The Complex Relationship Between Pain, Mental Health, and Quality-of-Life in Patients With Cirrhosis Undergoing Liver Transplant Evaluation.

GOALS AND BACKGROUND: Patients with cirrhosis undergoing liver transplant evaluation have high rates of pain and mental health comorbidities; both may significantly impair health-related quality of life (HRQL). We investigated the association between pain, anxiety/depression, and HRQL in this population. STUDY: In 62 patients with cirrhosis undergoing liver transplant evaluation, we performed 4 validated assessments to characterize: pain (Brief Pain Inventory-Short Form, BPI-SF), anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-8), and liver-specific HRQL (Chronic Liver Disease Questionnaire). The presence of pain was determined using the BPI-SF screening question. Linear regression was used to identify demographic or clinical factors predictive of pain severity (PS) and interference (PI) and to evaluate the association between pain, anxiety/depression, and HRQL. RESULTS: Seventy-one percent of patients reported pain, 26% had clinical depression, and 24% had moderate-severe anxiety. Neither liver disease severity, nor its complications were associated with pain (PS or PI), but anxiety and depression were predictors of pain on bivariate analysis. Only depression remained a significant predictor of PS (b=0.28, P<0.05) and PI (b=0.30, P<0.05) in multivariable models. HRQL was inversely associated with PS, PI, depression, and anxiety, but only anxiety (b=-0.14, P=0.003) remained associated with HRQL in the adjusted model. CONCLUSIONS: Pain is present in over 70% of patients with cirrhosis undergoing liver transplant evaluation. Anxiety and depression were highly correlated with pain and appeared to be key drivers in predicting poor HRQL. Evaluating and managing mental health comorbidities should be explored as a strategy to improve HRQL in patients with cirrhosis and pain.

Association between protein-energy malnutrition and healthcare use among adult patients after liver transplantation: A retrospective cohort study.

BACKGROUND: Protein-energy malnutrition is associated with poor surgical outcomes in liver transplant patients, but its impact on healthcare use has not been precisely characterized. We sought to quantify the burden of protein-energy malnutrition in hospitalized patients undergoing liver transplantation. METHODS: Current Procedural Terminology codes were used to identify United States hospitalizations between 2011 and 2018 for liver transplantation using the Nationwide Inpatient Sample. Patients <18 years old were excluded. Protein-energy malnutrition was identified by International Classification of Diseases Ninth and Tenth Revision codes. Multivariable regression was used to determine associations between protein-energy malnutrition and hospital outcomes, including hospital length of stay and hospital charges/costs. RESULTS: Of 9856 hospitalizations, 2835 (29%) had protein-energy malnutrition. Patients with protein-energy malnutrition had greater comorbidity burden and in-hospital acuity (eg, dialysis, sepsis, vasopressors, or mechanical ventilation). The adjusted median difference of protein-energy malnutrition vs no protein-energy malnutrition for length of stay was 6.4 days (95% CI, 5.6-7.1; P < 0.001), for hospital charges was $108,063 (95% CI, $93,172-$122,953; P < 0.001), and for hospital costs was $23,636 (95% CI, $20,390-$26,882; P < 0.001). CONCLUSION: Among patients undergoing liver transplantation, protein-energy malnutrition was associated with increased length of stay and hospital charges/costs. The additional cost of protein-energy malnutrition to liver transplantation programs was $23,636 per protein-energy malnutrition hospitalization. Our data justify the development of and investment in personnel and programs dedicated to reversing-or even preventing-protein-energy malnutrition in patients awaiting liver transplantation.

The burden of significant pain in the cirrhosis population: Risk factors, analgesic use, and impact on health care utilization and clinical outcomes.

BACKGROUND: We aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population. METHODS: We included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models. RESULTS: Among 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6). CONCLUSIONS: Pain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

Opioid use and risks in liver transplant candidates and recipients.

