Assessment of adverse events associated with remdesivir use for coronavirus disease 2019 using real-world data.

Background: Remdesivir has been used for treating patients with moderate to severe coronavirus disease 2019 (COVID-19) although there is conflicting evidence regarding its usefulness. Data regarding its safety largely come from the clinical trials conducted to support its emergency use authorization (EUA). This study aimed to identify the adverse events of remdesivir with disproportionately high reporting using real-world data.Research design and methods: The adverse event reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) by health-care professionals for drugs that have received EUA or approved for the treatment of COVID-19 in the US were studied. Adisproportionality analysis was performed to determine adverse events more frequently reported with remdesivir compared with other COVID-19 drugs in the database.Results: Elevated liver enzymes, acute kidney injury, raised blood creatinine levels, bradycardia, cardiac arrest, and death had disproportionately higher reporting with remdesivir as asuspect drug compared with other drugs. There is no significant difference in the reporting of these events based on patient sex or age.Conclusions: Our study confirms the drug label information regarding liver enzyme elevation. The renal and cardiac safety signals identified necessitate reevaluation for potential drug-labeling changes.

Advanced liver function assessment in patients with intestinal failure on long-term parenteral nutrition.

BACKGROUND & AIMS: Intestinal failure associated liver disease (IFALD) is one of the leading complications and causes of deaths in adult patients receiving home parenteral nutrition for chronic intestinal failure (CIF). Early diagnosis of IFALD is key to alleviate the progression of hepatic dysfunction. The aim of this study was to evaluate the capability of noninvasive liver function tests. METHODS: 90 adult patients with CIF receiving long-term home parenteral nutrition were included in a prospective cross-sectional study at our department between 2014 and 2017. All participants underwent dynamic liver function assessment (maximum liver function capacity [LiMAx] test, indocyanine green [ICG] test), transient elastography (FibroScan), blood tests and comprehensive nutritional status assessment. Univariate and multivariable analysis were performed to identify predictors of liver function. RESULTS: LiMAx, ICG test, and FibroScan highly correlated with standard liver function tests. Multivariable analysis identified intact ileum (B = 520.895; p = 0.010), digestive anatomy type 3 (B = 75.612; p = 0.025), citrulline level (B = 3.428; p = 0.040), parenteral olive oil intake (B = -0.570; p = 0.043), and oral intake (B = 182.227; p = 0.040) as independent risk factors affecting liver function determined by LiMAx test. ICG test and FibroScan showed no correlation with gastrointestinal and nutrition-related parameters. CONCLUSION: The LiMAx test is significantly associated with widely accepted risk factors for IFALD by multivariable analysis, whereas ICG test and FibroScan failed to show significant correlations. Liver function assessment by LiMAx test may therefore have the potential to detect alterations in liver function and identify patients at risk for the development of IFALD. Longitudinal studies are needed to investigate the impact of liver function determined by LiMAx test on long-term outcome in patients with CIF.

Receipt of American Heart Association-Recommended Preconception Health Care Among Privately Insured Women With Congenital Heart Defects, 2007-2013.

Background Our objective was to estimate receipt of preconception health care among women with congenital heart defects (CHD), according to 2017 American Heart Association recommendations, as a baseline for evaluating recommendation implementation. Methods and Results Using 2007 to 2013 IBM MarketScan Commercial Databases, we identified women with CHD diagnosis codes ages 15 to 44 years who became pregnant and were enrolled in health insurance for ≥11 months in the year before estimated conception. We assessed documentation of complete blood count, electrolytes, thyroid-stimulating hormone, liver function, ECG, comprehensive echocardiogram, and exercise stress test, using procedural codes, and outpatient prescription claims for US Food and Drug Administration category D and X cardiac-related medications. Differences were examined according to CHD severity, age, region of residence, year of conception, and documented encounters at obstetric and cardiology practices. We found 2524 pregnancies among 2003 women with CHD (14.4% severe CHD). In the 98.3% of women with a healthcare encounter in the year before conception, <1% received all and 22.6% received no American Heart Association-recommended tests or assessments (range: 54.4% for complete blood count to 3.1% for exercise stress test). Women with the highest prevalence of receipt of recommended care were 35 to 44 years old, pregnant in 2012 to 2013, or had a documented obstetric or cardiology encounter in the year before conception (P<0.05 for all). In 9.0% of pregnancies, ≥1 prescriptions for US Food and Drug Administration category D or X cardiac-related medications were filled in the year before conception. Conclusions A low percentage of women with CHD received American Heart Association-recommended preconception health care in the year before conception.

