Point-of-care Hepatitis C virus testing and linkage to treatment in an Australian inner-city emergency department.

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.

Rab35-dependent extracellular nanovesicles are required for induction of tumour supporting stroma.

Communication between diseased cells and the microenvironment is a complex yet crucial element in progression of varied pathological processes. Recent studies in cancer highlight an important role for small extracellular nanovesicles secreted by cancer cells as modulators of cancer-associated stroma, leading to enhanced angiogenesis and metastatic priming. The intrinsic factors regulating extracellular nanovesicle biogenesis and secretion are therefore relevant in studies of nano-communication in the cancer milieu. We generated prostate cancer cells bearing stable knockdown of several candidate vesicle regulating factors and examined the impact on cell health, vesicle secretion and on communication with fibroblastic stromal cells. We highlight that RAB11B and RAB35 regulate phenotypically distinct nanovesicle populations, each accounting for only around 20% of the total. Depleting RAB35, but not RAB11B leaves a remaining population of vesicles whose phenotype is insufficient for driving fibroblast to myofibroblast differentiation, leading to attenuated motile behaviours in 3D in vitro models. Co-implantation of tumour cells with stromal fibroblasts in xenografts similarly showed that RAB11B knockdown had little effect on growth rates in vivo. In contrast, significant attenuation in growth, and attenuation of myofibroblasts at the tumour site was evident when using RAB35-knockdown cells. The study concludes that a RAB35 regulated nanovesicle sub-population is particularly important for communication between cancer and stromal cells, and is required for generating a tumour-supportive microenvironment.

Dendritic cell reconstitution is associated with relapse-free survival and acute GVHD severity in children after allogeneic stem cell transplantation.

DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age- and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/µL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P=0.035), whereas high pDC/µL PB up to day 60 are associated with higher risk of relapse (P<0.001). The time-trend of DCs/µL PB for days 0-200 is a significant predictor of relapse-free survival for both mDCs (P<0.001) and pDCs (P=0.020). Jointly modelling DC reconstitution and complications improves on these simple criteria. Compared with BM, PBSC transplants tend to show slower mDC/pDC reconstitution (P=0.001, 0.031, respectively), but have no direct effect on relapse-free survival. These results suggest an important role for both mDCs and pDCs in the reconstituting immune system. The inclusion of mDCs and pDCs may improve existing models for complication prediction following allo-SCT.

Age-matched dendritic cell subpopulations reference values in childhood.

Dendritic cells (DCs) are the most potent antigen-presenting cells and are the key link between the innate and adaptive immune response. Only a few reports with study populations of up to 50 individuals have been published with age-based reference values for DC subpopulations in healthy children. Therefore, we aimed to establish reference ranges in a larger study population of 100 healthy children, which allowed age-matched subgroups. Most previous studies were performed using a dual-platform approach. In this study, a single-platform approach in a lyse no-wash procedure was used. DC subpopulations were defined as follows: CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD33(+) cells as myeloid DCs (mDCs) and CD45(+) CD85k(+) HLA-DR(+) CD14(-) CD16(-) CD123(+) cells as plasmacytoid DCs (pDCs). Reference ranges were established using a semi-parametric regression of age-matched absolute and relative DC counts. We found a significant decline with increasing age in the medians of mDCs (P = 0.0003) and pDCs per µl peripheral blood (PB) (P = 0.004) and in the 50%, 90% and 95% reference ranges. We also identified significantly lower absolute cell counts of mDCs per µl PB in girls than in boys for all age groups (P = 0.0015). Due to the larger paediatric study population and single-platform approach, this study may give a more precise overview of the normal age-matched development of DC subpopulations and may provide a basis for analyzing abnormal DC counts in different illnesses or therapies such as post stem cell transplantation.

Cost-effectiveness analysis comparing epidural, patient-controlled intravenous morphine, and continuous wound infiltration for postoperative pain management after open abdominal surgery.

