Indeterminate etiology of acute liver failure in North America: Less common, still grave prognosis.

BACKGROUND: The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND-ALF). In this study, we summarize findings from patients with IND-ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND-ALF. METHODS: Between 1998 and 2019, 3364 adult patients with ALF or acute liver injury (ALI) from 32 liver transplant centers were enrolled in the ALFSG registry. The primary clinical outcome of interest was 21-day transplant-free survival (TFS). RESULTS: Of the 3364 patients enrolled in the ALFSG registry, 3.4 % (n = 114) were adjudicated as true indeterminate. On multivariate analysis, patients with a lower bilirubin, lower INR, lack of use of mechanical ventilation and no clinical features of coma at baseline had a higher odds ratio of transplant free survival. The number of deaths were similar between patients with true-IND ALF versus patients with indeterminable ALF (29.8% vs. 27.2%), with almost half of the patients requiring liver transplant (42.1% vs. 45.7%). CONCLUSION: We illustrate the poor prognoses that true-IND-ALF and indeterminable ALF carry and the need for emergency liver transplantation in most cases.

Acute Liver Failure Guidelines.

Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.

Autoimmune hepatitis presenting as acute liver failure: A 20-year retrospective review of North America.

Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival. This study included adults hospitalized with acute liver failure enrolled in the Acute Liver Failure Study Group Registry between 1998 and 2019 from 32 centers within the US. The etiology of all cases was reviewed by the Adjudication Committee, and all cases identified as autoimmune hepatitis were included. Acute liver injury was defined as an INR ≥2.0 without encephalopathy and acute liver failure as INR ≥ 1.5 with encephalopathy. Laboratory and clinical data were reviewed. Variables significantly associated with 21-day transplant-free survival were used to develop a multivariable logistic regression model.  A total of 193 cases of acute liver failure secondary to autoimmune hepatitis were identified and reviewed. There were 161 patients (83.4%) diagnosed with acute liver failure on enrollment, and 32 (16.6%) developed acute liver failure during hospitalization. At 21 days, 115 (59.6%) underwent liver transplantation, 28 (14.5%) had transplant-free survival, and 46 (23.8%) died before liver transplantation. Higher admission values of bilirubin, INR, and coma grade were associated with worse outcomes. A prognostic index incorporating bilirubin, INR, coma grade, and platelet count had a concordance statistic of 0.84. Acute liver failure secondary to autoimmune hepatitis is associated with a high short-term mortality. We developed a model specifically for autoimmune hepatitis that may be helpful in predicting 21-day transplant-free survival and early identification of patients in need of expedited liver transplant evaluation.

Modifying Text Messages from a Faith-Based Physical Activity Intervention with Latino Adults in Response to the COVID-19 Pandemic.

BACKGROUND: Text messages are useful for health promotion and can be modified during public health emergencies. PURPOSE: Describe how we developed and implemented a physical activity (PA) text messaging component within a faith-based intervention, modified the text message content in response to the COVID-19 pandemic and evaluated participants' perceptions of the modified text messages. RESEARCH DESIGN AND STUDY SAMPLE: PA promotion text messages were delivered to predominately Spanish-speaking, churchgoing Latino adults (n = 284) in Los Angeles, California. In 2020, we modified the messages to disseminate COVID-19-related information and support and share virtual PA resources. DATA COLLECTION AND ANALYSIS: We analyzed quantitative and qualitative survey data to gauge participants' experiences with the text messages. RESULTS: COVID-19 related text messages were a feasible, acceptable addition to a PA intervention for a sample of Latinos. CONCLUSIONS: Throughout the pandemic, the messages enabled continued communication and support for PA and protection from COVID-19 in a population at high-risk of health inequities.

Linking churches and parks to promote physical activity among Latinos: Rationale and design of the Parishes & Parks cluster randomized trial.

