Recombinant human interleukin 6 in metastatic renal cell cancer: a phase II trial.

A phase II trial investigating the anti-tumour effects of recombinant human interleukin 6 (rhIL-6) in patients with metastatic renal cell cancer was carried out. RhIL-6 (150 microgram) was administered as a daily subcutaneous injection for 42 consecutive days on an outpatient basis. Forty-nine patients were studied, 12 with and 37 without previous immunotherapy. Forty patients were evaluable for response. A partial remission was noted in two patients, stable disease in 17 and progressive disease in 21. Toxicity was moderate and reversible and consisted mainly of fever, flu-like symptoms, nausea, weight loss and hepatotoxicity. Anaemia, leucocytosis and thrombocytosis and induction of acute phase protein synthesis were noted in most patients. In 15% of the patients anti-IL-6 antibodies developed, and were neutralising in only one patient. Baseline plasma IL-6 concentrations did not correlate with tumour behaviour before or after rhIL-6 treatment. In conclusion, rhIL-6 can be safely administered on an outpatient basis for prolonged period of time and has moderate, reversible toxicity. Its administration induces IL-6-antibody production in only a minority of patients. Antitmour effects of rhIL-6 in metastatic renal cancer are limited

Cross-national agreement on disability weights: the European Disability Weights Project

BACKGROUND: Disability weights represent the relative severity of disease stages to be incorporated in summary measures of population health. The level of agreement on disability weights in Western European countries was investigated with different valuation methods. METHODS: Disability weights for fifteen disease stages were elicited empirically in panels of health care professionals or non-health care professionals with an academic background following a strictly standardised procedure. Three valuation methods were used: a visual analogue scale (VAS); the time trade-off technique (TTO); and the person trade-off technique (PTO). Agreement among England, France, the Netherlands, Spain, and Sweden on the three disability weight sets was analysed by means of an intraclass correlation coefficient (ICC) in the framework of generalisability theory. Agreement among the two types of panels was similarly assessed. RESULTS: A total of 232 participants were included. Similar rankings of disease stages across countries were found with all valuation methods. The ICC of country agreement on disability weights ranged from 0.56 [95% CI, 0.52–0.62] with PTO to 0.72 [0.70–0.74] with VAS and 0.72 [0.69–0.75] with TTO. The ICC of agreement between health care professionals and non-health care professionals ranged from 0.64 [0.58–0.68] with PTO to 0.73 [0.71–0.75] with VAS and 0.74 [0.72–0.77] with TTO. CONCLUSIONS: Overall, the study supports a reasonably high level of agreement on disability weights in Western European countries with VAS and TTO methods, which focus on individual preferences, but a lower level of agreement with the PTO method, which focuses more on societal values in resource allocation

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Validation of a Chinese version of the dental anxiety inventory

Objectives: To translate the English version of Dental Anxiety Inventory (DAxI) and its short-form (SDAxI) and to validate their use in Hong Kong Chinese. Methods: The DAxI and SDAxI were translated into Chinese. A total of 500 adults (18-64 years) were interviewed, the Chinese DAxI, Symptom Checklist 90 (SCL-90), Depression Anxiety Stress Scales (DASS) and State-Trait Anxiety Inventory (STAI) were completed. Based on their initial DAxI scores, 135 interviewees were invited to attend a dental examination 1 month later. Then, the subjects completed the DAxI again, together with Beck Anxiety Inventory (BAI) which measured the state anxiety level of the participants. Two months after the initial interview, all 500 subjects were asked to complete the DAxI again. Another 300 adults were recruited and interviewed for the SDAxI validation. Results: Cronbach's alpha of the Chinese DAxI and SDAxI were 0.77 and 0.80 and the test-retest correlation coefficients were 0.90 and 0.84, respectively. High correlation between BAI and DAxI scores and its stability over time supported construct validity of the Chinese DAxI. Small positive correlations between the DAxI and other subscales of the SCL-90, DASS and STAI supported discriminant validity of the instrument. The SDAxI demonstrated comparable validity and reliability with DAxI. Conclusion: The translated Chinese DAxI demonstrated good validity and reliability. It is available for use in dental anxiety research in adult Chinese. In situations where a short-form is desirable, the Chinese SDAxI is a simple, valid, reliable and interpretable scale for measuring dental anxiety in both research and dental practice. © Blackwell Munksgaard, 2005.postprin

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective:To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to &lsquo;current practice&rsquo;. Method:The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria (&lsquo;equity&rsquo;; &lsquo;strength of evidence&rsquo;, &lsquo;feasibility&rsquo; and &lsquo;acceptability to stakeholders&rsquo;) is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6&ndash;17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios.Results:Compared to current practice, CBT by public psychologists is the most costeffective intervention for MDD in children and adolescents at A$9000 per DALY saved (95$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (&gt; 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders.Conclusions:Cognitive behavioural therapy provided by a public psychologist is the mosteffective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require &lsquo;start-up&rsquo; costs and attention to ensuring an adequate workforce.<br /

Central Exercise Action Increases the AMPK and mTOR Response to Leptin

AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus

Clinical and cost-effectiveness of computerised cognitive behavioural therapy for depression in primary care: Design of a randomised trial

<p>Abstract</p> <p>Background</p> <p>Major depression is a common mental health problem in the general population, associated with a substantial impact on quality of life and societal costs. However, many depressed patients in primary care do not receive the care they need. Reason for this is that pharmacotherapy is only effective in severely depressed patients and psychological treatments in primary care are scarce and costly. A more feasible treatment in primary care might be computerised cognitive behavioural therapy. This can be a self-help computer program based on the principles of cognitive behavioural therapy. Although previous studies suggest that computerised cognitive behavioural therapy is effective, more research is necessary. Therefore, the objective of the current study is to evaluate the (cost-) effectiveness of online computerised cognitive behavioural therapy for depression in primary care.</p> <p>Methods/Design</p> <p>In a randomised trial we will compare (a) computerised cognitive behavioural therapy with (b) treatment as usual by a GP, and (c) computerised cognitive behavioural therapy in combination with usual GP care. Three hundred mild to moderately depressed patients (aged 18–65) will be recruited in the general population by means of a large-scale Internet-based screening (<it>N </it>= 200,000). Patients will be randomly allocated to one of the three treatment groups. Primary outcome measure of the clinical evaluation is the severity of depression. Other outcomes include psychological distress, social functioning, and dysfunctional beliefs. The economic evaluation will be performed from a societal perspective, in which all costs will be related to clinical effectiveness and health-related quality of life. All outcome assessments will take place on the Internet at baseline, two, three, six, nine, and twelve months. Costs are measured on a monthly basis. A time horizon of one year will be used without long-term extrapolation of either costs or quality of life.</p> <p>Discussion</p> <p>Although computerised cognitive behavioural therapy is a promising treatment for depression in primary care, more research is needed. The effectiveness of online computerised cognitive behavioural therapy without support remains to be evaluated as well as the effects of computerised cognitive behavioural therapy in combination with usual GP care. Economic evaluation is also needed. Methodological strengths and weaknesses are discussed.</p> <p>Trial registration</p> <p>The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN47481236).</p