scholarly journals Beta-Blocker Treatment in Ventilated COVID-19 patients – A Cox Regression with Time Dependent Covariate Analysis

2021 ◽  
Author(s):  
Dipesh Mistry ◽  
Anower Hossain ◽  
Jianxia Sun ◽  
Tonny Veenith ◽  
Ranjit Lall ◽  
...  
Keyword(s):  
Heart Rate ◽  
Critically Ill ◽  
Beta Blocker ◽  
Cox Regression ◽  
Prospective Trial ◽  
Time Dependent ◽  
Beta Blockade ◽  
Covariate Analysis ◽  
Risk Of Death ◽  
Immortal Time Bias

Abstract Background: Patients with co-morbidities are particularly vulnerable to severe COVID-19 disease. Critically ill patients with COVID-19 frequently experience severe tachycardias and avoidance of these is important in some co-morbidities, for instance cardiovascular disease. There is growing interest in beta blockade in critical illness as their use been associated with improved outcomes in a variety of conditions. We report the real-world use of heart rate management in patients during the first wave of the COVID-19 pandemic. As retrospective data are prone to an Immortal Time Bias, we created a Cohort Trial such as might be used for a future prospective trial and used Time Dependent Covariate Analysis for its analysis. Methods: Data for all PCR-proven COVID-19 patients ventilated in the Intensive Care Unit (ICU) were extracted from the hospital databases. To compensate for the risk of immortal time bias, we restricted analysis to 144 patients who achieved a heart rate (HR) of 90 beats per minute for more than 12 hours and were treated with norepinephrine. We recorded time from these ‘entry criteria’ to first beta blocker dose. Those patients who did not receive a beta blocker were given a nominal time to beta blocker beyond the censor day. Outcome was mortality censored at 28 days.Results: In the study group, 83/144 patients (57.6%) received a beta blocker. The median interval from entry criteria to beta blocker was 7.91 days (IQR 3.89, 13.15) and median duration of treatment was 7.00 days (IQR 4.00, 14.00). Twenty-four beta blocker patients (28.9%) died within 28 days compared with 29 (47.5%) who did not (adjusted OR 0.43; 95% CI 0.20-0.95, P=0.036). Cox Regression with time-dependent covariate analysis revealed there was an increased, but not significant, risk of death with beta blocker delay (Hazard Ratio 1.42 p=0.264). Mortality was also reduced for each day treated with beta blockade (adjusted Odds Ratio 0.76, 95% CI 0.64-0.91; P=0.002).Conclusions: In a retrospective analysis of critically ill ventilated patients with COVID-19 who developed a tachycardia >90 beats per minute and were treated with norepinephrine, beta blockade was associated with reduced mortality.

scholarly journals Lack of Survival Advantage among Re-Resected Elderly Glioblastoma Patients: A SEER-Medicare Study

2020 ◽  
Author(s):  
Debra A Goldman ◽  
Anne S Reiner ◽  
Eli L Diamond ◽  
Lisa M DeAngelis ◽  
Viviane Tabar ◽  
...  
Keyword(s):  
Older Adults ◽  
Survival Benefit ◽  
Cox Regression ◽  
Geographic Region ◽  
Survival Advantage ◽  
Time Dependent ◽  
Poverty Level ◽  
Risk Of Death ◽  
Immortal Time Bias ◽  
Initial Resection