Controlled attenuation parameter for the assessment of liver steatosis in comparison with liver histology: a single-centre real life experience.

BACKGROUND AND AIMS: Accurate diagnosis and staging of non-alcoholic fatty liver disease are essential for the management of this disorder. Controlled attenuation parameter (CAP) has been suggested as a new noninvasive measurement made during transient elastography to assess liver steatosis. The aim of this study was to evaluate CAP as a diagnostic tool for identifying the presence and degree of hepatic steatosis in consecutive patients in an outpatient liver unit of a tertiary centre. METHODS: Between March 2015 and August 2016, all patients who underwent liver biopsy underwent liver stiffness measurement with simultaneous CAP determination using the FibroScan® M or XL probe. Steatosis, inflammatory activity and fibrosis were assessed using the histological SAF scoring system. In addition, fibrosis was scored according to the METAVIR system, and body mass index (BMI) and the underlying liver disease were also recorded. RESULTS: 224 patients were included in the analysis; 146 (65.2%) were male. Steatosis grades were distributed as follows: S0 n = 85 (37.9%), S1 n = 82 (36.6%), S2 n = 33 (14.7%), S3 n = 24 (10.7%). Mean BMI was 26.8 kg/m2, for the S0 group 24.9 kg/m2, S1 26.5 kg/m2, S2 27.3 kg/m2 and S3 32.5 kg/m2. The CAP differed significantly between steatosis groups S0 to S3. The area under receiver operating characteristics curve for S0 vs S1–S3 was 0.78, for S0/1 vs S2/3 0.83 and for S0–2 vs S3 0.82. Calculated cut-off values were 258.5 dB/m for S0 vs S1–3, 282.5 dB/m for S0/1 vs S2/3 and 307.5 dB/m for S0–2 vs S3. CONCLUSIONS: CAP values are strongly associated with the degree of steatosis irrespective of the underlying liver disease. Integrating CAP measurements in the standard work-up may identify patients with NAFLD.  .

Assessment of cholestasis in drug-induced liver injury by different methods.

Cholestasis in drug-induced liver injury (DILI) can be assessed by biochemical and pathologic methods, but the agreement between the 2 methods remains unclear.The aim of this study was to identify the accurate method for assessment of cholestasis in DILI.The DILI standard established and revised by the Council for International Organizations of Medical Sciences (CIOMS) (R values were calculated by liver function at different time points), cholestatic liver disease guideline (European Association for the Study of the Liver, EASL), and liver pathology were used to assess, compare, and analyze the cholestasis in 133 patients with DILI.The R values at different time points in CIOMS standard had no statistical difference for the assessment of cholestatic DILI (a = 0.05, χ = 1.51, P = .679). There were statistical differences among the results of CIOMS, EASL, and pathology (a = 0.05, χ = 99.97, P < .001). EASL standard had no statistical difference with pathology (a = 0.003, χ = 8.00, P = .005).CIOMS and EASL standards based on biochemical parameters underestimated cholestatic DILI, as compared to liver pathology.

Predictive Variables for Abnormal Comprehensive Metabolic Panel Testing and Potential Cost Savings in Children Receiving Pediatric Emergency Department Care.

