Characterization of a chromatin-associated TCF7L1 complex in human embryonic stem cells.

Human embryonic stem cells (hESCs) resemble the pluripotent epiblast cells found in the early postimplantation human embryo and represent the "primed" state of pluripotency. One factor that helps primed pluripotent cells retain pluripotency and prepare genes for differentiation is the transcription factor TCF7L1, a member of a small family of proteins known as T cell factors/Lymphoid enhancer factors (TCF/LEF) that act as downstream components of the WNT signaling pathway. Transcriptional output of the WNT pathway is regulated, in part, by the activity of TCF/LEFs in conjunction with another component of the WNT pathway, ß-CATENIN. Because TCF7L1 plays an important role in regulating pluripotency, we began to characterize the protein complex associated with TCF7L1 when bound to chromatin in hESCs using rapid immunoprecipitation of endogenous proteins (RIME).  Data are available via ProteomeXchange with identifier PXD047582. These data identify known and new partners of TCF7L1 on chromatin and provide novel insights into how TCF7L1 and pluripotency itself might be regulated.

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

BACKGROUND AND AIM: People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. METHODS: We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. RESULTS: Among 99 687 women aged ≥ 50 years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. CONCLUSIONS: Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Association between unstable diabetes mellitus and risk of pancreatic cancer.

BACKGROUND: Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS: We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS: Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.

Describing the acceptability and use of an opioid stewardship self-assessment tool in real-world settings.

BACKGROUND: The Stewardship Framework (Framework) was developed by an expert clinician group and was designed to provide a mechanism for continuous monitoring of improvement in opioid prescribing in acute hospitals. The aim of this study was to modify the Framework into an Opioid Stewardship Self-Assessment Tool (Self-Assessment Tool), and pilot test the acceptability and its use in a variety of acute hospital settings. METHODS: The Framework was converted into the Self-Assessment Tool to allow hospitals to undertake a gap analysis of their current opioid stewardship activities. To participate hospitals were required to establish a small team and complete the Self-Assessment Tool. Participating sites were recruited using purposive sampling. Responses were tabulated and coded to enable assessment. 'Acceptability' was defined as the completion of the Self-Assessment Tool (response rate, proportion of questions answered) and responder feedback relating to its content. The use of the Tool was categorised based on the level of detail of responses. RESULTS: Nineteen of the 20 facilities approached, agreed to participate. The 16 sites which established a small team to facilitate survey completion are included in the final analysis. The overall response rate was 96 % (413/432) for the (27 survey questions across 16 participating sites), 4 % (19/432) of questions were left unanswered or were not interpretable by the study team. Opportunities were identified to enhance the use of the Self-Assessment Tool, particularly to support its potential to assist reflection and planning of local strategies. CONCLUSION: This study demonstrated that the Self-Assessment Tool was an acceptable method of assessing a facility's opioid stewardship capabilities in a real-world setting. The next iteration will be modified using the insights on how the Tool was used by study participants.

Queensland Inpatient Diabetes Survey (QuIDS): patient experience survey evaluation.

BACKGROUND: Measurement of inpatient experience can allow for treatment tailored to patient preferences and needs. The patient experience of diabetes care has not been explored in Queensland hospitals. AIMS: To investigate the experiences of patients with diabetes when hospitalised using the Queensland Inpatient Diabetes Survey (QuIDS). METHODS: In 2019 and 2021, patient experience surveys were collected as part of the statewide QuIDS, a cross-sectional study assessing the quality of inpatient care received by people with diabetes in Queensland, Australia. Patient responses were categorised and frequencies reported as percentages. Free text comments were analysed using thematic analysis methods. Pooled descriptive data were presented. RESULTS: Responses were collected from 27 hospitals in 2019 (n = 526, 52.4% of all patients with diabetes) and 35 hospitals in 2021 (n = 709, 55.5%). Overall, patients were satisfied with their inpatient diabetes care. Areas for improvement identified by surveyed patients include the choice and timing of meals, staff knowledge about diabetes and increased diabetes self-management. Access to a specialist diabetes team was also identified as being potentially underutilised. Patient comments fell into four major themes: communication, food choices, patient autonomy and education. CONCLUSION: Many patients reported positive inpatient experiences; however, patients also expressed dissatisfaction with their inpatient diabetes care. Our data provide unique insight and an opportunity to improve standards of care and service provision for inpatients with diabetes.

Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer.

HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype.

Association between antihypertensive medicine use and risk of ovarian cancer in women aged 50 years and older.

BACKGROUND: Epithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. METHODS: Our nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. RESULTS: We found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). CONCLUSION: Our results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.

The impact of transition to a digital hospital on medication errors (TIME study).

