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Topics
- Antibiotics (2)
- Antimicrobial Stewardship (1)
- Central Line-Associated Bloodstream Infections (CLABSI) (1)
- Children/Adolescents (3)
- Clinical Decision Support (CDS) (1)
- Data (1)
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- Disparities (2)
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- Intensive Care Unit (ICU) (2)
- Kidney Disease and Health (1)
- Low-Income (1)
- Medication (3)
- Mortality (4)
- Newborns/Infants (1)
- Nursing (1)
- Obesity (1)
- Outcomes (3)
- Patient-Centered Outcomes Research (1)
- Prevention (1)
- Quality of Care (1)
- Racial and Ethnic Minorities (1)
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- (-) Sepsis (20)
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AHRQ Research Studies
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Research Studies is a compilation of published research articles funded by AHRQ or authored by AHRQ researchers.
Results
1 to 20 of 20 Research Studies DisplayedPak TR, Young J, McKenna CS
Risk of misleading conclusions in observational studies of time-to-antibiotics and mortality in suspected sepsis.
Important studies indicate that every hour of sepsis that elapses until antibiotics are administered increases mortality. The researchers of this study found determined that analyses in the influential studies often adjusted for limited covariates, included patients with long delays until antibiotic administration, combined sepsis and septic shock, and used linear models presuming each hour of delay has equal impact on the sepsis and the patient. The purpose of this study was to assess the effect of the analytic decisions on the relationships between time-to-antibiotics and mortality. The researchers retrospectively identified 104,248 adults admitted from 2015-2022 to five hospitals with suspected infection. The patients included 25,990 with suspected septic shock and 23,619 with sepsis without shock. The study found that changing covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed relationships between time-to-antibiotics and mortality. In a fully adjusted model of patients treated within 6 hours, every hour related with higher mortality for septic shock, but not sepsis without shock or suspected infection alone. Modeling every hour independently confirmed that every hour delay was related with greater mortality for septic shock, but only delays of greater than 6 hours were related with greater mortality for sepsis without shock.
AHRQ-funded; HS027170.
Citation: Pak TR, Young J, McKenna CS .
Risk of misleading conclusions in observational studies of time-to-antibiotics and mortality in suspected sepsis.
Clin Infect Dis 2023 Nov 30; 77(11):1534-43. doi: 10.1093/cid/ciad450..
Keywords: Antibiotics, Medication, Sepsis, Mortality, Quality of Care
Michelson KA, Bachur RG, Cruz AT
Multicenter evaluation of a method to identify delayed diagnosis of diabetic ketoacidosis and sepsis in administrative data.
The objectives of this study were to derive a method of automated identification of delayed diagnosis of two serious pediatric conditions in the emergency department (ED). Subjects were patients under the age of 21 who had two EDs encounters within 7 days, the second resulting in a diagnosis of new-onset diabetic ketoacidosis (DKA) or sepsis. The results showed that delayed diagnosis was present in 89 % of DKA patients seen twice within 7 days. 17 % of sepsis patients were deemed to have delayed diagnosis; the authors noted that many children with sepsis delayed diagnosis may be identified using the proposed approach with low specificity, indicating a need for manual case review. The fewer days between ED encounters was the most important characteristic associated with delayed diagnosis.
AHRQ-funded; HS026503.
Citation: Michelson KA, Bachur RG, Cruz AT .
Multicenter evaluation of a method to identify delayed diagnosis of diabetic ketoacidosis and sepsis in administrative data.
Diagnosis 2023 Nov; 10(4):383-89. doi: 10.1515/dx-2023-0019..
Keywords: Diabetes, Diagnostic Safety and Quality, Sepsis
Georgette N, Michelson K, Monuteaux M
A temperature- and age-adjusted shock index for emergency department identification of pediatric sepsis.
The objective of this retrospective cohort study was to derive a temperature- and age-adjusted mean shock index (TAMSI) for early identification of sepsis and septic shock in children with suspected infection. Researchers analyzed data on children who presented with suspected infection to a single emergency department over a 10-year period. Test characteristics for the TAMSI cutoffs were compared with those for the Pediatric Advanced Life Support (PALS) tachycardia or systolic hypotension cutoffs. The results showed that TAMSI achieved a similar negative likelihood ratio and improved positive likelihood ratio compared with PALS vital sign cutoffs for the prediction of septic shock, but did not improve on PALS for sepsis prediction among children with suspected infection.