OBJECTIVE: The aim of this study was to determine variables predictive of abnormal comprehensive metabolic panel (CMP) results in pediatric emergency department (PED) patients and the potential cost savings of a basic metabolic panel (BMP) versus a CMP. METHODS: This is a retrospective cross-sectional descriptive study of children (<18 y) at an urban academic PED (annual census, 22,000). Clinical data included 12 clinical variables: right upper quadrant pain, overdose, emesis, liver disorder, malignancy, heart disease, bleeding disorder, jaundice, right upper quadrant tenderness, hepatomegaly, ascites/peripheral edema and shock, and the liver function test (LFT) results not in a BMP (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total protein, and albumin). RESULTS: There were 207 children in the study population. The mean age was 8 years. There were 106 boys (51%).Variables significantly associated with abnormal LFT result were history of liver disease (P = 0.007), history of heart disease (P = 0.040), jaundice (P = 0.045), and hepatomegaly (P = 0.048). The false-negative rate was 16%. However, of the 10 patients for whom this false-negative rate remained true, the LFT values were marginally abnormal, and performance of further investigation of these results was minimal to none. There were 66 patients with no clinical variables and normal CMP results. With a cost difference of $21 between BMP and CMP, this gives a potential savings of $7125 if extrapolated for 1 year in our PED. CONCLUSIONS: Limiting testing to a BMP for patients with none of the 12 clinical variables has the potential annual cost savings of $7125.

Reducing liver function tests for statin monitoring: an observational comparison of two clinical commissioning groups.

BACKGROUND: Current liver function testing for statin monitoring is largely unnecessary and costly. Statins do not cause liver disease. Both reduction in test frequency and use of a single alanine transaminase (ALT) rather than a full seven analyte liver function test (LFT) array would reduce cost and may benefit patients. AIM: To assess LFT testing in relation to statin use and evaluate an intervention to reduce full-array LFTs ordered by GPs for statin monitoring. DESIGN AND SETTING: Two-year cross-sectional time series in two east London clinical commissioning groups (CCGs) with 650 000 patients. One CCG received the intervention; the other did not. METHOD: The intervention comprised local guidance on LFTs for statin monitoring and access to a single ALT rather than full LFT array. RESULTS: Of the total population, 17.6% were on statins, accounting for 43.2% of total LFTs. In the population without liver disease, liver function tests were 3.6 times higher for those on statins compared with those who were not. Following intervention there was a significant reduction in the full LFT array per 1000 people on statins, from 70.3 (95% confidence interval [CI] = 66.3 to 74.6) in the pre-intervention year, to 58.1 (95% CI = 55.5 to 60.7) in the post-intervention year (P<0.001). In the final month, March 2016, the rate was 53.2, a 24.3% reduction on the pre-intervention rate. CONCLUSION: This simple and generalisable intervention, enabling ordering of a single ALT combined with information recommending prudent rather than periodic testing, reduced full LFT testing by 24.3% in people on statins. This is likely to have patient benefit at reduced cost.

Extensive testing or focused testing of patients with elevated liver enzymes.

BACKGROUND & AIMS: Many patients have elevated serum aminotransferases reflecting many underlying conditions, both common and rare. Clinicians generally apply one of two evaluative strategies: testing for all diseases at once (extensive) or just common diseases first (focused). METHODS: We simulated the evaluation of 10,000 adult outpatients with elevated with alanine aminotransferase to compare both testing strategies. Model inputs employed population-based data from the US (National Health and Nutrition Examination Survey) and Britain (Birmingham and Lambeth Liver Evaluation Testing Strategies). Patients were followed until a diagnosis was provided or a diagnostic liver biopsy was considered. The primary outcome was US dollars per diagnosis. Secondary outcomes included doctor visits per diagnosis, false-positives per diagnosis and confirmatory liver biopsies ordered. RESULTS: The extensive testing strategy required the lowest monetary cost, yielding diagnoses for 54% of patients at $448/patient compared to 53% for $502 under the focused strategy. The extensive strategy also required fewer doctor visits (1.35 vs. 1.61 visits/patient). However, the focused strategy generated fewer false-positives (0.1 vs. 0.19/patient) and more biopsies (0.04 vs. 0.08/patient). Focused testing becomes the most cost-effective strategy when accounting for pre-test probabilities and prior evaluations performed. This includes when the respective prevalence of alcoholic, non-alcoholic and drug-induced liver disease exceeds 51.1%, 53.0% and 13.0%. Focused testing is also the most cost-effective strategy in the referral setting where assessments for viral hepatitis, alcoholic and non-alcoholic fatty liver disease have already been performed. CONCLUSIONS: Testing for elevated liver enzymes should be deliberate and focused to account for pre-test probabilities if possible. LAY SUMMARY: Many patients have elevated liver enzymes reflecting one of many possible liver diseases, some of which are very common and some of which are rare. Tests are widely available for most causes but it is unclear whether clinicians should order them all at once or direct testing based on how likely a given disease may be given the patient's history and physical exam. The tradeoffs of both approaches involve the money spent on testing, number of office visits needed, and false positive results generated. This study shows that if there are no clues available at the time of evaluation, testing all at once saves time and money while causing more false positives. However, if there are strong clues regarding the likelihood of a particular disease, limited testing saves time, money and prevents false positives.

