scholarly journals Out of Sight—Out of Mind: Impact of Cascade Reporting on Antimicrobial Usage

2020 ◽  
Vol 7 (2) ◽  
Author(s):  
Siyun Liao ◽  
Judith Rhodes ◽  
Roman Jandarov ◽  
Zachary DeVore ◽  
Madhuri M Sopirala
Keyword(s):  
Relative Risk ◽  
Positive Culture ◽  
Baseline Period ◽  
Adjusted Relative Risk ◽  
Test Results ◽  
Antibiotic Susceptibilities ◽  
Days Of Therapy ◽  
All Cause Mortality ◽  
Study Population ◽  
The Impact

Abstract Background There is a paucity of data evaluating the strategy of suppressing broader-spectrum antibiotic susceptibilities on utilization. Cascade reporting (CR) is a strategy of reporting antimicrobial susceptibility test results in which secondary (eg, broader-spectrum, costlier) agents may only be reported if an organism is resistant to primary agents within a particular drug class. Our objective was to evaluate the impact of ceftriaxone-based cascade reporting on utilization of cefepime and clinical outcomes in patients with ceftriaxone-susceptible Escherichia and Klebsiella clinical cultures. Methods We compared post-CR (July 2014–June 2015) with baseline (July 2013–June 2014), evaluating utilization of cefepime, cefazolin, ceftriaxone, ampicillin derivatives, fluoroquinolones, piperacillin/tazobactam, ertapenem, and meropenem; new Clostridium difficile infection; and length of stay (LOS) after the positive culture, 30-day readmission, and in-hospital all-cause mortality. Results Mean days of therapy (DOT) among patients who received any antibiotic for cefepime decreased from 1.229 days during the baseline period to 0.813 days post-CR (adjusted relative risk, 0.668; P < .0001). Mean DOT of ceftriaxone increased from 0.864 days to 0.962 days, with an adjusted relative risk of 1.113 (P = .004). No significant differences were detected in other antibiotics including ertapenem and meropenem, demonstrating the direct association of the decrease in cefepime utilization with CR based on ceftriaxone susceptibility. Average LOS in the study population decreased from 14.139 days to 10.882 days from baseline to post-CR and was found to be statistically significant (P < .0001). Conclusions In conclusion, we demonstrated significant association of decreased cefepime utilization with the implementation of a CR based on ceftriaxone susceptibility. We demonstrated the safety of deescalation, with LOS being significantly lower during the post-CR period than in the baseline period, with no change in in-hospital mortality.

scholarly journals Allopurinol initiation and all-cause mortality in the general population

2014 ◽  
Vol 74 (7) ◽  
pp. 1368-1372 ◽  
Author(s):  
Maureen Dubreuil ◽  
Yanyan Zhu ◽  
Yuqing Zhang ◽  
John D Seeger ◽  
Na Lu ◽  
...  
Keyword(s):  
General Population ◽  
Propensity Score ◽  
Adverse Effects ◽  
Serum Urate ◽  
Population Database ◽  
General Population Study ◽  
Risk Of Death ◽  
All Cause Mortality ◽  
Study Population ◽  
The Impact

BackgroundAllopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population.MethodsWe conducted an incident user cohort study with propensity score matching using a UK general population database. The study population included individuals aged ≥40 years who had a record of hyperuricaemia (serum urate level >357 μmol/L for women and >416 μmol/L for men) between January 2000 and May 2010. To closely account for potential confounders of allopurinol use and risk of death, we constructed propensity score matched cohorts of allopurinol initiators and comparators (non-initiators) within 6-month cohort accrual blocks.ResultsOf 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92).ConclusionsIn this general population study, allopurinol initiation was associated with a modestly reduced risk of death in patients with hyperuricaemia and patients with gout. The overall benefit of allopurinol on survival may outweigh the impact of rare serious adverse effects.