Digital transformation in healthcare improves the safety of health systems. Within our health service, a new digital hospital has been established and two wards from a neighbouring paper-based hospital transitioned into the new digital hospital. This created an opportunity to evaluate the impact of complete digital transformation on medication safety. Here we discuss the impact of transition from a paper-based to digital hospital on voluntarily reported medication incidents and prescribing errors. This study utilises an interrupted time-series design and takes place across two wards as they transition from a paper to a digital hospital. Two data sources are used to assess impacts on medication incidents and prescribing errors: (1) voluntarily reported medication incidents and 2) a chart audit of medications prescribed on the study wards. The chart audit collects data on procedural, dosing and therapeutic prescribing errors. There are 588 errors extracted from incident reporting software during the study period. The average monthly number of errors reduces from 12.5 pre- to 7.5 post-transition (p < 0.001). In the chart audit, 5072 medication orders are reviewed pre-transition and 3699 reviewed post-transition. The rates of orders with one or more error reduces significantly after transition (52.8% pre- vs. 15.7% post-, p < 0.001). There are significant reductions in procedural (32.1% pre- vs. 1.3% post-, p < 0.001), and dosing errors (32.3% pre- vs. 14% post-, p < 0.001), but not therapeutic errors (0.6% pre- vs. 0.7% post-, p = 0.478). Transition to a digital hospital is associated with reductions in voluntarily reported medication incidents and prescribing errors.

Can a novel constructivist theory-informed feedback intervention reduce prescribing errors ? A pre-post study.

CONTEXT: Medical interns (interns) find prescribing challenging and many report lacking readiness when commencing work. Errors in prescribing puts patients' safety at risk. Yet error rates remain high, despite education, supervision and pharmacists' contributions. Feedback on prescribing may improve performance. Yet, work-based prescribing feedback practices focus on rectifying errors. We aimed to explore if prescribing can be improved using a theory-informed feedback intervention. METHODS: In this pre-post study, we designed and implemented a constructivist-theory informed prescribing feedback intervention, informed by Feedback-Mark 2 Theory. Interns commencing internal medicine terms in two Australian teaching hospitals were invited to engage in the feedback intervention. Their prescribing was evaluated by comparing errors per medication order of at least 30 orders per intern. Pre/baseline (weeks 1-3) were compared with post intervention (weeks 8-9). Interns' baseline prescribing audit findings were analysed and discussed at individualised feedback sessions. These sessions were with a clinical pharmacologist (Site 1) and a pharmacist educator (Site 2). RESULTS: Eighty eight intern's prescribing over five 10-week terms was analysed from two hospitals. The frequency of prescribing errors significantly reduced at both sites after the intervention, across all five terms (p < 0.001).There were initially 1598 errors in 2750 orders (median [IQR] 0.48 [0.35-0.67] errors per order) and after the intervention 1113 errors in 2694 orders (median [IQR] 0.30 [0.17-0.50] errors per order). CONCLUSION: Our findings suggest interns' prescribing practices may improve as a result of constructivist -theory learner centred, informed feedback with an agreed plan. This novel intervention, contributed, to a reduction in interns' prescribing errors. This study suggests new strategies for improving prescribing safety should include the design and implementation of theory-informed feedback interventions.

Opioid dispensing 2008-18: a Queensland perspective.

Objective This study provides an overview of opioid dispensing in Queensland from 2008 to 2018 by recipient age, drug, oral morphine equivalent and remoteness. Methods Data were obtained from the Queensland Monitoring of Drugs of Dependence System database for 2008-18 and analysed using data from the Australian Bureau of Statistics to account for population growth. Opioid dispensing by age, drug, oral morphine equivalent and remoteness were assessed. Results The number of prescriptions for Schedule 8 opioid medicines dispensed in Queensland increased from 190 to 430 per 1000 population over the study period (2.3-fold increase). Oxycodone had the largest increase in dispensing over the study period of 3.1-fold, with tapentadol increasing rapidly since initial Pharmaceutical Benefits Scheme listing in 2013 to the third most dispensed opioid by 2018. By 2018, opioid dispensing among the oldest Queenslanders, those aged 85+ years, occurred at triple the rate for those aged 65-84 years. When adjusted to report oral morphine equivalents (OME) in milligrams (mg), there has been an increase of approximately 1.9-fold over the study period. Results were also presented by geographical area, including a heatmap and analysis by remoteness. Prescriptions dispensed per 1000 population were 416 for major cities, 551 for inner regional and 445 for outer regional, and highlight that inner and outer regional areas have higher rates of prescriptions when compared to major cities (32 and 7% higher, respectively). Conclusion This study highlights changes in opioid prescription dispensing by drug and OME, as well as the variation in dispensing rates when accounting for remoteness. Further studies to link statewide databases, and to better understand drivers for differences in dispensing by location, will provide valuable insights to further inform policy and service provision.

Perioperative Beta-Blocker Supply and Survival in Women With Epithelial Ovarian Cancer and a History of Cardiovascular Conditions.

