Summarizing causal differences in survival curves in the presence of unmeasured confounding

AbstractProportional hazard Cox regression models are frequently used to analyze the impact of different factors on time-to-event outcomes. Most practitioners are familiar with and interpret research results in terms of hazard ratios. Direct differences in survival curves are, however, easier to understand for the general population of users and to visualize graphically. Analyzing the difference among the survival curves for the population at risk allows easy interpretation of the impact of a therapy over the follow-up. When the available information is obtained from observational studies, the observed results are potentially subject to a plethora of measured and unmeasured confounders. Although there are procedures to adjust survival curves for measured covariates, the case of unmeasured confounders has not yet been considered in the literature. In this article we provide a semi-parametric procedure for adjusting survival curves for measured and unmeasured confounders. The method augments our novel instrumental variable estimation method for survival time data in the presence of unmeasured confounding with a procedure for mapping estimates onto the survival probability and the expected survival time scales.

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H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

10.21203/rs.3.rs-949930/v1 ◽

2021 ◽

Author(s):

Huy Gia Vuong ◽

Hieu Trong Le ◽

Tam N.M. Ngo ◽

Kar-Ming Fung ◽

James D. Battiste ◽

...

Keyword(s):

Cox Regression ◽

Fatal Outcome ◽

Extent Of Resection ◽

Tumor Location ◽

Genetic Alterations ◽

Integrated Analysis ◽

Prognostic Impact ◽

Kaplan Meier ◽

Hazard Ratios ◽

The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

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Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.636999 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zeming Liu ◽

Di Hu ◽

Jinpeng Li ◽

Qing Xia ◽

Yan Gong ◽

...

Keyword(s):

Liver Function ◽

Liver Enzymes ◽

Cox Regression ◽

Liver Function Tests ◽

Regression Analyses ◽

Survival Curves ◽

Severity Of Disease ◽

Kaplan Meier ◽

Hazard Ratios ◽

Disease Mortality

BackgroundCoronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients.MethodsPatient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality.ResultsLogistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19.ConclusionElevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

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Abstract 3230: Elevated Glucose and Mortality in Patients Hospitalized with Heart Failure

Circulation ◽

10.1161/circ.118.suppl_18.s_1117-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Mikhail Kosiborod ◽

Silvio Inzucchi ◽

John A Spertus ◽

Yongfei Wang ◽

Frederick A Masoudi ◽

...

Keyword(s):

Heart Failure ◽

Cox Regression ◽

Linear Trend ◽

Adverse Outcomes ◽

Entire Cohort ◽

Hazard Ratios ◽

Elevated Glucose ◽

Nationally Representative ◽

Support Resource ◽

The Impact

Background: While some professional societies recommend target-driven blood glucose (BG) control for all hospitalized patients, the association between elevated BG and adverse outcomes has not been well established in patients hospitalized with heart failure (HF). Methods: We evaluated a nationally representative cohort of 50,532 patients hospitalized with HF between 04/1998 – 06/2001. Admission BG was analyzed as a categorical variable (≤110, >110 –140, >140 –170, >170 –200, >200 mg/dL), and in 10 mg/dL increments. The association between BG and all-cause mortality over 30 days and 1 year was analyzed using Cox regression, both in the entire cohort and in patients with and without diabetes (DM). Results: After multivariable adjustment, there was no significant relationship between BG and 30-day mortality (for BG >110 to 140, >140 to 170, >170 to 200, and >200, hazard ratios and 95% confidence intervals were: 1.09 (0.98 –1.22), 1.27 (1.11–1.45), 1.16 (0.98–1.37), 1.00 (0.87–1.15) respectively vs. BG ≤110, P for linear trend 0.53). Results were similar for 1-year mortality, and did not differ between patients with and without DM (P values for DM*BG interaction 0.11 and 0.55 for 30-day and 1-year mortality respectively). A lack of association between BG and mortality over 30-days and 1-year was also observed when BG was analyzed in 10mg/dL increments (Figure ). Conclusions: We found no significant association between BG and mortality in a large cohort of hospitalized HF patients. While the impact of BG lowering on outcomes cannot be determined based on this study, our findings do not support resource-intensive interventions for BG monitoring and management in this patient group.