scholarly journals Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241264
Author(s):  
David A. Kolin ◽  
Scott Kulm ◽  
Paul J. Christos ◽  
Olivier Elemento
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Relative Risk ◽  
Type A ◽  
Blood Type ◽  
Adjusted Relative Risk ◽  
Test Results ◽  
Uk Biobank ◽  
Blood Types ◽  
Increased Risk

Background Coronavirus disease 2019 (Covid-19) has rapidly infected millions of people worldwide. Recent studies suggest that racial minorities and patients with comorbidities are at higher risk of Covid-19. In this study, we analyzed the effects of clinical, regional, and genetic factors on Covid-19 positive status. Methods The UK Biobank is a longitudinal cohort study that recruited participants from 2006 to 2010 from throughout the United Kingdom. Covid-19 test results were provided to UK Biobank starting on March 16, 2020. The main outcome measure in this study was Covid-19 positive status, determined by the presence of any positive test for a single individual. Clinical risk factors were derived from UK Biobank at baseline, and regional risk factors were imputed using census features local to each participant’s home zone. We used robust adjusted Poisson regression with clustering by testing laboratory to estimate relative risk. Blood types were derived using genetic variants rs8176719 and rs8176746, and genomewide tests of association were conducted using logistic-Firth hybrid regression. Results This prospective cohort study included 397,064 UK Biobank participants, of whom 968 tested positive for Covid-19. The unadjusted relative risk of Covid-19 for Black participants was 3.66 (95% CI 2.83–4.74), compared to White participants. Adjusting for Townsend deprivation index alone reduced the relative risk to 2.44 (95% CI 1.86–3.20). Comorbidities that significantly increased Covid-19 risk included chronic obstructive pulmonary disease (adjusted relative risk [ARR] 1.64, 95% CI 1.18–2.27), ischemic heart disease (ARR 1.48, 95% CI 1.16–1.89), and depression (ARR 1.32, 95% CI 1.03–1.70). There was some evidence that angiotensin converting enzyme inhibitors (ARR 1.48, 95% CI 1.13–1.93) were associated with increased risk of Covid-19. Each standard deviation increase in the number of total individuals living in a participant’s locality was associated with increased risk of Covid-19 (ARR 1.14, 95% CI 1.08–1.20). Analyses of genetically inferred blood types confirmed that participants with type A blood had increased odds of Covid-19 compared to participants with type O blood (odds ratio [OR] 1.16, 95% CI 1.01–1.33). A meta-analysis of genomewide association studies across ancestry groups did not reveal any significant loci. Study limitations include confounding by indication, bias due to limited information on early Covid-19 test results, and inability to accurately gauge disease severity. Conclusions When assessing the association of Black race with Covid-19, adjusting for deprivation reduced the relative risk of Covid-19 by 33%. In the context of sociological research, these findings suggest that discrimination in the labor market may play a role in the high relative risk of Covid-19 for Black individuals. In this study, we also confirmed the association of blood type A with Covid-19, among other clinical and regional factors.

scholarly journals 1027. Vancomycin Use in Community-Acquired Pneumonia: Assessing Inappropriate Therapy

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S361-S362
Author(s):  
Timothy Shan ◽  
Sara J Gore ◽  
Caitlin M McCracken ◽  
Gregory B Tallman ◽  
Haley K Holmer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Positive Culture ◽  
Empiric Therapy ◽  
Community Acquired Pneumonia ◽  
University Hospital ◽  
Inappropriate Therapy ◽  
Definitive Therapy ◽  
Days Of Therapy ◽  
Risk Patients ◽  
The Impact