BACKGROUND: Continuous wound infiltration (CWI), i.v. patient-controlled analgesia (i.v.-PCA), and epidural analgesia (EDA) are analgesic techniques commonly used for pain relief after open abdominal surgery. The aim of this study was to evaluate the cost-effectiveness of these techniques. METHODS: A decision analytic model was developed, including values retrieved from clinical trials and from an observational prospective cohort of 85 patients. Efficacy criteria were based on pain at rest (VAS ≤ 30/100 mm at 24 h). Resource use and costs were evaluated from medical record measurements and published data. Probabilistic sensitivity analysis (PSA) was performed. RESULTS: When taking into account all resources consumed, the CWI arm (€ 6460) is economically dominant when compared with i.v.-PCA (€ 7273) and EDA (€ 7500). The proportion of patients successfully controlled for their postoperative pain management are 77.4%, 53.9%, and 72.9% for CWI, i.v.-PCA, and EDA, respectively, demonstrating the CWI procedure to be both economically and clinically dominant. PSA reported that CWI remains cost saving in 70.4% of cases in comparison with EDA and in 59.2% of cases when compared with PCA. CONCLUSIONS: Device-related costs of using CWI for pain management after abdominal laparotomy are partly counterbalanced by a reduction in resource consumption. The cost-effectiveness analysis suggests that CWI is the dominant treatment strategy for managing postoperative pain (i.e. more effective and less costly) in comparison with i.v.-PCA. When compared with EDA, CWI is less costly with almost equivalent efficacy. This economic evaluation may be useful for clinicians to design algorithms for pain management after major abdominal surgery.

Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals.

BACKGROUND: Autoimmune atrophic body gastritis (ABG) and pernicious anaemia are prototypical, organ-specific autoimmune diseases whose prevalence in the general population is 2.0 vs 2 and 0.15-1%, respectively. The incidence of disease increases with age and is frequently associated with other autoimmune disorders such as type 1 diabetes mellitus (T1DM). Early diagnosis of ABG/pernicious anaemia is essential for the prevention and/or treatment before manifestations of chronic disease become irreversible. Parietal cell autoantibody detection via enzyme-linked immunosorbent assay is currently the most widely used biomarker of disease with diagnosis confirmed by subsequent immunohistochemistry via biopsy. METHODS: To improve the assay we designed a specific, molecularly defined radioimmunoprecipitation assay for early detection of ABG, targeting its major antigen, the gastric H+/K+ ATPase 4A subunit ATP4A. RESULTS: The major antigenic domain in ATP4A was tested against a panel of sera from new onset patients with T1DM which tested positive for the gold standard T1DM autoantibodies (IAA, IA2A, GAD65A, and ZnT8A). Significant immunoreactivity to ATP4A was measured (25%) while 6% of first-degree relatives of subjects with T1DM who were sero-negative for T1DM autoantigens were positive for ATP4A autoantibodies. ATP4A antibody prevalence increased with age of onset of T1DM, which is atypical of other T1DM autoantibodies. Immunoreactivity to ATP4A, unlike that of T1DM antigens, demonstrates a significant gender bias in newly diagnosed individuals with T1DM. CONCLUSION: Although the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG.

Psychological impact and acceptability of magnetic resonance imaging and X-ray mammography: the MARIBS Study.

BACKGROUND: As part of the Magnetic Resonance Imaging for Breast Screening (MARIBS), Study women with a family history of breast cancer were assessed psychologically to determine the relative psychological impact and acceptability of annual screening using magnetic resonance imaging (MRI) and conventional X-ray mammography (XRM). METHODS: Women were assessed psychologically at baseline (4 weeks before MRI and XRM), immediately before, and immediately after, both MRI and XRM, and at follow-up (6 weeks after the scans). RESULTS: Overall, both procedures were found to be acceptable with high levels of satisfaction (MRI, 96.3% and XRM, 97.7%; NS) and low levels of psychological morbidity throughout, particularly at 6-week follow-up. Low levels of self-reported distress were reported for both procedures (MRI, 13.5% and XRM, 7.8%), although MRI was more distressing (P=0.005). Similarly, higher anticipatory anxiety was reported before MRI than before XRM (P=0.003). Relative to XRM, MRI-related distress was more likely to persist at 6 weeks after the scans in the form of intrusive MRI-related thoughts (P=0.006) and total MRI-related distress (P=0.014). More women stated that they intended to return for XRM (96.3%) than for MRI (88%; P<0.0005). These effects were most marked for the first year of screening, although they were also statistically significant in subsequent years. CONCLUSION: Given the proven benefits of MRI in screening for breast cancer in this population, these data point to the urgent need to provide timely information and support to women undergoing MRI.

Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor kappa-B (NF-kappaB) signalling in human islets and in a mouse beta cell line.

AIMS/HYPOTHESIS: The destruction of pancreatic beta cells leading to type 1 diabetes in humans is thought to occur mainly through apoptosis and necrosis induced by activated macrophages and T cells, and in which secreted cytokines play a significant role. The transcription factor nuclear factor kappa-B (NF-kappaB) plays an important role in mediating the apoptotic action of cytokines in beta cells. We therefore sought to determine the changes in expression of genes modulated by NF-kappaB in human islets exposed to a combination of IL1beta, TNF-alpha and IFN-gamma. METHODS: Microarray and gene set enrichment analysis were performed to investigate the global response of gene expression and pathways modulated in cultured human islets exposed to cytokines. Validation of a panel of NF-kappaB-regulated genes was performed by quantitative RT-PCR. The mechanism of induction of BIRC3 by cytokines was examined by transient transfection of BIRC3 promoter constructs linked to a luciferase gene in MIN6 cells, a mouse beta cell line. RESULTS: Enrichment of several metabolic and signalling pathways was observed in cytokine-treated human islets. In addition to the upregulation of known pro-apoptotic genes, a number of anti-apoptotic genes including BIRC3, BCL2A1, TNFAIP3, CFLAR and TRAF1 were induced by cytokines through NF-kappaB. Significant synergy between the cytokines was observed in NF-kappaB-mediated induction of the promoter of BIRC3 in MIN6 cells. CONCLUSIONS/INTERPRETATION: These findings suggest that, via NF-kappaB activation, cytokines induce a concurrent anti-apoptotic pathway that may be critical for preserving islet integrity and viability during the progression of insulitis in type 1 diabetes.

Systematic review of utilities in abdominal aortic aneurysm.

INTRODUCTION: Two main treatments exist for the repair of abdominal aortic aneurysm (AAA). Open surgical repair has been the standard treatment, but more recently endovascular aneurysm repair (EVAR) has been introduced as a less invasive technique. To compare the long-term outcomes of these, utility outcomes have been suggested to be relevant. OBJECTIVE: To review studies comparing the utility outcomes of open repair and EVAR treatment for AAA. DESIGN: database search with strict inclusion and exclusion criteria. MATERIALS AND METHODS: The search was performed in PubMed and EMBASE covering terms relating to AAA and utility. Studies were analysed qualitatively. RESULTS: 10 studies of AAA met the review criteria. The comparative utility scores for the different treatments varied considerably between studies. A Canadian cohort study estimated EVAR as more favorable than open repair, while randomised controlled trials reported lower utilities with EVAR, except for one month post-surgery in the EVAR 1 trial. Furthermore, after screening for AAA, patients testing positive gave similar QoL-5D scores, but worse visual analogue scores than those testing negative. CONCLUSION: There were few studies calculating utilities in AAA, with inconsistent findings. The limited reporting of data prevents in-depth analysis to explain the differences.

Global gene expression profiling and histochemical analysis of the developing human fetal pancreas.

