scholarly journals 1574. Multivariate Regression Analysis to Determine Independent Predictors of Treatment Outcomes in the RESTORE-IMI 2 Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S785-S786
Author(s):  
Robert Tipping ◽  
Jiejun Du ◽  
Maria C Losada ◽  
Michelle L Brown ◽  
Katherine Young ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Clinical Response ◽  
Treatment Outcomes ◽  
Multivariate Regression ◽  
Multivariate Regression Analysis ◽  
Apache Ii Score ◽  
Double Blind ◽  
Mitt Population ◽  
Study Results ◽  
All Cause Mortality

Abstract Background In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was non-inferior to PIP/TAZ for treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in the primary endpoint of Day 28 all-cause mortality (D28 ACM) and the key secondary endpoint of clinical response (CR) at early follow-up (EFU; 7-14 d after end of therapy). We performed a multivariate regression analysis to determine independent predictors of treatment outcomes in this trial. Methods Randomized, controlled, double-blind, phase 3, non-inferiority trial comparing IMI/REL 500 mg/250 mg vs PIP/TAZ 4 g/500 mg, every 6 h for 7-14 d, in adult patients (pts) with HABP/VABP. Stepwise-selection logistic regression modeling was used to determine independent predictors of D28 ACM and favorable CR at EFU, in the MITT population (randomized pts with ≥1 dose of study drug, except pts with only gram-positive cocci at baseline). Baseline variables (n=19) were pre-selected as candidates for inclusion (Table 1), based on clinical relevance. Variables were added to the model if significant (p < 0.05) and removed if their significance was reduced (p > 0.1) by addition of other variables. Results Baseline variables that met criteria for significant independent predictors of D28 ACM and CR at EFU in the final selected regression model are in Fig 1 and Fig 2, respectively. As expected, APACHE II score, renal impairment, elderly age, and mechanical ventilation were significant predictors for both outcomes. Bacteremia and P. aeruginosa as a causative pathogen were predictors of unfavorable CR, but not of D28 ACM. Geographic region and the hospital service unit a patient was admitted to were found to be significant predictors, likely explained by their collinearity with other variables. Treatment allocation (IMI/REL vs PIP/TAZ) was not a significant predictor for ACM or CR; this was not unexpected, since the trial showed non-inferiority of the two HABP/VABP therapies. No interactions between the significant predictors and treatment arm were observed. Conclusion This analysis validated known predictors for mortality and clinical outcomes in pts with HABP/VABP and supports the main study results by showing no interactions between predictors and treatment arm. Table 1. Candidate baseline variables pre-selected for inclusion Figure 1. Independent predictors of greater Day 28 all-cause mortality (MITT population; N=531) Figure 2. Independent predictors of favorable clinical response at EFU (MITT population; N=531) Disclosures Robert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder)

scholarly journals A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study)

2020 ◽  
Author(s):  
Ivan Titov ◽  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Daniel Rodríguez Gonzalez ◽  
Aileen David-Wang ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Severe Renal Impairment ◽  
Apache Ii Score ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Gram Negative ◽  
Mitt Population ◽  
All Cause Mortality ◽  
Hospital Acquired

Abstract Background Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Methods This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7–14 days after completing therapy in the MITT population. Results Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, −5.3% [95% confidence interval {CI}, −11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, −3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. Conclusions Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. Clinical Trials Registration NCT02493764.

scholarly journals 1460. Imipenem/Cilastatin (IMI)/Relebactam (REL) in Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia (HABP/VABP): Subgroup Analyses of Critically Ill Patients in the RESTORE-IMI 2 Trial

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S732-S732
Author(s):  
Luke F Chen ◽  
Maria C Losada ◽  
Kathryn A Mahoney ◽  
Jiejun Du ◽  
Michelle L Brown ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Clinical Response ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Severe Renal Impairment ◽  
Study Drug ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Double Blind ◽  
Mitt Population

