Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, a major active ingredient in the root of Salvia miltiorrhiza Bunge

The extracts from the roots of Salvia miltiorrhiza Bunge (Danshen) are widely and traditionally used in the treatment of angina pectoris, acute myocardial infarct, hyperlipidemia and stroke in China and other Asian countries. In this study, we have investigated the role of P-glycoprotein (P-gp) in the intestinal absorption of tanshinone IIA (TSA), a major active constituent of Danshen, using several in vitro and in vivo models. The oral bioavailability of TSA was about 2.9

Cycling at 120 when compared to 80 rev/min increases the accumulated oxygen deficit but does not affect the precision of its calculation

The aim of the present study was to determine the influence of pedal rate on the precision and quantification of the accumulated oxygen deficit (AOD). Eight trained male triathletes completed a lactate threshold test, VO2 peak test, 10 x 3 min submaximal exercise bouts and a high-intensity exercise bout, all performed at 80 and 120 rev/min. For both pedal rates the intensities for the sub-maximal and high-intensity tests were relative to the lactate threshold and VO2 peak work rates. The VO2-power regressions were calculated using 5 intensities from above the lactate threshold combined with a y intercept value with VO2 measured after 3 min of exercise. For the 120 compared to the 80 rev/min tests, the lactate threshold work rate (255±13 versus 276±47 Watts) (p<0.01) and VO2 peak work rate (352±17 versus 382±20, Watts) (p<0.05) were lower at 120 rev/m. Conversely, the VO2 peak and the VO2 measured during the exhaustive exercise were the same for both pedal rates (p>0.05). Using linear regression modelling the slope of the VO2-power regression (0.0112 versus 0.010 L/Watt) (p<0.01), the estimated total energy demand (ETED) (5.13±0.75 versus 4.89±0.88 L/min) and the AOD (4.27±0.94 versus 3.66±1.25 L) (p<0.05) were greater at 120 rev/m. However, the 95% confidence interval for the ETED and the standard error of the predicted value were the same for both pedal rates (p>0.05). Our results demonstrate that pedal rate effects the size but not the precision of the calculated AOD and should therefore be considered when developing an AOD protocol.

Workforce trends in specialist and GP obstetric practice in Victoria

OBJECTIVE: To provide a contemporary picture of the general practitioner and specialist obstetric workforce in Victoria.

DESIGN, PARTICIPANTS AND SETTING: Postal census by questionnaire of all 317 Fellows and 961 Diplomates on the Victorian database of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists in September 2003.

MAIN OUTCOME MEASURES: Sex, age and geographical distributions and patterns of retirement from and recruitment to the GP and specialist obstetric workforce in Victoria.

RESULTS: 244 Fellows (77.0%) and 652 Diplomates (67.8%) participated. The average age of Diplomates was 42 years; only 20% were involved in procedural obstetrics. Of GPs practising procedural obstetrics, 56% intended to cease within 7 years. Two-thirds of specialist obstetricians continued to practise obstetrics. Among those ceasing obstetrics, almost half had done so since 2000. Among Fellows ceasing obstetric practice, there is a peak in the 50-60-years age group, but cessation of obstetric practice occurred across all age groups.

CONCLUSION: The proportion of GPs involved in procedural obstetrics has fallen markedly over the past decade, with half of those ceasing practice in the 40-50-years age group. New GPs entering the workforce with the Diploma and overseas doctors are unlikely to meet the procedural workforce shortfall. Attracting the large cohort of doctors aged 40-50 years back to obstetric practice must be a priority. Given the pattern of retirements from obstetrics, there will be insufficient numbers of specialists to maintain current levels of service. The reasons include non-participation in obstetrics by new graduates and international medical graduates, the inadequate number of new graduates, and the predominance of women among specialists aged under 40 years, whose work output tends to be affected by family commitments.

Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra.

Purpose. Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood–brain barrier (BBB) using several in vitro and in vivo models.
Materials and Methods. Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method.
Results. The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with
facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 T 0.09% at 1 min to 9.27 T 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Coperfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6j142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold higher than the wild-type mice.
Conclusions. These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drugglabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin.

Performance of a 120 m2 solar air heater for a commercial building in Victoria

The operation of two 60 m² solar air heaters serving a large studio teaching space has been monitored for a twelve month period. The solar contribution of the heaters was found to be less than 5%, and in some instances the heaters actually contributed to the space heating load. A validated mathematical model of the studio and it’s heating, ventilation and air conditioning system was used to investigate performance improvement strategies. It was found a different control strategy and recommissioned control sensors would substantially improve the solar air heater performance.

