Impact of Reduced Preincision Antibiotic Infusion Time on Surgical Site Infection Rates: A Retrospective Cohort Study.

OBJECTIVE: Our objective was to determine the impact of total preincision infusion time on surgical site infections (SSIs) and establish an optimal time threshold for subsequent prospective study. BACKGROUND: SSIs remain a major cause of morbidity. Although regulated, the total time of infusion of preincision antibiotics varies widely. Impact of infusion time on SSI risk is poorly understood. METHODS: All consecutive patients (n = 46,791) undergoing inpatient surgical intervention were retrospectively enrolled (2014-2015) and monitored for 1 year. Primary outcomes: the presence of SSI infection as predicted by reduced preoperative antibiotic infusion time. SECONDARY OUTCOMES: preintervention compliance, the impact of a quality improvement algorithm to optimize infusion time compliance. Multivariate logistic regression of the retrospective cohort demonstrated predictors of infection. Receiver-operating characteristic analysis demonstrated the timing threshold predictive of infection. Cost impact of avoidable infections was analyzed. RESULTS: Only 36.1% of patients received preincision infusion of vancomycin in compliance with national and institutional standards (60-120 min). Cephalosporin infusion times were 53 times more likely to be compliant [odds ratio (OR) 53.33, P < 0.001]. Vancomycin infusion times that were not compliant with national standards (less than standard 60-120 min) did not predict infection. However, significantly noncompliant, reduced preincision infusion time, significantly predicted SSI (<24.6 min infusion, AUC = 0.762). Vancomycin infusion, initiated too close to surgical incision, predicted increased SSI (OR = 4.281, P < 0.001). Implementation of an algorithm to improve infusion time, but not powered to demonstrate infection /reduction, improved vancomycin infusion start time (257% improvement, P < 0.001) and eliminated high-risk infusions (sub-24.6 min). CONCLUSIONS: Initially, vancomycin infusion rarely met national guidelines; however, minimal compliance breach was not associated with SSI implications. The retrospective data here suggest a critical infusion time for infection reduction (24.6 min before incision). Prospective implementation of an algorithm led to 100% compliance. These data suggest that vancomycin administration timing should be studied prospectively.

Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial.

BACKGROUND: Acute kidney injury often goes unrecognised in its early stages when effective treatment options might be available. We aimed to determine whether an automated electronic alert for acute kidney injury would reduce the severity of such injury and improve clinical outcomes in patients in hospital. METHODS: In this investigator-masked, parallel-group, randomised controlled trial, patients were recruited from the hospital of the University of Pennsylvania in Philadelphia, PA, USA. Eligible participants were adults aged 18 years or older who were in hospital with stage 1 or greater acute kidney injury as defined by Kidney Disease Improving Global Outcomes creatinine-based criteria. Exclusion criteria were initial hospital creatinine 4·0 mg/dL (to convert to µmol/L, multiply by 88·4) or greater, fewer than two creatinine values measured, inability to determine the covering provider, admission to hospice or the observation unit, previous randomisation, or end-stage renal disease. Patients were randomly assigned (1:1) via a computer-generated sequence to receive an acute kidney injury alert (a text-based alert sent to the covering provider and unit pharmacist indicating new acute kidney injury) or usual care, stratified by medical versus surgical admission and intensive care unit versus non-intensive care unit location in blocks of 4-8 participants. The primary outcome was a composite of relative maximum change in creatinine, dialysis, and death at 7 days after randomisation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01862419. FINDINGS: Between Sept 17, 2013, and April 14, 2014, 23,664 patients were screened. 1201 eligible participants were assigned to the acute kidney injury alert group and 1192 were assigned to the usual care group. Composite relative maximum change in creatinine, dialysis, and death at 7 days did not differ between the alert group and the usual care group (p=0·88), or within any of the four randomisation strata (all p>0·05). At 7 days after randomisation, median maximum relative change in creatinine concentrations was 0·0% (IQR 0·0-18·4) in the alert group and 0·6% (0·0-17·5) in the usual care group (p=0·81); 87 (7·2%) patients in the alert group and 70 (5·9%) patients in usual care group had received dialysis (odds ratio 1·25 [95% CI 0·90-1·74]; p=0·18); and 71 (5·9%) patients in the alert group and 61 (5·1%) patients in the usual care group had died (1·16 [0·81-1·68]; p=0·40). INTERPRETATION: An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. FUNDING: Penn Center for Healthcare Improvement and Patient Safety.

