The contribution of general practice based research to the development of national policy: case studies from Ireland and Australia

Background

This paper aims to describe the influence of general practice based research on the development of two specific policy initiatives, namely the Heartwatch Programme in Ireland and the Better Outcomes in Mental Health Care (BOiMHC) program in Australia. A case study approach was used to explore the extent to which relevant general practice based research shaped these initiatives.

Results

In both case studies, a range of factors beyond general practice based research shaped the initiative in question, including political will, the involvement of stakeholders (including key opinion leaders), and the historical context. Nonetheless, the research played an important role, and was not merely put to 'symbolic use' to support a position that had already been reached independently. Rather, both case studies provide examples of 'instrumental use': in the case of Heartwatch, the research was considered early in the piece; in the case of the BOiMHC program, it had a specific impact on the detail of the components of the initiative.

Conclusion

General practice based research can influence policy-making and planning processes by strengthening the foundation of evidence upon which they draw. This influence will not occur in a vacuum, however, and general practice researchers can maximise the likelihood of their work being 'picked up' in policy if they consider the principles underpinning knowledge transfer.

     

Raised bile acid concentrations in SIDS lungs at necropsy

Previous studies of the abnormal physical properties of lung surfactant derived from infants experiencing prolonged expiratory apnoea, or who have died of sudden infant death syndrome (SIDS), have led to a search for the agent responsible. Bronchoalveolar lavage (BAL) has been performed upon 12 infants under 12 months at necropsy and the rinsings analysed for up to 26 bile acids using high performance liquid chromatography, which requires nanomolar quantities. They were also analysed for simultaneously retrieved phospholipid and proteolipid-a minor component of lung surfactant-as markers of lavage efficiency. Total bile acid (TBA) was found to be higher in six SIDS cases, reaching a mean (SE) 8.54 (2.24) mumol/l in the BAL fluid compared with 4.66 (1.47) mumol/l in the six controls of similar age. When related to the concomitant surfactant yield, the TBA/ proteolipid and TBA/phospholipid ratios both showed highly significant differences between index lungs and controls, providing another postmortem marker of SIDS with potential for development as a test of risk. Since the bile:phospholipid ratio determines whether phospholipase A2 synthesises or hydrolyses phospholipid, the raised TBA/phospholipid ratio could be highly significant, causing this enzyme to function more like its role in the gut than in the lung.     

Which Carbohydrates Should We Recommend for Intravenous Nutrition?

In a short review solutions of glucose, fructose and invertose have been compared in regard to proteinsparing effects, side effects and infusion rates. It is concluded that fructose alone offers no advantage to glucose neither in the normal nor in the stressed organism. Compared with pure glucose and fructose solutions, higher amounts of carbohydrate can be administered as invertose, without increasing the risk of side effects.     

The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia.

Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D2/D3 dopamine receptors in human striatum. Here, the occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [18F]fallypride PET scan. Receptor occupancy was calculated as percent reduction in binding potential relative to unblocked values measured in seven normal volunteers. Mean D2/D3 receptor occupancy was statistically significantly higher in cortical (inferior temporal cortex 55%) than in striatal regions (putamen 36%, caudate 43%, p<0.005). While the maximum attainable receptor occupancy Emax approached 100% both in the striatum and cortex, the plasma concentration at 50% of Emax (ED50) was much higher in the putamen (950 ng/ml) than in the inferior temporal cortex (333 ng/ml). Clozapine binds preferentially to cortical D2/D3 receptors over a wide range of plasma concentrations. This selectivity is lost at extremely high plasma levels. Occupancy of cortical receptors approaches 60% with plasma clozapine in the range 350-400 ng/ml, which corresponds to the threshold for antipsychotic efficacy of clozapine. Extrastriatal binding of clozapine may be more relevant to its antipsychotic actions than striatal. However, further studies with an intraindividual comparison of untreated vs treated state are desirable to confirm this finding.     

Analysis of two inbred strains of mice derived from the SENCAR stock with different susceptibility to skin tumor progression

The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67% incidence of SCC, compared to 0% in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-beta1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.      

Six-month follow-up of children with obstructive sleep apnoea

OBJECTIVES: This study examined prospectively changes in development, temperament and sleep related behaviour in children referred for obstructive sleep apnoea (OSA) and polysomnographic sleep study, some of whom had surgical intervention. METHODOLOGY: Using a prospective cohort study design, parents of 56 children referred for OSA completed sleep and temperament questionnaires and their child was assessed developmentally at the time of the polysomnographic sleep study. Forty (72%) of the children were neurologically normal. At 6 months, 42 children were reassessed using sleep and temperament questionnaires and a developmental assessment. After excluding the primary snorers, subjects were categorised as having had intervention (n = 24) or not (n = 15), and differences over the 6-month period in Griffiths scores, temperament and sleep related behaviour were examined. RESULTS: Regardless of intervention status, there was an improvement in night-time and day-time sleep behaviour for the total group, though the extent of improvement was more marked in the intervention group. For the neurologically normal children, improvement in the sleep behaviour was only significant for the intervention group (P < 0.05). Intervention did not result in any significant changes in Griffiths developmental score or temperament. CONCLUSION: Surgical intervention improves sleep behaviour in children though not temperament or development.