Australian pharmacists' understanding of their continuing professional development obligations

Background The adoption of continuing professional development (CPD) in Australia is still relatively new [expand]. There is limited information on how Australian pharmacists have engaged with the CPD requirements for registration. Aim To explore Australian registered pharmacists’ understanding and engagement with the requirement for CPD credits for registration. Method The Pharmacy Board of Australia’s CPD requirements for registration was used as a guide to design an online survey to ascertain Australian pharmacists understanding and engagement in the acquisition of CPD credits for registration. Results A total of 278 pharmacists responded to the survey – 66% were female and 30% were male (4% did not disclose their gender). 63% of respondents felt that it would not be difficult to acquire 40 CPD credits annually; with pharmacists identifying that Group 1 activities were a preferred way of acquiring CPD credits. The majority of pharmacists (91%) believed that they knew what the current CPD requirements for general registration are and 77% felt that there has been enough guidance provided to assist them. Despite this, 26% of participants had never used self directed learning plans and 38% did not know how to undertake self-directed learning. 76% of participants were under the common misconception that CPD is synonymous with continuing education. Conclusion The majority of registered pharmacists believe they understand and can engage in the acquisition of CPD credits for registration. However, some aspects of the process was not understood. The key link of how this process aims to develop individual practice needs to be further developed within the profession.

Pharmacists' understanding of their CPD obligations

The article offers information on the requirement of the continuing professional development (CPD) training and lifelong learning for the legal registration of the Australian practitioners and pharmacists. Topics discussed include reviewing the competitiveness and pharmacy practice benefits, strategic planning for getting the requirement of CPD, and improving and broadening of the knowledge and developing the personal and professional qualities of pharmacists.

The disenfranchisement of prisoners : Roach v Electoral Commissioner & Anor - modernity v feudalism

David Brown takes a road trip to Canberra for the Roach fixture at the High Court where modernity is attempting a fight-back against the resurrection of civil death. With echoes of Hunter S Thompson as rugby league follower, the author recounts a trip to Canberra to observe a case in which Vickie Lee Roach, an Indigenous woman prisoner, challenged (successfully as it later turns out) the Howard government's 2006 legislation disenfranchising all serving prisoners.

Polymorphisms in inflammation pathway genes and endometrial cancer risk

BACKGROUND Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. METHODS To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. RESULTS Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. CONCLUSIONS These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis.

Use of simple pharmacokinetic modeling to characterize exposure of Australians to perfluorooctanoic acid and perfluorooctane sulfonic acid

Perflurooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been used for a variety of applications including fluoropolymer processing, fire-fighting foams and surface treatments since the 1950s. Both PFOS and PFOA are polyfluoroalkyl chemicals (PFCs), man-made compounds that are persistent in the environment and humans; some PFCs have shown adverse effects in laboratory animals. Here we describe the application of a simple one compartment pharmacokinetic model to estimate total intakes of PFOA and PFOS for the general population of urban areas on the east coast of Australia. Key parameters for this model include the elimination rate constants and the volume of distribution within the body. A volume of distribution was calibrated for PFOA to a value of 170ml/kgbw using data from two communities in the United States where the residents' serum concentrations could be assumed to result primarily from a known and characterized source, drinking water contaminated with PFOA by a single fluoropolymer manufacturing facility. For PFOS, a value of 230ml/kgbw was used, based on adjustment of the PFOA value. Applying measured Australian serum data to the model gave mean+/-standard deviation intake estimates of PFOA of 1.6+/-0.3ng/kgbw/day for males and females >12years of age combined based on samples collected in 2002-2003 and 1.3+/-0.2ng/kg bw/day based on samples collected in 2006-2007. Mean intakes of PFOS were 2.7+/-0.5ng/kgbw/day for males and females >12years of age combined based on samples collected in 2002-2003, and 2.4+/-0.5ng/kgbw/day for the 2006-2007 samples. ANOVA analysis was run for PFOA intake and demonstrated significant differences by age group (p=0.03), sex (p=0.001) and date of collection (p<0.001). Estimated intake rates were highest in those aged >60years, higher in males compared to females, and higher in 2002-2003 compared to 2006-2007. The same results were seen for PFOS intake with significant differences by age group (p<0.001), sex (p=0.001) and date of collection (p=0.016).