Systematic variable reduction for simplification of incisional hernia risk prediction instruments.

BACKGROUND: Incisional hernia (IH) is a complex, costly and difficult to manage surgical complication. We aim to create an accurate and parsimonious model to assess IH risk, pared down for practicality and translation in the clinical environment. METHODS: Institutional abdominal surgical patients from 2002 to 2019 were identified (N = 102,281); primary outcome of IH, demographic factors, and comorbidities were extracted. A 32-variable Cox proportional hazards model was generated. Reduced-variable models were created by systematic removal of variables 1-4 and 23-25 at a time. RESULTS: The c-statistic of the full 32-variable model was 0.7232. Four comorbidities decreased accuracy of the model: COPD, paralysis, cancer and combined autoimmune/hereditary collagenopathy or AAA diagnosis. The model with those 4 comorbidities removed had the highest c-statistic (0.7291). The most reduced model included 7 variables and had a c-statistic of 0.7127. CONCLUSION: Accuracy of an IH predictive model is only marginally affected by a vast reduction in end-user inputs.

Long-Term Abnormalities of Lipid Profile After a Single Episode of Sepsis.

Background: Acute disturbances of the lipid profile are commonplace during acute sepsis episode. However, their long-term persistence has not to be investigated despite pivotal role of dyslipidemia in several comorbidities excessively noted in sepsis survivors (stroke, cardiomyopathy). Methods: A total of 9,861 individuals hospitalized for a singular episode of sepsis between 2009 and 2019 were identified from electronic medical records. Lab measurements of total cholesterol (Tchol), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), very low-density lipoprotein (VLDL), triglycerides (TG), lipoprotein(a) [Lp (a)], apolipoprotein B (ApoB), and C-reactive protein (CRP). The data were examined as baseline values before sepsis, during hospitalization, and <3 months, 3-6 months, 6-12 months, 1-2 years, and more than 2 years from initial sepsis. Results: Significant reductions in HDL-c (HDLbaseline = 44.06 vs. HDLsepsis = 28.2; U = -37.79, p < 0.0001, Cohen's d = 0.22) and LDL-c serum levels were observed during and up to three months post sepsis, with females much less affected. In contrast, male subjects had derangement in HDL present for up to two years after a singular septic episode. Total cholesterol levels were slightly yet significantly elevated for up to two years after sepsis. TG were elevated up to one year [TGbaseline = 128.26 vs. TGsepsis = 170.27, t(8255) = -21.33, p < 0.0001, Cohen's d = 0.49] and normalized. Lp(a) was elevated up to two years after initial episode [Lp(a)baseline = 24.6 ± 16.06; Lp(a)sepsis-2year = 8.25 ± 5.17; Lp(a)morethan2years = 61.4 ± 40.1; ANOVA F (2, 24) = 7.39; p = 0.0032]. Response to statin therapy was blunted in sepsis survivors for several years after sepsis resolution. Significant drop-out in prescription of statins and niacin after sepsis was observed. Serum high sensitivity C-reactive protein was elevated for up to five years after sepsis resolution (H [6;1685] = 502.2; p < 0.0001). Discussion: Lipid abnormalities persisted long after the initial septic insult suggesting potential role in accelerating atherosclerosis and other abnormalities. In addition, sepsis seems to blunt statin effectiveness. Additionally, a significant and unexplained drop in statin use was seen in post-septic period. Conclusions: Our study suggests that persistent derangements of lipid profile components for up to two years after sepsis may be associated with altered risk of atherosclerosis-related events among sepsis survivors.

Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death.

OBJECTIVE: To evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS). METHODS: We used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death. RESULTS: We identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9-6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22-2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment. CONCLUSIONS: The AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies.

Development of a COVID-19 Application Ontology for the ACT Network.

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that that are critical to COVID-19 research. The ontology contains over 50,000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for SARS-CoV-2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of nine academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.

Development of a Coronavirus Disease 2019 (COVID-19) Application Ontology for the Accrual to Clinical Trials (ACT) network.

Clinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that are critical to COVID-19 research. The ontology contains over 50 000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for severe acute respiratory syndrome coronavirus 2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of 9 academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.

