subdistribution hazard
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Author(s):  
Marilyn L. Kwan ◽  
Richard K. Cheng ◽  
Carlos Iribarren ◽  
Romain Neugebauer ◽  
Jamal S. Rana ◽  
...  

PURPOSE The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. METHODS Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease–related risk factors, and stratified by treatment and body mass index (BMI). RESULTS A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m2) cases had higher risks overall and within treatment subgroups versus controls. CONCLUSION BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.


2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Georg Marcus Fröhlich ◽  
Marlieke E. A. De Kraker ◽  
Mohamed Abbas ◽  
Olivia Keiser ◽  
Amaury Thiabaud ◽  
...  

Background Since the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data. Aim This study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland. Methods This retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders. Results In 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54–78) than the patients with influenza (median 74 years; IQR: 61–84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22–4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00–3.00, p < 0.001) for ICU admission. Conclusion Community-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.


2021 ◽  
Vol 8 ◽  
Author(s):  
Peng He ◽  
Xiaoyong Yu ◽  
Yang Zha ◽  
Jing Liu ◽  
Hanmin Wang ◽  
...  

Objective: To determine whether there is an association between microhematuria and relapse or kidney disease progression in patients with primary membranous nephropathy (PMN).Methods: A cohort of 639 patients with biopsy-proven PMN from two centers was followed for a median of 40 months. The exposures were initial hematuria, time-averaged hematuria, and cumulative duration of hematuria. The outcomes were relapse and renal progression, which were defined by a 40% reduction in renal function or end-stage renal disease. Cox proportional hazards regression and competing risk analyses were performed to yield hazard ratios (HRs) and subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs). Sensitivity and interaction analyses were also performed.Results: After adjusting for confounders, a higher level of initial hematuria was associated with a 1.43 (95% CI, 1.15–1.78) greater hazard of relapse. Worsening hematuria remarkably increased the risk of short-term relapse (HR, 4.64; 3.29–6.54). Time-averaged hematuria (sHR, 1.35; 1.12–1.63) and cumulative duration of hematuria (sHR, 1.17; 1.02–1.34) were independent predictors of renal progression. Hematuria remission was related to a reduced risk of renal progression over time in patients with positive microhematuria (sHR, 0.63; 0.41–0.96).Conclusions: A higher level of initial hematuria was a remarkable predictor of relapse in patients with PMN, and the magnitude and persistence of microhematuria were independently associated with kidney disease progression.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 645-645
Author(s):  
Dianxu Ren ◽  
Oscar Lopez ◽  
Jennifer Lingler

Abstract Competing risk is an event that precludes the occurrence of the primary event of interest. For example, when studying risk factors associated with dementia, death before the onset of dementia serve as a competing event. A subject who dies is no longer at risk of dementia. This issue play more important role in ADRD research given the elderly population. Conventional methods for survival analysis assume independent censoring and ignore the competing events. However, there are some challenge issues using those conventional methods in the presence of competing risks. First, no one-to-one link between hazard function and cumulative incidence function (CIF), and Kaplan-Meier approach overestimates the cumulative incidence of the event of interest. Second, the effect of covariates on hazard rate cannot be directly linked to the effect of cumulative incidence (the risk). We will discuss two types of analyses in the presence of competing risk: Cause-specific hazard model and Fine-Gray subdistribution hazard model. Cause-specific hazard model directly quantify the cause-specific hazard among subjects who are at risk of developing the event of interest, while Fine-Gray subdistribution hazard model directly model the effects of covariates on the cumulative incidence function. The type of research questions (Association vs. Prediction) may guide the choice of different statistical approaches. We will illustrate those two competing risk analyses using the large national dataset from National Alzheimer’s Coordinating Center (NACC). We will analyze the association between baseline diabetes status and the incidence of dementia, in which death before the onset of dementia is a competing event.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 955-955
Author(s):  
Maria Roche-Dean ◽  
Sol Baik ◽  
Heehyul Moon ◽  
Norma Coe ◽  
Anna Oh ◽  
...  