AIMS/HYPOTHESIS: An immunohistochemical and genomic analysis of human pancreatic development from 9-23 weeks of fetal age was undertaken to provide a comparative analysis of human and murine islet development. METHODS: Human fetal pancreases obtained at gestational ages 9-23 weeks were processed in parallel for immunohistochemistry and gene expression profiling by Affymetrix microarrays. RESULTS: By 9-11 weeks, the pancreas was made up principally of mesenchymal tissue infiltrated by branched epithelial structures containing scattered hormone-negative neurogenin3-positive endocrine cells. Protoacinar structures emerged by 15-19 weeks, along with clusters of endocrine cells producing either glucagon or insulin. By 20-23 weeks, vascularised islet-like structures appeared. More than 70% of endocrine cells produced a single hormone at any age. Analysis of Ki67 immunoreactivity showed that the replicative rate of endocrine cells was low and suggested that the endocrine expansion was derived from hormone-negative precursors. Insulin, glucagon, somatostatin, ghrelin and pancreatic polypeptide transcripts were present at 9-10 weeks and increased progressively, commensurate with the expansion of endocrine cell volume. The human equivalent of a mouse endocrine secondary transition was not evident, neither in terms of morphology nor in dramatic changes in endocrine-specific transcriptional regulators. By contrast, exocrine genes showed a marked transition at around 11 weeks, associated with a greater than sixfold increase in exocrine gene transcripts. CONCLUSIONS/INTERPRETATION: The observed extension of terminal differentiation of human endocrine tissue into late gestation is in contrast with findings in the mouse. It indicates that the human fetal pancreas could provide an abundant islet precursor cell population that could be expanded ex vivo for therapeutic transplantation.

Dominant negative mutant forms of the cAMP response element binding protein induce apoptosis and decrease the anti-apoptotic action of growth factors in human islets.

AIMS/HYPOTHESIS: Transplantation of islets is a viable option for the treatment of diabetes. A significant proportion of islets is lost during isolation, storage and after transplantation as a result of apoptosis. cAMP response element binding protein (CREB) is an important cell survival factor. The aim of the present study was to determine whether preservation of CREB function is needed for survival of human islets. MATERIALS AND METHODS: To determine the effects of downregulation of CREB activity on beta cell apoptosis in a transplantation setting, adenoviral vectors were used to express two dominant negative mutant forms of CREB in human islets isolated from cadaveric donors. Markers of apoptosis were determined in these transduced islets under basal conditions and following treatment with growth factor. RESULTS: Expression of CREB mutants in human islets resulted in significant (p < 0.001) activation of caspase-9, a key regulatory enzyme in the mitochondrial pathway of apoptosis, when compared with islets transduced with adenoviral beta galactosidase. Immunocytochemical analysis showed the activation of caspase-9 to be predominantly in beta cells. Other definitive markers of apoptosis such as parallel activation of caspase-3, accumulation of cleaved poly-(ADP-ribose) polymerase and nuclear condensation were also observed. Furthermore, the anti-apoptotic action of growth factors exendin-4 and betacellulin in human islets exposed to cytokines was partially lost when CREB function was impaired. CONCLUSIONS/INTERPRETATION: Our findings suggest that impairment of CREB-mediated transcription could lead to loss of islets by apoptosis with potential implications in islet transplantation as well as in the mechanism of beta cell loss leading to diabetes.

Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy.

BACKGROUND: Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. METHODS: A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. RESULTS: Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. CONCLUSIONS: Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.

Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

One year comparison of costs of coronary surgery versus percutaneous coronary intervention in the stent or surgery trial.

