Temporal trends in the management and clinical outcomes of lower extremity arterial thromboembolism within a national Veteran population

Lower extremity arterial thromboembolism is associated with significant morbidity and mortality. We sought to establish temporal trends in the incidence, management and outcomes of lower extremity arterial thromboembolism within the Veterans Affairs Healthcare System (VAHS). We identified patients admitted to VAHS between 2003 and 2014 with a primary diagnosis of lower extremity arterial thromboembolism. Medical and procedural management were ascertained from pharmaceutical and administrative data. Subsequent rates of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality were calculated using Cox proportional hazards models. From 2003 to 2014, there were 10,636 patients hospitalized for lower extremity thromboembolism across 140 facilities, of which 8474 patients had adequate comorbid information for analysis. Age-adjusted incidence decreased from 7.98 per 100,000 patients (95% CI: 7.28–8.75) in 2003 to 3.54 (95% CI: 3.14–3.99) in 2014. On average, the likelihood of receiving anti-platelet or anti-thrombotic therapy increased 2.3% (95% CI: 1.2–3.4%) per year during this time period and the likelihood of undergoing endovascular revascularization increased 4.0% (95% CI: 2.7–5.4%) per year. Clinical outcomes remained constant over time, with similar rates of MALE, MACE and mortality at 1 year after adjustment. In conclusion, the incidence of lower extremity arterial thromboembolism is decreasing, with increasing utilization of anti-thrombotic therapies and endovascular revascularization among those with this condition. Despite this evolution in management, patients with lower extremity thromboembolism continue to experience high rates of amputation and death within a year of the index event.

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Prevalence and Prognostic Value of Heart Failure Stages: An Elderly Inpatient Based Cohort Study

Frontiers in Medicine ◽

10.3389/fmed.2021.639453 ◽

2021 ◽

Vol 8 ◽

Author(s):

Pei-Pei Zheng ◽

Si-Min Yao ◽

Di Guo ◽

Ling-ling Cui ◽

Guo-Bin Miao ◽

...

Keyword(s):

Heart Failure ◽

Cohort Study ◽

Prognostic Value ◽

Proportional Hazards ◽

Regression Tree ◽

Cox Proportional Hazards ◽

Hospitalized Patients ◽

Classification And Regression Tree ◽

Major Adverse Cardiovascular Events ◽

Cox Proportional Hazards Models

Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear.Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan–Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE.Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ2 = 69.62, P < 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174–6.098, P < 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112–3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014–6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate.Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B.Trial Registration: ChiCTR1800017204; 07/18/2018.

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Clinical Outcomes of Patients with Combined Idiopathic Pulmonary Fibrosis and Emphysema in the IPF-PRO Registry

Lung ◽

10.1007/s00408-021-00506-x ◽

2022 ◽

Author(s):

Hyun J. Kim ◽

Laurie D. Snyder ◽

Megan L. Neely ◽

Anne S. Hellkamp ◽

David L. Hotchkin ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Clinical Outcomes ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Baseline Variable ◽

Former Smokers ◽

The Impact ◽

Baseline Covariates

Abstract Purpose To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators’ review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. Results Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. Conclusion Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. Trial registration ClinicalTrials.gov, NCT01915511; registered August 5, 2013.

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Heparin-induced antibodies and cardiovascular risk in patients on dialysis

Thrombosis and Haemostasis ◽

10.1160/th08-03-0144 ◽

2008 ◽

Vol 100 (09) ◽

pp. 498-504 ◽

Cited By ~ 10

Author(s):

Jodi B. Segal ◽

Laura C. Plantinga ◽

Nancy E. Fink ◽

Jonathan S. Kerman ◽

Thomas S. Kickler ◽

...

Keyword(s):

Venous Thromboembolism ◽

Clinical Outcomes ◽

Vascular Access ◽

Cardiovascular Events ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Dialysis Patients ◽