Abstract Background HABP/VABP are serious infections associated with high mortality. Critically ill patients (pts) are at particularly high risk of adverse clinical outcomes. In the RESTORE-IMI 2 trial, IMI/REL was non-inferior to PIP/TAZ in primary and key secondary endpoints. We evaluated outcomes specifically in critically ill pts, according to several definitions, from that trial. Methods Randomized, controlled, double-blind, phase 3 trial in adult pts with HABP/VABP. Lower respiratory tract (LRT) specimens were obtained ≤48 hours prior to screening. Pts were randomized 1:1 to IMI/REL 500 mg/250 mg or PIP/TAZ 4 g/500 mg, given IV every 6 h for 7-14 d. The primary endpoint was Day 28 all-cause mortality (ACM) and the key secondary endpoint was clinical response at early follow-up (EFU; 7-14 d after completing therapy) in the modified intent-to-treat (MITT) population (randomized pts with ≥1 dose of study drug, excluding pts with only gram-positive cocci present on baseline Gram stain). This analysis assessed efficacy outcomes specifically in pts in the ICU and in pts with APACHE II score ≥15, both prespecified subgroups. In post-hoc analyses, outcomes were also specifically assessed in the subgroups of pts with moderate/severe renal impairment (creatinine clearance < 60 mL/min) and pts who received vasopressors. Results Of MITT pts (n=531) at baseline, 66.1% (175 IMI/REL, 176 PIP/TAZ) were in the ICU, 47.5% (125 IMI/REL, 127 PIP/TAZ) had APACHE-II score ≥15, and 24.7% (71 IMI/REL, 60 PIP/TAZ) had moderate/severe renal impairment. Further, 20.9% (54 IMI/REL, 57 PIP/TAZ) received vasopressors within 72 h of first dose of study drug and/or during the study. In each subgroup, baseline demographics, clinical characteristics, and causative LRT pathogens (mostly Enterobacterales, P. aeruginosa, and A. calcoaceticus-baumannii complex) were generally comparable between treatment arms. In pts with APACHE-II score ≥15, Day 28 ACM and clinical response rates with IMI/REL were favorable compared to PIP/TAZ (Table). Day 28 ACM was also favorable with IMI/REL in patients receiving vasopressors. Remaining outcomes were similar between treatment arms. Conclusion IMI/REL is an efficacious treatment option for critically ill pts with HABP/VABP. Table. Primary and key secondary efficacy outcomes by subgroup (MITT population) Disclosures Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck & Co., Inc. (Employee, Shareholder) Kathryn A. Mahoney, PharmD, Merck (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Michelle L. Brown, BS, Merck & Co., Inc. (Employee, Shareholder) Robert Tipping, MS, Merck & Co., Inc. (Employee, Shareholder) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Joan R. Butterton, MD, Merck & Co., Inc. (Employee, Shareholder) Amanda Paschke, MD MSCE, Merck & Co., Inc. (Employee, Shareholder)

Survival of Patients with Hematological Malignancy Admitted to the Intensive Care Unit (ICU): Prognostic Factors and Outcome Compared to Unselected Medical ICU Admissions.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3319-3319
Author(s):  
Quentin A. Hill ◽  
Anita Hill ◽  
Richard Kelly ◽  
Chetan Patalappa ◽  
Annika M. Whittle ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Hospital Mortality ◽  
Multivariate Regression ◽  
Hematological Malignancy ◽  
Multivariate Regression Analysis ◽  
Apache Ii Score ◽  
First Line ◽  
Icu Admission ◽  
Hospital Survival ◽  
Poor Outcome

Abstract Cancer patients have historically had a very poor outcome following ICU admission. Outcome has however improved over the last decade. We aim to identify factors that predict survival for critically ill patients with hematological malignancy and which can be readily identified prior to admission. This would improve selection of patients suitable for ICU admission, which represents a limited resource. We also assessed the ability of the APACHE II score to predict prognosis in these patients. Since the ICU admission case mix will vary between hospitals, one non-surgical admission within +/− 1 week of each hematological admission acted as a control group. Factors which might affect outcome were assessed by multivariate regression analysis. Factors included were age, hematological diagnosis (acute or chronic leukemia, myeloma, lymphoma), time from hematological diagnosis to ICU admission (0–6 months, 6–12 months, >12 months), degree of prior treatment (admission prior to diagnosis, during first line therapy, after first line), remission status, prior stem cell transplant, documented infection and length of neutropenia (none, 1–10 days, >10 days). For hematology patients, predicted hospital mortality was calculated from the APACHE II score by the formula of Knaus et al (Critical Care Medicine 1985). The APACHE scores of hematology patients were compared to controls by a two-sample t test. Predicted and actual mortalities were compared using a one sample test of proportion. The impact of mechanical ventilation (MV) on mortality was assessed by risk ratios. We identified 111 patients with hematological malignancy (acute leukemia n=42, chronic leukemia n=11, myeloma n=19 and lymphoma n=39) admitted to ICU in one teaching and three district general hospitals (November 2000 - January 2006). Median age of hematological patients was 59 years (range 17–84) and M: F ratio 1.22:1. Control patients (n=111) were similar with median age 63 years (range 17–86) and M: F ratio 1.09:1. For control patients, overall ICU and hospital survival rates were 70% and 55% respectively while survival for hematology patients was approximately half at 44% and 24% respectively. In multivariate regression analysis, only increasing age predicted poor outcome (p=0.016). There was a trend to poor outcome if patients were not in complete remission (p=0.066) or had documented infection (p=0.06). All other variables were not significant. APACHE scores were significantly higher in hematology patients (median 27) compared to controls (median 19) p<0.001. Predicted hospital mortality for hematology patients was 56%, significantly lower than actual mortality (77%) p<0.001. For controls, hospital survival was slightly reduced for MV v’s not receiving MV (risk ratio = 1.37; 95% C.I. = 0.91, 2.05). Hematology patients hospital survival was significantly worse for MV - 5/55, 9% v’s no MV 20/44, 45% (risk ratio = 5.00; 95% CI = 2.04, 12.50). The pre-admission variables assessed did not predict mortality and should not be used for this. Despite high APACHE scores, predicted hospital mortality underestimated mortality for patients with hematological malignancy. Need for MV still predicts poor outcome in this group but without MV nearly half survive to hospital discharge.