Opioid use is extremely prevalent among cirrhosis and liver transplant (LT) patients, despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and pre- and post-LT patients specifically. As a result there is significant center-level variability in opioid-related practice and policies. The existing data-largely based on retrospective observational studies-does suggest that opioids are associated with increased health resource utilization pre- and post-LT, and that they may precipitate hepatic encephalopathy (HE) in patients with cirrhosis and increase risk of graft loss and death post-LT. The strongest predictor of opioid use post-LT is opioid use prior to transplant; thus, a focus on safe opioid use in the pre- and peri-transplant periods is essential for minimizing opioid-related harms. We describe three strategies to guide LT providers, including: 1) Improved characterization of pain, mental health symptoms, and opioid and polysubstance use; 2) Minimization of opioid prescriptions for those at highest risk of adverse events; and 3) Safe prescribing strategies for those who do use opioids and for management of opioid use disorder (OUD). Ultimately, our goal is to improve quality of life and transplant outcomes among cirrhosis and LT patients, particularly those living with concurrent pain, mental health, and substance use disorders.

Cirrhosis Inpatients Receive More Opioids and Fewer Nonopioid Analgesics Than Patients Without Cirrhosis.

GOALS/BACKGROUND: Pain is common among cirrhosis patients, particularly those hospitalized with acute illness. Managing pain in this population is challenging due to concern for adverse events and lack of guidelines for analgesic use. We sought to characterize analgesic use among inpatients with cirrhosis compared with matched noncirrhosis controls, as well as hospital-level variation in prescribing patterns. METHODS: We utilized the Vizient Clinical Database, which includes clinical and billing data from hospitalizations at >500 US academic medical centers. We identified cirrhosis patients hospitalized in 2017-2018, and a matched cohort of noncirrhosis patients. Types of analgesic given-acetaminophen (APAP), nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvants (eg, gabapentinoids, antidepressants) were defined from inpatient prescription records. Conditional logistic regression was used to associate cirrhosis diagnosis with analgesic use. RESULTS: Of 116,363 cirrhosis inpatients, 83% received at least 1 dose of an analgesic and 58% had regular inpatient analgesic use, rates that were clinically similar to noncirrhosis controls. Cirrhosis inpatients were half as likely to receive APAP (26% vs. 42%, P <0.01) or NSAIDs (3% vs. 7%, P <0.01), but were more likely to receive opioids (59% vs. 54%, P <0.01), particularly decompensated patients (60%). There was notable variation in analgesic prescribing patterns between hospitals, especially among cirrhosis patients. CONCLUSIONS: Analgesic use was common among inpatients, with similar rates among patients with and without cirrhosis. Cirrhosis patients-particularly decompensated patients-were less likely to receive APAP and NSAIDs and more likely to receive opioid analgesics. Because of lack of evidence-based guidance for management of cirrhosis patients with pain, providers may avoid nonopioid analgesics due to perceived risks and consequently may overutilize opioids in this high-risk population.

Racial and Ethnic Disparities Among Patients Hospitalized for Acute Cholangitis in the United States.

GOALS: We sought to determine whether race/ethnicity is associated with hospitalization outcomes among patients admitted with acute cholangitis. BACKGROUND: Few studies have evaluated the association between race and outcomes in patients with acute cholangitis. STUDY: We analyzed United States hospitalizations from 2009 to 2018 using the Nationwide Inpatient Sample (NIS). We included patients 18 years old or above admitted with an ICD9/10 diagnosis of cholangitis. Race/ethnicity was categorized as White, Black, Hispanic, or Other. We used multivariable regression to determine the association between race/ethnicity and in-hospital outcomes of interest, including endoscopic retrograde cholangiopancreatography (ERCP), early ERCP (<48 h from admission), length of stay (LOS), and in-hospital mortality. RESULTS: Of 116,889 hospitalizations for acute cholangitis, 70% identified as White, 10% identified as Black, 11% identified as Hispanic, and 9% identified as Other. The proportion of non-White patients increased over time. On multivariate analysis controlling for clinical and sociodemographic variables, compared with White patients, Black patients had higher in-hospital mortality (adjusted odds ratio: 1.4, 95% confidence interval: 1.2-1.6, P <0.001). Black patients were also less likely to undergo ERCP, more likely to undergo delayed ERCP, and had longer LOS ( P <0.001 for all). CONCLUSIONS: In this contemporary cohort of hospitalized patients with cholangitis, Black race was independently associated with fewer and delayed ERCP procedures, longer LOS, and higher mortality rates. Future studies with more granular social determinants of health data should further explore the underlying reasons for these disparities to develop interventions aimed at reducing racial disparities in outcomes among patients with acute cholangitis.

Osmotic Demyelination Syndrome in Hospitalized Patients With Cirrhosis: Analysis of the National Inpatient Sample (NIS).

