Ustekinumab for the treatment of moderate to severe psoriasis

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ustekinumab for the treatment of moderate to severe psoriasis 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 main evidence came from three randomised controlled trials (RCTs), of reasonable methodological quality and measuring a range of clinically relevant outcomes. Higher proportions of participants treated with ustekinumab (45 mg and 90 mg) than with placebo or etanercept achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) after 12 weeks. There were also statistically significant differences in favour of ustekinumab over placebo for PASI 50 and PASI 90 results, and for ustekinumab over etanercept for PASI 90 results. A weight-based subgroup dosing analysis for each trial was presented, but the methodology was poorly described and no statistical analysis to support the chosen weight threshold was presented. The manufacturer carried out a mixed treatment comparison (MTC); however, the appropriateness of some of the methodological aspects of the MTC is uncertain. The incidence of adverse events was similar between groups at 12 weeks and withdrawals due to adverse events were low and less frequent in the ustekinumab than in the placebo or etanercept groups; however, statistical comparisons were not reported. The manufacturer's economic model of treatments for psoriasis compared ustekinumab with other biological therapies. The model used a reasonable approach; however, it is not clear whether the clinical effectiveness estimates from the subgroup analysis, used in the base-case analysis, were methodologically appropriate. The base-case incremental cost-effectiveness ratio for ustekinumab versus supportive care was 29,587 pounds per quality-adjusted life-year (QALY). In one-way sensitivity analysis the model was most sensitive to the number of hospital days associated with supportive care, the cost estimate for intermittent etanercept 25 mg and the utility scores used. In the ERG's scenario analysis the model was most sensitive to the price of ustekinumab 90 mg, the proportion of patients with baseline weight > 100 kg and the relative risk of intermittent versus continuous etanercept 25 mg. In the ERG's probabilistic sensitivity analysis ustekinumab had the highest probability of being cost-effective at conventional NICE thresholds, assuming the same price for the 45-mg and 90-mg doses; however, doubling the price of ustekinumab 90 mg resulted in ustekinumab no longer dominating the comparators. In conclusion, the clinical effectiveness and cost-effectiveness of ustekinumab in relation to other drugs in this class is uncertain. Provisional NICE guidance issued as a result of the STA states that ustekinumab is recommended as a treatment option for adults with plaque psoriasis when a number of criteria are met. Final guidance is anticipated in September 2009.

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.

The happiness and subjective well-being of people on haemodialysis

Happiness is a construct that has been gaining more prominence in both social and health research. The measure of happiness, subjective well-being, has not been rigorously explored in the end-stage kidney disease (ESKD) population.

Understanding context in knowledge translation: a concept analysis study protocol.

AIM: To conduct a concept analysis of clinical practice contexts (work environments) that facilitate or militate against the uptake of research evidence by healthcare professionals in clinical practice. This will involve developing a clear definition of context by describing its features, domains and defining characteristics. BACKGROUND: The context where clinical care is delivered influences that care. While research shows that context is important to knowledge translation (implementation), we lack conceptual clarity on what is context, which contextual factors probably modify the effect of knowledge translation interventions (and hence should be considered when designing interventions) and which contextual factors themselves could be targeted as part of a knowledge translation intervention (context modification). DESIGN: Concept analysis. METHODS: The Walker and Avant concept analysis method, comprised of eight systematic steps, will be used: (1) concept selection; (2) determination of aims; (3) identification of uses of context; (4) determination of defining attributes of context; (5) identification/construction of a model case of context; (6) identification/construction of additional cases of context; (7) identification/construction of antecedents and consequences of context; and (8) definition of empirical referents of context. This study is funded by the Canadian Institutes of Health Research (January 2014). DISCUSSION: This study will result in a much needed framework of context for knowledge translation, which identifies specific elements that, if assessed and used to tailor knowledge translation activities, will result in increased research use by nurses and other healthcare professionals in clinical practice, ultimately leading to better patient care.

Interview with Rebecca Emori

Rebecca Emori is a Papua New Guinean who studied at the University of Sydney in 2011-2012. She studied on an Australian Agency for International Development (AusAID) Scholarship and completed a Masters in Health Research. The interview was conducted in English on 9 July 2014 by Dr. Musawe Sinebare of the Pacific Adventist University. This set comprises: an interview recording in two parts, and a timed summary.

