scholarly journals Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 254 ◽  
Author(s):  
Caroline Derrick ◽  
P. Brandon Bookstaver ◽  
Zhiqiang K. Lu ◽  
Christopher M. Bland ◽  
S. Travis King ◽  
...  
Keyword(s):  
Cohort Study ◽  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Bloodstream Infections ◽  
Cox Proportional Hazards ◽  
Third Generation ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Definitive Therapy ◽  
The Impact

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

scholarly journals Effect on Survival of Longer Intervals Between Confirmed Diagnosis and Treatment Initiation Among Low-Income Women With Breast Cancer

2012 ◽  
Vol 30 (36) ◽  
pp. 4493-4500 ◽  
Author(s):  
John M. McLaughlin ◽  
Roger T. Anderson ◽  
Amy K. Ferketich ◽  
Eric E. Seiber ◽  
Rajesh Balkrishnan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
North Carolina ◽  
Low Income ◽  
Late Stage ◽  
Proportional Hazards ◽  
Treatment Initiation ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Impact

Purpose To determine the impact of longer periods between biopsy-confirmed breast cancer diagnosis and the initiation of treatment (Dx2Tx) on survival. Patients and Methods This study was a noninterventional, retrospective analysis of adult female North Carolina Medicaid enrollees diagnosed with breast cancer from January 1, 2000, through December, 31, 2002, in the linked North Carolina Central Cancer Registry–Medicaid Claims database. Follow-up data were available through July 31, 2006. Cox proportional hazards regression models were constructed to evaluate the impact on survival of delaying treatment ≥ 60 days after a confirmed diagnosis of breast cancer. Results The study cohort consisted of 1,786 low-income, adult women with a mean age of 61.6 years. A large proportion of the patients (44.3%) were racial minorities. Median time from biopsy-confirmed diagnosis to treatment initiation was 22 days. Adjusted Cox proportional hazards regression showed that although Dx2Tx length did not affect survival among those diagnosed at early stage, among late-stage patients, intervals between diagnosis and first treatment ≥ 60 days were associated with significantly worse overall survival (hazard ratio [HR], 1.66; 95% CI, 1.00 to 2.77; P = .05) and breast cancer–specific survival (HR, 1.85; 95% CI, 1.04 to 3.27; P = .04). Conclusion One in 10 women waited ≥ 60 days to initiate treatment after a diagnosis of breast cancer. Waiting ≥ 60 days to initiate treatment was associated with a significant 66% and 85% increased risk of overall and breast cancer–related death, respectively, among late-stage patients. Interventions designed to increase the timeliness of receiving breast cancer treatments should target late-stage patients, and clinicians should strive to promptly triage and initiate treatment for patients diagnosed at late stage.

scholarly journals Risk factors for dementia onset in older adults with metastatic renal cell carcinoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 701-702
Author(s):  
Samuel Miller ◽  
Lauren Wilson ◽  
Melissa Greiner ◽  
Jessica Pritchard ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Older Adults ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Impact

Abstract Renal dysfunction is a driver of dementia. It is also associated with renal cell carcinoma, possibly the result of the tumor itself or from cancer treatment. This study evaluates metastatic renal cell carcinoma (mRCC) as a risk factor for developing mild cognitive impairment or dementia (MCI/D) as well as the impact of RCC-directed therapies on the development of MCI/D. We identified all patients diagnosed with mRCC in SEER-Medicare from 2007-2015. The main outcome was incident MCI/D within one year of mRCC diagnosis or cohort entry. Exclusion criteria included age <65 at mRCC diagnosis and diagnosis of MCI/D within preceding year of mRCC diagnosis. Patients with mRCC (n=2,533) were matched to non-cancer controls (n=7,027) on age, sex, race, comorbidities and year. Cox proportional hazards regression showed that having mRCC (HR 8.52, 95% MCI/D 6.49-11.18, p<0.001) and being older (HR 1.05 for 1-year age increase, 95% MCI/D 1.03-1.07, p<0.001) were predictive of developing MCI/D. A second Cox proportional hazards regression of only patients with mRCC revealed that neither those initiating treatment with oral anticancer agents (OAAs) nor those who underwent nephrectomy were more likely to develop MCI/D. Black patients had a higher risk of dementia compared to white patients (HR 1.92, 95% MCI/D 1.02-3.59, p=0.047). In conclusion, patients with mRCC were more likely to develop MCI/D than those without mRCC. The medical and surgical therapies evaluated were not associated with increased incidence of MCI/D. The increased incidence of MCI/D in older adults with mRCC may be the result of the pathology itself.

