provided 8539 person-years at risk; the number of the expected breast cases was calculated on the basis of the Dorn and Cutler data on morbidity of cancer in 10 metropolitan areas of the United States. The number of expected breast cancer was 12.2; the number of observed cases was 21, the ratio between observed and expected cases being 1.71.

Unpacking the ‘black box’ of total pathogen burden: is number or type of pathogens most predictive of all-cause mortality in the United States?

2014 ◽  
Vol 143 (12) ◽  
pp. 2624-2634 ◽  
Author(s):  
A. M. SIMANEK ◽  
J. B. DOWD ◽  
A. ZAJACOVA ◽  
A. E. AIELLO
Keyword(s):  
United States ◽  
Smoking Status ◽  
The United States ◽  
Black Box ◽  
Health And Nutrition ◽  
All Cause Mortality ◽  
Specific Pathogen ◽  
Simplex Virus ◽  
Pathogen Burden

SUMMARYA ‘black box’ paradigm has prevailed in which researchers have focused on the association between the total number of pathogens for which individuals are seropositive (i.e. total pathogen burden) and various chronic diseases, while largely ignoring the role that seropositivity for specific combinations of pathogens may play in the aetiology of such outcomes and consequently mortality. We examined the association between total pathogen burden as well as specific pathogen combinations and all-cause mortality in the United States. Data were from individuals aged ⩾25 years tested for cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2 andHelicobacter pylori, with mortality follow-up to 31 December 2006 in the National Health and Nutrition Examination Survey (NHANES) III (N= 6522). We did not observe a statistically significant graded relationship between total pathogen burden level and all-cause mortality. Furthermore, compared to those seronegative for all four pathogens, the greatest statistically significant rate of all-cause mortality was for those CMV+/HSV-2+ (hazard ratio 1·95, 95% confidence interval 1·13–3·35) adjusting for age, gender, race/ethnicity, education level, body mass index (kg/m2) and smoking status. Interventions targeting prevention or treatment of particular pathogens may be more effective for reducing mortality than those focused solely on reducing overall pathogen burden.

scholarly journals Management of inhibitors in persons with non‐severe hemophilia A in the United States

2020 ◽  
Vol 96 (1) ◽  
Author(s):  
Ming Y. Lim ◽  
Dunlei Cheng ◽  
Michael Recht ◽  
Christine L. Kempton ◽  
Nigel S. Key
Keyword(s):  
United States ◽  
Hemophilia A ◽  
The United States ◽  
Severe Hemophilia

scholarly journals Myocardial contraction fraction predicts mortality for patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hang Liao ◽  
Ziqiong Wang ◽  
Liming Zhao ◽  
Xiaoping Chen ◽  
Sen He
Keyword(s):  
Mortality Rate ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
The Third ◽  
All Cause Mortality ◽  
Secondary Endpoints ◽  
Myocardial Contraction Fraction ◽  
Related Mortality

Abstract The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a novel volumetric measure of left ventricular myocardial shortening. The purpose of the present study was to assess whether MCF could predict adverse outcomes for HCM patients. A retrospective cohort study of 438 HCM patients was conducted. The primary and secondary endpoints were all-cause mortality and HCM-related mortality. The association between MCF and endpoints was analysed. During a follow-up period of 1738.2 person-year, 76 patients (17.2%) reached primary endpoint and 50 patients (65.8%) reached secondary endpoint. Both all-cause mortality rate and HCM-related mortality rate decreased across MCF tertiles (24.7% vs. 17.9% vs. 9.5%, P trend = 0.003 for all-cause mortality; 16.4% vs. 9.7% vs. 6.1%, P trend = 0.021 for HCM-related mortality). Patients in the third tertile had a significantly lower risk of developing adverse outcomes than patients in the first tertile: all-cause mortality (adjusted HR: 0.26, 95% CI: 0.12–0.56, P = 0.001), HCM-related mortality (adjusted HR: 0.17, 95% CI: 0.07–0.42, P < 0.001). At 1-, 3-, and 5-year of follow-up, areas under curve were 0.699, 0.643, 0.618 for all-cause mortality and 0.749, 0.661, 0.613 for HCM-related mortality (all P value < 0.001), respectively. In HCM patients, MCF could independently predict all-cause mortality and HCM-related mortality, which should be considered for overall risk assessment in clinical practice.