Australian gp's preferences for education about depression and related disorders

OBJECTIVE: To Investigate Australian general practitioners' experiences of accessing education about depression and their preferences for future education on depression and related disorders.
METHOD: Six hundred and eight anonymous surveys were distributed to GPs through 52 rural and urban divisions of general practice; 420 were retumed.
RESULTS: Educational formats involving direct contact with people having mental health expertise were highly valued. Distance education and web based technologies were least used. In the previous year, women and older GPs had spent more time on education about depression. Most intended to undertake more such education in the future and said that education in psychosocial strategies would be very useful. General practitioners' attitudes to further education about depression were influenced by their gender, practice location, and their previous mental health training.
DISCUSSION: More face-to-face training may be desirable to take advantage of GPs' willingness to spend more time on education about depression and related disorders.

A mechanistic study of the intestinal absorption of crypotanshinone, the major active constituent of Saliva miltiorrhiza

The nature of intestinal absorption of most herbal medicine is unknown. Cryptotanshinone (CTS) is the principal active constituent of the widely used cardiovascular herb Salvia miltiorrhiza (Danshen). We investigated the oral bioavailability of CTS in rats and the mechanism for its intestinal absorption using several in vitro and in vivo models:1) Caco-2 cell monolayers; 2) monolayers of MDCKII cells overexpressing P-glycoprotein
(PgP); and 3) single-pass rat intestinal perfusion with mesenteric vein cannulation. The systemic bioavailabilities of CTS after oral and intraperitoneal administration at 100 mg/kg were 2.05 and 10.60%, respectively. In the perfused rat intestinal model, permeability coefficients based on CTS disappearance from the luminal perfusate (P_lumen) were 6.7- to 10.3-fold higher than permeability coefficients based on drug appearance in venous blood (P_blood). P_blood significantly increased in the presence of the P-gP inhibitor, verapamil. CTS transport across Caco-2 monolayers was pH-, temperature- and ATP-dependent. The transport from the apical (AP) to the basolateral (BL) side was 3- to 9-fold lower than that from the BL to the AP side. Inclusion of verapamil (50 µM) in both AP and BL sides abolished the polarized CTS transport across Caco-2 cells. Moreover, CTS was significantly more permeable in the BL to AP than in the AP to BL direction in MDCKII and MDR1-MDCKII cells. The permeability coefficients in the BL to AP direction were significantly higher in MDCKII cells overexpressing PgP. These findings indicate that CTS is a substrate for PgP that can pump CTS into the luminal side.

Topotecan is a substrate for multidrug resistance associated protein 4

Topotecan (TPT) is a semisynthetic water-soluble derivative of camptothecin (CPT) used as second-line therapy in patients with metastatic ovarian carcinoma, small cell lung cancer, and other malignancies. However, both doselimiting toxicity and tumor resistance hinder the clinical use of TPT. The mechanisms for resistance to TPT are not fully defined, but increased efflux of the drug by multiple drug transporters including P-glycoprotein (PgP), multidrug resistance associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) from tumor cells has been highly implicated. This study aimed to investigate whether overexpression of human MRP4 rendered resistance to TPT by examining the cytotoxicity profiles using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay and cellular accumulation of TPT in HepG2 cells stably overexpressing MRP4. Two kinds of cell lines, HepG2 with insertion of an empty vector plasmid (V/HepG2), HepG2 cells stably expressing MRP4 (MRP4/HepG2), were exposed to TPT for 4 or 48 hr in the absence or presence of various MRP4 inhibitors including DL-buthionine-(S,R)-sulphoximine (BSO), diclofenac, celecoxib, or MK-571. The intracellular accumulation of TPT and paclitaxel (a PgP substrate) by V/HepG2 and MRP4/HepG2 cells was determined by incubation of TPT with the cells and the amounts of the drug in cells were determined by validated HPLC methods. The study demonstrated that MRP4 conferred a 12.03- and 6.86-fold resistance to TPT in the 4- and 48-hr drug-exposure MTT assay, respectively. BSO, MK-571, celecoxib, or diclofenac sensitised MRP4/HepG2 cells to TPT cytotoxicity and partially reversed MRP4-mediated resistance to TPT. In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2 cells compared to V/HepG2 cells, and one-binding site model was found the best fit for the MRP4-mediated efflux of TPT, with an estimated Km of 1.66 mM and Vmax of 0.341 ng/min/106 cells. Preincubation of MRP4/HepG2 cells with BSO (200 μM) for 24 hr, celecoxib (50 mM), or MK-571 (100 mM) for 2 hr significantly increased the accumulation of TPT over 10 min in MRP4/HepG2 cells by 28.0%, 37.3% and 32.5% (P < 0.05), respectively. By contrast, there was no significant difference in intracellular accumulation of paclitaxel in V/HepG2 and MRP4/HepG2 cells over 120 min. MRP4 also rendered resistance to adefovir dipivoxil (bis-POMPMEA) and methotrexate, two reported MRP4 substrates. MRP4 did not exhibit any significant resistance to other model drugs including vinblastine, vincristine, etoposide, carboplatin, cyclosporine and paclitaxel in both long (48 hr) and short (4 hr) drug-exposure MTT assays. These findings indicate that MRP4 confers resistance to TPT and TPT is the substrate for MRP4. Further studies are needed to explore the role of MRP4 in resistance to, toxicity and pharmacokinetics of TPT in cancer patients.