Frequency of Disparities in Laboratory Testing After Statin Initiation in Subjects ≥65 Years.

Laboratory testing is important for the safety of older adults initiating statins, but there has been little examination of laboratory testing disparities by race/ethnicity, age, gender, Medicaid eligibility, and multimorbidity. The study's purpose was to examine disparities in guideline-concordant baseline laboratory testing and abnormal laboratory values among a retrospective cohort of 76,868 Medicare fee-for-service beneficiaries from 10 states in the eastern United States who had dyslipidemia and initiated a statin from July 1 to November 30, 2011. Guideline-concordant assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was defined as evidence of an outpatient claim for either test within 180 days before or 14 days after the date of the index statin fill. In 2011, baseline laboratory testing rates were 89.3% for ALT and 88.8% for AST. Older adults were somewhat more likely to have ALT and AST testing if they were dually enrolled in Medicaid (relative risk 1.01, 95% confidence interval [CI] 1.00 to 1.02) or had multiple chronic conditions (relative risk 1.03, 95% CI 1.00 to 1.06 for 2 to 3 conditions; odds ratio [OR] 1.08, 95% CI 1.05 to 1.11 for 4 to 5 conditions; OR 1.14, 95% CI 1.11 to 1.17 for 6+ conditions), compared with 0 to 1 conditions. Non-Hispanic blacks were less likely to receive baseline testing (OR 0.97, 95% CI 0.96 to 0.98) than non-Hispanic Whites, and male beneficiaries were somewhat less likely to receive testing than female beneficiaries (OR 0.99, 95% CI 0.98 to 0.99). Abnormal values were rare. In conclusion, ALT and AST assessment after statin initiation was commonly done as recommended, and there were negligible disparities in testing rates for beneficiaries.

Request of laboratory liver tests in primary care in Spain: potential savings if appropriateness indicator targets were achieved.

AIMS: Liver laboratory tests are used to screen for liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. The aim of this study was to compare the liver laboratory tests requesting patterns by GPs in Spain, according to geographic and hospital characteristics, to investigate the degree of requesting appropriateness. MATERIALS AND METHODS: One hundred and forty-one clinical laboratories were invited to participate from diverse regions across Spain. They filed out the number of laboratory liver tests requested by GPs for the year 2012. Two types of appropriateness indicators were calculated: every test request per 1000 inhabitants or ratios of related tests requests. The indicator results obtained were compared between the different hospitals, according to their setting, location, and management. The savings generated, if each area would have achieved indicator targets, were calculated. RESULTS: We recruited 76 laboratories covering a population of 17,679,195 inhabitants. GPs requested 20,916,780 laboratory liver tests in the year 2012. No differences were obtained according to their setting. Lactate dehydrogenase and direct bilirubin per 1000 inhabitants were significantly higher in institutions with private management. Largest differences were observed between communities. Nine, 31, 0, and 13 laboratories, respectively, achieved the aspartate aminotransferase, lactate dehydrogenase, γ-glutamyl transpeptidase, and total bilirubin-related alanine aminotransferase indicator targets. Reaching ratios would have resulted in savings of €1,028,468. CONCLUSION: There was a high variability in the request of liver tests. This emphasizes the need to implement interventions to improve appropriate use of liver tests.

Doppler assessment of splanchnic arterial flow in patients with liver cirrhosis: correlation with ammonia plasma levels and MELD score.

