Early predictors of renal outcome in patients with proliferative lupus nephritis: a 36-month cohort study

Abstract Objectives To identify predictors of complete renal response (CRR) and renal flares in SLE patients with active proliferative LN. Methods This was a retrospective cohort study over 36 months including patients with biopsy-proven proliferative LN (class III/IV), from two European tertiary centres. CRR and renal flare were defined as proteinuria <0.5 g/day with normal renal function and proteinuria >1 g/day after CRR attainment, respectively. Demographic, clinical and analytic parameters were evaluated as early predictors of renal outcome, using survival analysis. Candidate variables were tested as predictors for CRR at time 0, 3 and 6 months after starting induction treatment. Potential predictors for renal flare were evaluated at time of reaching CRR. Variables with P < 0.10 on univariate analysis with log-rank tests were further tested with multivariate Cox proportional hazards regression models. Results We included 104 patients [81.7% female, mean (s.d.) age at baseline 32.0 (13.3) years]. Over follow-up, 91.7% reached CRR, within a median time of 6.0 months. Proteinuria <2 g/day at baseline [hazard ratio (HR) = 1.80, 95% CI 1.16, 2.79, P < 0.01] and 3 months (HR = 2.32, 95% CI 1.24, 4.32, P < 0.01) after starting induction therapy were independent predictors of CRR. Renal flares occurred in 18.4% of patients reaching CRR, after a mean time of 16.5 (8.6) months. Age up to 25 years at time of LN diagnosis (HR = 5.41, 95% CI 1.72, 16.97, P < 0.01) and positive anti-RNP (HR = 3.52, 95% CI 1.21, 10.20, P = 0.02) were independent predictors of renal flares. Conclusion In patients with SLE and proliferative LN, factors assessed at baseline and 3 months from starting induction treatment can predict CRR and renal flares once CRR is achieved.

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SAT0185 PREDICTORS OF POOR RENAL OUTCOME IN PATIENTS WITH PROLIFERATIVE LUPUS NEPHRITIS: A 36-MONTHS COHORT STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3775 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1034.2-1034

Author(s):

M. Luis ◽

A. R. Prata ◽

H. Assunção ◽

J. A. P. Da Silva ◽

L. Inês

Keyword(s):

Diabetes Mellitus ◽

Cohort Study ◽

Lupus Nephritis ◽

Induction Therapy ◽

Antihypertensive Drugs ◽

Univariate Analysis ◽

Unmet Need ◽

Renal Outcome ◽

Induction Treatment ◽

Renal Response

Background:The EULAR/ERA-EDTA recommendations for lupus nephritis (LN) state that renal response should be achieved within 12 months following induction therapy. However, there is an unmet need for early predictors of renal outcome in order to adjust the immunosuppression regimen and optimize the renal outcome.Objectives:To identify predictors of poor renal outcome at baseline, 3 months and 6 months after starting induction therapy.Methods:Retrospective cohort study over 36 months including patients with Systemic lupus erythematosus (SLE) fulfilling the ACR’97 and/or the SLICC’12 classification criteria and with biopsy-proven proliferative LN (class III/IV), enrolled in the CHUC Lupus Cohort from 1999 to 2018. Poor renal outcome was defined as longer time to complete renal response (CRR), characterized by proteinuria <0.5g/day and normal renal function, according to EULAR/ERA-EDTA criteria. Clinical-analytical characteristics at baseline, 3 months and 6 months after starting induction treatment were compared using survival analysis for time-to-CRR. Variables with p<0.25 on univariate analysis using Log-Rank tests were further evaluated as predictors applying multivariate Cox proportional hazards regression models (Backward Stepwise method, Wald-based) with estimation of hazard ratios (HR) and 95% confidence intervals (95%CI).Results:56 patients were included (76.8% female, age at LN diagnosis 30.0 ± 13.2 years). Over the follow-up, 51 patients (91.1%) achieved CRR, within a median time of 6.0 months. In multivariate analysis, predictors of poor renal outcome were proteinuria >2g/day at baseline (HR 1.98; 95%CI 1.04-3.77; p=0.037) and induction therapy with pulse cyclophosphamide (CYC), as compared to mycophenolate mofetil (MMF) (HR=2.05; 95%CI 1.07-3.94; p=0.030) (Figure 1). Diabetes mellitus (HR=6.0; 95%CI 1.24-29.07; p=0.026) and negative anti-RNP antibody (HR 3.17; 95%CI 1.27-7.93; p=0.013) at baseline predicted poor renal outcome at 3 months. At this timepoint, level of proteinuria and clearance rate were not predictive of renal response. At 6 months, no predictors of LN outcome were found for those patients that did not achieve CRR up to this timepoint. Use of glucocorticoid pulses and/or antihypertensive drugs did not predict LN outcome.Figure 1.Conclusion:In this SLE cohort, most patients with proliferative LN achieved CRR. Proteinuria above 2 g/day at baseline and diabetes mellitus were predictors of poor renal outcome, while positive anti-RNP was protective. Induction treatment with CYC was associated with poorer outcome as compared with MMF. Given the retrospective non-randomized nature of this study, caution is needed when drawing conclusions regarding both treatments efficacy.Disclosure of Interests:Mariana Luis: None declared, Ana Rita Prata: None declared, Helena Assunção: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Luís Inês: None declared