Human multidrug resistance associated protein 4 resitance to camtothecins

Purpose The multidrug resistance associated protein (MRP) 4 is a member of the adenosine triphosphate (ATP)-binding cassette transporter family. Camptothecins (CPTs) have shown substantial anticancer activity against a broad spectrum of tumors by inhibiting DNA topoisomerase I, but tumor resistance is one of the major reasons for therapeutic failure. P-glycoprotein, breast cancer resistance protein, MRP1, and MRP2 have been implicated in resistance to various CPTs including CPT-11 (irinotecan), SN-38 (the active metabolite of CPT-11), and topotecan. In this study, we explored the resistance profiles and intracellular accumulation of a panel of CPTs including CPT, CPT-11, SN-38, rubitecan, and 10-hydroxy-CPT (10-OH-CPT) in HepG2 cells with stably overexpressed human MRP4. Other anticancer agents such as paclitaxel, cyclophosphamide, and carboplatin were also included.
Methods HepG2 cells were transfected with an empty vehicle plasmid (V/HepG2) or human MRP4 (MRP4/HepG2). The resistance profiles of test drugs in exponentially growing V/HepG2 and MRP4/HepG2 cells were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay with 4 or 48 h exposure time of the test drug in the absence or presence of various MRP4 inhibitors. The accumulation of CPT-11, SN-38, and paclitaxel by V/HepG2 and MRP4/HepG2 cells was determined by validated high-performance liquid chromatography methods.
Results Based on the resistance folds from the MTT assay with 48 h exposure time of the test drug, MRP4 conferred resistance to CPTs tested in the order 10-OH-CPT (14.21) > SN-38 carboxylate (9.70) > rubitecan (9.06) > SN-38 lactone (8.91) > CPT lactone (7.33) > CPT-11 lactone (5.64) > CPT carboxylate (4.30) > CPT-11 carboxylate (2.68). Overall, overexpression of MRP4 increased the IC50 values 1.78- to 14.21-fold for various CPTs in lactone or carboxylate form. The resistance of MRP4 to various CPTs tested was significantly reversed in the presence of dl-buthionine-(S,R)-sulfoximine (BSO, a γ-glutamylcysteine synthetase inhibitor), MK571, celecoxib, or diclofenac (all MRP4 inhibitors). In addition, the accumulation of CPT-11 and SN-38 over 120 min in MRP4/HepG2 cells was significantly reduced compared to V/HepG2 cells, whereas the addition of celecoxib, MK571, or BSO significantly increased their accumulation in MRP4/HepG2 cells. There was no significant difference in the intracellular accumulation of paclitaxel in V/HepG2 and MRP4/HepG2 cells, indicating that P-glycoprotein was not involved in the observed resistance to CPTs in this study. MRP4 also conferred resistance to cyclophosphamide and this was partially reversed by BSO. However, MRP4 did not increase resistance to paclitaxel, carboplatin, etoposide (VP-16), 5-fluorouracil, and cyclosporine.
Conclusions Human MRP4 rendered significant resistance to cyclophosphamide, CPT, CPT-11, SN-38, rubitecan, and 10-OH-CPT. CPT-11 and SN-38 are substrates for MRP4. Further studies are needed to explore the role of MRP4 in resistance, toxicity, and pharmacokinetics of CPTs and cyclophosphamide.

Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs

Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of CYP3A4 is characterised by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYP isoenzymes to reactive metabolites capable of irreversibly binding covalently to CYP3A4. Approaches using in vitro, in silico and in vivo models can be used to study CYP3A4 inactivation by drugs. Human liver microsomes are always used to estimate inactivation kinetic parameters including the concentration required for half-maximal inactivation (K(I)) and the maximal rate of inactivation at saturation (k(inact)).Clinically important mechanism-based CYP3A4 inhibitors include antibacterials (e.g. clarithromycin, erythromycin and isoniazid), anticancer agents (e.g. tamoxifen and irinotecan), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine, verapamil and diltiazem), sex steroids and their receptor modulators (e.g. gestodene and raloxifene), and several herbal constituents (e.g. bergamottin and glabridin). Drugs inactivating CYP3A4 often possess several common moieties such as a tertiary amine function, furan ring, and acetylene function. It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs.Compared with reversible inhibition of CYP3A4, mechanism-based inhibition of CYP3A4 more frequently cause pharmacokinetic-pharmacodynamic drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesised CYP3A4 protein. The resultant drug interactions may lead to adverse drug effects, including some fatal events. For example, when aforementioned CYP3A4 inhibitors are coadministered with terfenadine, cisapride or astemizole (all CYP3A4 substrates), torsades de pointes (a life-threatening ventricular arrhythmia associated with QT prolongation) may occur.However, predicting drug-drug interactions involving CYP3A4 inactivation is difficult, since the clinical outcomes depend on a number of factors that are associated with drugs and patients. The apparent pharmacokinetic effect of a mechanism-based inhibitor of CYP3A4 would be a function of its K(I), k(inact) and partition ratio and the zero-order synthesis rate of new or replacement enzyme. The inactivators for CYP3A4 can be inducers and P-gp substrates/inhibitors, confounding in vitro-in vivo extrapolation. The clinical significance of CYP3A inhibition for drug safety and efficacy warrants closer understanding of the mechanisms for each inhibitor. Furthermore, such inactivation may be exploited for therapeutic gain in certain circumstances.

Cost-effectiveness of a family-based GP-mediated intervention targeting overweight and moderately obese children

Objective
 To assess from a societal perspective the incremental cost-effectiveness of a family-based GP-mediated intervention targeting overweight and moderately obese children. The intervention was modelled on the LEAP (live, eat and play) trial, a randomised controlled trial conducted by the Centre for Community Child Health, Melbourne, Australia in 2002–2003. This study was undertaken as part of the assessing cost-effectiveness (ACE) in obesity project which evaluated, using consistent methods, 13 interventions targeting unhealthy weight gain in children and adolescents.
Method
A logic pathway was used to model the effects of the intervention compared to no intervention on body mass index (BMI) and health outcomes (disability-adjusted life years—DALYs). Disease costs and health benefits were tracked until the cohort of eligible children reached the age of 100 years or death. Simulation-modelling techniques were used to present a 95% uncertainty interval around the cost-effectiveness ratio. The intervention was also assessed against a series of filters (‘equity’, ‘strength of evidence’, ‘acceptability’, ‘feasibility’, sustainability’ and ‘side-effects’) to incorporate additional factors that impact on resource allocation decisions.
Results
The intervention, as modelled, reached 9685 children aged 5–9 years with a BMI z-score of ≥3.0, and cost $AUD6.3M (or $AUD4.8M excluding time costs). It resulted in an incremental saving of 2300 BMI units which translated to 511 DALYs. The cost-offsets stemming from the intervention totalled $AUD3.6M, resulting in a net cost per DALY saved of $AUD4670 (dominated; $0.1M) (dominated means intervention costs more for less effect).
Conclusion
Compared to a ‘no intervention’ control group, the intervention was cost-effective under current assumptions, although the uncertainty intervals were wide. A key question related to the long-term sustainability of the small incremental weight loss reported, based on the 9-month follow-up results for LEAP.