Abstract Background Current Infectious Disease Society of America guidelines recommend anti-methicillin-resistant Staphylococcus aureus(MRSA) agents for treatment of community-acquired pneumonia (CAP) only in specific high-risk patients. There are limited data on duration of vancomycin use that is appropriate in hospitalized patients with CAP. The objective of this study was to evaluate the use of vancomycin for CAP among inpatients. Methods We conducted a retrospective cohort study of inpatients at Oregon Health and Science University Hospital from August 1st, 2017 to July 31st, 2018 who received IV vancomycin and had a pneumonia encounter ICD-9 diagnosis code. Patients with hospital or ventilator-associated pneumonia were excluded. Appropriate therapy was defined as empiric therapy with known risk-factors, concordant therapy with no de-escalation option, or concurrent sepsis or febrile neutropenia. Vancomycin appropriateness was assessed based on medical history and microbiology for both empiric and definitive therapy. We characterized patients receiving inappropriate therapy and calculated the proportion of inappropriate days of therapy (DOT). Results We identified 52 patients with CAP who were treated with vancomycin for a median of 2 DOT (Interquartile Range (IQR): 1–3). Approximately 21% (11/52) of patients had risk factors warranting vancomycin empiric therapy and 42% (22/52) had concurrent sepsis. Nine CAP patients received inappropriate courses of vancomycin, median of 1 day (IQR: 1–2.25) of inappropriate therapy. The most common reason for classifying use as inappropriate was a positive culture for organisms other than MRSA. Patients receiving inappropriate therapy were more frequently transferred from another hospital (44% vs. 30%, P = 0.22). Overall, 16% (20/125) of vancomycin DOT were inappropriate. Conclusion In our study,CAP patients accounted for a small number of pneumonia patients who received vancomycin. The median inappropriate DOT was relatively short, possibly indicating that identification and de-escalation was performed quickly. Further work is required to determine the impact of these findings on patients. Disclosures All authors: No reported disclosures.

scholarly journals Defining the Scope of Antimicrobial Stewardship Interventions on the Prescription Quality of Antibiotics for Surgical Intra-Abdominal Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 73
Author(s):  
Güzin Surat ◽  
Ulrich Vogel ◽  
Armin Wiegering ◽  
Christoph-Thomas Germer ◽  
Johan Friso Lock
Keyword(s):  
Antimicrobial Stewardship ◽  
Antibiotic Use ◽  
Baseline Period ◽  
Tertiary Hospital ◽  
Significant Decline ◽  
Wound Complications ◽  
Postoperative Therapy ◽  
Days Of Therapy ◽  
Abdominal Infections ◽  
The Impact

Background: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. Methods: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. Results: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8% to 45.2% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4% to 8.1 %, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8% to 6.5%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. Conclusions: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.

Abstract 12729: Impact of Chilli-pepper Intake on All-cause and Cardiovascular Mortality - A Systematic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Manpreet Kaur ◽  
Beni R Verma ◽  
Leon Zhou ◽  
Simrat Kaur ◽  
Yasser Sammour ◽  
...  
Keyword(s):  
Relative Risk ◽  
Cardiovascular Mortality ◽  
Animal Studies ◽  
Case Reports ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Inclusion Criteria ◽  
Chilli Pepper ◽  
All Cause Mortality ◽  
The Impact

Background: Chilli-pepper (CP) is well known for its anti-inflammatory, antioxidant, anticancer, and blood glucose regulation effects. However, the impact of CP on all-cause and cardiovascular mortality is not clear. Methods: A comprehensive search was performed using Ovid, Cochrane, Medline, Embase, and Scopus. We screened the studies from inception till January 16, 2020, and reported the outcomes of our interest after consumption of CP (Figure1a). The inclusion criteria were: all observational and randomized controlled trials reporting the outcomes of interest, and pediatric, animal studies, letters/case reports, reviews, abstracts, and book chapters were excluded. All-cause mortality was studied as the primary endpoint. Cardiovascular, cerebrovascular, and cancer-related deaths were studied as secondary outcomes. Results: From 4729 studies screened, four studies including 570,762 subjects met the inclusion criteria. Random-effects pooled analysis showed that there was a 25% reduction in the relative risk of all-cause mortality for regular CP consumers, compared to non-consumers (relative risk (RR): 0.75; 95% confidence intervals (CI): 0.64-0.88, p = 0.0004, Figure1b). Furthermore, there were a 26% and 23% reduction in the RR of death due to cardiovascular causes (RR: 0.74; 95% CI: 0.62-0.88, p=0.0006, Figure1c) and cancer (RR: 0.77; 95% CI: 0.71-0.84, p=0.0001, Figure 1d), respectively. However, there were no statistically significant differences in cerebrovascular accidents (RR: 0.76; 95% CI: 0.36-1.60, p=0.47). Conclusion: In a contemporary meta-analysis of 570,762 subjects, regular CP consumption was associated with a significant reduction in all-cause, cardiovascular, and cancer-related mortalities. Future studies are needed to better understand the potential mechanisms of the mortality benefits of CP consumption.

