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The Performance Indicators for Coding Quality (PICQ) is a data quality assessment tool developed by Australia's National Centre for Classification in Health (NCCH). PICQ consists of a number of indicators covering all ICD-10-AM disease chapters, some procedure chapters from the Australian Classification of Health Intervention (ACHI) and some Australian Coding Standards (ACS). The indicators can be used to assess the coding quality of hospital morbidity data by monitoring compliance of coding conventions and ACS; this enables the identification of particular records that may be incorrectly coded, thus providing a measure of data quality. There are 31 obstetric indicators available for the ICD-10-AM Fourth Edition. Twenty of these 31 indicators were classified as Fatal, nine as Warning and two Relative. These indicators were used to examine coding quality of obstetric records in the 2004-2005 financial year Australian national hospital morbidity dataset. Records with obstetric disease or procedure codes listed anywhere in the code string were extracted and exported from the SPSS source file. Data were then imported into a Microsoft Access database table as per PICQ instructions, and run against all Fatal and Warning and Relative (N=31) obstetric PICQ 2006 Fourth Edition Indicators v.5 for the ICD-10- AM Fourth Edition. There were 689,905 gynaecological and obstetric records in the 2004-2005 financial year, of which 1.14% were found to have triggered Fatal degree errors, 3.78% Warning degree errors and 8.35% Relative degree errors. The types of errors include completeness, redundancy, specificity and sequencing problems. It was found that PICQ is a useful initial screening tool for the assessment of ICD-10-AM/ACHI coding quality. The overall quality of codes assigned to obstetric records in the 2004- 2005 Australian national morbidity dataset is of fair quality. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a dreadful disease, marked by the uncontrolled proliferation of clonal plasma cells within the bone marrow. It is characterized by a highly heterogeneous clinical and molecular background, supported by severe genomic alterations. Important de-regulation of long non-coding RNA (lncRNA) expression, which can influence progression and therapy resistance, has been reported in MM patients. NEAT1 is a lncRNA essential for nuclear paraspeckles and is involved in the regulation of gene expression. We showed that NEAT1 supports MM proliferation, making this lncRNA an attractive therapeutic candidate. Here, we used a combinatorial strategy integrating transcriptomic and computational approaches with functional high-throughput drug screening to identify compounds that synergize with NEAT1 inhibition in restraining MM cell growth. AURKA inhibitors were identified as top-scoring drugs in these analyses. We showed that the combination of NEAT1 silencing and AURKA inhibitors in MM profoundly impairs microtubule organization and mitotic spindle assembly, finally leading to cell death. Analysis of the large publicly available CoMMpass dataset showed that, in MM patients, AURKA expression is strongly associated with reduced progression-free survival (P<0.0001) and overall survival (P<0.0001) probabilities and patients with high levels of expression of both NEAT1 and AURKA have a worse clinical outcome. Finally, using RNA-sequencing data from NEAT1 knockdown MM cells, we identified the AURKA allosteric regulator TPX2 as a new NEAT1 target in MM and as a mediator of the interplay between AURKA and NEAT1, therefore providing a possible explanation for the synergistic activity observed upon their combinatorial inhibition.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy, accounting for approximately 1% of all cancers. Despite recent advances in the treatment of MM, due to the introduction of proteasome inhibitors (PIs) such as bortezomib (BTZ) and carfilzomib (CFZ), relapses and disease progression remain common. Therefore, a major challenge is the development of novel therapeutic approaches to overcome drug resistance, improve patient outcomes, and broaden PIs applicability to other pathologies., Methods: We performed genetic and drug screens to identify new synthetic lethal partners to PIs, and validated candidates in PI-sensitive and -resistant MM cells. We also tested best synthetic lethal interactions in other B-cell malignancies, such as mantle cell, Burkitt's and diffuse large B-cell lymphomas. We evaluated the toxicity of combination treatments in normal peripheral blood mononuclear cells (PBMCs) and bone marrow stromal cells (BMSCs). We confirmed the combo treatment' synergistic effects ex vivo in primary CD138+ cells from MM patients, and in different MM xenograft models. We exploited RNA-sequencing and Reverse-Phase Protein Arrays (RPPA) to investigate the molecular mechanisms of the synergy., Results: We identified lysine (K)-specific demethylase 1 (LSD1) as a top candidate whose inhibition can synergize with CFZ treatment. LSD1 silencing enhanced CFZ sensitivity in both PI-resistant and -sensitive MM cells, resulting in increased tumor cell death. Several LSD1 inhibitors (SP2509, SP2577, and CC-90011) triggered synergistic cytotoxicity in combination with different PIs in MM and other B-cell neoplasms. CFZ/SP2509 treatment exhibited a favorable cytotoxicity profile toward PBMCs and BMSCs. We confirmed the clinical potential of LSD1-proteasome inhibition in primary CD138+ cells of MM patients, and in MM xenograft models, leading to the inhibition of tumor progression. DNA damage response (DDR) and proliferation machinery were the most affected pathways by CFZ/SP2509 combo treatment, responsible for the anti-tumoral effects., Conclusions: The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project., (© 2023. YUMED Inc. and BioMed Central Ltd.)

