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Biomedical subjects

K D Mullen

Publications and source records attributed to K D Mullen.

At least 19 recordsLinked to original sources
PubMed2001

A randomized, double-blind controlled trial of interferon alpha-2b and ribavirin vs. interferon alpha-2b and amantadine for treatment of chronic hepatitis C non-responder to interferon monotherapy.

BACKGROUND/AIMS: Interferon-based regimens (alone or with ribavairin) are standard therapies for chronic hepatitis C. The aim of this study was to compare a 24-week regimen of interferon alpha-2b + ribavirin (IFN + RIBA) to interferon alpha-2b + amantadine (IFN + AMANT) in non-responders to previous interferon monotherapy. METHODS: In a multi-center, double-blind clinical trial, 118 patients (non-responders to previous interferon monotherapy) were equally randomized into the two arms: interferon alpha-2b (3 MU thrice weekly) and ribavirin (800 mg daily) vs. interferon alpha-2b (3 MU thrice weekly) and amantadine (200 mg daily). RESULTS: After 24 weeks of therapy, HCV RNA became undetectable in 34.8% (95% CI: 23.7-49.2) of IFN + RIBA and 19.6% (95% CI: 10.6-34.7) of IFN + AMANT (P = 0.10). This response was sustained in 3.9% (95% CI: 1.0-14.9) of IFN + RIBA and 0% of IFN + AMANT (P = 0.16). Ten patients from IFN + AMANT (17%) and 12 patients (20%) from IFN + RIBA were discontinued before completion of therapy. Of these, 7% in IFN + AMANT and 12% in IFN + RIBA were discontinued due to adverse effects. CONCLUSIONS: Re-treatment of interferon non-responders with a 24-week course of IFN + AMANT was not associated with any sustained viral eradication. Although IFN + RIBA in this group was associated with a reasonable end of treatment response, relapses were common and sustained responses were low.

Adult↗
PubMed2000

Completion of upper endoscopic procedures despite paradoxical reaction to midazolam: a role for flumazenil?

Paradoxical excitation after benzodiazepine administration is well described. Although it is relatively uncommon, its occurrence can severely impede or even prevent the performance of upper endoscopy. We describe three cases in which paradoxical reactions to midazolam responded so well to flumazenil administration that the procedure was successfully completed in each instance. We review the limited literature on this topic and suggest that flumazenil may have greater utility in the management of this particular problem than is considered at present.

Adult↗
PubMed2000

Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease.

OBJECTIVE: Thrombocytopenia or leukopenia in patients with chronic liver disease is often attributed to functional overactivity of the spleen (hypersplenism). Despite being a fairly common phenomenon, there is a paucity of reports on the prevalence of this syndrome in stable chronic liver disease patients with or without severe fibrosis/cirrhosis. The aim of this study was to establish the prevalence of peripheral blood cytopenia in patients with nonalcoholic cirrhosis/severe fibrosis versus patients with mild or no fibrosis on liver biopsy. METHODS: This is a retrospective chart review of 235 patients who underwent a liver biopsy. One hundred ninety-one patients met strict criteria for study entry; 28 different clinical and laboratory variables were collected from their charts review, and data were then analyzed using the SPSS statistical package. RESULTS: Of the cirrhotic patients, 64% were noted to have platelet counts consistently below 150,000 (lower limit of normal in our laboratory; mean, 144.6 +/- 89.4; median, 114), whereas only 5.5% of noncirrhotic patients had thrombocytopenia (mean, 252.2 +/- 103.4; median, 238). Leukopenia (WBC, <3,500) was relatively rare in the cirrhotic/fibrotic group, having a prevalence of 5% (7.59 +/- 4.3) versus 3.3% (10.62 +/- 14.2) of noncirrhotic patients. CONCLUSIONS: Of the patients with cirrhosis, 64% had thrombocytopenia (platelet count, <150,000). The likelihood ratio of finding a platelet count of <100,000 in patients with cirrhosis, as opposed to patients without cirrhosis, is almost 12.

Biopsy, Needle↗
PubMed1999

Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon. The Consensus Interferon Study Group.

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment with consensus interferon (CIFN). Some nonresponders to initial IFN treatment have a transient response defined as undetectable HCV RNA or normalization of ALT during treatment, but subsequently have a "breakthrough" while still on treatment. The aim of this study was to determine if nonresponders who had breakthroughs responded differently to CIFN retreatment than nonresponders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 mcg CIFN or 3 MU IFN-alpha2b 3 times per week). HCV-RNA breakthroughs were observed in 86 of 467 (18%) of all treated patients, and ALT breakthroughs were observed in 90 of 467 (19%) of all treated patients. There was no association between breakthroughs and the presence of either binding or neutralizing anti-IFN antibodies. When the patients who were nonresponders to initial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared with 8% in prior nonresponders without breakthroughs (P =.102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in those without breakthroughs (P =.014). The data suggest that prior nonresponders with breakthroughs have a greater chance of responding to retreatment than do nonresponders without breakthroughs. However, most breakthrough patients would be missed unless repeated HCV-RNA testing were conducted during therapy.