Development of a Guideline for the Management of Ventilator-Associated Pneumonia Based on Local Microbiologic Findings and Impact of the Guideline on Antimicrobial Use Practices

2008 ◽  
Vol 29 (6) ◽  
pp. 525-533 ◽  
Author(s):  
Timothy H. Dellit ◽  
Jeannie D. Chan ◽  
Shawn J. Skerrett ◽  
Avery B. Nathens
Keyword(s):  
Mortality Rate ◽  
Antimicrobial Therapy ◽  
Late Onset ◽  
Baseline Period ◽  
Antimicrobial Use ◽  
Ventilator Associated Pneumonia ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
Before And After ◽  
The Impact

Objective.To describe the development of a guideline for the management of ventilator-associated pneumonia (VAP) based on local microbiologic findings and to evaluate the impact of the guideline on antimicrobial use practices.Design.Retrospective comparison of antimicrobial use practices before and after implementation of the guideline.Setting.Intensive care units at Harborview Medical Center, Seattle, Washington, a university-affiliated urban teaching hospital.Patients.A total of 819 patients who received mechanical ventilation and who underwent quantitative bronchoscopy between July 1, 2003, and June 30, 2005, for suspected VAP.Interventions.Implementation of an evidence-based VAP guideline that focused on the use of quantitative bronchoscopy for diagnosis, administration of empirical antimicrobial therapy based on local microbiologic findings and resistance patterns, tailoring definitive antimicrobial therapy on the basis of culture results, and appropriate duration of therapy.Results.During the baseline period, 168 (46.7%) of 360 patients had quantitative cultures that met the diagnostic criteria for VAP, compared with 216 (47.1%) of 459 patients in the period after the guideline was implemented. The pathogens responsible for VAP remained similar between the 2 periods, except that the prevalence of VAP due to carbapenem-resistant Acinetobacter species increased from 1.8% to 15.3% (P < .001), particularly in late-onset VAP. Compared with the baseline period, there was an improvement in antimicrobial use practices after implementation of the guideline: antimicrobial therapy was more frequently tailored on the basis of quantitative culture results (103 [61.3%] of 168 vs 150 [69.4%] of 216 patients; P = .034), there was an increase in the use of appropriate definitive therapy (135 [80.4%] of 168 vs 193 [89.4%] of 216 patients; P = .001), and there wasadecrease in the mean duration oftherapy (12.0vs 10.7days; P = .0014). The all-cause mortality rate was similar in the periods before and after the guideline was implemented (38 [22.6%] of 168 vs 46 [21.3%] of 216 patients; P = .756).Conclusions.Implementation of a guideline for the management of VAP that incorporated the use of quantitative bronchoscopy, the use of empirical therapy based on local microbiologic findings, tailoring of therapy on the basis of culture results, and use of shortened durations of therapy led to significant improvements in antimicrobial use practices without adversely affecting the all-cause mortality rate.

scholarly journals 1986. Impact of Two-Step Testing on the Diagnosis and Management of Clostridium difficile in a Multi-Hospital Healthcare System