Abstract Background The survival benefit of re-resection for glioblastoma (GBM) remains controversial, owing to the immortal time bias inadequately considered in many studies where re-resection was treated as a fixed, rather than time-dependent factor. Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we assessed treatment patterns for older adults and evaluated the association between re-resection and overall survival (OS), accounting for timing of re-resection. Methods This retrospective cohort study included elderly patients (age≥66) in the SEER-Medicare linked database diagnosed with GBM between 2006 and 2015 who underwent initial resection. Time-dependent Cox regression was used to assess the association between re-resection and OS, controlling for age, gender, race, poverty level, geographic region, marital status, comorbidities, receipt of radiation+temozolomide, and surgical complications. Results Our analysis included 3,604 patients with median age 74 (range: 66-96); 54% were men and 94% were white. After initial resection, 44% received radiation+temozolomide and these patients had a lower hazard of death (HR: 0.28, 95%CI: 0.26-0.31, p<0.001). In total, 9.5% (n=343) underwent re-resection. In multivariable analyses, no survival benefit was seen for patients who underwent re-resection (HR: 1.12, 95%CI: 0.99-1.27, p=0.07). Conclusions Re-resection rates were low among elderly GBM patients and no survival advantage was observed for patients who underwent re-resection. However, patients who received standard of care at initial diagnosis had a lower risk of death. Older adults benefit from receiving radiation+temozolomide after initial resection, and future studies should assess the relationship between re-resection and OS taking time of re-resection into account.

scholarly journals Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

2021 ◽  
Vol 14 ◽  
pp. 175628482110234
Author(s):  
Mario Romero-Cristóbal ◽  
Ana Clemente-Sánchez ◽  
Patricia Piñeiro ◽  
Jamil Cedeño ◽  
Laura Rayón ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Critically Ill ◽  
Cox Regression ◽  
Chronic Liver ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

scholarly journals Immortal Time Bias in Observational Studies of Time-to-Event Outcomes

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481878935 ◽  
Author(s):  
Parul Agarwal ◽  
Erin Moshier ◽  
Meng Ru ◽  
Nisha Ohri ◽  
Ronald Ennis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Effect ◽  
Cox Regression ◽  
Analytical Techniques ◽  
Time Dependent ◽  
Simulation Studies ◽  
Significant Treatment ◽  
Immortal Time Bias ◽  
Postmastectomy Radiation Therapy ◽  
Landmark Model

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.

scholarly journals Sepsis-associated Encephalopathy In ICU Admissions: Prevalence, Early Risk of Death, and its Early Prevent and Control

2020 ◽  
Author(s):  
Dao-Ming Tong ◽  
Shao-Dan Wang ◽  
Yuan-Wei Wang ◽  
Ying Wang ◽  
Yuan-Yuan Gu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Critically Ill ◽  
Cox Regression ◽  
Abdominal Cavity ◽  
Early Prevention ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Early Risk ◽  
Early Risk Factors ◽  
And Control

Abstract Background: Sepsis-associated encephalopathy (SAE) is a common encephalopathy in ICU. We are to definite whether SAE present an high prevalence rate and early risk factors for death in ICU 48 hours, while to cognize its important of early prevention/ control.Methods: We retrospectively enrolled patients with acute critically ill from ICU (January, 2015 to January, 2017). All patients were selected from onset to ICU ≤3 hours. The prevalence and some early risk factors of death in SAE was estimated by using a continuous head and thorax /abdominal cavity CT scans. Results: 748 critically ill adults were analyzed. The prevalence of sepsis within initial 48 hours was 40.4% (302/748). The median time from infection to sepsis was 9 hours ( range, 1-48 ). The SAE (93.4%, 282/302) was diagnosed in sepsis patients, and most of them (96.8%) presented multiple organ dysfunction syndromes (MODS). While the fatality of SAE was in 32.0% at initial 48 hours and 69.1% at initial 14 days. Cox regression analysis, unused antibiotic within initial 3 hours (OR, 0.39; 95% CI, 0.22-0.89), severe inflammatory storm (OR, 0.70; 95% CI, 0.58- 0.94), lower GCS (OR, 2.7; 95% CI, 1.5-3.6), and MODS (OR, 0.37; 95% CI, 0.26-0.96) were early risk factors for death in SAE. Early risk factors for predicting SAE were related to severe inflammatory storm (OR, 3.10; 95% CI, 2.28-4.33), MODS (OR, 3.57; 95% CI, 2.73- 4.67), and unused antibiotics within initial 3 hours (OR, 0.25; 95% CI, 0.11-0.56).Conclusions: SAE in ICU is an high prevalent acute brain dysfunction and most with MODS. The early bad prognosis in SAE was related to the failure of early prevention and control.