Cox Proportional Hazards Models ◽

Stage Renal Disease

SummaryThe clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to determine the prevalence of thrombocytopenia and heparin-induced thrombocytopenia (HIT), and (iii) to test whether HIA are associated with adverse outcomes. Sera from 740 patients treated by hemodialysis (HD, n=596) and peritoneal dialysis (PD, n=144) were tested for HIA (IgG, IgA or IgM) by masked investigators at approximately six months after enrolment in the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study. We assessed, with time-to-event Cox proportional hazards models, whether the presence of HIA predicted any of four clinical outcomes: arterial cardiovascular events, venous thromboembolism, vascular access occlusion and mortality. HIA prevalence was 10.3% overall. HIA positivity did not predict development of thrombocytopenia or any of the four clinical outcomes over a mean follow-up of 3.6 years, with hazard ratios for arterial cardiovascular events of 0.98 (95% confidence interval 0.70–1.37), venous thromboembolism 1.39 (0.17–11.5), vascular access occlusion 0.82 (0.40–1.71), and mortality 1.18 (0.85–1.64). Chronic intermittent heparin exposure was associated with a high seroprevalence of HIA. In dialysis patients these antibodies were not an independent risk factor for cardiovascular events and mortality. Our data do not suggest that dialysis patients should be monitored for HIA antibodies in the absence of thrombocytopenia.

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Characteristics and outcomes of an international cohort of 400,000 hospitalised patients with Covid-19

10.1101/2021.09.11.21263419 ◽

2021 ◽

Author(s):

◽

Christiana Kartsonaki

Keyword(s):

Clinical Outcomes ◽

Proportional Hazards ◽

Invasive Mechanical Ventilation ◽

Case Fatality ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Hospitalised Patients ◽

Male Sex ◽

Viable Model

Background: Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world's largest international, standardised cohort of hospitalised patients. Methods: The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV). Findings: 439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients. Interpretation: The size of our international database and the standardized data collection method makes this study a reliable and comprehensive international description of COVID-19 clinical features. This is a viable model to be applied to future epidemics.

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MO138ASSOCIATION OF NT-PROBNP WITH OBESITY IN CKD PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0016 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Ting-Yun Lin ◽

Szu-Chun Hung

Keyword(s):

Heart Failure ◽

Clinical Outcomes ◽

Body Mass ◽

Proportional Hazards ◽

Normal Weight ◽

Cox Proportional Hazards ◽

Asymptomatic Patients ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Ckd Stage

Abstract Background and Aims Obesity is associated with lower circulating levels of N-terminal pro-BNP (NT-proBNP) both in the general population and in patients with heart failure. In asymptomatic patients with CKD, NT-proBNP levels are generally elevated. The prevalence of obesity is markedly increasing among patients with CKD. However, whether obesity affects NT-proBNP levels and thresholds for increased risk of clinical outcomes is unclear. Method We examined the associations between NT-proBNP and obesity in 408 stage 3–5 CKD patients (268 men and 140 women; mean age 65±13 years) free of heart failure at baseline, who were categorized into 3 groups according to body mass index (BMI; kg/m2) as normal (<24.0), overweight (24.0–27.9), and obese (≥28.0). Multivariate Cox proportional hazards models were used to compare the risk associations of NT-proBNP with the composite of ESKD (needing chronic dialysis or kidney transplantation) or all-cause mortality across BMI categories. Results NT-proBNP levels were significantly lower in obese patients than in normal weight and overweight subjects (P <0.001). Within each CKD stage, NT-proBNP levels decreased with increasing BMI. In a multivariate analysis, NT-proBNP was inversely associated with obesity, as well as BMI and its fat and lean body mass components (all P <0.001), independent of demographics, comorbidities, and severity of CKD. During a median follow-up of 2.2 years, 117 patients progressed to ESKD and 46 patients died. Overall, higher NT-proBNP levels were independently associated with ESKD or death (HR, 1.52; 95% CI, 1.22–1.89). Specifically, higher NT-proBNP levels were consistently associated with poor outcomes in all BMI categories (P for interaction = 0.096). Conclusion Obese CKD patients have significantly lower NT-proBNP levels. Nevertheless, BMI category did not modify the relationship between NT-proBNP and clinical outcomes. Increased risk may be seen at relatively lower levels of NT-proBNP in obese CKD patients.

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Association of real-world agreement between HER2 expression and ERBB2 amplification with trastuzumab therapy benefit in advanced gastric/esophageal (adv GE) cancer patients (pts).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.310 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 310-310

Author(s):

Stacey Stein ◽

Jeremy Snider ◽

Margaret Elizabeth McCusker ◽

Rebecca A. Miksad ◽

Brian Michael Alexander ◽

...