BACKGROUND: Regular physical activity (PA) contributes to positive health outcomes, but a minority of US adults meet minimum guidelines for moderate-to-vigorous PA (MVPA) and muscle-strengthening, and Latinos are less likely than whites to meet these guidelines. Public parks can be leveraged for community PA but tend to be underutilized, while churches have reach within Latino communities and can influence parishioners' health. METHODS: We are conducting a cluster randomized controlled trial to examine the impact of a multilevel, faith-based intervention linking Catholic parishes (n = 14) to their local parks on adult Latino parishioners' (n = 1204) MVPA and health-related outcomes. Our approach targets multiple levels (individual, group, church, and neighborhood-park) to promote health-enhancing PA through park-based exercise classes led by kinesiology students, peer leader-led walking groups, park-based church events, church-based PA support activities, and environmental advocacy. Data are collected at churches by trained bilingual/bicultural research assistants using accelerometry, surveys, and biometric procedures. We will implement a set of hierarchical repeated-measure linear models to examine effects on the primary outcome (MVPA) and secondary outcomes (self-reported PA, heart rate/fitness, waist circumference, waist-to-hip ratio, body fat, mental health, and perceived social support for PA). We will also conduct a process evaluation. CONCLUSION: To our knowledge, this will be the first study examining efficacy of an integrated church and park-based intervention on Latino adults' PA and represents a scalable model of PA programming for low-income communities. The intervention makes use of innovative partnerships within and across sectors - faith-based, local parks/city government, and local universities - further facilitating sustainability. CLINICALTRIALS: govID: NCT03858868.

Church Contextual Factors Associated With Latinx Physical Activity and Park Use.

Churches can be important settings for promoting physical activity (PA) among Latinx populations. Little is known about what factors across the church context-social, organizational, and physical (outdoor spaces)-are associated with Latinx PA to inform faith-based PA interventions. This study investigated associations of church contextual factors with Latinx PA. We used cross-sectional data from a Latinx adult sample recruited from 6 churches that each had a nearby park in Los Angeles, California (n = 373). Linear or logistic regression models examined associations of church PA social support, PA social norms, perceived quality and concerns about the park near one's church, and church PA programming with 4 outcomes: accelerometer-based moderate-to-vigorous PA (MVPA) and self-reported adherence to PA recommendations, use of the park near one's church, and park-based PA. Park quality and concerns were positively associated with using the park near one's church. Church PA programming was positively associated with park-based PA. None of the factors were related to accelerometer-based MVPA or meeting PA recommendations. Findings suggest targeting church PA programming and nearby parks may be key to improving Latinx park use. Church and local parks department partnerships may help enhance park conditions to support churchgoing Latinx PA and health.

Psychometric Properties of the English-Spanish Vocabulary Inventory in Toddlers With and Without Early Language Delay.

PURPOSE: Despite the increasing population of dual language learners (DLLs) in the United States, vocabulary measures for young DLLs have largely relied on instruments developed for monolinguals. The multistudy project reports on the psychometric properties of the English-Spanish Vocabulary Inventory (ESVI), which was designed to capture unique cross-language measures of lexical knowledge that are critical for assessing DLLs' vocabulary, including translation equivalents (whether the child knows the words for the same concept in each language), total vocabulary (the number of words known across both languages), and conceptual vocabulary (the number of words known that represent unique concepts in either language). METHOD: Three studies included 87 Spanish-English DLLs (M age = 26.58 months, SD = 2.86 months) with and without language delay from two geographic regions. Multiple measures (e.g., caregiver report, observation, behavioral tasks, and standardized assessments) determined content validity, construct validity, social validity, and criterion validity of the ESVI. RESULTS: Monolingual instruments used in bilingual contexts significantly undercounted lexical knowledge as measured on the ESVI. Scores on the ESVI were related to performance on other measures of communication, indicating acceptable content, construct, and criterion validity. Social validity ratings were similarly positive. ESVI scores were also associated with suspected language delay. CONCLUSIONS: These studies provide initial evidence of the adequacy of the ESVI for use in research and clinical contexts with young children learning English and Spanish (with or without a language delay). Developing tools such as the ESVI promotes culturally and linguistically responsive practices that support accurate assessment of DLLs' lexical development. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.17704391.

A Randomized Controlled Trial Assessing the Effectiveness of the Háblame Bebé Mobile Application With Spanish-Speaking Mothers Experiencing Economic Hardship.