scholarly journals Acute kidney injury in severely injured patients admitted to the intensive care unit

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Alberto F. García ◽  
Ramiro Manzano-Nunez ◽  
Juan G. Bayona ◽  
Maria P. Naranjo ◽  
Dary Neicce Villa ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Acute Kidney Injury ◽  
Regression Analysis ◽  
Multivariate Regression ◽  
Kidney Injury ◽  
Multivariate Regression Analysis ◽  
Apache Ii Score ◽  
Severely Injured ◽  
Severely Injured Patients ◽  
Injured Patients

Abstract Background Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury (AKI) in severely injured patients admitted to the intensive care unit (ICU) for whom creatine kinase (CK) levels were available. Methods For this retrospective observational study, we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili (FVL) University Hospital. Our primary outcome was the incidence of AKI. Multivariate regression analysis was used to assess risk factors for this outcome. Results A total of 315 patients were included. The trauma mechanisms were blunt (n = 130), penetrating (n = 66) and blast (n = 44) trauma. The median (interquartile range, IQR) of injury severity score (ISS) was 21 (16–29). AKI developed in 75 patients (23.8%). Multivariate regression analysis revealed that the thoracic abbreviated injury scale (AIS) value (median (IQR) in the AKI group: 3 (0–4)), Acute Physiology and Chronic Health Evaluation (APACHE II) score (median (IQR) in the AKI group: 18 (10–27)), CK greater than 5000 U/L, lactic acid concentration at admission, and dobutamine administration were independently associated with AKI. Conclusion We found that age, APACHE II score, thoracic trauma, lactic acidosis, and dobutamine administration were independently associated with AKI. Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.

Epicardial fat thickness as arterial hypertension predictor in normotensive patients with abdominal obesity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Kuznetsova ◽  
M Druzhilov
Keyword(s):  
Blood Pressure ◽  
Regression Analysis ◽  
Blood Glucose ◽  
Waist Circumference ◽  
Arterial Hypertension ◽  
Multivariate Regression ◽  
Fasting Blood Glucose ◽  
Multivariate Regression Analysis ◽  
Epicardial Fat Thickness ◽  
Fat Thickness