GOAL: Characterize prevalence of osmotic demyelination syndrome (ODS) in hospitalized patients with cirrhosis. BACKGROUND: ODS is a serious complication of rapid serum sodium correction. Patients with cirrhosis experience labile sodium levels related to portal hypertension and diuretic use, often with rapid correction-intentional or unintentional-during hospitalizations. STUDY: We used validated International Classification of Diseases, Ninth Revision (ICD-9) codes to identify inpatients 18 years and older with cirrhosis from the 2009-2013 National Inpatient Sample, excluding those with liver transplantation during hospitalization. The primary outcome was ODS (ICD-9 341.8). Baveno IV defined decompensated cirrhosis (stages 3 and 4); Charlson Comorbidity Index identified severe comorbid illness (score >3). Logistic regression modeled factors associated with ODS. RESULTS: Of 547,544 adult inpatients with cirrhosis, 94 (0.02%) had ODS. Inpatients with versus without ODS were younger (54 vs. 57 y, P=0.0001), and more likely to have alcohol-related cirrhosis (58% vs. 33%, P<0.0001). ODS did not associate with decompensated cirrhosis (33% vs. 37%, P=0.43), specific complications (ascites 33% vs. 33%, P=0.97; hepatic encephalopathy 24% vs. 17%, P=0.06), or severe comorbid illness (12% vs. 16%, P=0.24). In both univariable and multivariable analysis, age [adjusted odds ratio (ORadj): 0.97, 95% confidence interval (CI): 0.95-0.99], female gender (ORadj: 1.53, 95% CI: 1.01-2.30), Hispanic race (ORadj: 0.41, 95% CI: 0.19-0.89), alcohol-related cirrhosis (ORadj: 2.65, 95% CI: 1.71-4.09), and congestive heart failure (ORadj: 0.37, 95% CI: 0.15-0.95) significantly associated with ODS. CONCLUSION: In hospitalized patients with cirrhosis, ODS is extremely rare, and associated with alcohol-related cirrhosis, younger age, and female gender. ODS is not associated with liver disease severity, specific complications including ascites, or comorbid disease.

Association Between Kidney Dysfunction Types and Mortality Among Hospitalized Patients with Cirrhosis.

BACKGROUND AND AIMS: Kidney dysfunction is associated with increased mortality among patients with cirrhosis. We investigated whether kidney dysfunction types [e.g., acute kidney injury (AKI), chronic kidney disease (CKD), and AKI on CKD] were differentially associated with inpatient mortality. METHODS: We utilized the nationwide inpatient sample, a nationally representative database, from 2007 to 2014. We included all hospitalizations with previously validated codes for cirrhosis or associated decompensated cirrhosis diagnoses. We defined kidney dysfunction types also from previously validated codes, and we grouped hospitalizations into the following diagnoses: normal, AKI, CKD, and AKI on CKD. Our primary outcome was inpatient mortality. RESULTS: There were 1,293,779 hospitalizations with cirrhosis sampled in this study. Of these hospitalizations, 849,193 (66%) had normal kidney function, 176,418 (14%) had AKI, 157,600 (12%) had CKD, and 110,568 (9%) had AKI on CKD. We found that the proportion of hospitalizations with AKI, CKD, and AKI on CKD increased significantly throughout the study period (p < 0.001, test for trend for all). Kidney dysfunction type was differentially associated with inpatient mortality, even after adjustment: as compared to those with CKD, normal kidney function: OR 0.75 [95 CI 0.73-0.78], AKI: OR 2.40 [95 CI 2.32-2.48], and AKI on CKD: OR 1.66 [95 CI 1.60-1.72]. DISCUSSION: Using a nationally representative cohort of all hospitalizations with cirrhosis, our study highlights that the burden of kidney dysfunction, especially AKI, among hospitalizations with cirrhosis is rising, and the inclusion of kidney dysfunction type may be an opportunity to improve prognostication.

Patterns of Inpatient Opioid Use and Related Adverse Events Among Patients With Cirrhosis: A Propensity-Matched Analysis.