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Evaluate the Impact of Diabetes on RA-related outcomes in an Electronic Health Record-Based Rheumatology Registry

The Journal of Rheumatology ◽

10.3899/jrheum.200486 ◽

2020 ◽

pp. jrheum.200486

Author(s):

Huifeng Yun ◽

Fenglong Xie ◽

Lang Chen ◽

Shuo Yang ◽

Leticia Ferri ◽

...

Keyword(s):

Linear Models ◽

Cox Regression ◽

Health Assessment ◽

Diabetic Patients ◽

Informatics System ◽

Diagnosis Codes ◽

Hazard Ratios ◽

Patients With Diabetes ◽

The Impact ◽

Diabetes Patients

Objective RA patients with diabetes might have worse clinical outcomes and adverse events compared to non-diabetes patients. We evaluated the effects of diabetes on HAQ (Health Assessment Questionnaire) change and outpatient infection in RA patients. Methods Using the ACR’s Rheumatology Informatics System for Effectiveness (RISE) EHR-based registry, we identified RA patients who had ≥1 rheumatologist visit with a HAQ measured (index visit) in 2016, ≥1 previous visit, and a subsequent outcome visit with same HAQ measured at 12 months (± 3 months). We identified diabetes by diagnosis codes, medications, or lab values. Outpatient infection was defined by diagnosis codes or anti-infective medications. We calculated mean HAQ change and incidence rate (IR) of outpatient infections among patients with and without diabetes. Generalized linear models and Cox regression were used to calculate the adjusted mean HAQ change and hazard ratios (HR). Results We identified 3,853 RA patients with diabetes and 18,487 without diabetes. The mean HAQ change between index and outcome visit among diabetes patients was 0.03 and non-diabetic was 0.002 (p<0.01). We identified 761 outpatient infections for diabetic patients with an IR of 22.6 (95% CI: 21.0-24.2) per 100 person years and 3,239 among non-diabetic patients with an IR of 19.8 (19.1-20.5). The adjusted HR of outpatient infection among diabetes was 0.99 (0.91-1.07), compared to non-diabetes patients. Conclusion RA patients with concomitant diabetes had greater worsening, or less improvement, in their functional status, suggesting additional interventions may be needed for RA patients with diabetes to optimize treatment and other comorbidities.

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The impact of cognitive dysfunction on mid- and long-term mortality after vascular surgery

10.21203/rs.3.rs-42677/v1 ◽

2020 ◽

Author(s):

Andras Szabo ◽

Nikoletta Czobor ◽

Adam Nagy ◽

Krisztina Toth ◽

Csaba Eke ◽

...

Keyword(s):

Vascular Surgery ◽

Cognitive Dysfunction ◽

Cox Regression ◽

Mmse Score ◽

Life Quality ◽

Relative Risks ◽

The Difference ◽

The Impact ◽

Long Term Mortality

Abstract Background: In the last decades prior studies noted the importance of frailty which is a frequently used term in perioperative risk evaluation. We investigated frailty syndrome as the psychological and socioeconomic elements of the human being. The aim of this study was assessing the importance of these factors for mortality after vascular surgery.Methods: In our prospective, observational study (ClinicalTrials.gov Identifier: NCT02224222) we examined 164 patients who underwent an elective vascular surgery between 2014 and 2017. At the point of admission they filled out a questionnaire, in this way the patients’ cognitive functions, depression and anxiety, social support and self-reported life quality were mapped. We used Cox regression and Kaplan-Meier method for relative risk calculation and survival analyses. Propensity score matching was performed to analyze the difference between patient and control, nation-wide population cohort. Effects of psychosocial factors on long term mortality were defined as primary outcome. Results: The patients mean age were 67.05 years (SD: 9.49 years). One out of four patients had some kind of cognitive impairment measured by Mini Mental State Examination with modified, more sensitive cut-off values. In univariate Cox regression higher MMSE score was associated decreased risk for all-cause mortality (OR: 0.883, 95% CI: 0.802-0.973, p=0.012). After clusters were created according to MMSE score relative risks were calculated. Even mild cognitive dysfunction could increase risk for long term mortality (AHR: 1.634, 95% CI: 1.118-2.368, p=0.009).Conclusion: Even mild cognitive dysfunction measured by the MMSE preoperatively could be an important risk factor for mortality after vascular surgery.

