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PubMed1998

Prognostic factors after conservative surgery and radiation therapy for early stage breast cancer.

A retrospective review was conducted of all early-stage breast cancer patients treated with breast-conservation surgery plus radiation therapy (BCS/RT) to determine mortality and recurrence rates and to evaluate prognostic factors for these outcomes. Between 1982 and 1988, 121 patients with stages I and II breast cancer were treated with BCS/RT at our institution. Most of the patients (83%) had re-excision of the initial biopsy site and at final surgical evaluation, only 4 patients had positive margins (3.2%). Median follow-up was 89.7 months. Cox proportional hazards regression models were used to select prognostic factors significant for breast cancer-specific mortality, overall disease recurrence, and local recurrence. Breast cancer survival rates were 92% at 5 years and 83% at 10 years. Prognostic factors predicting breast cancer mortality included positive lymph nodes (relative risk=.9; 95% confidence interval, 1.2,12.2) and a higher grade (relative risk=1.9; 95% confidence interval, 1.1,3.3). For disease recurrence, prognostic factors included positive nodes (relative risk=2.6; 95% confidence interval, 1.2, 5.5), and a negative progesterone-receptor status (relative risk=0.3; 95% confidence interval, 0.2, 0.8). Local recurrence rates were 2.5% at 5 years and 14% at 10 years. No prognostic factors were significant for local recurrence; however, most patients had negative margins after surgery.

Adult↗
PubMed2004

Colonic stent vs. emergency surgery for management of acute left-sided malignant colonic obstruction: a decision analysis.

BACKGROUND: Acute colonic obstruction because of malignancy is often a surgical emergency. Surgical decompression with colostomy with or without resection and eventual re-anastomosis is the traditional treatment of choice. Endoscopic colonic stent insertion effectively decompresses the obstructed colon, allowing for surgery to be performed electively. This study sought to determine the cost-effectiveness of colonic stent vs. surgery for emergent management of acute malignant colonic obstruction. METHODS: Decision analysis was used to calculate the cost-effectiveness of two competing strategies in a hypothetical patient presenting with acute, complete, malignant colonic obstruction: (1) emergent colonic stent followed by elective surgical resection and re-anastomosis; (2) emergent surgical resection followed by diversion (Hartmann's procedure) or primary anastomosis. Cost estimates were obtained from a third-party payer perspective. Primary outcome measures were mortality, stoma requirement, and total number of operative procedures. RESULTS: Colonic stent resulted in 23% fewer operative procedures per patient (1.01 vs. 1.32 operations per patient), an 83% reduction in stoma requirement (7% vs. 43%), and lower procedure-related mortality (5% vs. 11%). Colonic stent was associated with a lower mean cost per patient ($45,709 vs. $49,941). CONCLUSIONS: Colonic stent insertion followed by elective surgery appears more effective and less costly than emergency surgery under base-case conditions. This finding remains robust over a wide range of assumptions for clinical inputs in sensitivity analysis. Our findings suggest that colonic stent insertion should be offered, whenever feasible, as a bridge to elective surgery in patients presenting with malignant colonic obstruction.

Acute Disease↗
PubMed1996

Epstein-Barr virus exploits the normal cell pathway to regulate Rb activity during the immortalisation of primary B-cells.

Infection of human primary B-lymphocytes with Epstein-Barr virus (EBV) drives quiescent cells into continual proliferation and results in the outgrowth of immortal cell lines. This requires re-programming of the mechanisms that, in the absence of appropriate antigenic stimulation, normally prevent the proliferation of B-lymphocytes. Since the Retinoblastoma protein (pRb) and its relatives, p107 and p130, play critical roles in controlling the mammalian cell division cycle, we have investigated the expression and phosphorylation status of these proteins following EBV immortalisation of primary B-lymphocytes. In this report, we show that EBV drives the hyperphosphorylation of pRb. This is achieved by a strategy involving the altered expression of several components of the signal transduction pathway that normally regulates the phosphorylation status of pRb, including the up regulation of a number of cyclins and cyclin-dependent kinases and the down regulation of a subset of cyclin-dependent kinase inhibitors. The net result is the formation of active cyclin-dependent kinase complexes that are capable of phosphorylating and inactivating pRb. The results presented here identify the activation of a normal signal transduction pathway as an important component of the strategy used by EBV to drive cell proliferation.

B-Lymphocytes↗
PubMed2004

Re-examining comorbidity of Obsessive Compulsive and Attention-Deficit Hyperactivity Disorder using an empirically derived taxonomy.