Abstract Objective Arterial hypertension (HTN) is one of the most common diseases associated with obesity. Visceral obesity (VO) with dysfunctional visceral adipose tissue plays the main role in obesity induced HTN. Direct criteria of VO including echocardiographic epicardial fat thickness (EFT) may become an additional predictor of HTN. Purpose The aim was to assess the role of echocardiographic EFT (EEFT) as a predictor of HTN in normotensive patients with abdominal obesity (AO). Methods 526 normotensive men (according to ambulatory blood pressure monitoring (ABPM) without therapy) with AO (waist circumference (WC) &gt;94 cm) and SCORE &lt;5%, without cardiovascular diseases and diabetes mellitus were examined (age 45.1±5.0 years). The lipid and glucose profiles, creatinine, uric acid and C-reactive protein blood levels, albuminuria evaluation, echocardiography, carotid ultrasound, bifunctional ABPM were performed. The values of EEFT ≥75 percentile for persons 35–45 years and 46–55 years were 4.8 mm and 5.8 mm respectively. These values used as epicardial VO criteria. Patients with subclinical carotid atherosclerosis due to the lipid-lowering therapy administration (n=98) were excluded from the follow-up. Re-examination with ABPM was conducted on average through 46.3±5.1 months. Data were summarized as mean ± standard error, statistical analysis conducted with paired two-tailed t-tests, Pearson χ2 criterion and multivariate regression analysis. Results Data of 406 persons were available for analysis. HTN as average daily blood pressure ≥130/80 mm Hg was detected in 157 (38.7%) patients. These patients were characterized by initially higher values of age (45.9±4.6 years vs 44.3±4.9 years, p&lt;0.001), waist circumference (106.9±7.3 cm vs 104.2±7.3 cm, p&lt;0.001), body mass index (BMI) (32.0±3.3 kg/m2 vs 30.9±3.2 kg/m2, p&lt;0.001), average daily systolic and diastolic blood pressure (120.7/74.5±4.6/3.4 mm Hg vs 118.2/73.2±5.5/3.9 mm Hg, p&lt;0.001), EEFT (5.2±0.7 mm vs 4.4±1.0 mm, p&lt;0.001). The epicardial VO was initially detected in 95 (23.3%) patients. In patients with HTN the initial prevalence of epicardial VO was greater (58.0% vs 23.3%, p&lt;0.001). As predictors for the multivariate regression analysis the clinical and laboratory examinations data and EEFT were evaluated. According to the results a mathematical model for estimating the probability HTN was obtained: 0.696*fasting blood glucose + 0.198*systolic BP + 2.844*EFT – 40.166 (constant). Among these predictors EEFT was characterized by the highest standardized regression coefficient (0.302, p&lt;0.001) (0.295, p&lt;0.01 for fasting blood glucose, 0.035, p&lt;0.001 for systolic BP). The Hosmer-Lemeshow test value was 0.863, the total percentage of correct classifications was 86%, the area under the ROC-curve was 0.913. Conclusions EEFT (4.8 mm for persons 35–45 years and 5.8 mm for persons 46–55 years) may be an additional predictor of HTN in normotensive patients with AO. Funding Acknowledgement Type of funding source: None

Arterial stiffness could reflect increased cardiac load and reduced pulmonary function in the general population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Murai ◽  
T Sugiura ◽  
Y Dohi ◽  
H Takase ◽  
T Mizoguchi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
General Population ◽  
Arterial Stiffness ◽  
Pulmonary Function ◽  
Multivariate Regression ◽  
Troponin I ◽  
Augmentation Index ◽  
Smoking Status ◽  
Multivariate Regression Analysis ◽  
The Other

Abstract Background Pulmonary function is known to decrease with age and reduced pulmonary function has been reported to be associated with all-cause mortality and cardiovascular death. The association between pulmonary impairment and atherosclerosis was reported previously but has not been investigated sufficiently in the general population. Purpose We hypothesized that arterial stiffness could reflect increase of cardiac load and reduced pulmonary function. The present study aimed to investigate whether increased cardiac load and reduced pulmonary function could affect arterial stiffness in the general population. Methods Subjects undergoing their health check-up were enrolled. Plasma B-type natriuretic peptide (BNP) levels and serum high-sensitivity cardiac troponin I (hs-cTnI) levels were measured to evaluate cardiac load and myocardial damage. Radial augmentation index (rAI) was measured to investigate arterial stiffness using HEM-9000AI device. Subjects with an ST-T segment abnormality on the electrocardiogram, renal insufficiency, cancer, active inflammatory disease, or a history of cardiovascular events and pulmonary disease were excluded. Pulmonary function was assessed using spirometry by calculating forced vital capacity (FVC) as a percentage of predicted value (FVC%-predicted), forced expiratory volume in 1 second (FEV1) as a percentage of predicted value (FEV1%-predicted), and the ratio of FEV1 to FVC (FEV1/FVC). Results A total of 1100 subjects aged 57 years were enrolled and their median values of BNP and hs-cTnI were 15.5 and 2.3 pg/ml. The levels of rAI were significantly associated with the levels of BNP after adjustment for possible confounders in multivariate regression analysis, but were not with the levels of hs-TnI. While the parameters of pulmonary function were inversely associated with the levels of rAI and hs-cTnI after adjustment for possible confounders in the multivariate regression analysis, but not with the levels of BNP. The other multivariate regression analyses where BNP, hs-cTnI, parameters of pulmonary function, and the other possible factors were simultaneously included as independent variables revealed that the BNP levels and the FVC%-predicted or FEV1%-predicted, besides age, gender, smoking status, body mass index, blood pressure, heart rate, creatinine, fasting plasma glucose, and triglyceride, were significantly associated with the levels of rAI. Conclusions The significant associations of rAI with BNP and pulmonary function were revealed in the general population. These findings support that arterial stiffness could reflect increased cardiac load and reduced pulmonary function, in apparently healthy individuals. Funding Acknowledgement Type of funding source: None

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