Differences in Mid-Term Outcomes Between Patients Undergoing Thoracic Endovascular Aortic Repair for Aneurysm or Acute Aortic Syndromes: Report From the Global Registry for Endovascular Aortic Treatment

2021 ◽  
pp. 152660282110648
Author(s):  
Daniele Bissacco ◽  
Maurizio Domanin ◽  
Fred A. Weaver ◽  
Ali Azizzadeh ◽  
Charles C. Miller ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Mortality Rates ◽  
Thoracic Endovascular Aortic Repair ◽  
Endovascular Aortic Repair ◽  
Aortic Repair ◽  
Acute Aortic Syndromes ◽  
All Cause Mortality ◽  
Global Registry ◽  
Related Mortality

Purpose: To analyze differences in baseline characteristics, overall mortality, device-related mortality, and re-intervention rates in patients who underwent thoracic endovascular aortic repair (TEVAR) for descending thoracic aortic aneurysm (DTAA) with atherosclerotic/degenerative cause or acute aortic syndrome (AAS), using the Global Registry For Endovascular Aortic Treatment (GREAT). Materials and Methods: Patients submitted to TEVAR for AAS or DTAA, included in GREAT, were eligible for this analysis. Primary outcome was 30-day all-cause mortality rate. Secondary outcomes were 30-day aorta-related mortality and re-intervention rate, 1-year and 3-year all-cause mortality, aorta-related mortality and re-intervention rate. Results: Five-hundred and seventy-five patients were analyzed (305 DTAA and 270 AAS). Thirty-day mortality rate was 1.3% and 1.8% for DTAA and AAS, respectively (p=0.741). One-year and 3-year mortality rates were 6.2% versus 9.3 and 17.3% versus 15.9% for DTAA and AAS, respectively (p=0.209 and p=0.655, respectively). Aorta-related mortality rates at 30 days, 1 year and 3 years were 1.3%, 1.3%, and 2.6% for DTAA, 1.8%, 4.2%, and 4.2% for AAS (p=ns). Re-intervention rates at 30 days, 1 year, and 3 years were 1.3%, 4.3%, and 7.5% for DTAA, 3.3%, 8.1%, and 10.7% for AAS (p=ns). Furthermore, a specific analysis with similar outcomes was performed dividing follow-up in 3 periods (1-30 days, 31-365 days, 366-1096 days) and describing mutual differences between 2 groups and temporal trends in each group. Conclusion Patients who underwent TEVAR for DTAA or AAS experienced different mortality and re-intervention rates among years during mid-term follow-up. Although all-cause related deaths within 30 days were TEVAR-related, aorta-related deaths were more common for AAS patients within 1 year. A greater re-intervention rate was described for AAS patients, although only 1 year after TEVAR.

scholarly journals Practicing safety: a quality improvement intervention to test tools to enhance pediatric psychosocial care for children 0–3 years

2017 ◽  
Vol 19 (04) ◽  
pp. 365-377 ◽  
Author(s):  
Diane J. Abatemarco ◽  
Ruth S. Gubernick ◽  
Marianna D. LaNoue ◽  
Ryan T. Pohlig ◽  
Sara R. Slovin ◽  
...  
Keyword(s):  
United States ◽  
At Risk ◽  
Quality Improvement ◽  
Child Maltreatment ◽  
Repeated Measures ◽  
Quantitative Methods ◽  
Psychosocial Care ◽  
The United States ◽  
Community Resources

BackgroundChild maltreatment is a significant public health issue in the United States. Yet, fewer than half of pediatricians discuss behavioral, developmental, or parenting issues with parents.ObjectiveThis paper describes the testing of bundles of tools and processes, part of a larger intervention, Practicing Safety, targeted at changing physician and staff behavior to identify families at risk for child maltreatment, provide anticipatory guidance, refer to community resources, and follow-up and track at-risk families. The intervention was implemented with 14 pediatric primary care practices throughout the United States; the study was completed in 2011.MethodsA within-subjects repeated measures pre-post follow-up design was used to evaluate the intervention. Baseline and repeated measurements of pediatric practices’ processes were collected using qualitative and quantitative methods. In total, 14 core improvement teams from across the country tested three bundles of tools (maternal, infant, toddler) within a quality improvement framework over seven months.ResultsQuantitative results showed statistically significant adoption of tools and processes and enhancement of practice behaviors and office environmental supports. The increase in tool use was immediate and was sustained for six months after implementation. Qualitative data provided insight as to how meaningful the intervention was to the core improvement teams, especially with more complicated behaviors (eg, engaging social workers or community agencies for referrals). Barriers included lack of community resources. Findings showed unanticipated outcomes such as helping practices to become medical homes.ConclusionLessons learned included that practices appreciate and can adopt brief interventions that have meaningful and useful tools and process to enhance psychosocial care for children 0–3 and that do not place a burden on pediatric practice. An innovative, quality improvement strategy, intuitive to pediatricians, with a brief intervention may help prevent child maltreatment.

scholarly journals Hypomethylating Agent Therapy and Survival Among Older Patients with Chronic Myelomonocytic Leukemia in the United States: A Large Population-Based Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 394-394
Author(s):  
Amer M. Zeidan ◽  
Xin Hu ◽  
Jessica B. Long ◽  
Rong Wang ◽  
Scott F Huntington ◽  
...  
Keyword(s):  
United States ◽  
Survival Benefit ◽  
Older Patients ◽  
Research Funding ◽  
The United States ◽  
Chronic Myelomonocytic Leukemia ◽  
Equity Ownership ◽  
Myelomonocytic Leukemia ◽  
Observation Period

