Improved yield of recombinant human IFN-α2b from mammalian cells using heterologous signal peptide approach.

The Type I Interferon cytokine family member, Interferon-α2b (hIFN-α2b), modulates a number of important biological mechanisms including anti-proliferation, immunoregulation and antiviral responses. Due to its role in the immune system, hIFN-α2b has been used as a therapeutic modulator in hepatitis C as well as some forms of leukaemia. Clinical grade hIFN-α2b is typically produced in bacterial expression systems that involves complex refolding protocols and subsequent loss of yields. In this study, we describe an expression and purification system for hIFN-α2b from mammalian cells. Application of the Trypsin-1 signal peptide-propeptide domain significantly improved the expression and secretion of hIFN-α2b from HEK293 cells. We established a simple purification strategy that yields homogenous, pure hIFN-α2b that is stable and biologically active.

Supporting prostate cancer survivors in primary care: Findings from a pilot trial of a nurse-led psycho-educational intervention (PROSPECTIV).

PURPOSE: This study sought to test the acceptability and feasibility of a nurse-led psycho-educational intervention (NLPI) delivered in primary care to prostate cancer survivors, and to provide preliminary estimates of the effectiveness of the intervention. METHODS: Men who reported an ongoing problem with urinary, bowel, sexual or hormone-related functioning/vitality on a self-completion questionnaire were invited to participate. Participants were randomly assigned to the NLPI plus usual care, or to usual care alone. Recruitment and retention rates were assessed. Prostate-related quality of life, self-efficacy, unmet needs, and psychological morbidity were measured at baseline and 9 months. Health-care resource use data was also collected. An integrated qualitative study assessed experiences of the intervention. RESULTS: 61% eligible men (83/136) participated in the trial, with an 87% (72/83) completion rate. Interviews indicated that the intervention filled an important gap in care following treatment completion, helping men to self-manage, and improving their sense of well-being. However, only a small reduction in unmet needs and small improvement in self-efficacy was observed, and no difference in prostate-related quality of life or psychological morbidity. Patients receiving the NLPI recorded more primary care visits, while the usual care group recorded more secondary care visits. Most men (70%; (21/30)) felt the optimal time for the intervention was around the time of diagnosis/before the end of treatment. CONCLUSIONS: Findings suggest a nurse-led psycho-educational intervention in primary care is feasible, acceptable and potentially useful to prostate cancer survivors.

Commentary on 'Communicating Messages About Drinking': Using the 'Big Legal Guns' to Block Alcohol Health Warning Labels.

Like the tobacco industry, the alcohol industry, with the support of governments in alcohol exporting nations, is looking to international trade and investment law as a means to oppose health warning labels on alcohol. The threat of such litigation, let alone its commencement, has the potential to deter all but the most resolute governments from implementing health warning labeling.

Cost-effectiveness of different strategies to manage patients with sciatica.

The aim of this paper is to estimate the relative cost-effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed based on information from the findings from a systematic review of clinical effectiveness and cost-effectiveness, published sources of unit costs, and expert opinion. The assumption was that patients presenting with sciatica would be managed through one of 3 pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12-month period. One-way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was nonopioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was nonopioids, followed by biological agents, followed by epidural/nerve block and disk surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost-effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per quality-adjusted life year are higher, the economic model demonstrated that stepped approaches based on initial treatment with nonopioids are likely to represent the most cost-effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required.

Recommendations for international gambling harm-minimisation guidelines: comparison with effective public health policy.

Problem gambling represents a significant public health problem, however, research on effective gambling harm-minimisation measures lags behind other fields, including other addictive disorders. In recognition of the need for consistency between international jurisdictions and the importance of basing policy on empirical evidence, international conventions exist for policy on alcohol, tobacco, and illegal substances. This paper examines the evidence of best practice policies to provide recommendations for international guidelines for harm-minimisation policy for gambling, including specific consideration of the specific requirements for policies on Internet gambling. Evidence indicates that many of the public health policies implemented for addictive substances can be adapted to address gambling-related harms. Specifically, a minimum legal age of at least 18 for gambling participation, licensing of gambling venues and activities with responsible gambling and consumer protection strategies mandated, and brief interventions should be available for those at-risk for and experiencing gambling-related problems. However, there is mixed evidence on the effectiveness of limits on opening hours and gambling venue density and increased taxation to minimise harms. Given increases in trade globalisation and particularly the global nature of Internet gambling, it is recommended that jurisdictions take actions to harmonise gambling public health policies.