Abstract Objectives Paid care provided in the home or through community organizations includes important support services for older adults with dementia such as cleaning and personal care assistance. These services could delay the transition to long-term care, but access may differ across sociodemographic groups. This study examined the relationship between paid care and transitioning out of the community among diverse older adults with dementia. Methods Using data from 303 participants (29.4% Black) with probable dementia in the National Health and Aging Trends Study (2011-2019), subdistribution hazard models estimated the association between receiving paid care at baseline and the probability of transitioning out of the community over the next eight years. Covariate selection was guided by the Andersen model of healthcare utilization. Results Paid care was associated with lower risk of transitioning out of the community (SHR = 0.70, 95% CI [0.50, 0.98]). This effect was similar after controlling for predisposing factors and most prominent after controlling for enabling and need for services factors (SHR = 0.63, 95% CI [0.42, 0.94]) and was only evident among Whites. There were no racial differences in the use of paid care, but Black participants were less likely to transition out of the community than Whites despite evidencing greater care needs. Discussion Paid care services may help delay transitions out of the community. Future research should seek to explain racial differences in access to and/or preferences for home-based, community-based, and residential care.


2021 ◽  
Vol 8 ◽  
Author(s):  
Hui-Ting Wang ◽  
Yung-Lung Chen ◽  
Yu-Sheng Lin ◽  
Huang-Chung Chen ◽  
Shaur-Zheng Chong ◽  
...  

Objectives: Atrial fibrillation (AF) is linked to an increased risk of stroke and dementia. Atrial flutter (AFL) is also linked to an increased risk of stroke but at a different level of risk as compared to AF. Little is known about the difference in the risk of dementia between AF and AFL. This study aims to investigate whether the risk of dementia is different between AF and AFL.Methods: Patients with newly diagnosed AF and AFL during 2001–2013 were retrieved from Taiwan's National Health Insurance Research Database. Patients with incomplete demographic data, aged &lt;20 years, history of valvular surgery, rheumatic heart disease, hyperthyroidism, and history of dementia were excluded. The incidence of new-onset dementia was set as the primary outcome and analyzed in patients with AF and AFL after propensity score matching (PSM).Results: A total of 232,425 and 7,569 patients with AF and AFL, respectively, were eligible for analysis. After 4:1 PSM, we included 30,276 and 7,569 patients with AF and AFL, respectively, for analysis. Additionally, patients with AF (n = 29,187) and AFL (n = 451) who received oral anticoagulants were enrolled for comparison. The risk of dementia was higher in patients with AF compared with patients with AFL (subdistribution hazard ratio (SHR) = 1.52, 95% CI 1.39–1.66; p &lt; 0.0001) before PSM and remained higher in patients with AF (SHR = 1.14, 95% CI 1.04–1.25; p = 0.0064) after PSM. The risk of dementia was higher in patients with AF without previous history of stroke after PSM but the risk did not differ between patients with AF and AFL with previous history of stroke. Among patients who received oral anticoagulants, the cumulative incidences of dementia were significantly higher in patients with AF than in patients with AFL before and after PSM (all P &lt; 0.05).Conclusions: This study found that, among patients without history of stroke, the risk of dementia was higher in patients with AF than in patients with AFL, and CHA2DS2-VASc score might be useful for risk stratification of dementia between patients with AF and AFL.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2522-2522
Author(s):  
Jorge A Florindez ◽  
Izidore S. Lossos ◽  
Juan Pablo Alderuccio

Abstract INTRODUCTION: The Waldeyer ring represents a common location of diffuse large B-cell lymphoma (DLBCL) arising in the head and neck. Within the Waldeyer ring, tonsils are the most common site. Chemotherapy with or without consolidation with radiotherapy are the most common approaches. However, the benefit of radiotherapy over chemotherapy as a single approach in patients with localized DLBCL remains unclear. In this study we analyzed the survival effect of different treatment modalities along with clinical variables in two cohorts of patients with stage I DLBCL involving either the tonsils or the neck lymph nodes (LN). METHODS: This is a retrospective analysis of patients with stage I DLBCL with primary involvement of the tonsil or neck lymph nodes derived from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2015 with follow up through 2017. We concentrated our analysis on patients with Ann Arbor stage I and treated with chemotherapy and/or radiotherapy. We excluded cases without histologic confirmation, untreated, incomplete survival data or unknown cause of death. The major end-points of this study were overall survival (OS) and lymphoma-specific survival (LSS). Kaplan-Meier and log-rank test were used in the OS analysis with Cox proportional hazard regression model to assess predictors of OS. LSS was evaluated using competing risk analysis. The Fine and Gray subdistribution hazard model was used to assess the effect of demographic and treatment related variables on the risk of lymphoma-specific death. We reported subdistribution hazard ratios (SHR) with corresponding 95% confidence intervals. RESULTS: 1978 (tonsil: 311 and neck LN: 1667) patients with DLBCL met the inclusion criteria. Overall, most patients were ≥ 60 years (n=1130, 57.1%), male (n=1101, 55.7%), white (n=1631, 82.5%), non-Hispanic (n=1775, 89.7%), and treated with chemotherapy (n=935, 47.3%) followed by chemotherapy/radiotherapy (n=929, 47%). Patients &lt;60 years (48.9% vs 41.8%; P=0.019), non-White race (21.9% vs 16.7%; P=0.029) and Hispanic origin (14.1% vs 9.5%; P=0.013) were more common in DLBCL in tonsil compared to neck LN. Patients with tonsil DLBCL exhibited longer median OS compared to neck LN (16.2 vs. 14.2 years; P=0.033) (Figure 1A). In patients with tonsil DLBCL, consolidation with radiation did not lead to longer median 5-year OS (83.9%, 95%CI 76.7-89% vs 81.8%, 95%CI 74.1-87.4%; P=0.523) or LSS (HR=0.73, 95%CI 0.37-1.42; P=0.350) compared to chemotherapy (Figure 1B and Table 1). Contrary, patients with neck LN demonstrated better OS (5-year OS 82.6%, 95% 79.7-85.1 vs 72.2% 95%CI 68.9-75.2%; P&lt;0.001) and LSS (HR=0.55, 95%CI 1.51-3.14; P&lt;0.001) if they received consolidation with radiotherapy compared to chemotherapy only (Figure 1C and Table 2). CONCLUSION: Based on our analysis consolidation with radiotherapy does not improve OS or LSS in patients with stage I tonsil DLBCL treated with chemotherapy. Conversely, consolidation with radiation significantly improves survival in patients with localized LN DLBCL. Figure 1 Figure 1. Disclosures Lossos: NCI: Research Funding; Seattle Genetics: Consultancy; Stanford University: Patents & Royalties; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member.