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An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Journal of Clinical Medicine ◽

10.3390/jcm7110416 ◽

2018 ◽

Vol 7 (11) ◽

pp. 416 ◽

Cited By ~ 4

Author(s):

Kuan-Ju Lai ◽

Chew-Teng Kor ◽

Yao-Peng Hsieh

Keyword(s):

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Cox Regression ◽

Laboratory Data ◽

Study Cohort ◽

Dialysis Unit ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Adjusted Model ◽

The Impact

Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24–0.68, p = 0.001), 0.4 (95% CI 0.2–0.81, p = 0.01), and 0.47 (95% CI 0.19–1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69–0.9, p = 0.07), 0.79 (95% CI, 0.61–1.01, p = 0.06), and 0.79 (95% CI, 0.48–1.21, p = 0.32) for men and 0.57 (95% CI, 0.44–0.73, p < 0.001), 0.6 (95% CI, 0.41–0.87, p = 0.006), and 0.41 (95% CI, 0.26–0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis.

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Surrogate scores of advanced fibrosis in NAFLD/NASH do not predict mortality in patients with medium-to-high cardiovascular risk

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00058.2021 ◽

2021 ◽

Author(s):

Graciela E. Delgado ◽

Marcus E. Kleber ◽

Angela P. Moissl ◽

Babak Yazdani ◽

Alexander Kusnik ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Risk Scores ◽

Hazard Ratios ◽

Artery Disease ◽

Independent Association ◽

The Impact

Background: Untreated NAFLD may have significant consequences including an increase in mortality and cardiovascular injury. Thus, early detection of NAFLD is currently believed not only to prevent liver related but also cardiovascular mortality. However, almost nothing is known about co-existing NAFLD in patients with coronary artery disease (CAD). Aims: We investigated the impact of surrogates scores of fibrosis in NAFLD in a large cohort of patients referred to coronary angiography. Results: Modelling the common NALFD and fibrosis scores FIB-4 and NFS as splines revealed significant associations with all-cause and cardiovascular mortality when Cox regression models were only adjusted for cardiovascular risk factors that were not already included in the calculation of the scores. Stratifying the scores into quartiles yielded hazard ratios (95% CI) for all-cause and cardiovascular mortality for the 4th quartile vs the 1st quartile of 2.28 (1.90-2.75) and 2.11 (1.67-2.67) for FIB-4 and of 3.21 (2.61-3.94) and 3.12 (2.41-4.04) for NFS. However, we did not observe an independent association of FIB-4 or NFS with overall or cardiovascular mortality in our prospective CAD cohort after full adjustment for all cardiovascular risk factors (all-cause mortality HR 1.13 (0.904-1.41) and 1.17 (0.903-1.52); cardiovascular mortality HR 1.06 (0.8-1.41) and 1.02 (0.738-1.41). Thus, neither FIB-4 nor NFS, as surrogate markers for NAFLD/NASH, were independent risk factors for overall or cardiovascular mortality in patients with CAD. Conclusion: Our data shows that surrogate risk scores for NAFLD-related fibrosis do not add information in assessing the CVD events in patients with CAD proven by angiography.