PURPOSE: This study examined the effectiveness of a standalone mobile application (app), Háblame Bebé, for use in real-world settings without supplemental human interaction to promote Spanish-speaking mothers' language interactions with their young children and associated child bilingual (Spanish-English) language development. METHOD: Thirty-seven Spanish-speaking Latina mothers with lower incomes and their children were randomly assigned to experimental and wait-list control groups for 12 weeks. The experimental group was introduced to the app to learn how to provide language-promoting strategies in the home language and encouraged to use the app to track child vocabulary growth and overall development. Mother and child outcomes were measured before and after intervention via standardized assessments, direct observations, and parent report. Engagement and social validity data were also gathered. RESULTS: No statistically significant differences were identified between experimental and control groups. However, looking at the magnitude of the difference between groups, child outcomes consistently favored the experimental group (d = 0.2-0.4). Mothers reported high levels of acceptance of the intervention. CONCLUSIONS: Culturally and linguistically responsive app-based interventions have the potential to serve as a unique delivery model for speech-language pathologists and other professionals to share critical information on bilingual language development with parents of young children who are learning in a bilingual context. Clinical and research implications are discussed, including the consideration that low-intensity interventions may need to be paired with ongoing parent coaching. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.18461585.

Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study.

BACKGROUND & AIMS: Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. METHODS: A retrospective review of this prospective, multicenter cohort study of all APAP-ALF patients enrolled during the study period (1998-2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998-2007; recent, 2008-2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). RESULTS: Of 1190 APAP-ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). CONCLUSIONS: TFS in APAP-ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.

Private/marketplace insurance in community health centers 5 years post-affordable care act in medicaid expansion and non-expansion states.

Community health centers (CHCs) play an important role in providing care for the safety net population. After implementation of the Affordable Care Act, many patients gained insurance through state and federal marketplaces. Using electronic health record data from 702,663 patients in 257 clinics across 20 states, we sought to explore the following differences between Medicaid expansion and non-expansion state CHCs: (1) trends in private/marketplace insurance post-expansion, and (2) whether CHC patients retain private/marketplace insurance. We found that patients in non-expansion state CHCs relied more heavily on private/marketplace insurance than patients in expansion states and had increases in private/marketplace-insured visits from 2014 through 2018. Additionally, there appeared to be seasonal variation in private/marketplace-insured visits that were more pronounced in non-expansion states. While a greater percentage of patients in non-expansion states retained private/marketplace insurance than in expansion states, a greater percentage of those who did not retain it became uninsured. In comparison, a greater percentage of patients in expansion states who lost private/marketplace insurance gained other types of health insurance. CHCs' ability to provide adequate care for vulnerable populations relies, in part, on federal grants as well as reimbursement from insurers: decreases in either could result in reduced capacity or quality of care for patients seen in CHCs.

Tobacco use by pregnant Medicaid beneficiaries: Validating a claims-based measure in Oregon.

In Oregon, more than 4 in 5 pregnant women who smoke are covered by Medicaid. Although birth certificate data for smoking during pregnancy are not accessible in a timely manner, Medicaid claims data are available monthly and provide person-level data. This study utilized an individually linked database of Medicaid claims and birth certificate data to compare the prevalence of tobacco use diagnosis codes in Medicaid claims data to self-reported smoking during pregnancy reported on birth certificates. We computed the sensitivity and specificity of Medicaid claims data to ascertain tobacco use during pregnancy compared to self-report on linked birth certificates. Using logistic regression models, we also examined demographic, prenatal care, and behavioral health factors that predicted agreement between claims and birth certificates. From 2008 to 2013, 17.9% of women with Medicaid births reported smoking during pregnancy on birth certificates compared to 3.8% of non-Medicaid births. Tobacco-related claims during pregnancy were present for 12.6% of Medicaid births. Overall agreement between claims and birth certificates rose from 87.0% in 2008 to 90.2% in 2013; sensitivity rose from 43.0% to 62.2%. Sensitivity was lowest for Hispanic women and highest for White women, and declined as maternal education increased. Sensitivity was 33.9 percentage points higher for women with any mental illness diagnosis and 27.3 percentage points higher for women with any substance use disorder diagnosis. Specificity was greater than 95% in all years. Medicaid claims data may help in surveillance of maternal smoking rates and assessment of smoking cessation programs for female Medicaid beneficiaries of reproductive age.

Hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplant.