PURPOSE: To assess the clinical significance of blood flow velocity and resistance index (RI) in the visceral arteries of patients with liver cirrhosis with respect to plasma ammonia (NH3) level and liver function. METHODS: We included 80 patients with liver cirrhosis (58 men) and 20 healthy controls (11 men). Duplex Doppler ultrasonography was used to assess flow velocity and RI in the hepatic (HA), right (RRA), and left renal (LRA), and splenic (SA) (LA) artery. Plasma NH3 was measured by biochemistry. Liver function was assessed by MELD score (model of end-stage liver disease). RESULTS: HA, LRA, and SA systolic flow velocities were greater, whereas RRA diastolic velocity was lower in patients with liver cirrhosis than in controls RI was higher in LRA, RRA, SA, and HA in patients with liver cirrhosis than in controls. NH3 levels were significantly elevated in all patients with liver cirrhosis (p < 0.05) and significantly correlated with RI of RRA, LRA, and SA. CONCLUSION: We found greater renal, hepatic, and LA RI in patients with liver cirrhosis than in healthy controls. The correlation we found between elevated renal artery RI (≥0.70) and MELD score emphasizes the risk of renal dysfunction during progression of liver cirrhosis.

Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS): a prospective cohort study.

OBJECTIVE: To evaluate mildly abnormal liver function test (LFT) results in general practice among patients who do not have known liver disease. DESIGN: Prospective cohort study of people with abnormal LFT results identified in primary care. Participants were intensively investigated using a common protocol and followed up for 2 years. Substudies investigated the psychological sequelae of abnormal test results, clinicians' reasons for testing, decision options when LFT results were abnormal and early detection of liver fibrosis. SETTING: Eleven primary-care practices: eight in Birmingham and three in Lambeth. PARTICIPANTS: Adults with abnormal LFT results who did not have pre-existing or obvious liver disease. Eight analytes were included in the panel of LFTs. MAIN OUTCOME MEASURES: Statistical tests were used to identify the interactions between clinical features, the initial pattern of abnormal LFT results and (1) specific viral, genetic and autoimmune diseases, such as viral hepatitis, haemochromatosis and primary biliary cirrhosis; (2) a range of other serious diseases, such as metastatic cancer and hypothyroidism; (3) 'fatty liver' not associated with the above; and (4) the absence of detectable disease. RESULTS: Fewer than 5% of people with abnormal LFT results had a specific disease of the liver, and many of these were unlikely to need treatment. The diagnostic potential of the LFT panel is largely subsumed into just two analytes: alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Gamma-glutamyltransferase (GGT) offers a small increase in sensitivity at the margin at the cost of a large loss of specificity. Eighty-four per cent of abnormal LFT results remain abnormal on retesting 1 month later. In many cases, carrying out a definitive or specific test will be more efficient than repeating LFTs, with a view to specific testing only if the test remains abnormal. An ultrasound diagnosis of 'fatty liver' was present in nearly 40% of patients with abnormal LFTs and a small amount of weight loss over 2 years was associated with a reduced incidence of liver fat. There was a J-shaped relationship between alcohol intake and fatty liver in men. An abnormal LFT result causes temporary anxiety, which does not appear to promote sustained behaviour change. CONCLUSIONS: Liver disease is rare among people with abnormal LFT results in primary care. Only two analytes (ALT and ALP) are helpful in identifying the majority of liver disease. GGT adds little information in return for a high false-positive rate but it is sensitive to alcohol intake. LFT results seldom revert from abnormal to normal over a 1-month period, and modelling shows that repeating an abnormal LFT panel, as recommended in the current guidelines, is inefficient. LFTs are often undertaken to meet perceived patient need for a blood test, but as they are neither specific nor indicative of any particular disease they are among the least suitable tests for this purpose. Obesity and raised ALT provide strong evidence for a presumptive diagnosis of 'fatty' liver. Abnormal LFTs and 'fatty' liver provoke only short-term anxiety and neither is associated with sustained weight loss. Even a small amount of weight loss reduces liver fat. FUTURE WORK RECOMMENDATIONS: (1) the cases of 'fatty liver' and controls should be followed up in the long term to identify features that predict development of hepatosteatosis and then cirrhosis; (2) the acceptability of replacing the traditional six- to eight-analyte LFT panel with a drop down menu including the ALT/ALP combination should be evaluated. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Comparison of electronic laboratory reports, administrative claims, and electronic health record data for acute viral hepatitis surveillance.