Alanine Transaminase↗
PubMed1999

A continuous quality improvement initiative reduces inappropriate prescribing of prophylactic antibiotics for endoscopic procedures.

OBJECTIVE: Despite the availability of guidelines, most gastroenterologists do not administer prophylactic antibiotics appropriately to patients having endoscopic procedures. In 1994 we recognized that in our endoscopy unit, many patients were receiving antibiotics without proper indication. We devised a continuous quality improvement initiative to analyze and improve this problem. METHODS: Divisional guidelines for the appropriate administration of prophylactic antibiotics for endoscopy were drawn up in 1995. By retrospective analysis of our comprehensive endoscopy database we compared the rate of prophylactic antibiotic administration, and the proportion of antibiotics that were indicated before and after adoption of the divisional guidelines. RESULTS: A total of 1427 endoscopic procedures were done during a 6-month period in 1994 (before adoption of guidelines). Of these, 55 (3.85%) received antibiotics. In a 6-month period in 1996 after adoption of guidelines, 1452 procedures were performed and 29 of these (1.99%) received antibiotics. The odds ratio for receiving antibiotics appropriately in 1996, compared with 1994, was 3.4 (chi2 p = 0.016). Given an annual volume of 2900 procedures in our endoscopy unit, approximately 54 patients will avoid unnecessary antibiotics, yielding a cost saving of $1128 per year. CONCLUSIONS: A divisional continuous quality improvement initiative on antibiotic prophylaxis for endoscopy significantly reduced the proportion of patients receiving antibiotics unnecessarily. This quality improvement initiative enhanced the quality of care for patients having endoscopy and yielded a small cost saving. These improvements were achieved with minimal effort and cost to the division.

Academic Medical Centers↗
PubMed1999

Utility of hepatitis C virus serotypes in predicting response to treatment of chronic hepatitis C. Consensus Interferon Study Group.

Hepatitis C virus (HCV) genotyping has been shown to predict response to interferon, but is expensive. HCV serotyping is less expensive and simpler, and may be similarly useful. Using data from a large, randomized trial comparing consensus interferon (CIFN) and interferon alfa-2b (IFN alfa-2b) in patients with chronic HCV, we evaluated response rates based on HCV serotypes versus genotypes. Patients included in this analysis received subcutaneous injection of 9 microg CIFN (n = 232) or 3 MU IFN alfa-2b (n = 240) three times weekly for 24 weeks followed by 24 weeks of observation. Serum HCV RNA concentrations were measured regularly during treatment and at the end of both the treatment and post-treatment periods. Response to interferon was similar for HCV antibody types and their corresponding genotypes. The end-of-treatment HCV RNA rate of response (defined as undetectable serum on two consecutive assessments) was 29% for serotype 1 versus 24% for genotype 1 after CIFN; and 14% versus 15%, respectively, after IFN alfa-2b. Independently of treatment, patients infected with serotype or genotype 2 or 3 had a better therapeutic response than those infected with serotype or genotype 1. Similar results were obtained based on HCV antibody typing and genotyping, suggesting the potential of the former for predicting response to interferon.

Antiviral Agents↗
PubMed1998

Defective nonoxidative leucine degradation and endogenous leucine flux in cirrhosis during an amino acid infusion.