Pain is common among patients with cirrhosis, yet managing pain in this population is challenging. Opioid analgesics are thought to be particularly high risk in patients with cirrhosis, and their use has been discouraged. We sought to understand patterns of opioid use among inpatients with cirrhosis and the risks of serious opioid-related adverse events in this population. We used the Vizient Clinical Database/Resource Manager, which includes clinical and billing data from hospitalizations at more than 500 academic medical centers. We identified all nonsurgical patients with cirrhosis hospitalized in 2017-2018 as well as a propensity score-matched cohort of patients without cirrhosis. Inpatient prescription records defined patterns of inpatient opioid use. Conditional logistic regression compared rates of use and serious opioid-related adverse events between patients with and without cirrhosis. Of 116,146 nonsurgical inpatients with cirrhosis, 62% received at least one dose of opioids and 34% had regular inpatient opioid use (more than half of hospital days), rates that were significantly higher than in patients without cirrhosis (adjusted odds ratio [AOR] for any use, 1.17; 95% confidence interval [CI], 1.13-1.21; P < 0.001; AOR for regular use, 1.07; 95% CI, 1.02-1.11; P = 0.002). Compared with patients without cirrhosis, patients with cirrhosis more often received tramadol (P < 0.001) and less commonly received opioid/acetaminophen combinations (P < 0.001). Rates of serious opioid-related adverse events were similar in patients with and without cirrhosis (1.6% vs. 1.9%; AOR, 0.96; P = 0.63). Conclusion: Over half of patients with cirrhosis have pain managed with opioids during hospitalization. Patterns of opioid use differ in patients with cirrhosis compared with patients without cirrhosis, although rates of serious adverse events are similar. Future studies should further explore the safety and efficacy of opioids in patients with cirrhosis, with the goal of improving pain management and quality of life in this population.

Women who undergo liver transplant have longer length of stay post-transplant compared with men.

BACKGROUND: Women on the liver transplant waitlist are at greater risk of hospitalization compared with men, but whether this impacts length of stay (LOS) post-transplant is unknown. We aimed to evaluate gender disparities in post-transplant LOS, an important surrogate of health resource utilization post-transplant. METHODS: Using the UNOS/OPTN registry, we analysed all non-Status 1 adult deceased donor liver transplant recipients without exception points from 2008 to 2017. Poisson regression associated female gender with post-transplant LOS. RESULTS: Of 27 294 transplant recipients, 36% were women. Women were more likely to be hospitalized pretransplant than men (44% vs 39%, P < .01). Post-transplant, women were more likely to have prolonged (≥20d) LOS (25% vs 22%, P < .01). In univariable analysis, female gender was associated with longer post-transplant LOS (IRR 1.09, 95%CI 1.06-1.12, P < .01). Prolonged pretransplant admission was also associated with post-transplant LOS (IRR 1.83, 95%CI 1.77-1.89, P < .01). In multivariable analysis, female gender remained independently associated with post-transplant LOS (aIRR 1.05, 95%CI 1.02-1.08, P < .01), after adjustment for age, UNOS region, insurance type, MELDNa, cirrhosis complications, and donor risk index. Pretransplant hospitalization mediated this relationship, explaining 14.1% (95%CI 9.7%-25.4%) of the total effect. CONCLUSIONS: Women who undergo deceased donor liver transplant have increased healthcare utilization in the peritransplant period compared with men. Reducing gender disparities in liver transplantation, including the disproportionate burden of healthcare utilization by women pre- and post-transplant, will require interventions targeted at preventing hospitalization among women on the transplant waitlist and developing tools aimed at better characterizing the severity of end-stage liver disease in women.

Gender Differences Among Patients Hospitalized With Cirrhosis in the United States.

BACKGROUND AND AIMS: Gender disparities exist in outcomes among patients with cirrhosis. We sought to evaluate the role of gender on hospital course and in-hospital outcomes in patients with cirrhosis to help better understand these disparities. STUDY: We analyzed data from the National Inpatient Sample (NIS), years 2009 to 2013, to identify patients with any diagnosis of cirrhosis. We calculated demographic and clinical characteristics by gender, as well as cirrhosis complications. Our primary outcome was inpatient mortality. We used logistic regression to associate baseline characteristics and cirrhosis complications with inpatient mortality. RESULTS: Our cohort included 553,017 patients with cirrhosis admitted from 2009 to 2013. Women made up 39% of the cohort; median age was 57 with 66% non-Hispanic white. Women were more likely than men to have noncirrhosis comorbidities, including diabetes and hypertension but were less likely to have most cirrhosis complications, including ascites and variceal bleeding. Women were more likely than men to have acute bacterial infections (34.9% vs. 28.2%; P<0.001), and were less likely than men to die in the hospital on univariable (odds ratio, 0.88; 95% confidence interval, 0.86-0.90; P<0.001) and multivariable (odds ratio, 0.86; 95% confidence interval, 0.83-0.88; P<0.001) analysis. CONCLUSIONS: In patients hospitalized with cirrhosis, women have lower rates of hepatic decompensating events and higher rates of nonhepatic comorbidities and infections, resulting in lower in-hospital mortality. Understanding differences in indications for and disposition following hospitalization may help with the development of gender-specific cirrhosis management programs to improve long-term outcomes in women and men living with cirrhosis.

