Training on the use of a bespoke continuing professional development framework improves the quality of CPD records.

BACKGROUND: Using continuing professional development (CPD) as part of the revalidation of pharmacy professionals has been proposed in the UK but not implemented. We developed a CPD outcomes framework ('the framework') for scoring CPD records, where the score range was -100 to +150 based on demonstrable relevance and impact of the CPD on practice. OBJECTIVE: This exploratory study aimed to test the outcome of training people to use the framework, through distance-learning material (active intervention), by comparing CPD scores before and after training. SETTING: Pharmacy professionals were recruited in the UK in Reading, Banbury, Southampton, Kingston-upon-Thames and Guildford in 2009. METHOD: We conducted a randomised, double-blinded, parallel-group, before and after study. The control group simply received information on new CPD requirements through the post; the active intervention group also received the framework and associated training. Altogether 48 participants (25 control, 23 active) completed the study. All participants submitted CPD records to the research team before and after receiving the posted resources. The records (n = 226) were scored blindly by the researchers using the framework. A subgroup of CPD records (n = 96) submitted first (before-stage) and rewritten (after-stage) were analysed separately. MAIN OUTCOME MEASURE: Scores for CPD records received before and after distributing group-dependent material through the post. RESULTS: Using a linear-regression model both analyses found an increase in CPD scores in favour of the active intervention group. For the complete set of records, the effect was a mean difference of 9.9 (95 % CI 0.4-19.3), p value = 0.04. For the subgroup of rewritten records, the effect was a mean difference of 17.3 (95 % CI 5.6-28.9), p value = 0.0048. CONCLUSION: The intervention improved participants' CPD behaviour. Training pharmacy professionals to use the framework resulted in better CPD activities and CPD records, potentially helpful for revalidation of pharmacy professionals.

A framework for assessing continuing professional development activities for satisfying pharmacy revalidation requirements.

INTRODUCTION: The United Kingdom's pharmacy regulator contemplated using continuing professional development (CPD) in pharmacy revalidation in 2009, simultaneously asking pharmacy professionals to demonstrate the value of their CPD by showing its relevance and impact. The idea of linking new CPD requirements with revalidation was yet to be explored. Our aim was to develop and validate a framework to guide pharmacy professionals to select CPD activities that are relevant to their work and to produce a score sheet that would make it possible to quantify the impact and relevance of CPD. METHODS: We adapted an existing risk matrix, producing a CPD framework consisting of relevance and impact matrices. Concepts underpinning the framework were refined through feedback from 5 pharmacist teacher-practitioners. We then asked 7 pharmacists to rate the relevance of the framework's individual elements on a 4-point scale to determine content validity. We explored views about the framework through focus groups with 6 participants and interviews with 17 participants who had used it formally in a study. RESULTS: The framework's content validity index was 0.91. Feedback about the framework related to 3 themes of penetrability of the framework, usefulness to completion of CPD, and advancement of CPD records for the purpose of revalidation. DISCUSSION: The framework can help professionals better select CPD activities prospectively, and makes assessment of CPD more objective by allowing quantification, which could be helpful for revalidation. We believe the framework could potentially help other health professionals with better management of their CPD irrespective of their field of practice.

British pharmacy professionals' beliefs and participation in continuing professional development: a review of the literature.

OBJECTIVES Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. METHODS A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. KEY FINDINGS Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. CONCLUSIONS If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

SOP3: a web-based tool for selection of oligonucleotide primers for single nucleotide polymorphism analysis by Pyrosequencing.