scholarly journals HOUT-10. TREATMENT OUTCOME IN ADOLESCENTS AND YOUNG ADULTS (AYAS) WITH GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi114-vi114
Author(s):  
Josiah An ◽  
Adithya Chennamadhavuni ◽  
Sarah Mott ◽  
Rohan Garje
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Private Insurance ◽  
Multivariable Analysis ◽  
Treatment Modalities ◽  
Study Objective ◽  
Risk Of Death ◽  
Immortal Time Bias ◽  
Survival Difference ◽  
Increased Risk

Abstract BACKGROUND Glioblastoma is one of the most aggressive and commonly encountered brain tumors. Standard of care includes surgical resection with adjuvant or concurrent chemoradiation which is predominantly based on adult clinical trials. Our study objective was to assess whether survival differed in AYA compared to older adults. METHODS The National Cancer Database was used to identify patients with at least surgically resected glioblastoma from 2004 to 2016. Cox regression models were utilized to estimate the effect of treatment on overall survival (OS) while accounting for immortal time bias (3-months) and clustering within facility. RESULTS Among 51,718 patients with glioblastoma identified, 2,930 patients were AYA. Multivariable analysis (MVA) shows OS was significantly higher in AYA, female, non-white, high income, unilateral cancer patients with private insurance receiving treatments in high volume facilities. OS among AYA patients was significantly lower in surgery + (radiation or chemotherapy: S+(RT or CT) group compared to surgery only (S) (HR=1.33, 95% CI 1.06–1.65), but no significant survival difference between surgery + chemoradiation (S+C+RT) groups and surgery only (HR=0.97, 95% CI 0.83–1.14). Median survival is ~28 months in AYA among S and S+C+RT groups whereas significantly lower survival (median OS ~18 months) is seen in S+RT or CT. Non-AYA patients were at 2 times increased risk of death compared to AYA patients who received the same type of treatment. CONCLUSIONS In conclusion, AYA population has more than twice the median OS in comparison to non-AYA patients. Worse overall survival was seen among S+RT or CT in comparison to S and S+RT+CT in AYA group. For patients needing either chemotherapy or radiation with surgery, possibly a trimodal approach might provide better survival advantage. Prospective studies are needed to further explore optimal treatment modalities in this unique population.

scholarly journals The Prognostic Correlation of Heart Rate Variability at Diagnosis with Survival of Patients with Hepatocellular Carcinoma

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 890
Author(s):  
Ana-Maria Ciurea ◽  
Dan Ionuț Gheonea ◽  
Michael Schenker ◽  
Alina Maria Mehedințeanu ◽  
Georgică Costinel Târtea ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Tumor Size ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Early Therapy ◽  
Reactive Protein ◽  
Risk Of Death ◽  
Noninvasive Biomarker

Background: Heart rate variability (HRV) indices have been shown to be associated with prognosis in various types of cancer. This study aims to assess the ability of these indices to predict survival in hepatocellular carcinoma (HCC) patients after diagnosis. Methods: We retrospectively collected data from 231 patients diagnosed with HCC between January 2014 and March 2018. The baseline clinical-pathological variables and HRV indices (extracted from Holter electrocardiogram recordings) were analyzed. Results: Univariate and multivariate analyses were performed to identify the predictive value of the above factors for overall survival (OS). The univariate analysis revealed that an age > 60 years, hepatitis C, portal vein involvement (thrombosis), a tumor size > 5 cm, alpha-fetoprotein (AFP) > 400 ng/mL, serum albumin, and C-reactive protein (CRP) were risk factors for poor OS. Multivariable Cox regression analyses identified that a tumor size > 5 cm and AFP > 400 ng/mL predict poorer outcomes in HCC patients. It should be mentioned that, in both the univariate analysis and in the multivariate analysis, between HRV indices, SDNN (standard deviation of all normal-to-normal (NN) intervals) < 110 ms was an independent risk factor for OS with an HR of 3.646 (95% CI 2.143 to 6.205). Conclusion: This study demonstrates that HRV indices identify HCC patients at high risk of death and suggests that such monitoring might guide the need for early therapy in these types of patients, as well as the fact that HRV can be a potential noninvasive biomarker for HCC prognosis.