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S665-S666
Author(s):  
Angelina Davis ◽  
Todd Parker ◽  
Julia Coluccio ◽  
Kimberly Mann ◽  
Elizabeth Dodds Ashley ◽  
...  
Keyword(s):  
Health System ◽  
Community Health ◽  
Negative Binomial ◽  
Cohort Analysis ◽  
Antibiotic Use ◽  
Baseline Period ◽  
Post Intervention ◽  
Care Community ◽  
Days Of Therapy ◽  
The Impact

Abstract Background Distinguishing active C. difficile infection (CDI) from asymptomatic colonization remains a significant challenge. A multi-step testing algorithm can improve the diagnostic accuracy of CDI and associated antibacterial prescribing. This study evaluated the impact of two-step testing on CDI rates and management in a multi-hospital community health system. Methods Two-step C. difficile testing (PCR for initial screening followed by EIA for toxin detection) was implemented in 6 acute care community hospitals in April 2018. EIA testing was automatically performed on all stool samples with a positive C. difficile PCR result. Prior to implementation, PCR alone was used to identify CDI. Messaging attached to the PCR laboratory report alerted prescribers of discrepant results (PCR +/EIA -). Anti-C. difficile therapy was at the discretion of the prescriber. We performed a retrospective cohort analysis over a 2-year period to evaluate the effect of two-step testing on system-wide hospital-onset CDI (HO-CDI) per 10,000 patient-days (PD) and anti-CDI antimicrobial use (AU) in days of therapy (DOT) per 1,000 PD. Segmented negative binomial regression with hospital clustering was used to estimate predicted HO-CDI rate for the baseline period between April 1, 2017 through March 31, 2018 and the post-intervention between May 1, 2018 through March 31, 2019. The implementation date at all sites in April 2018 was unknown; therefore, this month was removed from the analysis. Anti-CDI agents included fidaxomicin, metronidazole, and oral vancomycin, but may have included non-CDI indications for metronidazole. Results A total of 115 HO-CDI cases were identified; 91 (79%) before and 24 (21%) after. Prior to implementation of two-step testing, CDI rates declined at 4% per month (P = NS). The rate immediately dropped by 36% (P = 0.004) after two-step testing was implemented, but the trend did not significantly change (P = 0.52, Figure 1). Community-onset CDI rates also decreased during this time period. Combined facility-wide anti-CDI agent use was 824.87 before and 838.21 DOT/1,000 PD after and did not significantly change. Conclusion Use of a two-step approach for CDI testing reduced HO-CDI rates, but did not have a significant impact on anti-CDI antibiotic use in a multi-hospital community health system. Disclosures All authors: No reported disclosures.

P2752Impact of different antithrombotic regimens on the outcomes of bioprosthetic valve replacement in elderly asian population

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Lu ◽  
R Chou ◽  
Y Tsai ◽  
P Huang
Keyword(s):  
Relative Risk ◽  
Valve Replacement ◽  
Asian Population ◽  
Hazard Ratio ◽  
Bioprosthetic Valve ◽  
Combination Group ◽  
P Value ◽  
Adjusted Relative Risk ◽  
All Cause Mortality ◽  
Bioprosthetic Valve Replacement