Prediction of perinatal depression from adolescence and before conception (VIHCS): 20-year prospective cohort study

BACKGROUND: Perinatal depression is a neglected global health priority, affecting 10-15% of women in high-income countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, and emotional difficulties and, in low-income settings, perinatal depression is associated with stunting and physical illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which women with perinatal depressive symptoms had a history of mental health problems before conception. METHODS: VIHCS is a follow-up study of participants in the Victorian Adolescent Health Cohort Study (VAHCS), which was initiated in August, 1992, in the state of Victoria, Australia. In VAHCS, participants were assessed for health outcomes at nine timepoints (waves) from age 14 years to age 29 years. Depressive symptoms were measured with the Revised Clinical Interview Schedule and the General Health Questionnaire. Enrolment to VIHCS began in September, 2006, during the ninth wave of VAHCS; depressive symptoms at this timepoint were measured with the Composite International Diagnostic Interview. We contacted women every 6 months (from age 29 years to age 35 years) to identify any pregnancies. We assessed perinatal depressive symptoms with the Edinburgh Postnatal Depression Scale (EPDS) by computer-assisted telephone interview at 32 weeks of gestation, 8 weeks after birth, and 12 months after birth. We defined perinatal depression as an EPDS score of 10 or more. FINDINGS: From a stratified random sample of 1000 female participants in VAHCS, we enrolled 384 women with 564 pregnancies. 253 (66%) of these women had a previous history of mental health problems at some point in adolescence or young adulthood. 117 women with a history of mental health problems in both adolescence and young adulthood had 168 pregnancies, and perinatal depressive symptoms were reported for 57 (34%) of these pregnancies, compared with 16 (8%) of 201 pregnancies in 131 women with no preconception history of mental health problems (adjusted odds ratio 8·36, 95% CI 3·34-20·87). Perinatal depressive symptoms were reported at one or more assessment points in 109 pregnancies; a preconception history of mental health problems was reported in 93 (85%) of these pregnancies. INTERPRETATION: Perinatal depressive symptoms are mostly preceded by mental health problems that begin before pregnancy, in adolescence or young adulthood. Women with a history of persisting common mental disorders before pregnancy are an identifiable high-risk group, deserving of clinical support throughout the childbearing years. Furthermore, the window for considering preventive intervention for perinatal depression should extend to the time before conception. FUNDING: National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Colonial Foundation, Australian Rotary Health Research and Perpetual Trustees.

Still serving hot soup? Two hundred years of a charitable food sector in Australia: a narrative review

OBJECTIVE: Despite the importance of the charitable food sector for a proportion of the Australian population, there is uncertainty about its present and future contributions to wellbeing. This paper describes its nature and examines its scope for improving health and food security. METHODS: The review, using systematic methods for public health research, identified peer-reviewed and grey literature relevant to Australian charitable food programs (2002 to 2012). RESULTS: Seventy publications met the criteria and informed this paper. The sector includes food banks, more than 3,000 community agencies and 800 school breakfast programs. It provides food for up to two million people annually. The scope extends beyond emergency food relief and includes case management, advocacy and other support. Weaknesses include a food supply that is sub-optimal, resource limitations and lack of evidence to evaluate or support their work towards food security. CONCLUSIONS: The sector supports people experiencing disadvantage and involves multiple organisations, working in a variety of settings, to provide food for up to 8% of the population. The limits on the sector's capacity to address food insecurity by itself must be acknowledged so that civil society, government and the food industry can support sufficient, nutritious and affordable food for all.

Methods for a population-based study of eye disease: the Melbourne Visual Impairment Project

The methodology of the Melbourne Visual Impairment Project, a major population-based survey of eye disease on 3,500 randomly selected individuals aged 40 years of age and over in the Melbourne metropolitan region, is presented. The aims of the study are to determine the distribution and determinants of eye disease in an urban population; the impact of eye disease on visual function and the activities of daily living; and the accessibility of eye health care services in the community. All procedures are conducted according to a standardised protocol to allow for comparison with other population-based studies, both in Australia and overseas. Information collected from this study will be employed in the development of recommendations related to eye health care service delivery and establishment of priorities for future public education programmes and health research.