PURPOSE: Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study. MATERIALS AND METHODS: Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects. RESULTS: Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery. CONCLUSION: Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.

The association between diabetes mellitus of different durations and risk of pancreatic cancer: an Australian national data-linkage study in women.

AIMS: The bidirectional association between diabetes mellitus (DM) and pancreatic cancer (PC) is established; however, the strength of association between duration of DM and risk of PC needs further investigation. METHODS: We conducted a case-control study nested within a population-based cohort of Australian women established using record linkage. Women diagnosed with PC from July 2007 to December 2013, were matched to five controls based on age and state of residence. DM was defined according to prescription of anti-diabetic medication from administrative prescription data. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for area-level socioeconomic status, rurality of residence, weighted comorbidity score, and predicted probability of obesity. RESULTS: The analyses included 7,267 cases and 35,978 controls. The mean age at the time of DM diagnosis was 71 years whereas the mean age at the time of diagnosis of PC was 76 years. A history of DM of any duration was associated with a 2-fold increase in risk of PC (OR=2.12; 95%CI:1.96-2.29) compared to having no history of DM. The risk decreased with increasing duration of DM. The highest risk was in those who had recent-onset DM (OR=8.08; 95%CI:6.88-9.50 for <12 months of DM), but the risk remained elevated with ≥5 years of DM (OR=1.40; 95%CI:1.27-1.55). CONCLUSION: The markedly increased risk of PC in those with recent-onset DM emphasises the need for further research to distinguish patients for whom new-onset DM is a manifestation of PC from those with type-2 DM. The elevated risk associated with long-standing DM suggests that preventing DM may contribute to a reduction in the incidence of PC.

The effect of Computerised Physician Order Entry on prescribing errors: An interrupted time-series study at a secondary referral hospital in Australia.

BACKGROUND: Computerised Physician Order Entry (CPOE) software is increasingly used across the world to improve medication safety. However, few high-quality studies have reviewed the impact of CPOE on prescribing errors and patient harm. OBJECTIVE: To investigate the effect of a hybrid CPOE-paper prescribing system on prescribing errors at a secondary hospital site. DESIGN: An interrupted time-series study was conducted by identifying prescribing errors via prospective medical chart review before and after the implementation of CPOE across three medical wards. PARTICIPANTS: The medication orders of all patients admitted to the medical wards during the study period were reviewed. INTERVENTION: Implementation of a CPOE across three medical wards. MEASURES: A blinded expert panel risk stratified the errors according to level of severity, preventability and potential for harm. Pearson's chi square and segmented regressions were used to determine if there were differences in prescribing errors pre- and post-CPOE implementation. KEY RESULTS: A total of 10,535 medication orders were reviewed pre-CPOE and 13,841 medication orders reviewed post-CPOE. Analysis demonstrated that after implementation of CPOE there were reductions in the proportion of orders with one or more of any error (-30.1%, 95 %CI: -36.5%, -23.7%, p < 0.001). Reductions in the proportion of orders with one or more errors were seen across the error categories of dosing errors (-20.1%, 95 %CI: -25.1%, -15%, p < 0.001), procedural/administrative errors (-18.9%, 95 %CI: -22.8%, -15%, p < 0.001), and therapeutic errors (-2.6%, 95 %CI: -4.1%, -1%, p = 0.002). Post-CPOE there were reductions in the proportion of orders with at least one non-intercepted serious error (-12.6%, 95 %CI: -16.4%, -8.8%, p < 0.001). CONCLUSION: The introduction of CPOE was associated with reductions in prescribing errors. There is also evidence that this translated into a reduced risk of harm to patients post-CPOE implementation through the reduction in actual adverse drug events.

A systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project.

BACKGROUND: Genomic variants which disrupt splicing are a major cause of rare genetic diseases. However, variants which lie outside of the canonical splice sites are difficult to interpret clinically. Improving the clinical interpretation of non-canonical splicing variants offers a major opportunity to uplift diagnostic yields from whole genome sequencing data. METHODS: Here, we examine the landscape of splicing variants in whole-genome sequencing data from 38,688 individuals in the 100,000 Genomes Project and assess the contribution of non-canonical splicing variants to rare genetic diseases. We use a variant-level constraint metric (the mutability-adjusted proportion of singletons) to identify constrained functional variant classes near exon-intron junctions and at putative splicing branchpoints. To identify new diagnoses for individuals with unsolved rare diseases in the 100,000 Genomes Project, we identified individuals with de novo single-nucleotide variants near exon-intron boundaries and at putative splicing branchpoints in known disease genes. We identified candidate diagnostic variants through manual phenotype matching and confirmed new molecular diagnoses through clinical variant interpretation and functional RNA studies. RESULTS: We show that near-splice positions and splicing branchpoints are highly constrained by purifying selection and harbour potentially damaging non-coding variants which are amenable to systematic analysis in sequencing data. From 258 de novo splicing variants in known rare disease genes, we identify 35 new likely diagnoses in probands with an unsolved rare disease. To date, we have confirmed a new diagnosis for six individuals, including four in whom RNA studies were performed. CONCLUSIONS: Overall, we demonstrate the clinical value of examining non-canonical splicing variants in individuals with unsolved rare diseases.