AHRQ-funded; HS026503.
Citation: Georgette N, Michelson K, Monuteaux M .
A temperature- and age-adjusted shock index for emergency department identification of pediatric sepsis.
Ann Emerg Med 2023 Oct; 82(4):494-502. doi: 10.1016/j.annemergmed.2023.03.026..
Keywords: Children/Adolescents, Emergency Department, Sepsis, Diagnostic Safety and Quality
Troncoso R, Garfinkel EM, Hinson JS
Do prehospital sepsis alerts decrease time to complete CMS sepsis measures?
This retrospective cohort study examined the effects of a prehospital sepsis alert protocol on decreasing time to complete Centers for Medicare and Medicaid Services (CMS) sepsis core measures. The study included patients transported via EMS from December 1, 2018 to December 1, 2019 who met the criteria of the Maryland Statewide EMS sepsis protocol and compared outcomes between patients who activated a prehospital sepsis alert and patients who did not activate a prehospital sepsis alert. The Maryland Institute for Emergency Medical Services Systems had developed a sepsis protocol that instructed EMS providers to notify the nearest appropriate facility with a sepsis alert if a patient 18 years of age and older is suspected of having an infection and also presented with at least two of the following: temperature >38 °C or <35.5 °C, a heart rate >100 beats per minute, a respiratory rate >25 breaths per minute or end-tidal carbon dioxide less than or equal to 32 mmHg, a systolic blood pressure <90 mmHg, or a point of care lactate reading greater than or equal to 4 mmol/L. Median time to achieve all four studied CMS sepsis core measures was 103 min for patients who received a prehospital sepsis alert and 106.5 min for patients who did not receive a prehospital sepsis alert. Median time to completion was shorter for serum lactate collection (28 min. vs 35 min.), blood culture collection (28 min. vs 38 min.), and intravenous fluid administration (54 min. vs 61 min.) but was not significantly different for antibiotic administration (94 min. vs 103 min.) among patients who triggered a sepsis alert. The results question the effectiveness of prehospital sepsis alert protocols on decreasing time to complete CMS sepsis core measures.
AHRQ-funded; HS026640.
Citation: Troncoso R, Garfinkel EM, Hinson JS .
Do prehospital sepsis alerts decrease time to complete CMS sepsis measures?
Am J Emerg Med 2023 Sep; 71:81-85. doi: 10.1016/j.ajem.2023.06.024..
Keywords: Sepsis, Hospitals
Kumar AJ, Parthasarathy C, Prescott HC
Pneumosepsis survival in the setting of obesity leads to persistent steatohepatitis and metabolic dysfunction.
The purpose of this study was to explore the long-term effect of sepsis on pre-existing NAFLD and hyperglycemia. The researchers randomized male mice to either a high-fat diet or a control diet (CD). After 24 weeks on the diet, mice were inoculated with Klebsiella pneumoniae (Kpa). To assess whether persistent inflammation could be reproduced in other abnormal liver environments, mice were also challenged with Kpa after exposure to a methionine-choline-deficient high-fat diet. Finally, a retrospective cohort of 65,139 patients was analyzed to evaluate whether obesity was related with liver injury after sepsis. The study found that after Kpa inoculation, high-fat diet mice had normalized fasting blood glucose without a change in insulin sensitivity but with a notable decrease in pyruvate utilization. Liver examination revealed focal macrophage collections and a unique inflammatory gene signature on RNA analysis. In the clinical cohort, preobesity, and class 1 and class 2 obesity were related with higher odds of elevated aminotransferase levels 1-2 years after sepsis.
Citation: Kumar AJ, Parthasarathy C, Prescott HC .
Pneumosepsis survival in the setting of obesity leads to persistent steatohepatitis and metabolic dysfunction.
Hepatol Commun 2023 Sep; 7(9). doi: 10.1097/hc9.0000000000000210..