Hyperammonemia syndrome, with high levels of ammonia and neurologic dysfunction, is a syndrome with historically high mortality that may occur after solid organ transplantation. Recently, this has been associated with infection due to Ureaplasma, mostly following lung transplantation. We describe the first case of hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplantation. Our patient rapidly recovered after specific antibiotic treatment. It is important to consider these infections in the differential diagnosis for encephalopathy post-transplant, as these organisms often do not grow using routine culture methods and polymerase chain reaction testing is typically required for their detection. This is particularly critical after liver transplantation, where a number of other etiologies may be considered as a cause of hyperammonemia syndrome.

Exploring Early Childhood Language Environments: A Comparison of Language Use, Exposure, and Interactions in the Home and Childcare Settings.

Purpose This study was conducted in a large Midwestern metropolitan area to examine the language environments at home and in center-based childcare for young children who are living in poverty. We compared child language use and exposure in the home and childcare settings using extended observations with automated Language Environment Analysis to gain a deeper understanding of the environmental factors that may affect change in language outcomes for young children. Method Thirty-eight children, along with parents (n = 38) and childcare providers (n = 14) across five childcare centers, participated in this study. Each child completed a standardized language assessment and two daylong recordings with Language Environment Analysis to determine the number of adult words, conversational turns, and child vocalizations that occurred in each setting. Data were analyzed at 5-min intervals across each recording. Results Comparisons between home recordings in this sample and a comparison group showed reliably higher rates of adult words and conversational turns in the home setting. Linear mixed-effects regression models showed significant differences in the child language environments, with the home setting providing higher levels of language input and use. These effects were still meaningful after accounting for the time of day, participant demographic characteristics, and child language ability. Conclusions Practical implications for supporting child language development across settings are discussed, and suggestions for further research are provided. Supplemental Material https://doi.org/10.23641/asha.12042678.

Acute Liver Failure of Indeterminate Etiology: A Comprehensive Systematic Approach by An Expert Committee to Establish Causality.

OBJECTIVES: In the United States, the Acute Liver Failure Study Group (ALFSG) registry lists approximately 11% of cases as of indeterminate etiology (IND-ALF) as determined by the respective local site principal investigator (PI). Traditionally, IND-ALF has prompted concern that other viruses or toxins might be implicated. We hypothesized that many IND- ALF cases would have an identifiable etiology upon further investigation. Improving the identification process should reduce the number of truly indeterminate cases. METHODS: Specific definitions for each etiology ("etiology-specific algorithms") were developed by a Causality Adjudication Committee that included six reviewers (each with 20 or more years of experience). Of 2718 patients with ALF, 303 initially deemed IND-ALF by site PIs underwent committee review guided by the algorithms. Acetaminophen (APAP) protein adducts were measured in sera when available, additional HEV testing was performed, and viral sequences sought by microarray analysis and metagenomic next-generation sequencing (mNGS). Study sites were asked to provide liver biopsy and/or explant reports and to update serological findings not reported previously. RESULTS: Nearly half (142, 46.9%) of the 303 IND-ALF cases could be reassigned to a single, defined etiology and rated as highly likely or probable; 11 additional cases, upon review, did not meet ALF criteria. Amongst reassigned etiologies, 45 were previously unrecognized APAP, 34 autoimmune hepatitis (AIH), 24 drug-induced liver injury (DILI), 13 various viral causes, 12 ischemia, and 14 miscellaneous other etiologies. The remaining 150, deemed true IND-ALF, represented just 5.5%. CONCLUSIONS: The indeterminate etiology in ALF includes patients with a diagnosis that is discernible after closer examination. Revision of etiologic diagnoses of indeterminate cases using added testing and expert opinion is useful in understanding all aspects of ALF.

Correction to: Top-down, Bottom-up and Sideways: the Multilayered Complexities of Multi-level Actors Shaping Forest Governance and REDD+ Arrangements in Madre de Dios, Peru.

The article Top-down, bottom-up and sideways: the multilayered complexities of multi-level actors shaping forest governance and REDD+ arrangements in Madre de Dios, Peru, written by Dawn Rodriguez-Ward, Anne M. Larson, Harold Gordillo Ruesta, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 3 January 2018 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on (25 April 2018) to

Top-down, Bottom-up and Sideways: The Multilayered Complexities of Multi-level Actors Shaping Forest Governance and REDD+ Arrangements in Madre de Dios, Peru.