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. In addition, adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. Here, to identify compounds that can increase the efficacy of PIs, we performed a functional screening using a library of small-molecule inhibitors covering key signaling pathways. Among the best synthetic lethal interactions, the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor UNC0642 displayed a cooperative effect with carfilzomib (CFZ) in numerous multiple myeloma (MM) cell lines, including drug-resistant models. In MM patients, EHMT2 expression correlated to worse overall and progression-free survival. Moreover, EHMT2 levels were significantly increased in bortezomib-resistant patients. We demonstrated that CFZ/UNC0642 combination exhibited a favorable cytotoxicity profile toward peripheral blood mononuclear cells and bone-marrow-derived stromal cells. To exclude off-target effects, we proved that UNC0642 treatment reduces EHMT2-related molecular markers and that an alternative EHMT2 inhibitor recapitulated the synergistic activity with CFZ. Finally, we showed that the combinatorial treatment significantly perturbs autophagy and the DNA damage repair pathways, suggesting a multi-layered mechanism of action. Overall, the present study demonstrates that EHMT2 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients.

Ectopic expression of RUNX2 has been reported in several tumors. In melanoma cells, the RUNT domain of RUNX2 increases cell proliferation and migration. Due to the strong link between RUNX2 and skeletal development, we hypothesized that the RUNT domain may be involved in the modulation of mechanisms associated with melanoma bone metastasis. Therefore, we evaluated the expression of metastatic targets in wild type (WT) and RUNT KO melanoma cells by array and real-time PCR analyses. Western blot, ELISA, immunofluorescence, migration and invasion ability assays were also performed. Our findings showed that the expression levels of bone sialoprotein (BSP) and osteopontin (SPP1) genes, which are involved in malignancy-induced hypercalcemia, were reduced in RUNT KO cells. In addition, released PTHrP levels were lower in RUNT KO cells than in WT cells. The RUNT domain also contributes to increased osteotropism and bone invasion in melanoma cells. Importantly, we found that the ERK/p-ERK and AKT/p-AKT pathways are involved in RUNT-promoted bone metastases. On the basis of our findings, we concluded that the RUNX2 RUNT domain is involved in the mechanisms promoting bone metastasis of melanoma cells via complex interactions between multiple players involved in bone remodeling.

Clinical documentation improvement (CDI) is a recent initiative gaining increased momentum in Australia. The benefits surrounding its success internationally include improved quality and patient safety outcomes and increased reimbursement. The premise of CDI is simple: engage clinicians to improve the clinical documentation in the medical record in "real time" so that it is fit for reporting, analysis and reimbursement. Every country has differing healthcare systems and this article has focused on validating the relevancy of CDI for the Australian healthcare environment.

The International Classification of Health Interventions (ICHI) is a member of the WHO Family of International Classifications, being developed to provide a common tool for reporting and analysing health interventions for statistical purposes. A web-based platform for classification development and update has been specifically developed to support the initial development step and then, after final approval, the continuous revision and update of the classification. The platform provides features for classification editing, versioning, comment management and URI identifiers. During the last 12 months it has been used for developing the ICHI Beta version, replacing the previous process based on the exchange of Excel files. At November 2017, 90 users have provided input to the development of the classification, which has resulted in 2913 comments and 2971 changes in the classification, since June 2017. Further work includes the development of an URI API for machine to machine communication, following the model established for ICD-11.

Objective:: The aim of this in vitro study was to evaluate and compare the effects of grinding, drilling, sandblasting, and ageing prefabricated teeth (PfT) on the shear bond strength (SBS) of orthodontic brackets, as well as the effects of surface treatments on the adhesive remnant index (ARI)., Methods:: One-hundred-ninety-two PfT were divided into four groups (n = 48): Group 1, no surface treatment was done; Group 2, grinding was performed with a cylindrical diamond bur; Group 3, two drillings were done with a spherical diamond bur; Group 4, sandblasting was performed with 50-µm aluminum oxide. Before the experiment, half of the samples stayed immersed in distilled water at 37oC for 90 days. Brackets were bonded with Transbond XT and shear strength tests were carried out using a universal testing machine. SBS were compared by surface treatment and by ageing with two-way ANOVA, followed by Tukey's test. ARI scores were compared between surface treatments with Kruskal-Wallis test followed by Dunn's test., Results:: Surface treatments on PfT enhanced SBS of brackets (p< 0.01), result not observed with ageing (p= 0.45). Groups II, III, and IV showed higher SBS and greater ARI than the Group 1 (p< 0.05). SBS was greater in the groups 3 and 4 (drilling, sandblasting) than in the Group 2 (grinding) (p< 0.05). SBS and ARI showed a positive correlation (Spearman's R2= 0.57; p< 0.05)., Conclusion:: Surface treatment on PfT enhanced SBS of brackets, however ageing did not show any relevance. Sandblasting and drilling showed greater SBS than grinding. There was a positive correlation between SBS and ARI.