Incorporating adverse event relatedness into dose-finding clinical trial designs

Dose-finding designs estimate the dose level of a drug based on observed adverse events. Relatedness of the adverse event to the drug has been generally ignored in all proposed design methodologies. These designs assume that the adverse events observed during a trial are definitely related to the drug, which can lead to flawed dose-level estimation. We incorporate adverse event relatedness into the so-called continual reassessment method. Adverse events that have ‘doubtful’ or ‘possible’ relationships to the drug are modelled using a two-parameter logistic model with an additive probability mass. Adverse events ‘probably’ or ‘definitely’ related to the drug are modelled using a cumulative logistic model. To search for the maximum tolerated dose, we use the maximum estimated toxicity probability of these two adverse event relatedness categories. We conduct a simulation study that illustrates the characteristics of the design under various scenarios. This article demonstrates that adverse event relatedness is important for improved dose estimation. It opens up further research pathways into continual reassessment design methodologies.

Why 'down under' is a cut above: a comparison of rates of and reasons for caesarean section in England and Australia

Background Most studies examining determinants of rising rates of caesarean section have examined patterns in documented reasons for caesarean over time in a single location. Further insights could be gleaned from cross-cultural research that examines practice patterns in locations with disparate rates of caesarean section at a single time point. Methods We compared both rates of and main reason for pre-labour and intrapartum caesarean between England and Queensland, Australia, using data from retrospective cross-sectional surveys of women who had recently given birth in England (n = 5,250) and Queensland (n = 3,467). Results Women in Queensland were more likely to have had a caesarean birth (36.2%) than women in England (25.1% of births; OR = 1.44, 95% CI = 1.28-1.61), after adjustment for obstetric characteristics. Between-country differences were found for rates of pre-labour caesarean (21.2% vs. 12.2%) but not for intrapartum caesarean or assisted vaginal birth. Compared to women in England, women in Queensland with a history of caesarean were more likely to have had a pre-labour caesarean and more likely to have had an intrapartum caesarean, due only to a previous caesarean. Among women with no previous caesarean, Queensland women were more likely than women in England to have had a caesarean due to suspected disproportion and failure to progress in labour. Conclusions The higher rates of caesarean birth in Queensland are largely attributable to higher rates of caesarean for women with a previous caesarean, and for the main reason of having had a previous caesarean. Variation between countries may be accounted for by the absence of a single, comprehensive clinical guideline for caesarean section in Queensland. Keywords: Caesarean section; Childbirth; Pregnancy; Cross-cultural comparison; Vaginal birth after caesarean; Previous caesarean section; Patient-reported data; Quality improvement

Mammographic density-a review on the current understanding of its association with breast cancer

There has been considerable recent interest in the genetic, biological and epidemiological basis of mammographic density (MD), and the search for causative links between MD and breast cancer (BC) risk. This report will critically review the current literature on MD and summarize the current evidence for its association with BC. Keywords 'mammographic dens*', 'dense mammary tissue' or 'percent dens*' were used to search the existing literature in English on PubMed and Medline. All reports were critically analyzed. The data were assigned to one of the following aspects of MD: general association with BC, its relationship with the breast hormonal milieu, the cellular basis of MD, the generic variations of MD, and its significance in the clinical setting. MD adjusted for age, and BMI is associated with increased risk of BC diagnosis, advanced tumour stage at diagnosis and increased risk of both local recurrence and second primary cancers. The MD measures that predict BC risk have high heritability, and to date several genetic markers associated with BC risk have been found to also be associated with these MD risk predictors. Change in MD could be a predictor of the extent of chemoprevention with tamoxifen. Although the biological and genetic pathways that determine and perhaps modulate MD remain largely unresolved, significant inroads are being made into the understanding of MD, which may lead to benefits in clinical screening, assessment and treatment strategies. This review provides a timely update on the current understanding of MD's association with BC risk.

Cancer : the to and fro of tumour spread

The spread of cells from the primary site of a solid tumour to distant sites remains the major cause of disease and death associated with these cancers. For tumour cells to spread, or metastasize, they must modify their 'anchored' state and detach from their neighbouring cells; migrate through tissues into the blood and lymph systems; survive in these circulation systems; and then leave the vessels at an appropriate site to form another tumour1. Many of these events are favoured by conversions between two cellular states — the epithelial and mesenchymal phenotypes. But the role of these transitions in cancer metastasis is controversial. Writing in Cancer Cell, Tsai et al.2 and Ocaña et al.3 help to clarify this issue...