scholarly journals 558 PREVALENCE AND IMPACT OF FRAILTY IN PATIENTS HOSPITALISED WITH COVID-19. THE SALFORD EXPERIENCE IN WAVES 1 AND 2

2021 ◽  
Vol 50 (Supplement_2) ◽  
pp. ii14-ii18
Author(s):  
A Khan ◽  
F R Espinoza ◽  
T Kneen ◽  
A Dafnis ◽  
H Allafi ◽  
...  
Keyword(s):  
Prospective Observational Study ◽  
Proportional Hazards ◽  
Hospital Admissions ◽  
Cox Proportional Hazards ◽  
Vulnerable Group ◽  
Clinical Frailty Scale ◽  
Patient Demographics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Impact

Abstract Introduction The COVID-19 pandemic has had an extensive impact on the frail older population, with significant rates of COVID-related hospital admissions and deaths amongst this vulnerable group. There is little evidence of frailty prevalence amongst patients hospitalised with COVID-19, nor the impact of frailty on their survival. Methods Prospective observational study of all consecutive patients admitted to Salford Royal NHS Foundation (SRFT) Trust between 27th February and 28th April 2020 (wave 1), and 1st October to 10th November 2020 (wave 2) with a diagnosis of COVID-19. The primary endpoint was in-hospital mortality. Patient demographics, co-morbidities, admission level disease severity (estimated with CRP) and frailty (using the Clinical Frailty Scale, score 1–3 = not frail, score 4–9 = frail) were collected. A Cox proportional hazards regression model was used to assess the time to mortality. Results A total of 693 (N = 429, wave 1; N = 264, wave 2) patients were included, 279 (N = 180, 42%, wave 1; N = 104, 38%, wave 2) were female, and the median age was 72 in wave 1 and 73 in wave 2. 318 (N = 212, 49%, wave 1; N = 106, 39%, wave 2) patients presenting were frail. There was a reduction in mortality in wave 2, adjusted Hazard ratio (aHR) = 0.60 (95%CI 0.44–0.81; p = 0.001). There was an association between frailty and mortality aHR = 1.57 (95%CI 1.09–2.26; p = 0.015). Conclusion Frailty is highly prevalent amongst patients of all ages admitted to SRFT with COVID-19. Higher scores of frailty are associated with increased mortality.

scholarly journals Incorporating sampling weights into robust estimation of Cox proportional hazards regression model, with illustration in the Multi-Ethnic Study of Atherosclerosis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Colleen M. Sitlani ◽  
Thomas Lumley ◽  
Barbara McKnight ◽  
Kenneth M. Rice ◽  
Nels C. Olson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Regression Model ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Robust Methods ◽  
Time To Event ◽  
Sampling Weights ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

Abstract Background Cox proportional hazards regression models are used to evaluate associations between exposures of interest and time-to-event outcomes in observational data. When exposures are measured on only a sample of participants, as they are in a case-cohort design, the sampling weights must be incorporated into the regression model to obtain unbiased estimating equations. Methods Robust Cox methods have been developed to better estimate associations when there are influential outliers in the exposure of interest, but these robust methods do not incorporate sampling weights. In this paper, we extend these robust methods, which already incorporate influence weights, so that they also accommodate sampling weights. Results Simulations illustrate that in the presence of influential outliers, the association estimate from the weighted robust method is closer to the true value than the estimate from traditional weighted Cox regression. As expected, in the absence of outliers, the use of robust methods yields a small loss of efficiency. Using data from a case-cohort study that is nested within the Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study, we illustrate differences between traditional and robust weighted Cox association estimates for the relationships between immune cell traits and risk of stroke. Conclusions Robust weighted Cox regression methods are a new tool to analyze time-to-event data with sampling, e.g. case-cohort data, when exposures of interest contain outliers.

scholarly journals Vasoactive Biomarkers Associated With Long-Term Incidence of Symptomatic Peripheral Arterial Disease and Mortality