The metabolic fate of leucine's first and second carbon may be different depending on the tissue in which leucine is metabolized, as well as the prevailing hormonal milieu of that tissue. However, previous studies of leucine kinetics in humans have used only leucine labeled (as tracer) at the first carbon position. Because cirrhosis is associated with factors (such as insulin resistance and altered fuel substrate utilization) that may influence how leucine is degraded, the kinetics of leucine's first and second carbon using a simultaneous infusion of [1-14C] leucine and [2-13C] leucine were studied in the postabsorptive state and during an amino acid infusion in 6 stable cirrhotic patients and 6 matched controls. The data were normalized for different body compartments that were quantified from the dilution of H2 [180] and bromide. The body cell mass, but not body weight or fat-free body mass, was decreased in cirrhosis (P < .001). In response to the amino acid infusion, total leucine appearance from proteolysis and leucine's incorporation into protein increased significantly in both groups, but were higher in cirrhotic patients. Endogenous protein breakdown decreased in normals but remained unchanged in cirrhosis. These alterations in leucine metabolism became more prominent when data were expressed based on the body cell mass rather than on body weight. The oxidation of leucine's first carbon (C1) was decreased in cirrhosis, but the oxidation of leucine's second carbon (C2) did not differ between groups during both the postabsorptive period and the amino acid infusion, while nonoxidative leucine degradation [the difference between the oxidation of leucine's (C1) and (C2)] was also decreased in cirrhosis. In addition, there was a positive correlation between nonoxidative leucine degradation (which represents leucine incorporation into fat), and the respiratory quotient obtained from indirect calorimetry (r = .87; P < .001). These data suggest that the extent of leucine carbon oxidation is dependent on whether fat or carbohydrate is the prevailing fuel substrate. In addition, cirrhotic patients have decreased nonoxidative leucine degradation and are unable to suppress endogenous protein breakdown normally in response to amino acid administration. These abnormalities may contribute to the diminished fat stores and body cell mass commonly observed in cirrhosis.

Adult↗
PubMed1998

Early hepatitis C virus-RNA responses predict interferon treatment outcomes in chronic hepatitis C. The Consensus Interferon Study Group.

In previous studies employing interferons (IFNs) in the treatment of chronic hepatitis C, there have been few reliable predictors of sustained responses. We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon (CIFN) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses. Data from two large treatment trials, one of IFN-naive patients and one of retreated relapsers and nonresponders, were used, including serum samples at 2-week intervals in the naive study and 8-week intervals in the retreatment study. Patients received initial CIFN (9 microgram) treatment for 6 months and were assessed 6 months after treatment. There were 28 sustained viral responders of 232 CIFN-treated patients. Of the sustained responders, 48% had already cleared HCV RNA from serum (<100 copies/mL) by week 2, 78% by week 4, 81% by week 6, and 96% by week 12. Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later. Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN. Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment. Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy.

Antiviral Agents↗
PubMed1997

Relationship of nutritional status to length of stay, hospital costs, and discharge status of patients hospitalized in the medicine service.

OBJECTIVE: This study was conducted to determine the relationship, if any, between nutritional status, length of stay (LOS) in hospital, discharge placement, readmission rates, and hospital costs and charges in patients hospitalized in the medicine service. DESIGN: Data regarding medical diagnosis, LOS, hospital costs, charges, discharge destination, and readmission rates were collected prospectively from medical records and through patient interviews on patients admitted to the medical service who were classified to be at risk or not at risk for malnutrition on the basis of established criteria (weight for height < 75% ideal body weight, admission serum albumin level < 30 g/L, or > or = 10% unintentional weight loss within 1 month before admission). SUBJECTS: All patients admitted directly to any of three medicine units during December 1994 who met study criteria were included in the study. Off-service patients, transfer patients, and patients discharged before screening (usually admitted and discharged within 72 hours) were excluded. Data were collected on 173 patients. STATISTICAL ANALYSIS PERFORMED: At-risk and not at-risk patients were compared for LOS, costs and reimbursement, and discharge placement (to home, to home with home health care services, or to another facility for further care). Two sample t tests and alpha survival analysis technique were used to compare continuous variables between the two study cohorts. Nonparametric tests were used for LOS and readmission data. chi 2 Tests were used for categoric variables. An alpha level of .05 was used throughout to determine statistical significance. RESULTS: Median LOS in the not-at-risk population (n = 56) was significantly greater than in the not-at-risk population (n = 117): 6 days (25th percentile = 4 days, 75th percentile = 8 days) vs 4 days (25th percentile = 3 days, 75th percentile = 7 days) (P < .01). Mean hospitalization cost per patient was also higher in the at-risk group ($6,196 vs $4,563, P < .02). Readmission rate per month of follow-up was not significantly different. At-risk patients were significantly less likely to be discharged home with self-care (23[41%] vs 77 [66%], P < .05). At-risk patients were significantly more likely to use home health care service than not-at-risk patients (17[31%] vs 14 or [12%], P < .001). APPLICATIONS: Patients at risk for malnutrition had significantly higher LOS, costs, and home health care needs, despite the fact that 51, or 91%, received nutrition intervention while hospitalized. Further research should explore the use of nutrition screening and intervention before, during, and after hospitalization to ensure that appropriate nutrition intervention, as indicated by medical patients' clinical condition and nutritional risk status, is initiated and continued.

Cohort Studies↗
PubMed1997

Primary prophylaxis of variceal bleeding in cirrhosis: a cost-effectiveness analysis.