Differential Impact of Age Among Liver Transplant Candidates With and Without Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fastest-rising cause of cancer-related mortality in the United States and is a leading indication for liver transplantation (LT). Changes have been noted in the age of the population with chronic liver disease, but how this change affects patients with HCC is unknown. This study aims to characterize trends and transplant-associated outcomes among patients ≥65 years old listed for LT with HCC. Using the United Network for Organ Sharing database, we analyzed all patients ≥18 years old listed for LT during 2003-2017 in the United States in 2 groups (<65 or ≥65 years). Time trends between HCC and non-HCC patients were compared and stratified by disease etiology. Competing-risks and Cox proportional hazards regressions associated HCC and age with wait-list and post-LT survival. There were 161,724 LT candidates included: 14% were ≥65 years old at listing and 25% had HCC. The proportion of patients ≥65 years old rose significantly faster among those with HCC, as compared with those without HCC (Δ = 0.80; P < 0.001). Age ≥65 years was significantly associated with both wait-list mortality (adjusted subhazard ratio, 1.51; 95% confidence interval [CI], 1.40-1.64) and post-LT mortality (adjusted hazard ratio, 1.50; 95% CI, 1.41-1.60) in the multivariate analysis. There were significant interactions between age and HCC on both wait-list (P < 0.001) and post-LT mortality (P = 0.04), suggesting that older age does not impact patients with HCC as much as patients without HCC. The proportion of older adults with HCC listed for LT has nearly tripled from 2003 to 2017, and the rapidly growing population of older adults with HCC may provide an opportunity to expand LT access without compromising outcomes.

Hospitalized Women With Cirrhosis Have More Nonhepatic Comorbidities and Associated Complications Than Men.

Gender differences in the natural history of chronic liver disease have been well-described. Women have lower rates of chronic liver disease and slower fibrosis progression, yet higher rates of waitlist mortality.1,2 Although previous studies have identified several clinical factors including height and creatinine that explain some of this transplant disparity, most have used data from administrative records, which are limited in their ability to identify clinically relevant differences and opportunities for intervention to reduce disparities.3-5 Additionally, most studies have focused on the period between waitlist and transplant, failing to capture gender differences in access to transplant.3,6 In the present study, we took advantage of a multicenter inpatient cohort with granular clinical data to characterize how women and men with cirrhosis differ, to stimulate future research aimed at reducing the well-established gender disparity in liver transplantation.

Women on the liver transplantation waitlist are at increased risk of hospitalization compared to men.

BACKGROUND: Hospital admissions are common among patients with cirrhosis, but patient factors associated with hospitalization have not been well characterized. Given recent data suggesting increased liver transplant waitlist dropout among women, we hypothesized that women on the liver transplant waitlist would have increased rates of hospitalization compared with men. AIM: To evaluate the role of gender on risk of hospitalization for patients on the liver transplant waitlist, in order to help explain gender disparities in waitlist outcomes. METHODS: Patients listed for liver transplant at a single center in the United States were prospectively enrolled in the Functional Assessment in Liver Transplantation Study. Patients included in this retrospective analysis included those enrolled between March 2012 and December 2014 with at least 12 mo of follow up and without hepatocellular carcinoma. The primary and secondary outcomes were hospitalization and total inpatient days within 12 mo, respectively. Logistic and negative binomial regression associated baseline factors with outcomes. RESULTS: Of the 392 patients, 41% were female, with median (interquartile range) age 58 years (52-63) and model for end- stage liver disease 18 (15-22). Within 12 mo, 186 (47%) patients were hospitalized ≥ 1 time; 48% were readmitted, with a median of 8 (4-15) inpatient days. More women than men were hospitalized (54% vs 43%; P = 0.03). In univariable analysis, female sex was associated with an increased risk of hospitalization [odds ratios (OR) 1.6, 95% confidence interval (CI) 1.0-2.4; P = 0.03], which remained significant on adjusted multivariable analysis (OR 1.6, 95%CI: 1.1-2.6; P = 0.03). Female gender was also associated with an increased number of inpatient days within 12 mo in both univariable and multivariable regression. CONCLUSION: Women with cirrhosis on the liver transplant waitlist have more hospitalizations and inpatient days in one year compared with men, suggesting that the experience of cirrhosis differs between men and women, despite similar baseline illness severity. Future studies should explore gender-specific vulnerabilities to help explain waitlist disparities.

