Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF). Numerous studies have shown that APAP hepatotoxicity in mice involves mitochondrial dysfunction, and recent data suggest this is also the case in humans. We have previously shown that glutamate dehydrogenase (GDH), mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) fragments can be measured in circulation of overdose patients as mechanistic biomarkers of mitochondrial damage and damage-associated molecular patterns. In the present study, our goal was to determine if these biomarkers are higher in serum from non-survivors of APAP-induced ALF (AALF) compared with survivors. GDH, mtDNA and nDNA fragments were measured in serum from AALF patients who did (n = 34) or did not (n = 35) recover. Importantly, all three were significantly increased in patients who died compared with those who survived (GDH: 450±73 vs. 930±145 U/L; mtDNA: 21±6 vs. 48±13 and 33±10 vs. 43±7 ng/mL for two different genes; nDNA fragments: 148±13 vs. 210±13 % of control). Receiver operating characteristic (ROC) curve analyses revealed that nDNA fragments, GDH and mtDNA were predictive of outcome (AUC, study admission: 0.73, 0.70 and 0.71 or 0.76, respectively, p < 0.05; AUC, time of peak ALT: 0.78, 0.71 and 0.71 or 0.76, respectively, p < 0.05) and the results were similar to those from the model for end-stage liver disease (MELD) (AUC, peak MELD: 0.77, p < 0.05). Conclusions Our data suggest that patients with more mitochondrial damage are less likely to survive, demonstrating that mitochondria are central in the mechanisms of APAP hepatotoxicity in humans. Clinically, serum nDNA fragments, GDH and mtDNA could be useful as part of a panel of biomarkers to predict patient outcome.

IMPORTANCEIn 2008, Medicare implemented the Hospital-Acquired Conditions (HACs) Initiative, a policy denying incremental payment for 8 complications of hospital care, also known as never events. The regulation's effect on these events has not been well studied.OBJECTIVE To measure the association between Medicare's nonpayment policy and 4 outcomes addressed by the HACs Initiative: central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), hospital-acquired pressure ulcers (HAPUs), and injurious inpatient falls. DESIGN, SETTING, AND PARTICIPANTSQuasi-experimental study of adult nursing units from 1381 US hospitals participating in the National Database of Nursing Quality Indicators (NDNQI), a program of the American Nurses Association. The NDNQI data were combined with American Hospital Association, Medicare Cost Report, and local market data to examine adjusted outcomes. Multilevel models were used to evaluate the effect of Medicare's nonpayment policy on never events.EXPOSURES United States hospitals providing treatment for Medicare patients were subject to the new payment policy beginning in October 2008. MAIN OUTCOMES AND MEASURESChanges in unit-level rates of HAPUs, injurious falls, CLABSIs, and CAUTIs after initiation of the policy. RESULTS Medicare's nonpayment policy was associated with an 11% reduction in the rate of change in CLABSIs (incidence rate ratio [IRR], 0.89; 95% CI, 0.83-0.95) and a 10% reduction in the rate of change in CAUTIs (IRR, 0.90; 95% CI, 0.85-0.95), but was not associated with a significant change in injurious falls (IRR, 0.99; 95% CI, 0.99-1.00) or HAPUs (odds ratio, 0.98; 95% CI, 0.96-1.01). Consideration of unit-, hospital-, and market-level factors did not significantly alter our findings. CONCLUSIONS AND RELEVANCEThe HACs Initiative was associated with improvements in CLABSI and CAUTI trends, conditions for which there is strong evidence that better hospital processes yield better outcomes. However, the HACs Initiative was not associated with improvements in HAPU or injurious fall trends, conditions for which there is less evidence that changing hospital processes leads to significantly better outcomes.

Background Many hospitals classify inpatient falls as assisted (if a staff member is present to ease the patient’s descent or break the fall) or unassisted for quality measurement purposes. Unassisted falls are more likely to result in injury, but there is limited research quantifying this effect or linking the assisted/unassisted classification to processes of care. A study was conducted to link the assisted/unassisted fall classification to both processes and outcomes of care, thereby demonstrating its suitability for use in quality measurement. This was only the second known published study to quantify the increased risk of injury associated with falling unassisted (versus assisted), and the first to estimate the effects of falling unassisted (versus assisted) on the likelihood of specific levels of injury. Methods A cross-sectional analysis of falls from all available 2011 data for 6,539 adult medical, surgical, and medical-surgical units in 1,464 general hospitals participating in the National Database of Nursing Quality Indicators® (NDNQI®) was performed. Results Participating units reported 166,883 falls (3.44 falls per 1,000 patient-days). Excluding repeat falls, 85.5% of falls were unassisted. Assisted and unassisted falls were associated with different processes and outcomes: Fallers in units without a fall prevention protocol in place were more likely to fall unassisted than those with a protocol in place (adjusted odds ratio [aOR], 1.39 [95% confidence interval (CI), 1.32, 1.46]), and unassisted falls were more likely to result in injury (aOR, 1.59 [95% CI, 1.52, 1.67]). Conclusions The assisted/unassisted fall classification is associated with care processes and patient outcomes, making it suitable for quality measurement. Unassisted falls are more likely than assisted falls to result in injury and should be considered as a target for future prevention efforts.

Acetaminophen (APAP)-induced acute liver failure (ALF) remains a major clinical problem. Although a majority of patients recovers after severe liver injury, a subpopulation of patients proceeds to ALF. Bile acids are generated in the liver and accumulate in blood during liver injury, and as such, have been proposed as biomarkers for liver injury and dysfunction. The goal of this study was to determine whether individual bile acid levels could determine outcome in patients with APAP-induced ALF (AALF). Serum bile acid levels were measured in AALF patients using mass spectrometry. Bile acid levels were elevated 5-80-fold above control values in injured patients on day 1 after the overdose and decreased over the course of hospital stay. Interestingly, glycodeoxycholic acid (GDCA) was significantly increased in non-surviving AALF patients compared with survivors. GDCA values obtained at peak alanine aminotransferase (ALT) and from day 1 of admission indicated GDCA could predict survival in these patients by receiver-operating characteristic analysis (AUC = 0.70 for day 1, AUC = 0.68 for peak ALT). Of note, AALF patients also had significantly higher levels of serum bile acids than patients with active cholestatic liver injury. These data suggest measurements of GDCA in this patient cohort modestly predicted outcome and may serve as a prognostic biomarker. Furthermore, accumulation of bile acids in serum or plasma may be a result of liver cell dysfunction and not cholestasis, suggesting elevation of circulating bile acid levels may be a consequence and not a cause of liver injury.