OBJECTIVES: To compare initial and one year costs of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in the stent or surgery trial. DESIGN: Prospective, unblinded, randomised trial. SETTING: Multicentre study. PATIENTS: 988 patients with multivessel disease. INTERVENTIONS: CABG and stent assisted PCI. MAIN OUTCOME MEASURES: Initial hospitalisation and one year follow up costs. RESULTS: At one year mortality was 2.5% in the PCI arm and 0.8% in the CABG arm (p = 0.05). There was no difference in the composite of death or Q wave myocardial infarction (6.9% for PCI v 8.1% for CABG, p = 0.49). There were more repeat revascularisations with PCI (17.2% v 4.2% for CABG). There was no significant difference in utility between arms at six months or at one year. Quality adjusted life years were similar 0.6938 for PCI v 0.6954 for PCI, Delta = 0.00154, 95% confidence interval (CI) -0.0242 to 0.0273). Initial length of stay was longer with CABG (12.2 v 5.4 days with PCI, p < 0.0001) and initial hospitalisation costs were higher (7321 pounds sterling v 3884 pounds sterling for PCI, Delta = 3437 pounds sterling, 95% CI 3040 pounds sterling to 3848 pounds sterling). At one year the cost difference narrowed but costs remained higher for CABG (8905 pounds sterling v 6296 pounds sterling for PCI, Delta = 2609 pounds sterling, 95% CI 1769 pounds sterling to 3314 pounds sterling). CONCLUSIONS: Over one year, CABG was more expensive and offered greater survival than PCI but little added benefit in terms of quality adjusted life years. The additional cost of CABG can be justified only if it offers continuing benefit at no further increase in cost relative to PCI over several years.

Retrospective analysis of the occurrence of internal malignancy in patients treated with PUVA between 1986 and 1999 in South Warwickshire.

Concerns were raised in our department when four of our patients receiving PUVA treatment developed internal malignancy. We reviewed the medical and phototherapy case notes of patients who received either systemic or bath PUVA therapy in our department between 1986 and 1999. Among the 197 patients for whom we were able to trace the hospital records we identified five patients with internal malignancies. Over the same period (1986-1999) we calculated, using the Kaplan-Meier nonparametric estimator, that 4.6 cases of internal malignancy would have been anticipated in our study population. Therefore PUVA therapy did not appear to be a risk factor for internal malignancy.

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

AIMS: To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. METHODS AND RESULTS: Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. CONCLUSIONS: Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use.

Cost effectiveness of treatment options in advanced breast cancer in the UK.

OBJECTIVE: To compare clinical and economic study data for docetaxel, paclitaxel and vinorelbine in the treatment of anthracycline-resistant advanced breast cancer. STUDY DESIGN AND METHODS: A Markov decision-analysis model to simulate the clinical course of a 'typical' patient with advanced breast cancer during salvage chemotherapy was updated with response rates and adverse effect rates from phase III clinical trial data for docetaxel, paclitaxel and vinorelbine. Costs were taken from UK national databases and hospitals. Utilities were estimated from 30 oncology nurses in the UK using the standard gamble method. PERSPECTIVE: National Health Service. RESULTS: When compared with other chemotherapeutic agents, docetaxel has been shown to increase response rate, time to progression and survival in patients with advanced breast cancer. In the base-case analysis, the incremental cost-utility ratio for docetaxel versus paclitaxel was pound1995 per quality-adjusted life year (QALY) gained (1998 values). The incremental cost-utility ratio for docetaxel versus vinorelbine was pound14 055 per QALY gained. In the comparison with vinorelbine, docetaxel provided the equivalent of an additional 92 days of perfect health. Sensitivity analyses confirmed the robustness of the model and the validity of the base-case analysis results. Even in the worst case scenarios, docetaxel remained cost effective compared with paclitaxel and vinorelbine. CONCLUSIONS: These findings support the use of the taxoids, notably docetaxel, in the management of advanced breast cancer.

An investigation of psychological distress in patients who have been treated for head and neck cancer.

There is now ample evidence that psychological distress is common in patients with head and neck cancer and that psychology has a role in reducing this distress. In this study, the prevalence, nature, and correlates of distress were investigated, in 18 patients who were no longer being actively treated but were attending a follow-up clinic or support group (n= 9 each). Four of the patients had appreciable psychological distress and four each had anxiety or depression of at least borderline importance. The degree of depression and distress decreased with increasing age and there were trends for depression to decrease with time after the onset of the illness and to be slightly less common among those attending the support group (2/9 compared to 4/9). Numerous psychosocial difficulties were reported and perceptions of support available from friends and family were mixed. There are implications for services, and in particular, patients need to be given clear information about the resources available to give them psychosocial support.