Hodgkin lymphoma patients have an increased incidence of idiopathic acquired aplastic anemia.

Idiopathic acquired aplastic anemia (AA) is a rare lymphocyte-mediated bone marrow aplasia. No specific mechanisms or triggers of AA have been identified. We recently observed several patients who developed AA after Hodgkin lymphoma (HL). We hypothesized that the co-occurrence of HL and AA is not random and may be etiologically significant. To test this hypothesis, we determined the incidence of AA in HL patients at our institution. We identified four patients with co-occurring HL and AA, with the incidence of AA in HL patients >20-fold higher compared to the general population. We identified 12 additional patients with AA and HL through a systematic literature review. Of the 16 total patients,15 (93.8%) developed AA after or concurrent with a HL diagnosis. None of the patients had marrow involvement by HL. Five of 15 patients were in complete remission from HL at the time of AA diagnosis, and six had a concurrent presentation with no prior cytotoxic therapy, with diagnostic timeframe information unavailable for four patients. The median interval between HL diagnosis and AA onset was 16 months, ranging from concurrent to 14 years after a HL diagnosis. The median survival after AA diagnosis was 14 months (range: 1 month to 20 years). Our results show that patients with HL have a higher incidence of AA compared to the general population and suggest that HL-related immune dysregulation may be a risk factor for AA. Better recognition and management of AA in HL patients is needed to improve outcomes in this population.

Attributable Risk and Time Course of Colistin-Associated Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: Despite colistin's longstanding reported association with nephrotoxicity, the attributable risk and timing of toxicity onset are still unknown. Whether substantial toxicity occurs during the initial 72 hours of exposure has important implications for early treatment decisions. The objective of this study was to compare colistin-exposed patients with a matched control group given other broad spectrum antibiotics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study in patients treated for multidrug-resistant Pseudomonas, Klebsiella, or Acinetobacter spp. Colistin-exposed patients were matched to unexposed controls using propensity scores. AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria. Incidence rate ratios and risk differences of AKI in the matched cohort were estimated with the generalized estimating equation Poisson regression model. Risk factors for AKI were tested for effect modification in the matched cohort. RESULTS: The study included 150 propensity-matched pairs with similar types of infection, similar delays to effective treatment, and similar baseline characteristics. Incidence of AKI was 77 of 150 (51%) in the colistin group versus 33 of 150 (22%) in matched controls (risk difference, 29%; 95% confidence interval, 19 to 39), corresponding to a number needed to harm of 3.5. Early toxicity was apparent, because AKI risk was higher in colistin-exposed patients at 72 hours of exposure (incidence rate ratio, 1.9; 95% confidence interval, 1.1 to 3.5). In both groups, hospital mortality in patients who experienced AKI was lower if kidney function returned to baseline during hospitalization. The effect of colistin exposure on AKI risk varied inversely according to baseline hemoglobin concentration. CONCLUSIONS: Colistin is associated with substantial excess AKI that is apparent within the first 72 hours of treatment. Colistin's toxicity varied according to baseline hemoglobin concentration. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_03_15_CJASNPodcast_18_4_M.mp3.

Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study.

BACKGROUND: Stroke may be the initial manifestation of atrial fibrillation (AF). Limited studies, however, have evaluated racial differences in stroke before the diagnosis of AF. OBJECTIVE: We assessed racial differences in strokes that occurred before and after AF diagnosis in the Penn Atrial Fibrillation Free study. METHODS: The Penn Atrial Fibrillation Free study consists of 56,835 patients from the University of Pennsylvania Health System who were free of AF at the index visit. We developed an inception cohort of 3507 patients with incident AF and without any remote history of stroke. RESULTS: Among the AF inception cohort, there were 538 patients with ischemic strokes and 54 with hemorrhagic strokes. Nearly half (n = 254; 47%) of the ischemic strokes occurred within a 6-month period before the diagnosis of AF. Of these, the majority of strokes occurred either on the day of (n = 158) or within a 7-day period before (n = 30) the diagnosis of incident AF. The remaining 284 (53%) ischemic strokes occurred a median of 3.6 years (interquartile range 1.9-5.4 years) after AF diagnosis. Compared with whites, blacks had an independently higher risk of having an ischemic stroke either before (adjusted odds ratio 1.37; 95% confidence interval 1.03-1.81) or after (adjusted hazard ratio 1.67; 95% confidence interval 1.30-2.14) AF diagnosis. CONCLUSION: In the population with incident AF, nearly half of the ischemic strokes occurred before the diagnosis of AF. Compared with whites, blacks had a higher risk of developing an ischemic stroke that persisted whether the stroke occurred in the period either before or after AF diagnosis.