Keyword(s):

Clinical Outcomes ◽

Real World ◽

Proportional Hazards ◽

Standard Of Care ◽

Cox Proportional Hazards ◽

Her2 Status ◽

Trastuzumab Therapy ◽

Cox Proportional Hazards Models ◽

Tissue Specimens ◽

Erbb2 Amplification

310 Background: Trastuzumab (T) plus chemotherapy is standard of care for pts with HER2+ adv GE cancer. Selection for T relies on HER2+ result by immunohistochemistry (IHC) +/- in-situ hybridization (ISH); ERBB2 amplification by comprehensive genomic profiling (CGP) also predicts benefit. As CGP use increases, it is important to explore associations of IHC/ISH and CGP result agreement with clinical outcomes in pts with adv GE cancer. Methods: Pts with adv GE cancer were selected from the Flatiron Health-Foundation Medicine (FMI) clinico-genomic database (CGDB), a nationwide de-identified EHR-derived clinical database linked to FMI genomic data. Pts treated from 01/2011-12/2018 with CGP data for tissue specimens collected before 1L were included. Agreement between HER2 status by IHC +/- ISH v ERBB2 amplification by CGP was assessed. For 1L containing T, time to tx discontinuation (TTD) and overall survival (OS) from 1L start stratified by HER2:ERBB2 agreement and ERBB2 copy number (CN) [ERBB2+ = CN >4] were estimated with unadjusted Kaplan-Meier analysis and adjusted (practice type, sex, age at adv dx) hazard ratios (aHR) from Cox proportional hazards models. Results: Of 596 HER2-tested pts with adv GE cancer in CGDB, 174 (29%) were HER2+ by IHC/ISH. Median age at adv dx was 63 y; 76.5% were male and 97% had adenocarcinoma. Overall HER2:ERBB2 agreement was 91%. Of 123 HER2+ 1L T-treated pts, median TTD and OS were longer for HER2+:ERBB2+ (concordant; n = 93) v HER2+:ERBB2- pts (discordant; n = 30): TTD, 5.2 v 0.8 months, aHR 0.46 (0.29-0.70); OS 14.8 v 7.5 months, aHR 0.38 (0.21-0.68). Median OS was 22.0 vs 8.4 months for 1L T-treated pts with ERBB2 CN > 30 (median) v CN ≤30 (aHR 0.69 [0.37-1.27]). Conclusions: In this large real-world clinico-genomic dataset, HER2:ERBB2 agreement was high in tested pts with adv GE cancer. 1L T-treated pts with discordant tests (HER2+:ERBB2-) had significantly shorter TTD and OS. Pts with higher ERBB2 CN had longer OS, but this finding was not significant after adjusting for covariates. Further research is needed to explore associations between HER2:ERBB2 agreement and clinical outcomes in this population.

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Temporal Trends in Cardiovascular Complications in People With or Without Type 2 Diabetes: The Fremantle Diabetes Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa215 ◽

2020 ◽

Vol 105 (7) ◽

pp. e2471-e2482 ◽

Cited By ~ 2

Author(s):

Wendy A Davis ◽

Edward W Gregg ◽

Timothy M E Davis

Keyword(s):

Type 2 Diabetes ◽

Lower Extremity ◽

Proportional Hazards ◽

Temporal Trends ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Lower Extremity Amputation ◽

All Cause Mortality ◽

Extremity Amputation

Abstract Context There is evidence that diabetes-related complications are declining but most data sources have limitations. Objective To characterize temporal changes in incidence rates (IRs) of chronic complications and mortality in well-characterized, community-based Australians. Design Longitudinal observational study. Setting Urban population. Participants Participants with type 2 diabetes from the Fremantle Diabetes Study phases I (FDS1; n = 1291 recruited 1993-1996) and II (FDS2; n = 1509 recruited 2008-2011) age-, sex,- and ZIP code-matched 1:4 to people without diabetes. Main outcome measures First hospitalizations for/with myocardial infarction (MI), stroke, heart failure (HF), lower extremity amputation, and cardiovascular disease (CVD) and all-cause mortality. Five-year IRs, IR ratios for those with versus without diabetes in FDS1 and FDS2, and IR differences (IRDs), were calculated. Results The 13,995 participants had a mean age of 64.8 years and 50.4% were males. There were lower IR ratios for MI, stroke, HF, and CVD death in FDS2 versus FDS1. IRDs for people with versus without type 2 diabetes had reduced by >50% between phases for MI, stroke, HF, lower extremity amputation, and CVD death, with no change in IRD for all-cause mortality. Within the pooled type 2 diabetes cohort, FDS2 versus FDS1 participation was an independent inverse predictor of stroke, HF, CVD death, and all-cause mortality after adjustment in Cox proportional hazards models. Conclusions Cardiovascular outcomes in Australians have improved since the 1990s, especially in type 2 diabetes. The difference in all-cause mortality between those with and without type 2 diabetes has persisted despite longer survival.