Persistent opioid use after hospital discharge in Australia: a systematic review.

Objective This systematic review identified studies that provided an estimate of persistent opioid use following patient discharge from hospital settings in Australia. Methods A literature search was performed on 5 December 2020, with no date restrictions to identify studies that reported a rate of persistent opioid use following patient discharge from Australian Hospitals. The search strategy combined all terms relating to the themes 'hospital patients', 'prescribing', 'opioids' and 'Australia'. Studies that dealt solely with cancer, palliative care or addiction medicine were excluded. The databases searched in this review were Embase, PubMed, Scopus, CINAHL, and International Pharmaceutical Abstracts. Studies were assessed for bias using the Newcastle-Ottawa Scale and considered against international literature. Results In total, 13 publications are included for final analysis in this review. Of these, 11 articles relate to post-surgical opioid use. With one exception, studies were of a 'good' quality. Methods of data collection in included studies were a mixture of those conducting follow up of patients directly over time and those utilising dispensing databases. Persistent opioid use among surgical patients generally ranged from 3.9 to 10.5% at between 2 and 4 months after discharge. Conclusions How rates of persistent opioid use following hospital encounters in Australia are established, and how long after discharge rates are reported, is heterogeneous. Literature primarily relates to post-surgical patients, with very few studies investigating other settings such as encounters with the emergency department.

Cost and Capability Compromises in STEM Instrumentation for Low-Voltage Imaging.

Low-voltage transmission electron microscopy (≤80 kV) has many applications in imaging beam-sensitive samples, such as metallic nanoparticles, which may become damaged at higher voltages. To improve resolution, spherical aberration can be corrected for in a scanning transmission electron microscope (STEM); however, chromatic aberration may then dominate, limiting the ultimate resolution of the microscope. Using image simulations, we examine how a chromatic aberration corrector, different objective lenses, and different beam energy spreads each affect the image quality of a gold nanoparticle imaged at low voltages in a spherical aberration-corrected STEM. A quantitative analysis of the simulated examples can inform the choice of instrumentation for low-voltage imaging. We here demonstrate a methodology whereby the optimum energy spread to operate a specific STEM can be deduced. This methodology can then be adapted to the specific sample and instrument of the reader, enabling them to make an informed economical choice as to what would be most beneficial for their STEM in the cost-conscious landscape of scientific infrastructure.

Nitrogen-based Bisphosphonate Use and Ovarian Cancer Risk in Women Aged 50 Years and Older.

BACKGROUND: There are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype. METHODS: We conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia's universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes. CONCLUSION: Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.

Retrospective study of the prevalence and characteristics of adverse drug events in adults who present to an Australian emergency department.

OBJECTIVE: To determine the burden, on the ED, of harm from unintentional adverse drug events (ADEs) in the community. METHODS: A retrospective, observational study of 936 randomly selected presentations to a level 6 ED at a principal referral hospital in Brisbane, Australia, in November 2017. Clinical records were screened by a pharmacist, who identified suspected ADEs. All suspected ADEs and a random selection of presentations without ADEs were reviewed by an expert panel, which classified, by consensus: occurrence and type of ADE, contribution of ADE to presentation, severity of harm and preventability of presentation. Medication-related ED presentations (ADE-Ps) and potential ADEs were, respectively, defined as presentations directly attributable to an ADE, and medication events that occurred but did not cause the ED presentation. Descriptive data analysis was performed. RESULTS: The median (interquartile range) age of patients was 40 (27-58) years, with 49.7% (95% confidence interval [CI] 46.5-52.9) being male. The prevalences of ADE-Ps and potential ADEs were 9.2% (95% CI 7.5-11.3) and 5.0% (95% CI 3.8-6.6), respectively. The severity of harm was classified as 'death or likely permanent harm' in 4.7% (95% CI 0.2-9.1) of ADE-Ps, 'temporary harm' (89.5%, 95% CI 83.1-96.0) and 'minimal or no harm' (5.8%, 95% CI 0.9-10.8). Most (79.1%, 95% CI 70.5-87.7) ADE-Ps were preventable. CONCLUSIONS: There is a high burden on emergency care because of unintended medication harm in the community. Interventions to reduce such harm are likely to require a co-ordinated primary, acute and public healthcare response. The high proportion of presentations with potential ADEs indicates opportunity for harm mitigation in the ED.