Optimal QT interval correction formula in sinus tachycardia for identifying cardiovascular and mortality risk: Findings from the Penn Atrial Fibrillation Free study.

BACKGROUND: The QT interval measures cardiac repolarization, and prolongation is associated with adverse cardiovascular outcomes and death. The exponential Bazett correction formula overestimates the QT interval during tachycardia. OBJECTIVE: We evaluated 4 formulas of QT interval correction in individuals with sinus tachycardia for the identification of coronary artery disease, heart failure, and mortality. METHODS: The Penn Atrial Fibrillation Free study is a large cohort study of patients without atrial fibrillation. The present study examined 6723 Penn Atrial Fibrillation Free study patients without a history of heart failure and with baseline sinus rate ≥100 beats/min. Medical records were queried for index clinical parameters, incident cardiovascular events, and all-cause mortality. The QT interval was corrected by using Bazett (QT/RR(0.5)), Fridericia (QT/RR(0.33)), Framingham [QT + 0.154 * (1000 - RR)], and Hodges (QT + 105 * (1/RR - 1)) formulas. RESULTS: In 6723 patients with a median follow-up of 4.5 years (interquartile range 1.9-6.4 years), the annualized cardiovascular event rate was 2.3% and the annualized mortality rate was 2.2%. QT prolongation was diagnosed in 39% of the cohort using the Bazett formula, 6.2% using the Fridericia formula, 3.7% using the Framingham formula, and 8.7% using the Hodges formula. Only the Hodges formula was an independent risk marker for death across the range of QT values (highest tertile: hazard ratio 1.26; 95% confidence interval 1.03-1.55). CONCLUSION: Although all correction formulas demonstrated an association between QTc values and cardiovascular events, only the Hodges formula identified one-third of individuals with tachycardia that are at higher risk of all-cause mortality. Furthermore, the Bazett correction formula overestimates the number of patients with a prolonged QT interval and was not associated with mortality. Future work may validate these findings and result in changes to automated algorithms for QT interval assessment.

Dialysis versus nondialysis in patients with AKI: a propensity-matched cohort study.

BACKGROUND AND OBJECTIVES: The benefit of the initiation of dialysis for AKI may differ depending on patient factors, but, because of a lack of robust evidence, the decision to initiate dialysis for AKI remains subjective in many cases. Prior studies examining dialysis initiation for AKI have examined outcomes of dialyzed patients compared with other dialyzed patients with different characteristics. Without an adequate nondialyzed control group, these studies cannot provide information on the benefit of dialysis initiation. To determine which patients would benefit from initiation of dialysis for AKI, a propensity-matched cohort study was performed among a large population of patients with severe AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Adults admitted to one of three acute care hospitals within the University of Pennsylvania Health System from January 1, 2004, to August 31, 2010, who subsequently developed severe AKI were included (n=6119). Of these, 602 received dialysis. Demographic, clinical, and laboratory variables were used to generate a time-varying propensity score representing the daily probability of initiation of dialysis for AKI. Not-yet-dialyzed patients were matched to each dialyzed patient according to day of AKI and propensity score. Proportional hazards analysis was used to compare time to all-cause mortality among dialyzed versus nondialyzed patients across a spectrum of prespecified variables. RESULTS: After propensity score matching, covariates were well balanced between the groups, and the overall hazard ratio for death in dialyzed versus nondialyzed patients was 1.01 (95% confidence interval, 0.85 to 1.21; P=0.89). Serum creatinine concentration modified the association between dialysis and survival, with a 20% (95% confidence interval, 9% to 30%) greater survival benefit from dialysis for each 1-mg/dl increase in serum creatinine concentration (P=0.001). This finding persisted after adjustment for markers of disease severity. Dialysis initiation was associated with more benefit than harm at a creatinine concentration ≥ 3.8 mg/dl. CONCLUSIONS: Dialysis was associated with increased survival when initiated in patients with AKI who have a more elevated creatinine level but was associated with increased mortality when initiated in patients with lower creatinine concentrations.