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Bidirectional Association Between Knee Osteoarthritis and Depressive Symptoms: A Nationwide Cohort Study

Innovation in Aging ◽

10.1093/geroni/igaa057.710 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 220-220

Author(s):

Han Lu ◽

Shaomei Shang ◽

Limin Wang ◽

Hongbo Chen

Keyword(s):

Cohort Study ◽

Depressive Symptoms ◽

Knee Osteoarthritis ◽

Proportional Hazards ◽

Depression Scale ◽

Cox Proportional Hazards ◽

Depression Symptoms ◽

Physical And Mental Health ◽

Bidirectional Association ◽

Bidirectional Relationship

Abstract Both knee osteoarthritis (KOA) and depressive symptoms are common health issues affecting the quality of life of old adults. Although it is presumed that KOA has a bidirectional relationship with the depressive symptoms, no cohort study has proven it. This is the first study to determine the strength of association for the bidirectional relationship between KOA and depressive symptoms. Data were gathered from the nationally survey of China Health and Retirement Longitudinal Study in 2011-2015. The presence of depressive symptoms was defined by the 10-item Center for Epidemiologic Studies Depression Scale score of 10 or higher. The adjusted Cox proportional hazards regression model was conducted to estimate hazards ratios (HRs). Controlled covariates include gender, age, education, marital status, residence, number of chronic diseases, and disability. The analysis of KOA predicting the depressive symptoms onset consisted of 4,377 participants free from depressive symptoms at baseline. During 4 years follow-up, diagnosed KOA participants were more likely to have depressive symptoms than their peers without KOA (HR = 1.50, 95% CI: 1.23-1.83). The parallel analysis of depressive symptoms predicting KOA onset included 6,848 participants without KOA at baseline, those with depressive symptoms had a higher relative risk of developing KOA (HR = 1.64, 95% CI: 1.41-1.92). Our results provide compelling evidence that the KOA-depressive symptoms association is bidirectional, highlighting the importance of evaluating the relationship between physical and mental health among older people. Particularly, taking this association into consideration in the risk assessment and primary prevention of KOA and depression symptoms.

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The incidence of mental disorder increases after hip fracture in older people: a nationwide cohort study

BMC Geriatrics ◽

10.1186/s12877-021-02195-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ling-Yin Kuo ◽

Po-Ting Hsu ◽

Wen-Tien Wu ◽

Ru-Ping Lee ◽

Jen-Hung Wang ◽

...

Keyword(s):

Cohort Study ◽

Hip Fracture ◽

Geriatric Patients ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Control Group ◽

Research Database ◽

Fracture Group ◽

Related Risk ◽

And Control

Abstract Background People living with dementia seem to be more likely to experience delirium following hip fracture. The association between mental disorders (MD) and hip fracture remains controversial. We conducted a nationwide study to examine the prevalence of MD in geriatric patients with hip fractures undergoing surgery and conducted a related risk factor analysis. Material and methods This retrospective cohort study used data from Taiwan’s National Health Insurance Research Database between 2000 and 2012 and focused on people who were older than 60 years. Patients with hip fracture undergoing surgical intervention and without hip fracture were matched at a ratio of 1:1 for age, sex, comorbidities, and index year. The incidence and hazard ratios of age, sex, and multiple comorbidities related to MD and its subgroups were calculated using Cox proportional hazards regression models. Results A total of 1408 patients in the hip fracture group and a total of 1408 patients in the control group (no fracture) were included. The overall incidence of MD for the hip fracture and control groups per 100 person-years were 0.8 and 0.5, respectively. Among MD, the incidences of transient MD, depression, and dementia were significantly higher in the hip fracture group than in the control group. Conclusions The prevalence of newly developed MD, especially transient MD, depression, and dementia, was higher in the geriatric patients with hip fracture undergoing surgery than that in the control group. Prompt and aggressive prevention protocols and persistent follow-up of MD development is highly necessary in this aged society.