BACKGROUND: Using an empirically derived instrument to reduce the assessor bias inherent in structured diagnostic interviews, we sought to re-examine and validate the putative comorbidity between Obsessive Compulsive Disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHOD: We examined the correlation between Child Behavior Checklist (CBCL) syndrome, competence, and composite scores in children with: 1) OCD plus ADHD (OCD + ADHD), N = 47; 2) OCD without comorbid ADHD (OCD), N = 33; 3) ADHD without comorbid OCD (ADHD) N = 43; and 4) comparison controls recruited from general pediatric clinics,N = 32. RESULTS: CBCL findings in our ADHD children were similar to previous findings reported in ADHD youth, irrespective of the presence or absence of comorbid OCD. Comorbid youth generally had additive scores on the CBCL scales, reflecting the independent contribution of symptomatic and functional impairment from each disorder. CONCLUSION: These findings suggest that when ADHD-like symptoms are seen in OCD youth, they reflect a true comorbid state of OCD plus ADHD. The CBCL may provide a rapid assessment tool to identify comorbid ADHD in OCD youth.

Adolescent↗
PubMed1998

Fluctuations in cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila.

The precise cell-cycle alternation of S phase and mitosis is controlled by alternating competence of nuclei to respond to S-phase-inducing factors [1]. Nuclei acquire competence to replicate at the low point in cyclin-dependent kinase (Cdk) activities that follows mitotic destruction of cyclins. The elevation of Cdk activity late in G1 is thought to drive cells into S phase and to block replicated DNA from re-acquiring replication competence [2]. Whereas mitosis is normally required to eliminate the cyclins prior to another cycle of replication, experimental elimination of Cdk activity in G2 can restore competence to replicate [3-6]. Here, we examine the roles of Cdks in the endocycies of Drosophila [7]. In these cycles, rounds of discrete S phases without intervening mitoses result in polyteny. Cyclins A and B are lost in cells as they enter endocycles [8,9], and pulses of Cyclin E expression drive endocycle S phases [10-12]. To address whether oscillations of Cyclin E expression are required for endocycles, we expressed Cyclin E continuously in Drosophila salivary glands. Growth of the cells was severely inhibited, and a period of DNA replication was induced but further replication was inhibited. This replication inhibition could be overcome by the kinase inhibitor 6-dimethylaminopurine (6-DMAP), but not by expression of subunits of the transcription factor E2F. These results indicate that endocycle S phases require oscillations in Cdk activity, but, in contrast to oscillations in mitotic cells, these occur independently of mitosis.

Animals↗
PubMed1996

Halothane-induced liver injury in guinea-pigs: importance of cytochrome P450 enzyme activity and hepatic blood flow.

The basis for susceptibility to halothane-induced liver necrosis in guinea-pigs was examined. In hepatic microsomes, the following were similar in susceptible and resistant animals: total cytochrome (CYP) P450 (P450), phenobarbital-inducible pathways of mixed function oxidation (androstenedione 6 beta- and 16 beta-hydroxylase activities) and the CyP2E1-catalysed pathway of N-nitrosodimethylamine N-demethylase activity. Similarly, immunohistochemical staining of CYP2E1 protein was equivalent in livers from susceptible and resistant guinea-pigs. Prior treatment with the P450-inhibitors, metyrapone and SKF-525A ameliorated halothane-induced liver damage in susceptible animals. Conversely, in resistant guinea-pigs, stimulation of hepatic CYP2E1 activity by treatment with 4-methylpyrazole produced severe hepatotoxicity after re-exposure to halothane. These results confirm the conclusions of others, that P450-mediated metabolism produces halothane-induced liver necrosis in the guinea-pig model but, as in other work, the data fail to explain why no difference in activity of these enzymes could be found between susceptible and resistant guinea-pigs. To establish whether a differential effect on hepatic blood flow between susceptible and resistant guinea-pigs could explain this paradox, studies were performed using a radiolabelled microsphere technique. The effect of halothane on lowering cardiac output was identical in both groups of animals and halothane significantly reduced hepatic arterial but not portal blood flow. The effect on arterial blood flow was more profound in susceptible guinea-pigs (0.67 +/- 0.17% of injected microspheres) than in resistant animals (0.99 +/- 0.13%; P < 0.005). It is concluded that P450-catalysed metabolism and reduced hepatic blood flow are both necessary to produce halothane-induced liver injury in susceptible guinea-pigs, but it is the effect of halothane on hepatic arterial blood flow that differs between susceptible and resistant animals.