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Plasma cell-free DNA (cfDNA) profiling of copy number variation (CNV) to identify poor prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.176 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 176-176

Author(s):

Edmond Michael Kwan ◽

Heidi Fettke ◽

Patricia Bukczynska ◽

Nicole Ng ◽

Christine Hauser ◽

...

Keyword(s):

Clinical Outcomes ◽

Proportional Hazards ◽

Prognostic Significance ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Castration Resistant Prostate Cancer ◽

Pten Loss ◽

Cox Proportional Hazards Models ◽

Taxane Chemotherapy ◽

Independent Cohort

176 Background: Multiple tumour tissue studies have demonstrated the prognostic utility of CNVs in mCRPC. However, accurate assessment of CNVs in plasma cfDNA remains challenging, and prognostic significance has not been well characterized. Using a large customized panel, we correlated plasma CNVs with clinical outcomes in a contemporary cohort of mCRPC patients. Methods: Deep targeted sequencing was performed using a 180-gene cfDNA panel (Predicine) in 56 patients commencing AR pathway inhibitors (enzalutamide or abiraterone; n = 34) or taxane chemotherapy (n = 22) at two Australian institutions. Kaplan-Meier estimates and Cox proportional-hazards models were used to correlate CNVs with progression-free survival (PFS) and overall survival (OS). Significant results were validated in an independent cohort (Mayo Clinic, n = 144). Results: Median follow-up was 19.4 months (mo; IQR 11.3-31.9). The most common CNVs in the Australian cohort are shown (Table). OS was significantly decreased in patients with PI3KCA gain (median 21.7 mo vs 6.6 mo, p < 0.0001), PTEN loss (24.8 mo vs 11.7 mo, p = 0.0019) and AR gain (21.7 mo vs 12.0 mo, p = 0.0083). Furthermore, all three alterations independently predicted for poor survival in multivariable analyses (MVA; Table). Findings in the independent cohort showed similar OS results in MVA: PIK3CA gain (HR 2.0, p = 0.07), PTEN loss (HR 1.7, p = 0.08) and AR gain (HR 1.7, p = 0.03). Conclusions: Sequencing of plasma cfDNA revealed that PTEN loss, and PIK3CA and AR gain are associated with inferior clinical outcomes in patients commencing contemporary systemic treatment. These data support therapeutic strategies co-targeting the PI3K and AR pathways in mCRPC.[Table: see text]

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Temporal trends in cause-specific readmissions and their risk factors in heart failure patients in Sweden

European Heart Journal ◽

10.1093/ehjci/ehaa946.0944 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

X Cui ◽

J Zhou ◽

A Pivodic ◽

U Dahlstrom ◽

J Ge ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Proportional Hazards ◽

Temporal Trends ◽

Cox Proportional Hazards ◽

Funding Source ◽

Cox Proportional Hazards Models ◽

Swedish Society ◽

Incidence Risk ◽

The Impact

Abstract Background It remains unclear whether readmissions of patients with heart failure (HF) have decreased over time in an era of improved therapy and management of HF. This study aimed to determine the temporal short- and long-term trends of cause-specific rehospitalization and their risk factors in a Swedish context. Methods HF patients in the Swedish Heart Failure Registry (SwedeHF) were investigated. Maximum follow-up time was 1 year. Outcomes included the first occurrence of all-cause, cardiovascular (CV) and HF rehospitalizations. Cox proportional hazards models were performed to determine the impact of increasing years on risk for rehospitalization and its known risk factors. Results Totally, 25,644 index-hospitalized HF patients SwedeHF from 2004 to 2011 were enrolled in the study. For 8 years, the incidence risk of 1-year all-cause rehospitalization remained unchanged, whereas the incidence risk of CV (P=0.038) or HF (P=0.0038) rehospitalization decreased. After adjustment for age and sex, a 3% decrease per every second year was observed for 1-year CV and HF rehospitalizations (P<0.05). However, time to the first occurring all-cause, CV and HF rehospitalization did not change significantly from 2004–2011 (P-values 0.13–0.87). When two study periods (2004–2005 vs. 2010–2011) were compared, the risk factor profile for rehospitalization was found to change. Conclusions Throughout the 8-year study period, CV- and HF-related rehospitalizations decreased, whereas all-cause rehospitalization remained unchanged, indicating a parallel increase in non-CV rehospitalization in the HF patients. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The SwedeHF was funded by the Swedish Society of Cardiology and the Swedish Heart-Lung Foundation.

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