This study examines the role multilevel governance plays in the adoption of sustainable landscape management initiatives in emerging arrangements aimed at reducing emissions from deforestation and forest degradation (REDD+). It sheds light on the challenges these multiple layers of actors and interests encounter around such alternatives in a subnational jurisdiction. Through transcript analysis of 93 interviews with institutional actors in the region of Madre de Dios, Peru, particularly with regard to five sites of land-use change, we identified the multiple actors who are included and excluded in the decision-making process and uncovered their complex interactions in forest and landscape governance and REDD+ arrangements. Madre de Dios is a useful case for studying complex land-use dynamics, as it is home to multiple natural resources, a large mix of actors and interests, and a regional government that has recently experienced the reverberations of decentralization. Findings indicate that multiple actors shaped REDD+ to some extent, but REDD+ and its advocates were unable to shape land-use dynamics or landscape governance, at least in the short term. In the absence of strong and effective regional regulation for sustainable land use alternatives and the high value of gold on the international market, illegal gold mining proved to be a more profitable land-use choice. Although REDD+ created a new space for multilevel actor interaction and communication and new alliances to emerge, the study questions the prevailing REDD+ discourse suggesting that better coordination and cooperation will lead to integrated landscape solutions. For REDD+ to be able to play a role in integrated landscape governance, greater attention needs to be paid to grassroots actors, power and authority over territory and underlying interests and incentives for land-use change.

Conceptualizing a Public Health Prevention Intervention for Bridging the 30 Million Word Gap.

Early childhood experience is a social determinant of children's health and well-being. The well-being of young children is founded on their relationships and interactions with parents and family members in the home, caregivers, and teachers in early education, and friends and families in the greater community. Unfortunately, the early language experience of infants and toddlers from low-income families is typically vastly different than children from middle- and higher-income families. Hart and Risley (Meaningful differences in the everyday experience of young American children. Brookes, Baltimore, 1995) described a "30 Million Word Gap" experienced by age four for children from poor families compared to economically advantaged families as measured by the number of words delivered by adults in the home to their children. This discrepancy between groups is associated with a deficit in vocabulary growth over time (Hart and Risley in Meaningful differences in the everyday experience of young American children. Brookes, Baltimore, 1995; in The social world of children learning to talk. Brookes, Baltimore, MD, 1999; in Am Educ (Spring), 1-9. http://isites.harvard.edu/fs/docs/icb.topic1317532.files/09-10/Hart-Risley-2003.pdf , 2003), and readiness when they enter preschool and kindergarten compared to their more advantaged classmates. The purpose of this paper is to conceptualize a population-level public health prevention approach to research addressing the harmful impacts of the Word Gap. The approach includes use of evidence-based practices to improve children's language environments to foster their early language and literacy learning in early childhood. After a brief review of the Word Gap, we discuss four aspects: a conceptual framework, a community leadership team as driver of the local intervention, evidence-based language interventions for reducing the gap and promoting child language, and the measurements needed. Implications are discussed.

State Clean Indoor Air Laws and smoking among adults with poor mental health.

Persons with mental illness smoke at twice the rate of the general United States (US) population and die an average of 25-years younger, often from preventable diseases. This study seeks to determine whether disparities in smoking have increased over the past decade and whether Clean Indoor Air Laws (CIALs) are associated with changes in smoking among those with poor mental health. We used a fixed-effects model for estimation. CIALs were associated with 15 per cent decreased odds of smoking among adults in the US. Among those with poor mental health, these same laws had no effect. Between 2000 and 2010, the disparity in smoking rates between these two populations has steadily increased from 1.8 to 2.2 times greater. Given the lack of association between tobacco laws and smoking among those with poor mental health, alternative and more targeted tobacco reduction efforts may be necessary.

Outcomes in Adults With Acute Liver Failure Between 1998 and 2013: An Observational Cohort Study.

BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. DESIGN: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440). SETTING: 31 liver disease and transplant centers in the United States. PATIENTS: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. LIMITATIONS: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. CONCLUSION: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.