scholarly journals Finding The Source Of Bacterial Sepsis And Its Impact On Sepsis Related Outcome, The Bundle That Fumble

2020 ◽  
Vol 41 (S1) ◽  
pp. s235-s235
Author(s):  
Rahul Garg ◽  
Tushar shaw ◽  
Vandana K.E ◽  
Chiranjay Mukhopadhyay
Keyword(s):  
Blood Culture ◽  
Critically Ill ◽  
Sofa Score ◽  
Cox Regression ◽  
Categorical Variables ◽  
Common Source ◽  
Anatomical Site ◽  
Care Hospital ◽  
Specific Patient ◽  
Risk Of Death

Background: Sepsis is currently one of the important global health issues due to its complexity from pathophysiologic, clinical, and therapeutic viewpoints. Most sepsis-related studies are from the West, where all the patients were grouped together failing to identify specific patient populations that may actually benefit from a particular intervention. We investigated the characteristics and impact of the source of infection on sepsis-related ICU outcomes among critically ill adult patients Methods: A prospective ICU based observational study was conducted over 15 months in a tertiary-care hospital in southern India. Our study included all critically ill patients (18 years old) who were admitted either with existing a new episode of sepsis with suspected or documented bacterial infections within 24 hours of ICU admission with SOFA score 2. Basic demographics, the clinical presentation with the anatomical site of infection and outcome were noted. Categorical variables were compared using the 2 test, and continuous variables were compared using 1-way analysis of variance (ANOVA). Cox regression was used to determine the effect of sepsis source on 28-day mortality. Results: Among the 4,548 patients screened during the study period, 400 were recruited, with a mean age of 55.716 years, among whom 276 (61%) were men. The mean SOFA score at admission was 9.92.7. Bacteremia was observed among 99 cases (24.8%), predominantly gram-negative sepsis (65 of 99, 65.6%). The source for blood culture positivity was determined in 48 of 99 cases (48.4%). Successful isolation of the bacteria was achieved from other anatomical sites in 115 patients (37.8%) where blood culture remained negative. The most common source of sepsis was lung (67 of 400, 16.7%) followed by skin and soft-tissue infection (56 of 400, 14%). Patients treated with steroids were more prone to develop a respiratory infection (P = .001), whereas renal impairment was correlated with urinary tract infection (P = .001). Patients with respiratory infections had a longer ICU stay (P < .001). The overall in-hospital mortality was 37.2%. Multivariable Cox regression showed patients with genitourinary infection (HR, 2.23; P = .04) and implantable devices (HR, 11.30; P = .17) were at higher risk of death. Conclusions: Site-specific infection was a significant predictor of mortality in our study. These factors should be taken into consideration and warrant further evaluation to understand their specific roles in adverse outcomes among a cohort of patients diagnosed with sepsis.Funding: NoneDisclosures: None

HAGE (DDX43) protein expression as an independent biomarker of poor clinical outcome of breast cancer (BC) and potential as a therapeutic target for ER-negative BC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
Stephen Chan ◽  
Tarek M. A. Abdel-Fatah ◽  
Stephanie McArdle ◽  
Paul Moseley ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Protein Expression ◽  
Cox Regression ◽  
Positive Impact ◽  
Prospective Trial ◽  
Fold Increase ◽  
Distant Metastases ◽  
Poor Clinical Outcome ◽  
Risk Of Death