Abstract Background: The hypomethylating agents (HMAs) azacitidine and decitabine were approved for treatment of myelodysplastic syndromes (MDS) in the United States (US) in 2004 and 2006, respectively, with demonstrated survival benefit for azacitidine among patients with higher risk MDS. Based on accumulating clinical and biologic evidence, chronic myelomonocytic Leukemia (CMML) has been reclassified as a clinical entity distinct from MDS. Despite a lack of evidence regarding a survival benefit associated with use of HMAs in CMML, HMAs are used for management of CMML in the US. Here, we take advantage of a natural experiment -market entry of HMAs- to assess whether HMA use is associated with survival among older adults with CMML. Methods: In a retrospective cohort study, we used the Surveillance, Epidemiology, and End Results (SEER- Medicare database to identify older adults (≥ 66 years in age) diagnosed with CMML (the International Classification of Diseases for Oncology 3rd edition histology 9945) in the 2001-2011 period, with follow-up through end of 2013. We identified HMA users based on procedure codes from claims, limiting to those who initiated therapy after their CMML diagnosis. We used Kaplan-Meier methods and log-rank test to analyze unadjusted survival. We used propensity score matching (PSM) method to match patients diagnosed during 2007-2011 who received HMAs (Post-HMA-users) with patients diagnosed in 2001-2003 who never received HMAs (Pre-HMA-non-users) during the study period. The covariates used for PSM included age at diagnosis, sex, race, zip code, education, neighborhood income, modified Elixhauser comorbidity count and disability status score (a claims-based surrogate for performance status), hospitalizations for bleeding or infection, and receipt of red blood cell and/or platelet transfusions prior to diagnosis. We did not match HMA users to HMA non-users in the post 2006 era to minimize impact of unobserved variables that might affect the decision to use HMAs. To test the competing hypothesis that survival improved as a result of other treatments/supportive care over the observation period, we also matched and compared CMML patients who never received HMAs in the pre-HMA and post-HMA periods. We used Cox proportional hazards models to assess the change in survival according to HMA use or time period. Results: A total of 1,868 individuals with CMML were eligible, of whom 1723 (92.2%) had died during follow-up. The median age at diagnosis was 79 years (interquartile range [IQR]: 73-84), 90.3% were white, and 60.7% were males. Median overall survival (OS) from diagnosis was 13 (95% confidence interval [CI]: 12-14) months. During follow-up, 259 patients (13.9%) received HMAs including 120 patients who received only azacitidine (6.4%), 81 who received only decitabine (4.3%), and 58 patients (3.1%) who received both drugs. Among those who received any HMA therapy, the median duration from diagnosis to first initiation of the HMA was 3 (IQR: 1-11) months. Only 18 patients (1%) underwent allogeneic stem cell transplantation (alloSCT) during follow-up. From diagnosis, the unadjusted median OS of patients who received any HMA during study was 22 (95% CI: 19-25) months compared to 11 (95% CI: 9-12) months for those who never received a HMA during study (p<.001). Among 180 Post-HMA-users and 328 Pre-HMA-non-users who were PS-matched, the median survival was 19 months in Post-HMA-users compared to 11 months in Pre-HMA-non-users (hazard ratio [HR] = 0.49, 95% CI: 0.38-0.64; p<.001, Figure 1). We also PS-matched 290 Pre-HMA-Non-users with 509 post-HMA-non-users and found that the two groups had similar mortality rates (HR = 1.06, 95% CI: 0.87-1.29; p=.55). Conclusions: In one of largest cohorts reported, we found that only a small percentage (14%) of older patients diagnosed with CMML received HMA therapy. Moreover, only 1% underwent alloSCT, the only potentially curative therapy. Our results suggest that use of HMA is associated with a 51% reduction in risk of death in CMML patients who received HMA after 2006 compared to propensity score matched patients who were diagnosed before 2004 and did not receive HMAs. The association is probably not attributable to potential improvement in other treatments/supportive care over the observation period. Our findings provide strong evidence for a survival benefit associated with the use of HMA in CMML. Figure 1 Figure 1. Disclosures Zeidan: Ariad: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Huntington:Oncosec Medical: Equity Ownership; Celgene: Consultancy, Honoraria; Exelixis: Equity Ownership; Geron: Equity Ownership; Johnson & Johnson: Consultancy; Pharmacyclics: Honoraria. Podoltsev:Ariad: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Gore:Celgene: Research Funding. Ma:celgene: Consultancy, Honoraria. Davidoff:PhRMA: Research Funding.

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