Keywords: Sepsis, Obesity
Michelson KA, Bachur RG, Grubenhoff JA
Outcomes of missed diagnosis of pediatric appendicitis, new-onset diabetic ketoacidosis, and sepsis in five pediatric hospitals.
This study’s objective was to determine 90-day complication rates and hospital utilization after a missed diagnosis of pediatric appendicitis, new-onset diabetic ketoacidosis (DKA), or sepsis. The authors evaluated patients under 21 years of age visiting five pediatric emergency departments (EDs) with a study condition. Case patients included had a preceding ED visit within 7 days of diagnosis and underwent case review to confirm a missed diagnosis. The authors compared complication rates and utilization between case and control patients after adjusting for age, sex, and insurance. They analyzed 29,398 children with appendicitis, 5366 with DKA, and 3622 with sepsis, of whom 429, 33, and 46, respectively, had a missed diagnosis. Patients with a missed appendicitis or DKA diagnosis had more hospital days and readmissions, but there were no significant differences for those with sepsis. Those with missed appendicitis were more likely to have abdominal abscess drainage or perforated appendicitis. Those with missed DKA were more likely to have cerebral edema, mechanical ventilation, or death. Those with missed sepsis were less likely to have mechanical ventilation.
AHRQ-funded; HS026503.
Citation: Michelson KA, Bachur RG, Grubenhoff JA .
Outcomes of missed diagnosis of pediatric appendicitis, new-onset diabetic ketoacidosis, and sepsis in five pediatric hospitals.
J Emerg Med 2023 Jul; 65(1):e9-e18. doi: 10.1016/j.jemermed.2023.04.006..
Keywords: Children/Adolescents, Sepsis, Diabetes, Diagnostic Safety and Quality
Dhudasia MB, Benitz WE, Flannery DD
Diagnostic performance and patient outcomes with c-reactive protein use in early-onset sepsis evaluations.
This study’s objective was to determine performance of C-reactive protein (CRP) in the diagnosis of early-onset sepsis, and to assess patient outcomes with and without routine use of CRP in infants in the neonatal intensive care unit (NICU). This retrospective cohort study looked at infants admitted to 2 NICUs from 2009 to 2014. During the time period, 10,134 infants were admitted, 89.9% had CRP, and 74.5% had blood culture obtained within 3 days of birth. CRP obtained plus/minus 4 hours had a sensitivity of 41.7%, specificity 89.9%, and positive likelihood ratio 4.12 in diagnosis of early-onset sepsis. When obtained 24-72 hours after blood culture, sensitivity of CRP increased significantly (89.5%), but specificity (55.7%) and positive likelihood ratio (2.02) decreased. Comparing the periods with (n = 4977) and without (n = 5135) routine use of CRP, the authors observed lower rates of early-onset sepsis evaluation (74.5% vs 50.5%), antibiotic initiation (65.0% vs 50.8%), and antibiotic prolongation in the absence of early-onset sepsis (17.3% vs 7.2%) in the later period.
AHRQ-funded; HS027468.
Citation: Dhudasia MB, Benitz WE, Flannery DD .
Diagnostic performance and patient outcomes with c-reactive protein use in early-onset sepsis evaluations.
J Pediatr 2023 May; 256:98-104.e6. doi: 10.1016/j.jpeds.2022.12.007..
Keywords: Newborns/Infants, Sepsis, Diagnostic Safety and Quality
Denstaedt SJ, Cano J, Wang XQ
Blood count derangements after sepsis and association with post-hospital outcomes.
Estimating long-term prognosis for sepsis survivors remains challenging. Prolonged inflammation following sepsis is linked to a higher likelihood of readmission and mortality. Complete blood count (CBC) parameters, as indicators of inflammation, might hold prognostic significance for sepsis survivors when measured at the time of hospital discharge. The purpose of this study was to assess the additional value of CBC parameters in predicting 90-day outcomes in sepsis survivors, beyond clinical features alone. Electronic health records were utilized to identify sepsis-related hospitalizations at US Veterans Affairs hospitals involving live discharge and relevant laboratory data (2013-2018). The researchers examined the relationship between eight CBC parameters and 90-day outcomes (mortality, readmission, cause-specific readmissions) using multivariable logistic regression models. The study found 155,988 eligible sepsis hospitalizations. Anemia and lymphopenia were the most prevalent blood count abnormalities at discharge. In multivariable models, all parameters correlated with the primary outcome of 90-day mortality or readmission and enhanced model discrimination beyond clinical features alone. Hemoglobin exhibited the highest prognostic distinction, with a 1.5-fold increase in the incidence of the primary outcome in the lowest quintile compared to the highest quintile Hemoglobin and neutrophil-lymphocyte ratio contributed the most added value in predicting the primary outcome and 90-day mortality independently. Absolute lymphocyte count offered minimal value in forecasting 90-day outcomes.