CONTEXT: Public health surveillance systems for acute hepatitis are limited: clinician reporting is insensitive and electronic laboratory reporting is nonspecific. Insurance claims and electronic health records are potential alternative sources. OBJECTIVE: To compare the utility of laboratory data, diagnosis codes, and electronic health record combination data (current and prior viral hepatitis studies, liver function tests, and diagnosis codes) for acute hepatitis A and B surveillance. DESIGN: Retrospective chart review. SETTING: Massachusetts ambulatory practice serving 350 000 patients per year. PARTICIPANTS: All patients seen between 1990 and 2008. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value of immunoglobulin M (IgM), International Classification of Disease-Ninth Revision (ICD-9) diagnosis codes, and combination electronic health record data for acute hepatitis A and B. RESULTS: During the study period, there were 111 patients with positive hepatitis A IgMs, 154 with acute hepatitis A ICD-9 codes, and 77 with positive IgM and elevated liver function tests. On review, 79 cases were confirmed. Sensitivity and positive predictive value were 100% and 71% (95% confidence interval, 62%-79%) for IgM, 94% (92%-100%) and 48% (40%-56%) for ICD-9 codes and 97% (92%-100%) and 100% (96%-100%) for combination electronic health record data. There were 14 patients with positive hepatitis B core IgMs, 2564 with acute hepatitis B ICD-9 codes, and 125 with suggestive combinations of electronic health record data. Acute hepatitis B was confirmed in 122 patients. Sensitivity and positive predictive value were 9.4% (5.2%-16%) and 86% (60%-98%) for hepatitis B core IgM, 73% (65%-80%) and 3.6% (2.9%-4.4%) for ICD-9 codes, and 96% (91%-99%) and 98% (94%-99%) for electronic health record data. CONCLUSIONS: Laboratory surveillance using IgM tests overestimates the burden of acute hepatitis A and underestimates the burden of acute hepatitis B. Claims data are subject to many false positives. Electronic health record data are both sensitive and predictive. Electronic health record-based surveillance systems merit development.

Assessment of liver function among nickel-plating workers in Egypt.

Currently no reports are available from Egypt regarding occupational exposure to nickel and its effects on the liver. The aim of this study was to assess the liver function of workers occupationally exposed to nickel. Standard liver function tests were applied to blood samples from 25 nickel-plating workers in Damietta, Egypt and 30 administrative workers as a reference group. Levels of urine nickel, measured by inductively coupling plasma-emission spectroscopy, were significantly higher in nickel-exposed workers compared with the reference group. The levels of alanine aminotransferase and aspartate aminotransferase were significantly higher in nickel-exposed workers. The level of serum albumin was significantly negatively correlated and the levels of serum aminotransferases, and serum gamma-glutamyl-transpeptidase were significantly positively correlated with urine nickel levels. Liver function is compromised in nickel-plating workers compared with non-exposed administrative workers.

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE).

BACKGROUND: Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs. METHODS/DESIGN: A population-based retrospective cohort study will follow up all those who have had an incident liver function test (LFT) in primary care to subsequent liver disease or mortality over a period of 15 years (approx. 2.3 million tests in 99,000 people). The study is set in Primary Care in the region of Tayside, Scotland (pop approx. 429,000) between 1989 and 2003. The target population consists of patients with no recorded clinical signs or symptoms of liver disease and registered with a GP. The health technologies being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and liver biopsy. The study will utilise the Epidemiology of Liver Disease In Tayside (ELDIT) database to determine the outcomes of liver disease. These are based on hospital admission data (Scottish Morbidity Record 1), dispensed medication records, death certificates, and examination of medical records from Tayside hospitals. A sample of patients (n = 150) with recent initial ALF tests or invitation to biopsy will complete questionnaires to obtain quality of life data and anxiety measures. Cost-effectiveness and cost utility Markov model analyses will be performed from health service and patient perspectives using standard NHS costs. The findings will also be used to develop a computerised clinical decision support tool. DISCUSSION: The results of this study will be widely disseminated to primary care, as well as G.I. hospital specialists through publications and presentations at local and national meetings and the project website. This will facilitate optimal decision-making both for the benefit of the patient and the National Health Service.

Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program.

PURPOSE: Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. METHODS: Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n = 7226) or rosiglitazone (n = 1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. RESULTS: Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two 'Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth 'Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. CONCLUSION: Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented.

[HEPASCORE: a decision-support system for the identification, clinical staging and functional assessment of hepatopathies]. / HEPASCORE: un sistema di supporto alla decisione per l'identificazione, la stadiazione clinica e la valutazione funzionale delle epatopatie.

A decision support system (HEPASCORE) has been developed to optimize the application of objective criteria for qualitative and quantitative assessment of liver function; clinical and laboratory data are automatically processed, and conclusions are explained. Early recognition of abnormal liver states is performed according to a sequential approach, based at first on clinical rules utilizing data from history and physical examination, then confirming or denying the hypothesis by means of selected laboratory tests. Once an abnormal condition is defined, clinical severity can be evaluated by use of suitable scores, either prognostic or focused on major clinical complications. In addition, selected sets of biochemical tests can be used to score one or more functional aspects. Lastly, whenever quantitative estimates of residual liver function are requested, dynamic tests can be applied to measure meaningful parameters such as functioning liver mass and functional hepatic plasma flow. HEPASCORE has been successfully applied to exclude liver abnormalities in subjects at risk, to follow up liver patients, to predict the natural outcomes of severe liver diseases, to foresee the adverse effects of drugs undergoing first-pass liver extraction and the side effects of invasive procedures. While the proposals contained in the system could be further modified for specific needs, they reflect a satisfactory methodological approach, and the program serves as a useful support to decisions regarding the identification and functional evaluation of hepatopathies. The system was developed with Microsoft Access 7.0 and runs on a personal computer under Windows 95.

Evaluation of various models of hyaluronan kinetics for assessment of liver function.

The purpose of this study of various models of hyaluronan kinetics has been to find the most appropriate model for estimation of parameters which characterize liver endothelial cell function. Five theoretical models for serum hyaluronan distribution and elimination were evaluated by computer analysis of serial measurements of the mass concentration of hyaluronan in serum following an intravenous bolus dose. Three of the models were based on one-compartment distribution of intravenously injected hyaluronan. Model 1A, with assumed first-order elimination, was found to be compatible with measured data and had identifiable parameters. Model 1B, with assumed non-linear Michaelis-Menten kinetics, was also found to be compatible but the Michaelis-Menten constant (K(m)) was not well determined. In model 1C, with non-linear Michaelis-Menten elimination kinetics, K(m) was set to a fixed value of 340 micrograms l-1, and the remaining parameters were well determined and the model was found to be compatible. Two models with an assumed two-compartment distribution of intravenously injected hyaluronan, were not acceptable due to unidentified parameters not discriminating between patients and healthy persons. In conclusion, model 1C, with one-compartment distribution and non-linear Michaelis-Menten kinetics, best fulfilled the criteria of validity and was accepted for further evaluation of clinical materials.

Pronóstico vital en insuficiencia hepática aguda grave: valor de los índices cuantitativos de evaluación / Life prognosis in severe acute hepatic failure: value of assessment quantitative index

The aim of this study was to assess the predictive value for mortality of admission and daily APACHE II score, mortality due to multiple organ failure and the organ failure score in patients with acute hepatic failure. We retrospectively studied 15 such patients admitted to an intensive care unit. Thirteen patients died (87 percent) and their admission APACHE II score was 22ñ7.5 compared to 21ñ8.5 in survovors. Daily APACHE II score, mortality due to multiple organ failure and multiple organ failure score had a 100 percent sensitivity to predict mortality and a 69.2, 76.9 and 76.9 percent specificity respectively. The predictive accuracies of multiple organ failure and multiple organ failure score were 80 percent and significantly better than the accuracy of admission APACHE II score (53 percent). We conclude that these prognostic scores can be useful in the assessment of patients with acute hepatic failure