Animals↗
PubMed2003

Matriculating student perceptions of changes to the admissions interview process at the University of Wisconsin Medical School: a prospective, controlled comparison.

PURPOSE: The purpose of this study was to assess whether changes in the admissions interview process improved matriculating students' perceptions of the quality of the admissions interview process. METHODS: We surveyed matriculating medical students for a 3-year period. Over this period, the admissions process and procedures went through a review and then a re-engineering. The survey provided 1 year of baseline data (while the review was undertaken), 1 year of data as recommendations from the review were progressively implemented, and 1 year of data on full implementation of recommendations. RESULTS: From baseline to full implementation, there were statistically significant increases (p < .05) in the percentage of matriculating students who found the University of Wisconsin (UW) Medical School interview process useful (31% increase), thorough (50% increase) and better than that of other medical schools (28% increase). There was also a statistically significant decrease in the percentage of matriculating students who found the UW Medical School interview process to be less impressive than other schools (29% decrease) and in need of improvement (45% decrease). EDUCATIONAL SIGNIFICANCE/CONCLUSIONS: Changes made in the UW Medical School's interview process yielded significant increases in perceptions of the quality of the experience by matriculating students. Since interviewing is expensive for both the institution and the applicant, it should have a clear purpose. The manner in which interviews are conducted should be critically reviewed periodically to ensure that the interview continues to meet its intended needs.

Humans↗
PubMed2003

Re-thinking approaches to undergraduate health professional education: Interdisciplinary Rural Placement Program.

The Interdisciplinary Rural Placement Program involved the development, implementation and evaluation of a common rural primary health care module. Designed for undergraduate nursing, medical and pharmacy students of the University of Tasmania, students undertook clinical experiences and a collaborative primary health care project at two different Rural Health Teaching Sites across Tasmania. The aim of the project was for interdisciplinary students to work and learn together to enhance their understanding of the cooperative and collaborative nature of professional practice among rural health care workers. This paper will describe the development and implementation of the Interdisciplinary Rural Placement Program and critically discuss the outcomes in relation to nursing. In this paper, three issues will be explored. Firstly, how student nurses questioned their sense of subordination when in fact the level of recognition by their interdisciplinary peers led them to refute this. Secondly, concerns with overcoming the difficulties of coordinating student recruitment and conflicting timetables, while working within existing curricula, will be discussed. The final issue explores the student nurses' recognition that despite inherent tensions and conflict, the need to work as a cohesive and cooperative interdisciplinary team was vital. This project highlighted the challenges that health professions continue to work through in contemporary practice and education sectors. A key recommendation for education providers is that true interdisciplinary education must be achieved through an experiential framework.

Attitude of Health Personnel↗
PubMed2005

Psychosocial treatment for opiate abuse and dependence.

BACKGROUND: Substance dependence is a major social and public health problem; therefore it is a priority to develop effective treatments. The treatment of opioid dependence is complex. Previous Cochrane reviews have explored the efficacy of pharmacotherapy for opiate dependence. This current review focuses on the role of psychosocial interventions alone for the treatment of opiate dependence. There are many different psychosocial interventions offered to opiate addicts, which are widely spread. There is some evidence for the effectiveness of psychosocial interventions, but no systematic review has even been carried out. OBJECTIVES: To assess the efficacy and acceptability of psychosocial interventions alone for treating opiate use disorders. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, and LILACS; reference searching; personal communication; conference abstracts; unpublished trials; book chapters on treatment of opioid abuse/ dependence. SELECTION CRITERIA: The inclusion criteria for all randomised-controlled trials were that they should focus on psychosocial interventions alone for treating opioid use disorders. DATA COLLECTION AND ANALYSIS: Reviewers extracted the data independently using relative risks, weighted mean difference and number needed to treat estimated, when possible. The reviewers assumed that people who died or dropped out had no improvement (intention to treat analysis) and tested the sensitivity of the final results to this assumption. MAIN RESULTS: Five studies fit the study criteria. These analysed Contingency Management, Brief Reinforcement Based Intensive Outpatient Therapy coupled with Contingency Management, Cue Exposure therapy, Alternative Program for Methadone Maintenance Treatment Program Drop-outs (MMTP) and Enhanced Outreach-Counselling Program. All the treatments were studied against the control (standard) treatment; therefore it was not possible to identify which type of psychosocial therapy was most effective. The main findings were that both Enhanced Outreach Counselling and Brief Reinforcement Based Intensive Outpatient Therapy coupled with Contingency Management had significantly better outcomes than standard therapy within treatment. This was regarding relapse to opioid use, re-enrollment in treatment and retention in treatment. At 1-month and 3- month follow up the effects of Reinforcement Based Intensive Outpatient Therapy were not sustained. There was no further follow up of the Enhanced Outreach Counselling group. The Alternative Program for MMTP Drop-outs and the behavioural therapies of Cue Exposure and Contingency Management alone were no better than the control (standard) therapy. As the studies were heterogeneous, it was not possible to pool the results and perform a meta-analysis. AUTHORS' CONCLUSIONS: The available evidence has low numbers and is heterogeneous. At present psychosocial treatments alone are not adequately proved treatment modalities or superior to any other type of treatment. It is important to develop a better evidence base for psychosocial interventions to assist in future rationale planning of opioid use drug treatment services. Large-scale randomised trials are required with longer follow up stating methods of randomisation, allocation concealment and blinding. Where possible this should include intention to treat analysis, with power calculations performed prior to the trial. These studies can be designed and delivered to provide usable data for better understanding of this important component of intervention in the field of dependence.