SOP3 is a web-based software tool for designing oligonucleotide primers for use in the analysis of single nucleotide polymorphisms (SNPs). Accessible via the Internet, the application is optimized for developing the PCR and sequencing primers that are necessary for Pyrosequencing. The application accepts as input gene name, SNP reference sequence number, or chromosomal nucleotide location. Output can be parsed by gene name, SNP reference number, heterozygosity value, location, chromosome, or function. The location of an individual polymorphism, such as an intron, exon, or 5' or 3' untranslated region is indicated, as are whether nucleotide changes in an exon are associated with a change in an amino acid sequence. SOP3 presents for each entry a set of forward and biotinylated reverse PCR primers as well as a sequencing primer for use during the analysis of SNPs by Pyrosequencing. Theoretical pyrograms for each allele are calculated and presented graphically. The method has been tested in the development of Pyrosequencing assays for determining SNPs and for deletion/insertion polymorphisms in the human genome. Of the SOP3-designed primer sets that were tested, a large majority of the primer sets have successfully produced PCR products and Pyrosequencing data.

Gene combination transfer to block autoimmune damage in transplanted islets of Langerhans.

Islet transplantation therapy would be applicable to a wider range of diabetic patients if donor islet acceptance and protection were possible without systemic immunosuppression of the recipient. To this aim, gene transfer to isolated donor islets ex vivo is one method that has shown promise. This study examines the combined effect of selected immunomodulatory and anti-inflammatory genes known to extend the functional viability of pancreatic islet grafts in an autoimmune system. These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP), were transferred to isolated NOD donor islets ex vivo then transplanted to NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge. The length of time the recipient remained euglycemic was used to measure the ability of the transgenes to protect the graft from autoimmune destruction. Although the results of these cotransfections gave little evidence of a synergistic relationship, they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic T cells.

HLA class II DRB high resolution genotyping by pyrosequencing: comparison of group specific PCR and pyrosequencing primers.

Sequencing of alleles of the highly polymorphic, multiple loci HLA-DRB gene family was performed by pyrosequencing using purified DNA from the 11(th) International Histocompatibility Workshop human lymphoblastiod cell lines as well as genomic DNA isolated from blood samples obtained from healthy adult volunteers. Genomic DNA was prepared from donors whose blood had been stored either frozen or as dried blood spots. Pyrosequence-based typing was optimized for identifying alleles of the HLA-DRB1, -3, -4, and -5 genes. The procedure should be applicable to other HLA loci including the class I genes HLA-A and -B that, along with HLA-DRB, are crucial for histocompatibility matching of tissue antigens during transplantation. Computer simulation of pyrosequencing data suggest that alleles of HLA-DRB1, -3, -4, and -5 were readily identifiable by pyrosequencing as were their heterozygous allelic combinations. Pyrosequencing primers were designed to specifically sequence HLA loci of interest even in a background of other amplified, closely related sequences such as alleles of the pseudogene HLA-DRB6, -7, -8, and -9. Polymorphic residues of HLA-DRB genes were identified within each pyrosequencing reaction, obtained by 50 to 70 nucleotide read lengths. Heterozygous allelic combinations of HLA genes were analyzed and compared successfully to genotyping of alleles by sequence-specific oligonucleotide probe hybridization as well as allele specific polymerase chain reaction protocols. Pyrosequence-based typing is compatible with genotyping of allelic combinations expected from heterozygous individuals, resulting in nucleotide resolution of the highly polymorphic HLA system. Using a single pyrosequence instrument, complete typing of HLA-DRB genes can be performed daily on hundreds of individuals for high resolution histocompatibility genotyping studies.

Recovery of the endogenous beta cell function in the NOD model of autoimmune diabetes.