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Regular Use of VKA Prior to COVID-19 Associated with Lower 7-Day Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Cohort Study

Nutrients ◽

10.3390/nu13010039 ◽

2020 ◽

Vol 13 (1) ◽

pp. 39

Author(s):

Pierre Ménager ◽

Olivier Brière ◽

Jennifer Gautier ◽

Jérémie Riou ◽

Guillaume Sacco ◽

...

Keyword(s):

Cohort Study ◽

Vitamin K ◽

Frail Elderly ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Clinical Severity ◽

Survival Times ◽

Short Term Mortality

Background. Vitamin K concentrations are inversely associated with the clinical severity of COVID-19. The objective of this cohort study was to determine whether the regular use of vitamin K antagonist (VKA) prior to COVID-19 was associated with short-term mortality in frail older adults hospitalized for COVID-19. Methods. Eighty-two patients consecutively hospitalized for COVID-19 in a geriatric acute care unit were included. The association of the regular use of VKA prior to COVID-19 with survival after 7 days of COVID-19 was examined using a propensity-score-weighted Cox proportional-hazards model accounting for age, sex, severe undernutrition, diabetes mellitus, hypertension, prior myocardial infarction, congestive heart failure, prior stroke and/or transient ischemic attack, CHA2DS2-VASc score, HAS-BLED score, and eGFR. Results. Among 82 patients (mean ± SD age 88.8 ± 4.5 years; 48% women), 73 survived COVID-19 at day 7 while 9 died. There was no between-group difference at baseline, despite a trend for more frequent use of VKA in those who did not survive on day 7 (33.3% versus 8.2%, p = 0.056). While considering “using no VKA” as the reference (hazard ratio (HR) = 1), the HR for 7-day mortality in those regularly using VKA was 5.68 [95% CI: 1.17; 27.53]. Consistently, COVID-19 patients using VKA on a regular basis had shorter survival times than the others (p = 0.031). Conclusions. Regular use of VKA was associated with increased mortality at day 7 in hospitalized frail elderly patients with COVID-19.

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Anhedonia as a Potential Risk Factor of Alzheimer’s Disease in a Community-Dwelling Elderly Sample: Results from the ZARADEMP Project

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041370 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1370

Author(s):

David Vaquero-Puyuelo ◽

Concepción De-la-Cámara ◽

Beatriz Olaya ◽

Patricia Gracia-García ◽

Antonio Lobo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potential Risk ◽

Proportional Hazards ◽

Univariate Analysis ◽

Population Sample ◽

Public Health Problem ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Major Public Health Problem

(1) Introduction: Dementia is a major public health problem, and Alzheimer’s disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04–5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.

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Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block

European Heart Journal ◽

10.1093/ehjci/ehaa946.3358 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Kochav ◽

R.C Chen ◽

J.M.D Dizon ◽

J.A.R Reiffel

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Class I ◽

Class Iii ◽

Bundle Branch Block ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

History Of ◽

Propensity Score Stratification

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None

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Gamma frailty model for survival risk estimation: an application to cancer data

Epidemiologic Methods ◽

10.1515/em-2021-0005 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

K. M. J. Krishna ◽

T. Traison ◽

Sejil Mariya Sebastian ◽

Preethi Sara George ◽

Aleyamma Mathew

Keyword(s):

Proportional Hazards ◽

Risk Estimation ◽

Univariate Analysis ◽

Frailty Model ◽

Cox Proportional Hazards ◽

Information Criteria ◽

Frailty Models ◽

Event Analysis ◽

Global Test ◽

Cancer Data

Abstract Objectives: In time to event analysis, the risk for an event is usually estimated using Cox proportional hazards (CPH) model. But CPH model has the limitation of biased estimate due to unobserved hidden heterogeneity among the covariates, which can be tackled using frailty models. The best models were usually being identified using Akaike information criteria (AIC). Apart from AIC, the present study aimed to assess predictability of risk models using survival concordance measure. Methods: CPH model and frailty models were used to estimate the risk for breast cancer patient survival, and the frailty variable was assumed to follow gamma distribution. Schoenfeld global test was used to check the proportionality assumption. Survival concordance, AIC and simulation studies were used to identify the significance of frailty. Results: From the univariate analysis it was observed that for the covariate age, the frailty has a significant role (θ = 2.758, p-value: 0.0004) and the corresponding hazard rate was 1.93 compared to that of 1.38 for CPH model (age > 50 vs. ≤ 40). Also the covariates radiotherapy and chemotherapy were found to be significant (θ = 5.944, p-value: <0.001 and θ = 16, p-value: <0.001 respectively). Even though there were only minor differences in hazard rates, the concordance was higher for frailty than CPH model for all the covariates. Further the simulation study showed that the bias and root mean square error (RMSE) obtained for both the methods was almost the same and the concordance measures were higher for frailty model by 12–15%. Conclusions: We conclude that the frailty model is better compared to CPH model as it can account for unobserved random heterogeneity, and if the frailty coefficient doesn’t have an effect it gives exactly the same risk as that of CPH model and this has been established using survival concordance.