Humans↗
PubMed1976

Flow rates of components in digesta of pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum, and fed semipurified, hard wheat, and soft wheat diets.

Four pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum were used to study flow rates of total digesta, insoluble dry matter, nitrogen, and amino acids entering and leaving the small intestine. The pigs received a semipurified diet, a hard wheat diet, or a soft wheat diet. These were approximately isonitrogenous. A higher rate of passage of digesta through the proximal duodenum and terminal ileum were measured in pigs receiving the hard wheat diet. Peak flow of digesta at the duodenum of all pigs occurred at 1 h post feeding. Peak flow of digesta at the ileum occurred at 9 h post feeding on the soft wheat diet, but somewhat earlier on the hard wheat and semipurified diet. More nitrogen and essential amino acids flowed in the solid fraction of duodenal digesta during the first 2 h post feeding for the wheat diets and 4 h post feeding for the semipurified diet. It was concluded that flow rate of most nutrients from the stomach and through the small intestine of pigs is modified by the composition and texture of the food ingested. It is postulated that efficiency of mixing of digesta with digestive secretions in the stomach is a major factor influencing rate of flow.

Amino Acids, Essential↗
PubMed2003

A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection.

OBJECTIVES: To determine the prevalence of resistance amongst urinary tract pathogens against antimicrobials used to treat urinary tract infections (UTIs) in the UK to provide data to help direct empirical therapy. METHOD: During 1999-2000, a total of 1291 bacterial isolates causing UTI were collected from 8 centres in the UK. Isolates were cultured from patients with (1). community-acquired UTI in those less than 65 years old (397), (2). hospital-acquired UTI other than those admitted with pyelonephritis (394), (3). pyelonephritis (108) and (4). community-acquired UTI in those greater than 65 years old (392). After re-identification, MICs for a range of antimicrobials were determined and interpreted using NCCLS procedures and interpretive guidelines. RESULTS: Escherichia coli was the predominant pathogen in all categories but the total percentage for each category varied (56.3-77.3%). The next three pathogens of importance were Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis which varied in prevalence slightly from category to category. The activity of amoxycillin against E. coli (51.3% susceptible) was greatly reduced as a result of beta-lactamase production and only partially restored by the addition of clavulanic acid (78.8% susceptible). Cefuroxime was very active against E. coli using parenteral form breakpoints (97.1% susceptible) but less so using oral form breakpoints (68.6% susceptible). Cefuroxime was inactive against Enterococcus spp. and Pseudomonas spp. Nitrofurantoin was very active against isolates of E. coli (96.3% susceptible) and E. faecalis but not against K. pneumoniae, P. mirabilis or Pseudomonas aeruginosa. Overall susceptibility to trimethoprim ranged from 58.1% to 84.5% for the most prevalent pathogens. Ciprofloxacin was highly active against the UTI pathogens examined in this study with susceptibilities of between 88.6% and 97.7% for the most prevalent pathogens (E. coli, n=864, 97.7% susceptible) and was the only oral agent tested with activity against Pseudomonas spp. CONCLUSION: These data provide much needed information on the prevalence of antimicrobial resistance amongst pathogens currently causing UTI in the UK.