Abstract Background Lifelong antithrombotic therapy is necessary for patients undergoing mechanical valve replacement. However, the optimal regimen and duration of antithrombotic agents are still controversial for patients underwent bioprosthetic valve replacement. Purpose We investigated the effect of different antithrombotic strategies on the prognosis of patients underwent bioprosthetic valve replacement in the elder Asian population. Methods Based on the National Health Insurance Database in Taiwan, 1227 patients elderly than 50 years-old and underwent bioprosthetic valve replacement between 2003 to 2010 were enrolled for analysis. Patients were classified according to their antithrombotic therapies within 3 months after bioprosthetic valve replacements. Results The 1227 patients were stratified to three groups, including aspirin alone (19.6%), warfarin alone (60.6%), and the combined use of aspirin and warfarin (19.9%) within 3 months after surgery. After adjusting propensity scores, the warfarin group (relative risk: 0.69, 95% CI: 0.54–0.88) and the combination group (relative risk: 0.57, 95% CI: 0.42–0.79) both had lower mortality rate compared to the aspirin alone group. Neither increasing major bleeding risk (adjusted relative risk: 0.62, 95% CI: 0.15–2.68) nor decreasing ischemic stroke risk (adjusted relative risk: 0.64, 95% CI: 0.36–1.14) was noticed in the combination group. Incidence and risk of antithrombotics Crude Model 1 Model 2 Hazard Ratio (95% CI) p-value Hazard Ratio (95% CI) p-value Hazard Ratio (95% CI) p-value All cause mortality   Antiplatelet user Reference Reference Reference   Warfarin user 0.65 (0.52–0.81) <0.001 0.71 (0.56–0.91) 0.006 0.69 (0.54–0.88) 0.002   Antiplatelet + warfarin user 0.59 (0.44–0.81) 0.001 0.63 (0.46–0.85) 0.003 0.57 (0.42–0.79) 0.001   Ischemic stroke antiplatelet user as reference   Warfarin user 0.77 (0.51–1.17) 0.224 0.85 (0.55–1.33) 0.485 0.82 (0.52–1.27) 0.369   Antiplatelet + warfarin user 0.63 (0.36–1.10) 0.102 0.67 (0.38–1.21) 0.185 0.64 (0.36–1.14) 0.130   Major bleeding antiplatelet user as reference   Warfarin user 0.32 (0.10–1.05) 0.061 0.71 (0.14–3.60) 0.674 0.40 (0.11–1.40) 0.150   Antiplatelet + warfarin user 0.57 (0.14–2.39) 0.444 1.56 (0.26–9.46) 0.627 0.62 (0.15–2.68) 0.526 Model 1: Adjusted for all covariates; Model 2: Adjusted for propensity score of using warfarin. Conclusion Comparing with aspirin alone, warfarin only or combined warfarin with aspirin therapy have a lowering one-year all-cause mortality rate without increasing the occurrence of bleeding events.

scholarly journals An Individual Participant Data Meta-Analysis of 13 Randomized Trials to Evaluate the Impact of Prophylactic Use of Heparin in Oncological Patients

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 626-626
Author(s):  
Holger Schünemann ◽  
Matthew Ventresca ◽  
Mark Crowther ◽  
Marcello Di Nisio ◽  
Matthias Briel ◽  
...  
Keyword(s):  
Relative Risk ◽  
Research Funding ◽  
Meta Analysis ◽  
Cancer Type ◽  
Adjusted Relative Risk ◽  
Individual Participant Data ◽  
Trial Duration ◽  
Individual Participant ◽  
Conference Attendance ◽  
The Impact