1013 Background: Recently, we have confirmed that HAGE is involved in promoting proliferation as assessed by increased thymidine incorporation and our preliminary results using shRNA to permanently knockdown HAGE expression also suggests the involvement of HAGE in tumor motility and metastasis. In this study we aimed to analyze the expression of HAGE in large well-characterized BC cohorts to determine its relationship with other clinico-pathological parameters and to investigate its prognostic value. Methods: HAGE protein expression was assessed in: a) 40 normal breast tissue (NBT), b) 60 invasive BCs and their matching NBT, c) BC cell lines, d) A series of 1650 consecutive cases of primary BC who treated with adjuvant CMF and/or endocrine therapies. Further validation was performed in 2 independent series of high risk ER- BC: a) 300 ER –BC who did not received any CT and b) 396 ER- BC treated with adjuvant anthracycline (ATC) based CT. Results: The NBT showed negative HAGE expression (HAGE-) throughout. HAGE overexpression (HAGE+) was observed in 10% of BC and was significantly associated with aggressive clinico-pathological features including: ER-, high grade and triple negative phenotypes. Moreover, HAGE+ expression showed an adverse outcome with a 2-4 fold increase in the risk of death, recurrence and metastases (ps<0.00001) compared to HAGE-; ps<0.0001. Using a multivariate Cox regression model including ER status, grade, size and tumour stage, HAGE expression was confirmed as a powerful independent prognostic factor (p<0.0001). The poor clinical outcome of HAGE+ was further confirmed in high risk (NPI>3.4) ER- patients who did not received any CT (p<0.0001). While, adjuvant CT either CMF or ATC had a positive impact on HAGE+/high risk ER- BC as HAGE+ had a similar risk of death, recurrence and distant metastases to HAGE- expression. Conclusions: This is the first report which shows HAGE to be a potential predictor for poor prognosis in BC patients, and may be an attractive novel target for molecular and vaccine therapy for those patients. A prospective trial of adjuvant chemotherapy/vaccine to confirm this finding is warranted.

Patient related outcomes in cancer patients in Croatia.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS6650-TPS6650
Author(s):  
Dragan Trivanovic ◽  
Irena Hrstic ◽  
Anuska Budisavljevic ◽  
Boris Kopic ◽  
Bruno Nincevic
Keyword(s):  
Quality Of Life ◽  
Cancer Treatment ◽  
Cancer Care ◽  
Cox Regression ◽  
Prospective Trial ◽  
Cancer Type ◽  
Risk Of Death ◽  
Patient Reported ◽  
Clinic Visits

TPS6650 Background: Accurate evaluation of symptom intensities is essential for optimal cancer care and improving the quality of life of patients. An inappropriate interpretation of symptoms may lead to treatment outcomes failure, overdose of medication, or may leave the patients undertreated. However, the perception of symptoms can vary between the treating physician and patient. Physicians appear to underestimate the patient symptoms. And this variation in the perception of side effects can lead to wrong assumptions and subsequent treatment changes, affecting treatment effectiveness and quality of life. There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, leaving open the question of whether the benefits of systems to reveal self-reports outweigh their added cost. There are several tools for assessment of symptoms in oncology. In cancer treatment clinical trials, the standard source of adverse symptom data is clinician reporting by use of items from PRO-CTCAE, developed by NCI. To address these questions, we conducted a single-center prospective trial to test whether systematic tablet computer-based collection of patient-reported symptoms during chemotherapy treatment, with automated alerts to clinicians for severe adverse events (grade 3-4) will change in questionnaire score at 6 months compared with baseline. Secondary endpoints will include difference in unscheduled clinic visits frequency, and survival. Methods: Patients initiating chemotherapy at General Hospital Pula Oncology Clinic for advanced or metastatic gastrointestinal, lung, breast, genitourinary, or gynecologic cancers will be enrolled in a nonblinded, prospective trial of self-reporting of symptoms, compare with usual care. Patients receiving chemotherapy and their clinicians will be independently asked on the same day to complete 10 symptoms (including fatigue, pain, nausea, vomiting, diarrhea, dysgeusia, appetite, sleep disturbance, fever and hair loss). Participants will remain on study until discontinuation of cancer treatment, withdrawal, or death. All participants will provide written informed consent and followed for up to 28 months or until death. To compare how patient’s vs clinician’s reports relate to clinical events, a time-dependent Cox regression model adjusted for covariates including cancer type, age, sex, and education level will be used to measure associations between reaching particular grade severity thresholds with the risk of death and unscheduled clinic visits. Clinical trial information: 2019-000855-15.

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