Adolescent↗
PubMed1976

Energy and nitrogen metabolism of diseased chickens: aflatoxicosis.

1. New Hampshire chicks were fed on diets containing 0 (control), 0-7 (A), or 1-1 (B) ppm of aflatoxin B1. In two trials 1-d-old chicks were offered ad libitum the three diets for 14 d. The gaseous exchange of five chickens from each group was measured for 3 or 4 d, the same diets being fed, at 2, 3, 4 and 5 weeks of age in two series of experiments. The controls were fed at the lower intake of the two other groups. Following each series of experiments at the various ages, birds were starved for 24 h and their heat production was re-measured over the next 24 h. 2. Mortality was highest and growth and food conversion poorest where the diet with the highest aflatoxin concentration was fed. Mortality was confined to the first 2 weeks. 3. Performance of birds in the chambers was improved in the second series due to differences in food intake. It also improved with age suggesting some resistance to the toxin. 4. Mean respiratory quotient was 0-97 for fed chickens on diet B. This was significantly different from 0-92 for the two other groups. Similarly, during starvation the RQ was 0-76 compared with 0-73. 5. birds fed on diet B generally grew better, retained more nitrogen and had a better energy balance in the respiration chambers than the other two groups. Metabolisability of dietary energy was less (68.5%) for all groups at 2 to 3 weeks than when older (70%) but availability of ME was the same (71%) for all groups. 6. Heat production (kJ/kg0-75) of starved birds on diet B was significantly lower than the other two groups, while endogenous nitrogen excretion was higher. 7. Water consumption (ml/g food and g/100 g body weight) was greatest for birds on diet B. 8. Although aflatoxin in the diet substantially reduced intake there was no indication that at these reduced levels of intake, nitrogen or energy metabolism were measurably impaired.

Aflatoxins↗
PubMed1999

Estimating the prevalence of problem drug use in inner London: a discussion of three capture-recapture studies.

AIMS: To provide an evidence base of estimates of the prevalence of problem drug use in inner London. DESIGN: Re-analysis of three capture-recapture studies using subjects aged 15-49 years, that aim to estimate the hidden population from analysing the overlaps between three data sources. SETTING: Newham (1995) Camden and Islington (C&I) (1993/4) and Lambeth, Southwark and Lewisham (LSL) (1992). PARTICIPANTS: Each study collected data from three sources of problem drug users including: the Regional Drug Misuse Database, specialist drug agencies, HIV tests, social services, police arrests and court records. In LSL opiate users were analysed separately. The studies identified 1832 individuals in LSL, 543 in Newham, and 1321 in C&I. MEASUREMENTS: Poisson models were fitted to the data testing different interactions between the data sources representing potential dependencies. The simplest model was selected on the basis of its AIC score and log-likelihood ratio tests. FINDINGS: The number of hidden problem drug users were estimated to be 12,500 (95% CI 9600-16,100) in LSL with 4400 (3200-6100) opiate users; 7000 (5000-10,000) in C&I and 3800 (2000-7200) in Newham. The prevalence of problem drug use in those aged 15-49 was estimated to be 3.1% (2.5-3.9%) in LSL with 1.3% (1.0-1.6%) opiate users; and 3.6% (2.7-4.9%) and 3.3% (1.9-5.7%) in C&I and Newham, respectively. CONCLUSIONS: Despite the inherent problems with capture-recapture methods, our three studies establish an evidence base for estimates of problem drug use in London. It is important that a larger study is carried out in London.

Adolescent↗
PubMed2002

Preferential loss of Death Associated Protein kinase expression in invasive pituitary tumours is associated with either CpG island methylation or homozygous deletion.

Death Associated Protein kinase (DAP kinase) a novel calmodulin-dependent serine/threonine kinase was first identified as a positive mediator of programmed cell death. Loss of DAP kinase expression was first demonstrated in highly metastatic cells, whilst re-expression of the protein resulted in delayed local tumour growth and a decreased incidence of metastasis. Although loss of DAP kinase expression has been reported in several cell lines derived from human malignancies the mechanisms responsible have not been defined. In this study we have examined 32 sporadic pituitary tumours for expression of the DAP kinase protein and transcript. In addition, we examined the methylation and deletion status of the DAP kinase CpG island as possible mechanisms for the inactivation of the DAP kinase gene. Eleven of 32 (34%) tumours had undetectable DAP kinase expression, by Western blot and/or RT-PCR analysis. Loss of DAP kinase expression was significantly (P=0.004) associated with invasive tumours (10 of 17; 59%) compared to their non-invasive (1 of 15; 7%) counterparts. Of 11 tumours that failed to express DAP kinase, five (45%) showed de novo methylation of the CpG island contained within the promoter region, while four (36%) had evidence of homozygous deletion of this region. Statistical analysis showed that loss of DAP kinase expression was significantly (P=<0.001) associated with methylation or deletion of the DAP kinase CpG island. With two exceptions, none of the remaining tumours or five histologically normal post-mortem pituitaries examined had evidence of methylation or deletion within this region. To our knowledge this is the first report that describes two mutually exclusive mechanisms associated with loss of DAP kinase gene expression. In addition, we also show that loss of the DAP kinase protein and associated genetic aberrations preferentially segregates with tumours that show an invasive phenotype.