Per-capita alcohol consumption and all-cause male mortality in Australia, 1911-2006.

AIMS: Given the variety of relationships found between alcohol consumption and health using individual data (both negative and positive), the likely impact of changes in population-level alcohol consumption on health at the population level is not clear. This paper uses historical data from 1911 to 2006 to assess the relationship between changes in per-capita alcohol consumption on total male mortality in Australia. METHODS: A longitudinal aggregate study using Australian per-capita alcohol consumption and mortality data from 1911 to 2006. Analysis is undertaken using autoregressive integrated moving average time-series methods. RESULTS: Per-capita pure alcohol consumption has a significant association with male all-cause mortality, with an increase (decrease) of 1 l per-capita per year associated with a 1.5% increase (decrease) in male mortality (controlling for female mortality and smoking rates). The association between per-capita consumption and mortality was significant for all age groups, with a particularly strong effect among 15-29 year olds. CONCLUSION: These results place Australia in the group of countries for which a positive association between per-capita alcohol consumption and total mortality can be demonstrated. Thus, despite the beneficial effects of alcohol consumption on health found in many studies, increases in consumption at the population level in Australia are associated with declines in population health. Thus, per-capita alcohol consumption in Australia is a significant contributor to rates of male mortality, particularly among young adults, suggesting an interaction between per-capita consumption and risky episodic drinking. The policies aiming to reduce population-level alcohol consumption and episodic risky drinking have the potential to substantially improve population-health outcomes in Australia, particularly among young men.

Warnings on alcohol containers and advertisements: international experience and evidence on effects.

ISSUES: In light of possible introduction of alcohol warning labels in Australia and New Zealand, this paper discusses the international experience with and evidence of effects of alcohol warning labels. APPROACH: The report describes international experience with providing information and warnings concerning the promotion or sale of alcoholic beverages, and considers the evidence on the effects of such information and warnings. The experience with and evaluations of the effects of tobacco warning labels are also considered. KEY FINDINGS: The most methodologically sound evaluations of alcohol warning labels are based on the US experience. Although these evaluations find little evidence that the introduction of the warning label in the USA had an impact on drinking behaviour, there is evidence that they led to an increase in awareness of the message they contained. In contrast, evaluations of tobacco warning labels find clear evidence of effects on behaviour. IMPLICATIONS: There is a need and opportunity for a rigorous evaluation of the impacts of introducing alcohol warning labels to add to the published work on their effectiveness. The experience with tobacco labels might guide the way for more effective alcohol warning labels. CONCLUSION: Alcohol warning labels are an increasingly popular alcohol policy initiative. It is clear that warning labels can be ineffective, but the tobacco experience suggests that effective warning labels are possible. Any introduction of alcohol warning labels should be evaluated in terms of effects on attitudes and behaviour.

Personality disorder, depression and functioning: results from the ODIN study.

BACKGROUND: There is little information of the prevalence of personality disorder (PD) in those with depressive disorder in community samples; neither is there any data on the impact of PD on service utilisation or outcome in this setting. METHODS: A two stage screening study to identify cases of depressive disorder using SCAN in five European countries. Personality assessed 6 months after the diagnostic interview. Follow-up for 1 year using symptom and social function measures. RESULTS: Personality disorder is present in 22% of a community sample with depressive disorders but the range varied from 13.7% to 33.3% across countries. Cluster C formed 43% of the total. Long-term psychotropic drug use was more common in the PD group even after depression was controlled. Those with PD had higher symptom scores at the outset and, although the PD group was more likely to be cases at follow-up, this disappeared when the depression score was co-varied. Only initial social function predicted outcome at 6 and 12 months. LIMITATIONS: The use of a non-treatment seeking population may limit the application of the findings to clinical populations. CONCLUSIONS: PD is common even in a non-treatment seeking population with depressive disorder. It impacts upon outcome at 6 and 12 months but this is related to the initial severity of depressed mood. Social function is the only independent predictor of outcome and should be assessed separately.