AHRQ-funded; HS026725
Citation: Denstaedt SJ, Cano J, Wang XQ .
Blood count derangements after sepsis and association with post-hospital outcomes.
Front Immunol 2023 Feb 28;14:1133351. doi: 10.3389/fimmu.2023.1133351.
Keywords: Sepsis, Outcomes
Chiotos K, Blumenthal J, Boguniewicz J
Antibiotic indications and appropriateness in the pediatric intensive care unit: a 10-center point prevalence study.
The purpose of this study was to describe indications and appropriateness of antibiotic orders in pediatric intensive care unit (PICU) patients. The study found that of 1462 patients admitted to participating PICUs, 58% had at least 1 antibiotic order, with 1277 antibiotic orders being reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock, nonoperative prophylaxis, empiric therapy for sepsis or septic shock, community-acquired pneumonia, and post-operative prophylaxis. Appropriateness was evaluated for 985 orders for which an evidence-based heading for appropriateness could be created. Of these, 34% were categorized as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock, sepsis or septic shock, CAP, ventilator-associated infections, and post-operative prophylaxis. The proportion of antibiotics classified as inappropriate differed across institutions.
AHRQ-funded; HS026393.
Citation: Chiotos K, Blumenthal J, Boguniewicz J .
Antibiotic indications and appropriateness in the pediatric intensive care unit: a 10-center point prevalence study.
Clin Infect Dis 2023 Feb 8; 76(3):e1021-e30. doi: 10.1093/cid/ciac698..
Keywords: Children/Adolescents, Intensive Care Unit (ICU), Antibiotics, Medication, Antimicrobial Stewardship, Sepsis
Goto M, Hasegawa S, Balkenende EC
Effectiveness of ultraviolet-c disinfection on hospital-onset gram-negative rod bloodstream infection: a nationwide stepped-wedge time-series analysis.
This study evaluated the effectiveness of enhanced terminal room cleaning with ultraviolet C (UV-C) disinfection in reducing gram-negative rod (GNR) infections. The authors used information regarding UV-C use and the timing of implementation through a survey of all Veterans Health Administration (VHA) hospitals providing inpatient acute care from January 2010 and December 2018. Among 128 Veterans Health Administration hospitals, 120 provided complete survey responses with 40 reporting implementations of UV-C systems. UV-C use was associated with a 19% lower incident of hospital-onset (HO) GNR bloodstream infection (BSI).
AHRQ-funded; HS027472.
Citation: Goto M, Hasegawa S, Balkenende EC .
Effectiveness of ultraviolet-c disinfection on hospital-onset gram-negative rod bloodstream infection: a nationwide stepped-wedge time-series analysis.
Clin Infect Dis 2023 Jan 13; 76(2):291-98. doi: 10.1093/cid/ciac776..
Keywords: Central Line-Associated Bloodstream Infections (CLABSI), Healthcare-Associated Infections (HAIs), Hospitals, Prevention, Sepsis
Mohr NM, Okoro U, Harland KK
Outcomes associated with rural emergency department provider-to-provider telehealth for sepsis care: a multicenter cohort study.
The objective of this multicenter cohort study was to test the hypothesis that provider-to-provider tele-emergency department (tele-ED) care is associated with more 28-day hospital-free days and improved Surviving Sepsis Campaign (SSC) guideline adherence in rural emergency departments. Medical records of patients with sepsis were taken from rural hospitals in an established, on-demand, video tele-ED Midwestern network. Findings suggest that tele-ED cases did not have more 28-day hospital-free days or 28-day in-hospital mortality. A subgroup of patients treated by advanced practice providers suggest that mortality was lower in the cohort with tele-ED use in spite of no significant difference in complete SSC adherence. The researchers concluded that rural emergency department patients treated with provider-to-provider tele-ED care in a developed network showed similar clinical outcomes to those treated without.