In light of accumulating evidence that the endocrine pancreas has regenerative properties and that hematopoietic chimerism can abrogate destruction of beta cells in autoimmune diabetes, we addressed the question of whether recovery of physiologically adequate endogenous insulin regulation could be achieved in the nonobese diabetic (NOD) mice rendered allogeneic chimerae. Allogeneic bone marrow (BM) was transplanted into NOD mice at the preclinical and overtly clinical stages of the disease using lethal and nonlethal doses of radiation for recipient conditioning. Islets of Langerhans, syngeneic to the BM donors, were transplanted under kidney capsules of the overtly diabetic animals to sustain euglycemia for the time span required for recovery of the endogenous pancreas. Nephrectomies of the graft-bearing organs were performed 14 weeks later to confirm the restoration of endogenous insulin regulation. Reparative processes in the pancreata were assessed histologically and immunohistochemically. The level of chimerism in NOD recipients was evaluated by flow cytometric analysis. We have shown that as low as 1% of initial allogeneic chimerism can reverse the diabetogenic processes in islets of Langerhans in prediabetic NOD mice, and that restoration of endogenous beta cell function to physiologically sufficient levels is achievable even if the allogeneic BM transplantation is performed after the clinical onset of diabetes. If the same pattern of islet regeneration were shown in humans, induction of an autoimmunity-free status by establishment of a low level of chimerism, or other alternative means, might become a new therapy for type 1 diabetes.

Gene transfer of manganese superoxide dismutase extends islet graft function in a mouse model of autoimmune diabetes.

Islet transplantation is a promising cure for diabetes. However, inflammation, allorejection, and recurrent autoimmune damage all may contribute to early graft loss. Pancreatic islets express lower levels of antioxidant genes than most other tissues of the body, and beta-cells in particular are sensitive to oxidative damage. Therefore, damage from oxidative stress may pose a major obstacle to islet replacement therapy in that both the islet isolation and transplantation processes generate oxygen radicals. To determine whether antioxidant gene overexpression in isolated pancreatic islets can prevent oxidative damage and prolong islet function after transplantation, we used the NOD mouse model to study oxidative stress encountered during both transplantation and autoimmune attack. We transferred an antioxidant gene, manganese superoxide dismutase (MnSOD), by adenoviral infection into isolated islets that were transplanted into streptozotocin-treated NODscid recipient mice. Functioning islet grafts were subsequently exposed to diabetogenic spleen cells and monitored until graft failure. The results show that islet grafts overexpressing MnSOD functioned approximately 50% longer than control grafts. This significant prolongation of graft function suggests that the antioxidant activity of MnSOD is beneficial to transplanted islet survival and may be used in combination with other strategies aimed at islet graft protection.

Distinct characteristics and features of allogeneic chimerism in the NOD mouse model of autoimmune diabetes.

The adaptation of allogeneic chimerism in treatment of autoimmune diabetes has been shown as a promising approach in numerous studies in both experimental and clinical settings. Establishment of hemopoietic chimerism in NOD mice is the most adequate animal model to study mechanisms involved in the multiple aspects of the curative effects of chimerism in autoimmunity-prone individuals. However, there are some discrepancies in the current literature for parameters and criteria used to characterize chimerism in the NOD model. This study was aimed to standardize the criteria for the different pathological stages of diabetogenesis in chimeric versus unmanipulated NOD mice. We report two well-defined scoring systems and a new Index N for the assessment of the pathological characteristics of diabetogenesis and GVHD in chimeric NOD mice. Also, we have demonstrated that, in the NOD model, recipient conditioning resulting in as low as 1% of chimerism is sufficient to promote engraftment of the BM donor-specific islets of Langerhans.

Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes.

Indoleamine 2,3-dioxygenase (IDO) catalyzes the breakdown of the amino acid tryptophan into kyneurenine. It has been shown that IDO production by placental trophoblasts prevents the attack of maternal T-cells activated in response to the paternal HLA alleles expressed by the tissues of the fetus. In this article, we show that adenoviral gene transfer of IDO to pancreatic islets can sufficiently deplete culture media of tryptophan and consequently inhibit the proliferation of T-cells in vitro. Experiments in vivo have also demonstrated that transplantation of IDO-expressing islets from prediabetic NOD mouse donors into NODscid recipient mice is associated with a prolongation in islet graft survival after adoptive transfer of NOD diabetogenic T-cells. This protection is attributed to the depletion of tryptophan at the transplantation site beneath the kidney capsule. These results suggest that local modulation of tryptophan catabolism may be a means of facilitating islet transplantation as a therapy for type 1 diabetes.