Older patient participation in discharge medication communication: an observational study.

OBJECTIVE: To describe the extent to which older patients participate in discharge medication communication, and identify factors that predict patient participation in discharge medication communication. DESIGN: Observational study. SETTING: An Australian metropolitan tertiary hospital. PARTICIPANTS: 173 older patients were observed undertaking one medication communication encounter prior to hospital discharge. OUTCOME: Patient participation measured with MEDICODE, a valid and reliable coding framework used to analyse medication communication. MEDICODE provides two measures for patient participation: (1) Preponderance of Initiative and (2) Dialogue Ratio. RESULTS: The median for Preponderance of Initiative was 0.7 (IQR=0.5-1.0) and Dialogue Ratio was 0.3 (IQR=0.2-0.4), indicating healthcare professionals took more initiative and medication encounters were mostly monologue rather than a dialogue or dyad. Logistic regression revealed that patients had 30% less chance of having dialogue or dyads with every increase in one medication discussed (OR 0.7, 95% CI 0.5 to 0.9, p=0.01). Additionally, the higher the patient's risk of a medication-related problem, the more initiative the healthcare professionals took in the conversation (OR 1.5, 95% CI 1.0 to 2.1, p=0.04). CONCLUSION: Older patients are passive during hospital discharge medication conversations. Discussing less medications over several medication conversations spread throughout patient hospitalisation and targeting patients at high risk of medication-related problems may promote more active patient participation, and in turn medication safety outcomes.

Relationship Between Research Culture and Research Activity of Medical Doctors: A Survey and Audit.

PURPOSE: To describe the research capacity and culture, and research activity (publications and new projects) of medical doctors across a health service and determine if the research activity of specialty groups correlated with their self-reported "team" level research capacity and culture. METHODS: Cross-sectional, observational survey and audit of medical doctors at a tertiary health service in Queensland. The Research Capacity and Culture (RCC) validated survey was used to measure self-reported research capacity/culture at organisation, team and individual levels, and presence of barriers and facilitators to research. An audit of publications and ethically approved research projects was used to determine research activity. RESULTS: Approximately, 10% of medical doctors completed the survey (n= 124). Overall, median scores on the RCC were 5 out of 10 for organisational level, 5.5 for specialty level, and 6 for individual level capacity and culture; however, specialty-level scores varied significantly between specialty groups (range 3.1-7.8). Over 80% of participants reported lack of time and other work roles taking priority as barriers to research. One project was commenced per year for every 12.5 doctors employed in the health service, and one article was published for every 7.5. There was a positive association between a team's number of publications and projects and their self-reported research capacity and culture on the RCC. This association was stronger for publications. CONCLUSION: Health service research capacity building interventions may need a tailored approach for different specialty teams to accommodate for varying baselines of capacity and activity. When evaluating these initiatives, a combination of research activity and subjective self-report measures may be complementary.

Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma.

Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy.

A new method to detect loss of heterozygosity using cohort heterozygosity comparisons.

BACKGROUND: Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. METHODS: DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. RESULTS: Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. CONCLUSIONS: We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.

Relapsed plasma cell leukaemia presenting with aggressive extramedullary plasmacytomas in the meninges and testis--a missed opportunity for induction CNS prophylaxis.

After initial treatment, a 54-year-old male with plasma cell leukaemia developed extramedullary relapse in the testis and meninges without evidence of bone marrow involvement. We postulate that the central nervous system (CNS) and testis may have served as sanctuary sites for the disease during initial treatment. A role for CNS prophylaxis in plasma cell leukaemia is suggested.

Central nervous system prophylaxis in haematological malignancies.

Given the poor prognosis of central nervous system (CNS) involvement in haematological malignancies, management is directed towards prevention. CNS prophylaxis may take the form of intrathecal therapy, cranial irradiation, systemic therapy or some combination of these. The toxicity of these methods is an important consideration. A risk-orientated approach to the delivery of CNS prophylaxis in each disorder is required.