AHRQ-funded; HS025753.
Citation: Mohr NM, Okoro U, Harland KK .
Outcomes associated with rural emergency department provider-to-provider telehealth for sepsis care: a multicenter cohort study.
Ann Emerg Med 2023 Jan;81(1):1-13. doi: 10.1016/j.annemergmed.2022.07.024..
Keywords: Rural Health, Emergency Department, Telehealth, Health Information Technology (HIT), Sepsis, Outcomes
Jones JM, Fingar KR, Miller MA
AHRQ Author: Miller MA; Heslin KC
Racial disparities in sepsis-related in-hospital mortality: using a broad case capture method and multivariate controls for clinical and hospital variables, 2004-2013.
The objective of this study was to use a broad method of capturing sepsis cases to estimate 2004-2013 trends in in-hospital sepsis mortality rates by race/ethnicity. Mortality rates adjusted for patient characteristics were higher for all minority groups than for white patients. After adjusting for hospital characteristics, sepsis mortality rates in 2013 were similar for white, black, and Hispanic patients.
AHRQ-authored.
Citation: Jones JM, Fingar KR, Miller MA .
Racial disparities in sepsis-related in-hospital mortality: using a broad case capture method and multivariate controls for clinical and hospital variables, 2004-2013.
Crit Care Med 2017 Dec;45(12):e1209-e17. doi: 10.1097/ccm.0000000000002699.
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Keywords: Disparities, Healthcare Cost and Utilization Project (HCUP), Mortality, Racial and Ethnic Minorities, Sepsis
Rhee C, Dantes R, Epstein L
Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014.
The researchers estimated the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. In clinical data from 409 hospitals, sepsis was present in 6 percent of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014.
AHRQ-funded; HS025008.
Citation: Rhee C, Dantes R, Epstein L .
Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014.
JAMA 2017 Oct 3;318(13):1241-49. doi: 10.1001/jama.2017.13836.
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Keywords: Data, Electronic Health Records (EHRs), Hospitals, Mortality, Sepsis
Xavier Moore J, Donnelly JP, Griffin R
Community characteristics and regional variations in sepsis.
This study aimed to determine the influence of community characteristics upon regional variations in sepsis incidence and case fatality. The study concluded that regional variations in sepsis incidence may be partly explained by community poverty. Other community characteristics do not explain regional variations in sepsis incidence or case fatality.
AHRQ-funded; HS013852.
Citation: Xavier Moore J, Donnelly JP, Griffin R .
Community characteristics and regional variations in sepsis.
Int J Epidemiol 2017 Oct 1;46(5):1607-17. doi: 10.1093/ije/dyx099..
Keywords: Disparities, Low-Income, Mortality, Sepsis, Social Determinants of Health
Chaudhary NS, Donnelly JP, Moore JX
Association of baseline steroid use with long-term rates of infection and sepsis in the REGARDS cohort.
Prior studies associate steroid use with infection risk but were limited to select populations and short follow-up periods. This population-based cohort study sought to determine the association of steroid risk with long-term risks of community- acquired infections and sepsis. It concluded that baseline steroid use was associated with increased long-term risks of community-acquired infections and sepsis.
AHRQ-funded; HS013852.
Citation: Chaudhary NS, Donnelly JP, Moore JX .
Association of baseline steroid use with long-term rates of infection and sepsis in the REGARDS cohort.
Crit Care 2017 Jul 13;21(1):185. doi: 10.1186/s13054-017-1767-1.
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Keywords: Healthcare-Associated Infections (HAIs), Medication, Sepsis, Risk
Donnelly JP, Safford MM, Shapiro NI
Application of the Third International Consensus Definitions for Sepsis (Sepsis-3) Classification: a retrospective population-based cohort study.
The Consensus Definitions present clinical criteria for the classification of patients with sepsis. Researchers investigated incidence and long-term outcomes of patients diagnosed with these classifications, which are currently unknown. Their findings support the use of the elevated sepsis-related organ failure assessment (SOFA) score from Sepsis-3, and elevated quick SOFA (qSOFA) score from Sepsis-3 classifications to identify patients with infection who are at elevated risk of poor outcomes.