Abstract Background: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing the risk of venous thromboembolism (VTE) and through a direct anti-tumour effect. Study-level meta-analysis indicates a reduction in VTE and provide moderate certainty that a small survival benefit exists; it is unclear if patients with specific cancers benefit more or less. Utilizing data from randomized controlled trials (RCT), this individual participant data meta-analysis examines the impact of heparin on survival, VTE and major bleeding in oncological patients randomized to low-molecular weight heparin (LMWH) or no LMWH. Methods: We performed a comprehensive systematic search for all RCTS (last search date March 2017) and contacted authors and sponsors to obtain individual participant data of patients with solid cancers and no other indication for prophylactic or therapeutic anticoagulation. We utilized the GRADE approach to evaluate the certainty of evidence and produce an evidence profile. All analyses followed the intention-to-treat principle. We calculated the impact on mortality through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We adjusted the analysis for age, cancer type and metastasis status. To investigate whether intervention effects vary by predefined subgroups, including type of cancer, we tested interaction terms in the statistical model. Results: A total of 18 RCTs (n=10,041 participants) were eligible for inclusion and we obtained data from 82.4% of the participants (13 RCTs, n=8,278; n=4,139 for LMWH and n=4,139 for no LMWH). The meta-analysis revealed an adjusted relative risk of mortality within one year of 0.99 (95% CI: 0.95, 1.03) and a hazard ratio of 0.97 (95% CI: 0.82, 1.14) after one year. The relative risk for VTE was 0.58 (95% CI: 0.48, 0.71), 0.57 (95% CI: 0.44, 0.74) for symptomatic deep vein thrombosis and 0.58 (95%CI: 0.44, 0.77) for symptomatic pulmonary embolism, separately. For every 1,000 patients treated, approximately 16 fewer would experience symptomatic DVT and 16 fewer would experience any PE. The adjusted relative risk for major bleeding throughout trial duration was 1.24 (95% CI: 0.91, 1.69; P=0.17). Subgroup analysis, by cancer type, of VTE occurrence throughout trial duration identified lung cancer OR=0.52 (95% CI: 0.39, 0.68; P&lt;0.001) and pancreatic cancer OR=0.55 (95% CI: 0.35, 0.88; P=0.01) patients as experiencing the greatest benefit from LMWH treatment. The certainty of the evidence for the outcomes was moderate to high. Conclusion: LMWH reduces risk of VTE without increasing risk of bleeding but does not improve survival across all patients. Funding: Canadian Institutes of Health Research knowledge synthesis grant, KRS 126594 Registration: International Prospective Register for Systematic Reviews (PROSPERO), CRD42013003526. Disclosures Schünemann: Canadian Institutes of Health Research: Research Funding. Crowther: Alexion: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Leo Pharma: Research Funding; Pfizer: Honoraria; Portola: Consultancy; Shinogi: Consultancy. Macbeth: Pfizer: Other: Provision of Dalteparin for FRAGMATIC trial; Cancer Research UK: Research Funding. Griffiths: Pfizer: Consultancy, Other: Comment: I run an academic clinical trials unit, have received educational/investigator intiated research grants from companies that make these heparin agents. As consultant &gt; 3 years ago, advised Pfizer on clinical trial designs unrelated to this study., Research Funding. Van Es: Pfizer: Employment, Other: Comment: Dr. van Es reports personal fees from Pfizer as a member of their advisory board. These fees are unrelated to this project.. Streiff: Roche: Research Funding; Portola: Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding. Ageno: BMS-Pfizer: Consultancy, Honoraria; Bayer AG: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria. Bozas: PharmaMar: Honoraria. McBane: Bristol Myers Squibb: Other: Research grant for cancer associated VTE. Maraveyas: Bayer: Other: Personal fees and conference attendance; Bristol-Myers Squibb: Other: Grants and personal fees; Leo Pharma: Other: Grants, personal fees and conference attendance; Pfizer: Other: Personal fees. Loprinzi: Bristol Myers: Other: Grant - unrelated to this project; Janssen: Other: Grant - unrelated to this project.

scholarly journals Proteinuria as an independent predictor of stroke: Systematic review and meta-analysis

2020 ◽  
Vol 15 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Dearbhla M Kelly ◽  
Peter M Rothwell
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Blood Pressure ◽  
Relative Risk ◽  
Cohort Studies ◽  
Stroke Risk ◽  
Independent Predictor ◽  
Adjusted Relative Risk ◽  
Vascular Risk ◽  
The Impact

Background Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined. Aim We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure. Summary of review We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria ± glomerular filtration rate. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by χ 2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc analyses was assessed using the Newcastle–Ottawa Scale. We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; pooled crude relative risk 2.00, 95%CI 1.63–2.46; p < 0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 1.72, 1.51–1.95; p < 0.001), albeit with considerable heterogeneity between studies (p < 0.001; I2 = 77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline blood pressure measure (10 studies; pooled adjusted relative risk = 1.92, 1.39–2.66; p < 0.001); history or treated hypertension (four studies; pooled adjusted relative risk = 1.76, 1.13–2.75, p = 0.013); multiple blood pressure measurements over months to years (four studies; relative risk = 1.68, 1.33–2.14; p < 0.001). Conclusions Even after extensive adjustment for hypertension, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors.

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