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THE IMPACT OF NATURAL DISASTERS ON MANUFACTURING: PLANT-LEVEL ANALYSIS FOR THE GREAT HANSHIN-AWAJI EARTHQUAKE

The Singapore Economic Review ◽

10.1142/s0217590816400105 ◽

2016 ◽

Vol 61 (01) ◽

pp. 1640010 ◽

Cited By ~ 2

Author(s):

YUSUKE MATSUKI ◽

SHUNSUKE MANAGI

Keyword(s):

Estimation Method ◽

Manufacturing Industries ◽

First Year ◽

Manufacturing Plant ◽

Factor Productivity ◽

Difference In Differences ◽

The Difference ◽

Plant Level ◽

The Impact ◽

Level Analysis

This paper investigates the impact of the Great Hanshin-Awaji earthquake on plant input, output, total factor productivity (TFP) and exit using Japanese plant-level manufacturing data. We employ the difference-in-differences (DID) estimation method to identify the effects of the quake and find that the quake had an impact on manufacturing. The results suggest that production was influenced by the quake, particularly in the first year after the quake. Furthermore, the quake did not influence manufacturing industries uniformly. The effects are different based on specifications, variables, and industries. However, the quake had little impact on the exit of plants.

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Irradiation of the Subventricular Zone and Subgranular Zone in High- and Low-Grade Glioma Patients: an Atlas-based Analysis on Overall Survival

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab193 ◽

2022 ◽

Author(s):

Danique E Bruil ◽

Szabolcs David ◽

Steven H J Nagtegaal ◽

Sophia F A M de Sonnaville ◽

Joost J C Verhoeff

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Low Grade ◽

Subgranular Zone ◽

Mr Images ◽

Repair Capacity ◽

Kaplan Meier ◽

Hazard Ratios ◽

Reduce Tumor Growth ◽

The Impact

Abstract Background Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p<0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p<0.001; multivariate: 1.055/Gy, p<0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, p<0.001). No correlations between dose and OS were found for LGG patients. Conclusion Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

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The Impact of Palliative Transurethral Resection of the Prostate on the Prognosis of Patients With Bladder Outlet Obstruction and Metastatic Prostate Cancer: A Population-Matched Study

Frontiers in Surgery ◽

10.3389/fsurg.2021.726534 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kun Fang ◽

Pan Song ◽

Jiahe Zhang ◽

Luchen Yang ◽

Peiwen Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Transurethral Resection ◽

Bladder Outlet Obstruction ◽

Metastatic Prostate Cancer ◽

Cox Regression ◽

Outlet Obstruction ◽

Survival Curves ◽

Cancer Specific Survival ◽

The Impact ◽

Surgical Group

Objective: This study aimed to evaluate the survival outcomes of patients with bladder outlet obstruction (BOO) and metastatic prostate cancer (mPCa) after having a palliative transurethral resection of the prostate (pTURP) surgery.Methods: We identified patients with mPCa between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received pTURP and non-surgical therapy were identified. A propensity-score matching was introduced to balance the covariate. Kaplan–Meier analysis and COX regression were conducted to evaluate the overall survival (OS) and cancer-specific survival (CSS) outcomes.Results: A total of 36,003 patients were identified; 2,823 of them were in the pTURP group and 33,180 were in the non-surgical group. The survival curves of the overall cohort showed that the pTURP group was associated with worse outcomes in both OS (HR: 1.12, 95% CI: 1.07–1.18, p < 0.001) and CSS (HR: 1.08, 95% CI: 1.02–1.15, p = 0.004) compared with the non-surgical group. The mean survival time in the overall cohort of the pTURP group was shorter than the non-surgical group in both OS [35.13 ± 1.53 vs. 40.44 ± 0.59 months] and CSS [48.8 ± 1.27 vs. 55.92 ± 0.43 months]. In the matched cohort, the pTURP group had significantly lower survival curves for both OS (HR: 1.25, 95% CI: 1.16–1.35, p < 0.001) and CSS (HR: 1.23, 95% CI: 1.12–1.35, p < 0.001) than the non-surgical group. pTURP significantly reduced the survival months of the patients (36.49 ± 0.94 vs. 45.52 ± 1.23 months in OS and 50.1 ± 1.49 vs. 61.28 ± 1.74 months in CSS). In the multivariate COX analysis, pTURP increased the risk of overall mortality (HR: 1.19, 95% CI: 1.09–1.31, p < 0.001) and cancer-specific mortality CSS (HR: 1.23, 95% CI: 1.14–1.33, p < 0.001) compared with the non-surgical group.Conclusions: For mPCa patients with BOO, pTURP could reduce OS and CSS while relieving the obstruction.

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