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Extraskeletal osteosarcoma: A large series treated at a single institution

Rare Tumors ◽

10.1177/2036361317749651 ◽

2018 ◽

Vol 10 ◽

pp. 203636131774965 ◽

Cited By ~ 3

Author(s):

Haotong Wang ◽

Ruoyu Miao ◽

Alex Jacobson ◽

David Harmon ◽

Edwin Choy ◽

...

Keyword(s):

Prognostic Factors ◽

Proportional Hazards ◽

Survival Curve ◽

Treatment Options ◽

Univariate Analysis ◽

Soft Tissue Sarcomas ◽

Cox Proportional Hazards ◽

Wide Resection ◽

Incomplete Resection ◽

Extraskeletal Osteosarcoma

Purpose: This study is to present a large cohort of extraskeletal osteosarcoma (ESOS) and evaluate prognostic factors and treatment options. Methods: Medical records were reviewed retrospectively for 41 patients with extraskeletal osteosarcoma that was diagnosed by pathology, and treated at our institution between 1960 and 2016. Kaplan-Meier analysis and Cox proportional hazards regression were used to identify variables that affect survival outcomes. Results: 41 patients were identified from 952 osteosarcomas. 32 patients had non-metastatic disease. Prognostic factors were identified by univariate analysis and multi-variate analysis. Surgery ( p<0.001), and surgery type ( p<0.001) both were shown to significantly affect overall survival (OS). Chemotherapy and radiation therapy (RT) did not show any significant effect on OS, local recurrence, or progression free survival as a whole. However for patients who had incomplete resection with residual tumor RT improved OS ( p=0.03). The survival curve for ESOS follows more closely that of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Conclusions: ESOS is a very rare tumor. Attempt to achieve wide resection is the treatment of choice. However for patients who are not able to achieve complete resection, RT may improve OS. The behavior of ESOS more closely follows that of NRSTS than osteosarcoma of the bone.

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Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer

Cancers ◽

10.3390/cancers13225629 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5629

Author(s):

Yusuke Sugino ◽

Takeshi Sasaki ◽

Manabu Kato ◽

Satoru Masui ◽

Kouhei Nishikawa ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Psoas Muscle ◽

Hounsfield Unit ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cross Sectional

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

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Creatinine-to-body weight ratio is a predictor of incident diabetes: a population-based retrospective cohort study

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00776-8 ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Jiacheng He

Keyword(s):

Body Weight ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Proportional Hazards ◽

Weight Ratio ◽

Threshold Effect ◽

Population Based ◽

Cox Proportional Hazards ◽

Incident Type

Abstract Purpose Creatinine to body weight (Cre/BW) ratio is considered the independent risk factor for incident type 2 diabetes mellitus (T2DM), but research on this relationship is limited. The relationship between the Cre/BW ratio and T2DM among Chinse individuals is still ambiguous. This study aimed to evaluate the correlation between the Cre/BW ratio and the risk of T2DM in the Chinese population. Methods This is a retrospective cohort study from a prospectively collected database. We included a total of 200,658 adults free of T2DM at baseline. The risk of incident T2DM according to Cre/BW ratio was estimated using multivariable Cox proportional hazards models, and a two-piece wise linear regression model was developed to find out the threshold effect. Results With a median follow-up of 3.13 ± 0.94 years, a total of 4001 (1.99%) participants developed T2DM. Overall, there was an L-shaped relation of Cre/BW ratio with the risk of incident T2DM (P for non-linearity < 0.001). When the Cre/BW ratio (× 100) was less than 0.86, the risk of T2DM decreased significantly as the Cre/BW ratio increased [0.01 (0.00, 0.10), P < 0.001]. When the Cre/BW ratio (× 100) was between 0.86 and 1.36, the reduction in the risk of developing T2DM was not as significant as before [0.22 (0.12, 0.38), P < 0.001]. In contrast, when the Cre/BW ratio (× 100) was greater than 1.36, the reduction in T2DM incidence became significantly flatter than before [0.73 (0.29,1.8), P = 0.49]. Conclusion There was an L-shaped relation of Cre/BW ratio with incidence of T2DM in general Chinese adults. A negative curvilinear association between Cre/BW ratio and incident T2DM was present, with a saturation effect predicted at 0.86 and 1.36 of Cre/BW ratio (× 100).

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