Entecavir for the treatment of chronic hepatitis B infection

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturer's mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturer's lifetime treatment scenario for HBeAg-negative patients and the ERG's 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.

Investigation of consumer satisfaction with cognitive-behaviour therapy and sertraline in the treatment of adolescent depression

Objective: A new instrument, the Adolescent Depression Treatment Satisfaction Questionnaire (ADTSQ) was devised to measure the consumer satisfaction of depressed adolescents and their parents. The objectives of the paper were to present the psychometric proper ties ofthe ADTSQ and to investigate the relative consumer satisfaction with cognitive-behavioural therapy (CBT), sertraline (SRT) and a combined treatment of CBT and SRT (COMBINED) for the treatment of adolescent depression. In addition, participants were asked to rank their most preferred treatment from the following approaches: medication, individual counselling, group program and family therapy.Method: Thirty-eight adolescents with a unipolar depressive disorder and 37 parents who participated in a randomized clinical trial of CBT versus SRT versus COMBINED completed the ADTSQ following the completion of acute treatment.Results: The ADTSQ was found to have high internal consistency and exploratory factor analysis detected three underlying factors. High levels of consumer satisfaction were reported by both adolescents and parents in all three treatments. Those treated with CBT treatments reported higher levels of skill acquisition than those treated with SRT. Of the four treatment approaches, most parents and adolescentsrated individual counsellingas their first preference.Conclusions: The ADTSQ is a useful measure of consumer satisfaction for depressed adolescents and their parents. CBT, SRT and COMBINED were shown to have high consumer satisfaction with CBT's higher skills training content reflected in the participants' reports. Individual counselling was perceived as the most favourable choice of treatment for adolescent depression. Although limitations associated with the measurement of consumer satisfaction and of the study are acknowledged, it is recommended that the inclusion of consumer satisfaction measures be considered in clinical trials that examine treatment efficacy.

The treatment of sex offenders : evidence, ethics, and human rights

Public policy is necessarily a political process with the law and order issue high on the political agenda. Consequently, working with sex offenders is fraught with legal and ethical minefields, including the mandate that community protection automatically outweighs offender rights. In addressing community protection, contemporary sex offender treatment is based on management rather than rehabilitation. We argue that treatment-as-management violates offender rights because it is ineffective and unethical. The suggested alternative is to deliver treatment-as-rehabilitation underpinned by international human rights law and universal professional ethics. An effective and ethical community–offender balance is more likely when sex offenders are treated with respect and dignity that, as human beings, they have a right to claim.

Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial.

While statins target many of the pathways to neuroprogression in schizophrenia, the safety and efficacy of statins for treating schizophrenia has never been examined. This is an 8-week randomized double blind controlled clinical trial examining the efficacy and safety of adjunctive lovastatin (20 mg/day) treatment or placebo for people with schizophrenia. The baseline characteristics of the two groups were not different. Endpoint changes in Positive and Negative Syndrome Scale (PANSS) total and subscale scores did not differ between the two groups. However there was a significant difference between the doses of risperidone used in the two groups. The mean dose in the lovastatin and placebo groups were 4.8(1.8) and 3.4(1.4) mg/day, respectively (P<.03). No serious adverse events were reported. Slowness of movements, muscle rigidity, increased appetite, and decreased energy were the most common adverse effects, and these rates did not differ between the two groups. This study failed to demonstrate a benefit of lovastatin on symptoms of schizophrenia. This combination was well tolerated. However, a higher dosage of risperidone was used for treating the disorder in those taking concomitant lovastatin compared to placebo.

Cognitive-reminiscence therapy for the treatment of depression in young adults

 This thesis aimed to evaluate a novel psychotherapy for young adults with depressive symptoms, cognitive-reminiscence therapy, and the underlying mechanisms of change. The results from a clinical trial showed large effects in reducing depressive symptoms, evidence for the mechanisms of change, and that young adults found this treatment helpful and appealing

Bevacizumab for the treatment of high-grade glioma: an update after phase III trials.

Gliomas are highly vascular and rich in VEGF, which promotes angiogenesis. Bevacizumab is a monoclonal antibody against VEGF, inhibiting angiogenesis by preventing receptor activation. Early Phase II clinical trials using bevacizumab in both newly diagnosed and recurrent high-grade gliomas (HGG) showed promising results, but these have not been confirmed in recent Phase III trials. This review is an update including recently reported Phase II and III study results.

Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. Trial registration: Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.