AHRQ-funded; HS013852.
Citation: Donnelly JP, Safford MM, Shapiro NI .
Application of the Third International Consensus Definitions for Sepsis (Sepsis-3) Classification: a retrospective population-based cohort study.
Lancet Infect Dis 2017 Jun;17(6):661-70. doi: 10.1016/s1473-3099(17)30117-2.
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Keywords: Sepsis, Diagnostic Safety and Quality, Patient-Centered Outcomes Research, Outcomes
Sudduth CL, Overton EC, Lyu PF
Filtering authentic sepsis arising in the ICU using administrative codes coupled to a SIRS screening protocol.
Using administrative codes and minimal physiologic and laboratory data, researchers sought a high-specificity identification strategy for patients whose sepsis initially appeared during their ICU stay. They concluded that selected administrative codes coupled to SIRS criteria and applied to patients admitted to ICU can yield up to 94 percent authentic sepsis patients. However, only 1/3 of patients thus identified appeared to become septic during their ICU stay.
AHRQ-funded; HS000055.
Citation: Sudduth CL, Overton EC, Lyu PF .
Filtering authentic sepsis arising in the ICU using administrative codes coupled to a SIRS screening protocol.
J Crit Care 2017 Jun;39:220-24. doi: 10.1016/j.jcrc.2017.01.012.
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Keywords: Diagnostic Safety and Quality, Intensive Care Unit (ICU), Hospitalization, Sepsis
Bhattacharjee P, Churpek MM, Snyder A
Detecting sepsis: are two opinions better than one?
Researchers conducted a study to characterize the agreement between different providers' suspicion of infection and the correlation with patient outcomes using prospective data from a general medicine ward. They concluded that provider disagreement regarding suspected infection is common, with RNs suspecting infection more often, suggesting that a collaborative model for sepsis detection may improve timing and accuracy.
AHRQ-funded; HS000078.
Citation: Bhattacharjee P, Churpek MM, Snyder A .
Detecting sepsis: are two opinions better than one?
J Hosp Med 2017 Apr;12(4):256-58. doi: 10.12788/jhm.2721.
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Keywords: Diagnostic Safety and Quality, Nursing, Risk, Sepsis
Bhattacharjee P, Edelson DP, Churpek MM
Identifying patients with sepsis on the hospital wards.
The goal of this review was to discuss recent advances in the detection of sepsis in patients on the hospital wards. The investigators discuss data highlighting the benefits and limitations of the systemic inflammatory response syndrome (SIRS) criteria for screening patients with sepsis, such as its low specificity, as well as newly described scoring systems, including the proposed role of the quick sepsis-related organ failure assessment (qSOFA) score.
AHRQ-funded; HS000078.
Citation: Bhattacharjee P, Edelson DP, Churpek MM .
Identifying patients with sepsis on the hospital wards.
Chest 2017 Apr;151(4):898-907. doi: 10.1016/j.chest.2016.06.020..
Keywords: Clinical Decision Support (CDS), Diagnostic Safety and Quality, Hospitalization, Sepsis
Banerjee T, Meyer TW, Shafi T
Free and total p-cresol sulfate levels and infectious hospitalizations in hemodialysis patients in CHOICE and HEMO.
P-cresol sulfate (PCS), a prototype protein-bound uremic retention solute, has been shown to exert toxic effects in vitro. The researchers explored the relationship between free and total PCS and indoxyl sulfate (IS) with infection-related hospitalizations (IH) and septicemia in 2 cohorts. Their results suggest an association between higher concentrations of free PCS and infection-related and sepsis-related hospitalizations in hemodialysis patients.
AHRQ-funded; HS008365.
Citation: Banerjee T, Meyer TW, Shafi T .
Free and total p-cresol sulfate levels and infectious hospitalizations in hemodialysis patients in CHOICE and HEMO.
Medicine 2017 Feb;96(6):e5799. doi: 10.1097/md.0000000000005799.
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Keywords: Hospitalization, Kidney Disease and Health, Kidney Disease and Health, Digestive Disease and Health, Sepsis