Acetaminophen-induced Acute Liver Failure Is More Common and More Severe in Women.

BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described. METHODS: We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n = 250) or acetaminophen-induced ALF (n = 912) from January 2000 through September 2016. We analyzed data on patient presentation, disease course, demographics, medical and psychiatric history, medication use, substance use, and details of acetaminophen ingestion. Sex differences in continuous and categorical variables were evaluated by Wilcoxon rank-sum and χ2 analysis or the Fisher exact test. Our primary aim was to evaluate sex differences in the presentation and clinical course of acetaminophen-induced acute liver injury or liver failure, and our secondary goal was to compare overall and transplant-free survival between sexes. RESULTS: Most patients with acetaminophen-induced ALI (68%) or ALF (76%) were women. Higher proportions of women than men had psychiatric disease (60% of women vs 48% of men, P < .01) and had co-ingestion with sedating agents (70% of women vs 52% of men, P < .01)-more than half of which were opioids. Higher proportions of women had severe hepatic encephalopathy (HE) (68% of women vs 58% of men), and required intubation (67% of women vs 59% of men, P values <.03). Higher proportions of women used vasopressors (26% of women vs 19% of men, P = .04) or mannitol (13% of women vs 6% of men, P < .01); proportions of male vs female patients with transplant-free survival were similar (68%). On adjusted analysis, women had higher risk of severe HE (adjusted odds ratio [AOR], 1.66; 95% CI, 1.17-2.35). We found a significant interaction between sex and co-ingestion of sedating agents (P < .01); co-ingestion increased odds of severe HE in women 2-fold (AOR, 1.86; 95% CI, 1.28-2.69; P < .01) but not in men (AOR; 0.62; 95% CI, 0.34-1.13; P = .12). CONCLUSIONS: In an analysis of the Acute Liver Failure Study Group cohort, we found acetaminophen-induced ALI and ALF to be more common among women. Women have greater critical care needs than men, and increased risk for severe HE, which could be due in part to increased use of sedatives. Future studies should investigate sex differences in acetaminophen metabolism and hepatotoxicity, particularly among users of opioids.

Characteristics of paid malpractice claims settled in and out of court in the USA: a retrospective analysis.

OBJECTIVE: An analysis of paid malpractice claims judged in court compared with those settled out of court may help explain perceptions of malpractice risk. DESIGN: A retrospective analysis and cross-sectional comparison of malpractice claims. Evaluated trends in the number and proportion of paid claims, and mean payment amount by resolution type; identified patient, physician and claim characteristics associated with each resolution type. Examined the effects of resolution type on payment amount and time to claim resolution. SETTING: Claims paid on behalf of US physicians reported in the National Practitioner Data Bank (NPDB) from 2005 to 2009. MAIN OUTCOME MEASURES: Type of resolution, claim characteristics, payment amount and time to resolution. RESULTS: Between 2005 and 2009, there were 58 667 claims paid on behalf of US physicians. Of these paid claims, 56 850 (96.9%) were settled outside court, and 1817 (3.1%) were judged in court. There was no significant change in the proportion of paid claims resolved by settlement versus judgement over time (p=0.83); nor was there a significant change in the mean payment amount in either resolution group (settlement, p=0.94; judgement, p=0.36). The claims in which the physicians were under 50, had prior malpractice reports, which were paid by a state malpractice programme, for adverse events to a fetus, and for surgical or obstetric error were more likely to be judged in court. The mean payment amount (US$592 283 vs US$317 447, p<0.01), per cent of payments over US$1 million (41.82% vs 15.43%, p<0.01), and time to decision (6.50 years vs 4.93 years, p<0.01) were significantly higher in judged claims. CONCLUSIONS: Although only a very small percentage of paid malpractice claims in the USA are judged in court, a number of characteristics differ between settled and judged claims. Such differences may influence perceptions of malpractice risk and future reform efforts.