Clincial pharmacogenetics and potential application in personalized medicine

The current `fixed-dosage strategy' approach to medicine, means there is much inter-individual variation in drug response. Pharmacogenetics is the study of how inter-individual variations in the DNA sequence of specific genes affect drug responses. This article will highlight current  pharmacogenetic knowledge on important drug metabolizing enzymes, drug transporters and drug targets to understand interindividual variability in drug clearance and responses in clinical practice and potential use in  personalized medicine. Polymorphisms in the cytochrome P450 (CYP) family may have had the most impact on the fate of pharmaceutical drugs. CYP2D6, CYP2C19 and CYP2C9 gene polymorphisms and gene duplications account for the most frequent variations in phase I metabolism of drugs since nearly 80% of drugs in use today are metabolised by these enzymes. Approximately 5% of Europeans and 1% of Asians lack CYP2D6 activity, and these  individuals are known as poor metabolizers. CYP2C9 is another clinically significant drug metabolising enzyme that demonstrates genetic variants. Studies into CYP2C9 polymorphism have highlighted the importance of the CYP2C9*2 and CYP2C9*3 alleles. Extensive polymorphism also occurs in a majority of Phase II drug metabolizing enzymes. One of the most important polymorphisms is thiopurine S-methyl transferases (TPMT) that catalyzes the S-methylation of thiopurine drugs. With respect to drug transport  polymorphism, the most extensively studied drug transporter is  P-glycoprotein (P-gp/MDR1), but the current data on the clinical impact is limited. Polymorphisms in drug transporters may change drug's distribution, excretion and response. Recent advances in molecular research have revealed many of the genes that encode drug targets demonstrate genetic polymorphism. These variations, in many cases, have altered the targets sensitivity to the specific drug molecule and thus have a profound effect on drug efficacy and toxicity. For example, the β2-adrenoreceptor, which is encoded by the ADRB2 gene, illustrates a clinically significant genetic variation in drug targets. The variable number tandem repeat polymorphisms in serotonin transporter (SERT/SLC6A4) gene are associated with response to antidepressants. The distribution of the common variant alleles of genes that encode drug metabolizing enzymes, drug transporters and drug targets has been found to vary among different populations. The promise of pharmacogenetics lies in its potential to identify the right drug at the right dose for the right individual. Drugs with a narrow therapeutic index are thought to benefit more from pharmacogenetic studies. For example, warfarin serves as a good practical example of how pharmacogenetics can be utilized prior to commencement of therapy in order to achieve maximum efficacy and minimum toxicity. As such, pharmacogenetics has the potential to achieve optimal quality use of medicines, and to improve the efficacy and safety of both prospective and licensed drugs.

Building research capacity in General Practice : Incorporating research as a component of GP vocational training

Aims & rationale/Objectives : Australian research shows that most GP registrar supervisors lack confidence to support registrar research projects and themselves have little or no research experience. Assisting registrars to develop critical thinking skills and an understanding of research methods sufficient to enable active use of these tools in general practice is one of the curriculum statements in the RACGP Training Program Curriculum. A University Department of Rural Health (UDRH) and a General Practice Education and Training (GPET) organisation formed a partnership to: Engage basic term registrars in group research and concurrent research skills training program; Improve research skills, confidence, and knowledge; and Contribute research findings relevant to general practice.

Methods : Registrars' initial research knowledge and confidence was measured by a questionnaire. In addition to a final focus group, feedback via evaluation forms was sought from the 11 registrars and two GPET supervisors at the conclusion of each research training session.

Principal findings : Approaches

Implications : Research skills development training and involvement in research can be successfully integrated into a GP vocational training program.

Chronic disease self-management programs : perspectives on enablers and barriers to GP and patient engagement

Aims & rationale/Objectives : Chronic disease self-management programs (CDSMP) are increasingly being integrated into the health system to improve the care of people with chronic conditions. Despite activity at both policy and program levels, GPs as the 'gatekeepers' to the health system have generally not been well informed or engaged in this process. This study, in collaboration with 3 Victorian Divisions of General Practice, sought both GP and patient perspectives on enablers and barriers to engagement in self-management programs.
Methods : Interviews were conducted with GPs (n=20) and consumers (n=45) purposefully recruited from metropolitan and rural Victoria, representing key demographics of interest including low socioeconomic areas.
Principal findings : Lack of education/information and uncertainty about the effectiveness of self-management programs were key barriers for both GP and patient engagement. Programs that were sustainable and utilised existing community resources were viewed as enablers to increase uptake. GP and patient preferences for disease specific or generic CDSMP differed.
Discussion : Outcomes from the recent Council of Australian Governments' meeting suggest that self-management will be a centerpiece in forthcoming chronic disease initiatives. International evidence has highlighted the need for GP and patient engagement as critical in ensuring the recruitment of a critical mass of individuals to participate in CDSMP to ensure the sustainability of such initiatives. Insight from this study indicates that GPs and patients are not well informed about self-management, have different preferences to current policy trends and identifies several other barriers which need to be addressed if CDSMP are to be successful.
Implications : Identification of barriers and enablers of GP and patient engagement in self-management is essential in shaping current policy initiatives and delivery of future programs. This is supported by international evidence which indicates strongly that GP engagement in particular is crucial to the success of these programs.
Presentation type : Paper