Angiology ◽  
2021 ◽  
pp. 000331972098773
Author(s):  
Ardwan Dakhel ◽  
Gunnar Engström ◽  
Olle Melander ◽  
Stefan Acosta ◽  
Shahab Fatemi ◽  
...  
Keyword(s):  
Cohort Study ◽  
Peripheral Arterial Disease ◽  
Proportional Hazards ◽  
Arterial Disease ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Peripheral Arterial

We evaluated if plasma biomarkers can predict incident peripheral arterial disease (PAD) and mortality in a longitudinal cohort study. Men (n = 3618) and women (n = 1542) were included in the Malmö Preventive Project and underwent analysis of: C-terminal endothelin-1 (CT-proET-1), N-Terminal prosomatostatin (NT-proSST), midregional proatrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and copeptin. Participants were followed up for incident PAD and mortality until December 31, 2016. Median follow-up was 11.2 years (interquartile range 9.4-12.2). Cumulative incidence of PAD was 4.3% (221/5160), 4.5% in men (164/3618) and 3.7% in women (57/1542; P = .174). In an adjusted Cox proportional hazards regression model, higher CT-proET-1 (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.4-2.3), NT-proSST (HR 1.5; 95% CI 1.2-2.0), and MR-proANP (HR 1.7; 95% CI 1.3-2.3) were independently associated with incident PAD, and higher CT-proET-1 (HR 1.3; 95% CI 1.2-1.5), NT-proSST (HR 1.2; 95% CI 1.1-1.3), MR-proANP (HR 1.4; 95% CI 1.3-1.6), PCT (HR 1.1; 95% CI 1.0-1.2), and copeptin (HR 1.2; 95% CI 1.1-1.4) were independently associated with mortality. Increased levels of CT-proET-1, NT-proSST, and MR-proANP were independently associated with incident PAD, whereas all the vasoactive biomarkers were independently associated with mortality during follow-up.

scholarly journals Adipose Tissue Lipophilic Index and Risk of Ischemic Stroke—A Danish Case-Cohort Study

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1570 ◽  
Author(s):  
Linda Tram ◽  
Stine Krogh Venø ◽  
Christina Dahm ◽  
Birthe H. Thomsen ◽  
Martin Berg Johansen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Fatty Acid Profiles ◽  
Unknown Mechanism ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Hazard Ratios

Diet may influence the risk of ischemic stroke by several mechanisms. A potential and hitherto unknown mechanism may relate to an effect on the lipophilic index, which is a new and convenient indicator of membrane fluidity. This study investigated the association between the adipose tissue lipophilic index and ischemic stroke and its subtypes. A case-cohort study was conducted based on the Danish cohort study Diet, Cancer, and Health, which includes 57,053 subjects aged 50–64 years at enrolment. A subcohort (n = 3500) was randomly drawn from the whole cohort. All ischemic stroke cases were validated and categorized into subtypes. The lipophilic index was calculated based on fatty acid profiles in adipose tissue. Subjects were divided into quintiles and a weighted Cox proportional hazards regression model was used to calculate hazard ratios. After appropriate exclusions, a subcohort of 3194 subjects and 1752 cases of ischemic stroke were included. When comparing the fifth quintile of the lipophilic index with the first quintile, the hazard ratio for ischemic stroke was 0.92 (95% confidence interval 0.75, 1.13) and the trend across quintiles was not statistically significant (p = 0.1727). In conclusion, no association was found between the lipophilic index and ischemic stroke or its subtypes.

scholarly journals A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Natalie A. Finch ◽  
Evan J. Zasowski ◽  
Kyle P. Murray ◽  
Ryan P. Mynatt ◽  
Jing J. Zhao ◽  
...  
Keyword(s):  
Trough Concentration ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Time Curve ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Concentration Time ◽  
Trough Concentrations ◽  
The Impact ◽  
Quasi Experiment

ABSTRACT Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

scholarly journals Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

2021 ◽  
pp. 1-21
Author(s):  
Anne Mette L. Würtz ◽  
Mette D. Hansen ◽  
Anne Tjønneland ◽  
Eric B. Rimm ◽  
Erik B. Schmidt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Similar Pattern ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Heterogeneous Group ◽  
Dietary Guidelines ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

2021 ◽  
Author(s):  
Sanhe Liu ◽  
Yongzhi Li ◽  
Diansheng Cui ◽  
Yuexia Jiao ◽  
Liqun Duan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Stratification ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Muscle Invasive Bladder Cancer ◽  
Clinicopathologic Characteristics ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

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