Apoptosis Regulatory Proteins↗
PubMed2004

Racial differences in responses to interferon-beta-1a in chronic hepatitis C unresponsive to interferon-alpha: a better response in Chinese patients.

Re-treatment with interferon-alpha alone for chronic hepatitis C nonresponders to interferon-alpha monotherapy is almost ineffective. This multicentre, randomized, parallel-group, dose-finding study evaluated the efficacy of interferon-beta-1a in the treatment of chronic hepatitis C patients unresponsive to interferon-alpha. A total of 267 patients were randomized to one of four groups: subcutaneous interferon-beta-1a 12 MIU (44 microg) or 24 MIU (88 microg) administered three times weekly or daily. Patients were treated for 48 weeks and then followed up for an additional 24 weeks. There was a trend towards a dose-response relationship regarding virological [loss of detectable serum hepatitis C virus (HCV) RNA] and biochemical response (normalization of serum alanine aminotransferase). Overall, 22 patients (8.3%) had a virological response at the end of treatment; nine patients (3.4%) had a sustained virological response (SVR). Strikingly, 21.7% (5/23) of Chinese patients achieved SVR. Univariate analysis revealed that race was the only variable related to SVR [odds ratio (OR) 16.6; 95% CI 4.1-67.3; P < 0.0001]. Multiple logistic regression analysis also confirmed that more Chinese patients achieved SVR than non-Chinese patients (OR 12.3; 95% CI 2.6-59.3; P = 0.0017). In addition, complete clearance of HCV-RNA occurred earlier in Chinese than in non-Chinese responders (median 2 vs 30 weeks; P = 0.020). Thirty-six patients were withdrawn from treatment because of adverse events. Most adverse events were mild or moderate in severity. In conclusion, interferon-beta-1a provided considerable clinical benefit in Chinese patients with chronic hepatitis C unresponsive to interferon-alpha. The evaluation of interferon-beta-1a in this setting is progressing.

Adolescent↗
PubMed1999

Hepatitis C: an economic evaluation of extended treatment with interferon.

OBJECTIVES: To re-evaluate the cost effectiveness of treating hepatitis C virus (HCV) infection with interferon alfa (IF alpha) in Australia, taking into account changes in clinical practice. DESIGN: A decision-analytic method (Markov model) was used to simulate the costs and effects of 6 months and 12 months of treatment with IF alpha versus no treatment (conventional management). Both costs and effects were modelled over 30 years. DATA SOURCES: Published meta-analysis of the effectiveness of treatment, professional judgement about treatment protocols, scheduled medical fees, diagnosis-related costs for hospital admission, and a literature search for quality-of-life weights. PATIENTS: A hypothetical cohort of 1000 patients with chronic HCV infection aged 40 years at the start of treatment. MAIN OUTCOME MEASURES: Incremental costs per life-year gained and per quality-adjusted life-year (QALY) gained. RESULTS: Compared with no treatment, IF alpha treatment for 6 months results in an extra 94.2 life-years or 320.1 QALYs at an extra cost of $1.8 million (after discounting at 3%) in a cohort of 1000 patients. Discounted cost per life-year gained is $19,110, which is about a quarter of the cost reported in 1994. The discounted cost per QALY gained is $5625. Extended treatment for another 6 months results in an additional 89.0 life-years saved or 170.8 QALYs gained at an incremental discounted cost of $15,835 per life-year gained and $8250 per QALY gained. CONCLUSIONS: The cost effectiveness of IF alpha treatment for HCV infection has improved as a result of better patient selection, cost reductions and enhanced effectiveness of extended treatment. The results are sensitive to assumptions made about quality of life and the discount rate.

Antiviral Agents↗