Revascularization and tissue regeneration of an empty root canal space is enhanced by a direct blood supply and stem cells

Background Regenerative endodontics is an innovative treatment concept aiming to regenerate pulp, dentin and root structures. In the diseased or necrotic tooth, the limitation in vascular supply renders successful tissue regeneration/generation in a whole tooth challenging. The aim of this study is to evaluate the ability of vascularized tissue to develop within a pulpless tooth using tissue engineering techniques. Materials and methods A pulpless tooth chamber, filled with collagen I gel containing isolated rat dental pulp cells (DPC) and angiogenic growth factors, was placed into a hole created in the femoral cortex or into its own tooth socket, respectively. The gross, histological and biochemical characteristics of the de novo tissue were evaluated at 4 and 8weeks post-transplantation. Results Tooth revascularization and tissue generation was observed only in the femur group, confirming the important role of vascular supply in tissue regeneration. The addition of cells and growth factors significantly promoted connective tissue production in the tooth chamber. Conclusion Successful revascularization and tissue regeneration in this model demonstrate the importance of a direct vascular supply and the advantages of a stem cell approach. © 2012 John Wiley & Sons A/S.

Determining epithelial contribution to in vivo mesenchymal tumour expression signature using species-specific microarray profiling analysis of xenografts

Gene expression profiling using microarrays and xenograft transplants of human cancer cell lines are both popular tools to investigate human cancer. However, the undefined degree of cross hybridization between the mouse and human genomes hinders the use of microarrays to characterize gene expression of both the host and the cancer cell within the xenograft. Since an increasingly recognized aspect of cancer is the host response (or cancer-stroma interaction), we describe here a bioinformatic manipulation of the Affymetrix profiling that allows interrogation of the gene expression of both the mouse host and the human tumour. Evidence of microenvironmental regulation of epithelial mesenchymal transition of the tumour component in vivo is resolved against a background of mesenchymal gene expression. This tool could allow deeper insight to the mechanism of action of anti-cancer drugs, as typically novel drug efficacy is being tested in xenograft systems.

Breast cancer stem cells and epithelial mesenchymal plasticity : implications for chemoresistance

Tumour heterogeneity is a key characteristic of cancer and has significant implications relating to tumour response to chemotherapy as well as patient prognosis and potential relapse. It is being increasingly accepted that tumours are clonal in origin, suggestive of a tumour arising from a deregulated or mutated cell. Cancer stem cells (CSC) possess these capabilities, and with appropriate intracellular triggers and/or signalling from extracellular environments, can purportedly differentiate to initiate tumour formation. Additionally through epithelial mesenchymal plasticity (EMP), where cells gain and maintain characteristics of both epithelial and mesenchymal cell types, epithelial-derived tumour cells have been shown to de-differentiate to acquire cancer stem attributes, which also impart chemotherapy resistance. This new paradigm places EMP centrally in the process of tumour progression and metastasis, as well as modulating drug response to current forms of chemotherapy. Furthermore, EMP and CSCs have been identified in cancers arising from different tissue types making it a possible generic therapeutic target in cancer biology. Using breast cancer (BrCa) as an example, we summarise here the current understanding of CSCs, the role of EMP in cancer biology - especially in CSCs and different molecular subtypes, and the implications this has for current and future cancer treatment strategies.

Progress in epithelial-mesenchymal transition research

The field of research of epithelial-mesenchymal transitions, EMT, and its reverse, mesenchymal-epithelial transitions, MET, has expanded very rapidly indeed from its beginnings, heralded by Professor Betty Hay in the 1970s and 1980s. This expansion has involved the realisation that the EMT was not just an interesting phenomenon of early developmental morphogenetic cell behaviour, but bore remarkable resemblance to clinically crucial pathological events in cancer invasion. Not surprisingly, this discipline soon became numerically dominant in the EMT publication field. Simultaneously, the EMT concept has been extended to normal physiological wound healing. Exploration revealed that these resemblances were more than skin deep: the same sets of growth factors, receptors, transcription factors, epigenetic marks and signalling pathways turned up repeatedly in EMTs and METs in a variety of contexts, both pathological and normal. This molecular genetic research in turn uncovered similarities of the EMT signature to that of fibrosis, a set of diseases which is of enormous clinical importance, rivalling that of cancer. Most recently, and more surprisingly, the EMT signature has shown considerable similarity to that found in stem cell and cancer stem cell biology.

An adipoinductive role of inflammation in adipose tissue engineering : key factors in the early development of engineered soft tissues

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage

A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial-mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0-3, 6-9 or 10-13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.