BACKGROUND & AIMS: Prophylaxis against the first variceal bleeding has been proposed to reduce morbidity and mortality in cirrhotic patients. No previous information is available regarding the cost-effectiveness of prophylaxis. The aim of this study was to compare the cost-effectiveness of variceal bleeding prophylaxis with propranolol, sclerotherapy, and shunt surgery in cirrhotic patients stratified by bleeding risk. METHODS: A hypothetical cohort was stratified according to bleeding risk. The natural history of cirrhosis with esophageal varices was simulated using a Markov model. Transitional probabilities extracted from published studies and costs were obtained from our institution's billing department. Sensitivity analyses were performed for important variables. RESULTS: Propranolol results in cost savings ranging between $450 and $14,600 over a 5-year period. The extent of cost savings depended on the individual patient's bleeding risk. In addition, propranolol increased the quality-adjusted life expectancy by 0.1-0.4 years. Sclerotherapy was significantly less cost-effective than propranolol and had no advantage on quality of life. Shunt surgery was effective therapy for prevention of bleeding but decreased life expectancy and quality of life in some risk groups and was not cost-effective. CONCLUSIONS: Propranolol is the only cost-effective form of prophylactic therapy for preventing initial variceal bleeding in cirrhosis regardless of bleeding risk.

Cost-Benefit Analysis↗
PubMed1997

Precipitation of overt encephalopathy in the portacaval shunted rat: towards the development of an adequate model of chronic portal systemic encephalopathy.

OBJECTIVE: To assess the feasibility of developing a model of overt portal-systemic encephalopathy (PSE) in rats with a surgically constructed portacaval anastomosis (PCA). DESIGN: The ability of increasing the load of nitrogenous substances in the gastrointestinal tract and/or further decreasing hepatocellular function to induce overt encephalopathy in rats with a PCA was determined. METHODS: The load of nitrogenous substances in the gastrointestinal tract was increased by feeding a pure horse-meat diet or by gavaging with blood. Partial hepatectomy and the induction of cirrhosis were used to decrease hepatocellular function further. The severity of encephalopathy was assessed using a neurobehavioural scale. RESULTS: Overt encephalopathy was not induced in rats by a PCA alone, by a PCA plus a horse-meat diet, by a PCA plus induction of cirrhosis, or by a PCA plus a 50% hepatectomy. Predominantly mild, but overt, encephalopathy was induced in rats with a PCA alone by gavaging with blood and a higher incidence of more severe overt encephalopathy was induced in rats with a PCA combined with either cirrhosis or partial hepatectomy by gavaging with blood. Although these models of PSE were associated in some instances with plasma ammonia concentrations about 25 times higher than normal, no seizures were observed. CONCLUSION: A syndrome that resembles overt PSE in humans can be induced in the rat with a PCA by further reducing hepatocellular function and also gavaging with blood. Although the rat with a PCA has been. extensively used as a model in studies relating to the pathogenesis of PSE, a syndrome resembling overt PSE in humans cannot readily be induced in rats with a PCA.

Ammonia↗
PubMed1996

Pathogenesis of hepatic encephalopathy: potential future approaches.

Attempting to forecast future trends in research is difficult enough in any area but is well nigh impossible with the volatile field of hepatic encephalopathy (HE). Undaunted in this review it is suggested that more frequent use of intact animal models of HE to probe the pathogenesis of HE will occur with newly developed pharmacological agents. This process would be greatly facilitated by wide acceptance of a discrete number of reproducible animal models of this syndrome. Brief comments are made on the current status on some of the current hypotheses. Greater utilization of patients with subclinical HE for clinical studies will occur. Continuing interest in nuclear magnetic resonance imaging and spectroscopy findings peculiar to HE will be seen over the next decade.

Animals↗
PubMed1996

Hepatic encephalopathy.

The syndrome of hepatic encephalopathy has mystified physicians since the time of Hippocrates, and it continues to do so. It is difficult to succinctly define, diagnose with certainty, or attempt to explore its pathogenesis. The literature on this topic is confusing and often contradictory. Nevertheless, very effective empirical therapy has been devised for this syndrome. We discuss selected aspects of diagnosis, pathogenesis, clinical manifestations, and treatment of hepatic encephalopathy. Emphasis is placed on the three-pronged clinical strategy to manage hepatic encephalopathy that encompasses both diagnostic and treatment measures. The burgeoning area of subclinical hepatic encephalopathy is discussed in more detail than in most reviews of this topic. We also propose a new term for the field-acute liver failure-associated hepatic encephalopathy (ALFA-HE)-to replace the unsatisfactory older term, fulminant hepatic failure.

Hepatic Encephalopathy↗