2021 ◽  
pp. 1-8
Author(s):  
Seo Yeon Yoon ◽  
Seok-Jae Heo ◽  
Yong Wook Kim ◽  
Seung Nam Yang ◽  
Hyun-Im Moon

Background: Ankylosing spondylitis (AS) is an immune-mediated, chronic inflammatory rheumatic disorder. The etiology of Parkinson’s disease (PD) is multifactorial; however, inflammation is receiving an increasing amount of attention as an underlying cause of the neurodegenerative process of PD. Objective: We performed a nationwide longitudinal, population-based matched cohort study to assess the association with the later development of parkinsonism in Korea. Methods: This study was conducted using records from the Health Insurance Review and Assessment Service database. The cumulative incidence rate of PD was estimated. Fine–Gray subdistribution hazard models were used to identify hazards associated with PD development based on the presence of AS. Exposure to anti-inflammatory drugs was measured and analyzed to determine the protective effect of these medications. Additionally, the hazard ratio (HR) for atypical parkinsonism was estimated. Results: The results of the Fine–Gray subdistribution hazard model revealed that the HR for PD development in the AS group was 1.82 (95%confidence interval [CI], 1.38–2.39, p <  0.001). A significant decrease in PD development was observed in patients with AS taking non-steroidal anti-inflammatory drugs (NSAIDs). The HR for atypical parkinsonism in the AS group was 3.86 (95%CI, 1.08–13.78, p <  0.05). Conclusion: We found that AS was associated with an increased risk of PD and atypical parkinsonism. NSAIDs used for AS control have some protective effects against PD. Further studies assessing whether biological treatment mitigates PD risk in patients with high activity are warranted.


2021 ◽  
Author(s):  
Shekoufeh Gorgi Zadeh ◽  
Charlotte Behning ◽  
Matthias Schmid

Abstract With the popularity of deep neural networks (DNNs) in recent years, many researchers have proposed DNNs for the analysis of survival data (time-to-event data). These networks learn the distribution of survival times directly from the predictor variables without making strong assumptions on the underlying stochastic process. In survival analysis, it is common to observe several types of events, also called competing events. The occurrences of these competing events are usually not independent of one another and have to be incorporated in the modeling process in addition to censoring. In classical survival analysis, a popular method to incorporate competing events is the subdistribution hazard model, which is usually fitted using weighted Cox regression. In the DNN framework, only few architectures have been proposed to model the distribution of time to a specific event in a competing events situation. These architectures are characterized by a separate subnetwork/pathway per event, leading to large networks with huge amounts of parameters that may become difficult to train. In this work, we propose a novel imputation strategy for data preprocessing that incorporates the subdistribution weights derived from the classical model. With this, it is no longer necessary to add multiple subnetworks to the DNN to handle competing events. Our experiments on synthetic and real-world datasets show that DNNs with multiple subnetworks per event can simply be replaced by a DNN designed for a single-event analysis without loss in accuracy.


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