Drug-Drug Interactions and Actual Harm to Hospitalized Patients: A Multicentre Study Examining the Prevalence Pre- and Post-Electronic Medication System Implementation.

INTRODUCTION: Drug-drug interactions (DDIs) have potential to cause patient harm, including lowering therapeutic efficacy. This study aimed to (i) determine the prevalence of potential DDIs (pDDIs); clinically relevant DDIs (cDDIs), that is, DDIs that could lead to patient harm, taking into account a patient's individual clinical profile, drug effects and severity of potential harmful outcome; and subsequent actual harm among hospitalized patients and (ii) examine the impact of transitioning from paper-based medication charts to electronic medication management (eMM) on DDIs and patient harms. METHODS: This was a secondary analysis of the control arm of a controlled pre-post study. Patients were randomly selected from three Australian hospitals. Retrospective chart review was conducted before and after the implementation of an eMM system, without accompanying clinical decision support alerts for DDIs. Harm was assessed by an expert panel. RESULTS: Of 1186 patient admissions, 70.1% (n = 831) experienced a pDDI, 42.6% (n = 505) a cDDI and 0.9% (n = 11) an actual harm in hospital. Of 15,860 pDDIs identified, 27.0% (n = 4285) were classified as cDDIs. The median number of pDDIs and cDDIs per 10 drugs were 6 [interquartile range (IQR) 2-13] and 0 (IQR 0-2), respectively. In cases where a cDDI was identified, both drugs were 44% less likely to be co-administered following eMM (adjusted odds ratio 0.56, 95% confidence interval 0.46-0.73). CONCLUSION: Although most patients experienced a pDDI during their hospital stay, less than one-third of pDDIs were clinically relevant. The low prevalence of harm identified raises questions about the value of incorporating DDI decision support into systems given the potential negative impacts of DDI alerts.

Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study.

INTRODUCTION: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors. METHOD: Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses. ANALYSIS: Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model. ETHICS: National Mutual Acceptance ethical approval was obtained from the Sydney Children's Hospitals Network Human Research Ethics Committee (HREC). Local approvals were sought in each jurisdiction. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC. DISSEMINATION: Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.

Medication use and hospital-acquired acute kidney injury: an electronic health record-based study.

BACKGROUND AND AIMS: Medications remain an important contributor to the development of acute kidney injury (AKI). This study aimed to examine associations between (i) administration of medications known to reduce glomerular filtration rate (GFR), that is, GFR modifiers and subsequent hospital-acquired AKI; and (ii) potentially medication-related AKI and patient adverse outcomes. METHODS: A retrospective cohort study utilising electronic health record data of patients admitted to a tertiary hospital in Australia in 2015. Timing of medication administration was compared with timing of AKI development. AKI cases were identified using an algorithm based on serum creatinine level changes. Multilevel regression models were applied with adjustment for relevant demographic and clinical factors. RESULTS: Among 11 503 admissions, AKI was identified in 955 patients (8.3%) and 637 (66.7% of 955) were preceded by administration of a GFR modifier. Patients without prior AKI were 17% more likely to develop AKI after administration of these medications (adjusted odds ratio 1.17, 95% confidence interval (CI) 1.003-1.37). Older age and comorbidity with diabetes, acute myocardial infarction, peripheral vascular disease, liver cirrhosis and multiple myeloma were also significant predictors. Patients with potentially medication-related AKI were 11.69 times more likely to die in hospital (95% CI 7.84-17.43) and stayed 3.49 times longer in hospital (95% CI 3.26-3.73), compared with those without AKI. CONCLUSIONS: Administration of medications contributing to the reduction of GFR is associated with an increased risk of hospital-acquired AKI and worse patient outcomes. Caution is required when prescribing these medications to patients at risk of developing AKI, and monitoring patients for deterioration is needed if administered.

Association between timing and adequacy of antibiotics and adverse outcomes in patients with sepsis and septic shock: A multicentre retrospective cohort study.

OBJECTIVES: To investigate the association between the timing and adequacy of antibiotics administered to patients presenting with culture-positive sepsis and septic shock to the ED and in-hospital mortality and/or intensive care unit (ICU) admission. METHODS: Multicentre retrospective cohort study of ED presentations at four metropolitan hospitals in Sydney, Australia between January 2017 and November 2019. Encounters for patients aged ≥16 years meeting specified criteria for sepsis or septic shock with antibiotic administration within the first 6 h of presentation were included. RESULTS: Of 7611 encounters included in the study, 2328 (31%) were culture positive, and 2228 (29%) met the criteria for septic shock. In culture-positive sepsis encounters, partial or inadequate antibiotic coverage was associated with higher risk of death or ICU admission (adjusted odds ratio [AOR] 1.50, 95% confidence interval [CI] 1.04-2.06 and 1.95, 95% CI 1.28-2.99, respectively). This effect was not significant in septic shock encounters (AOR 1.10, 95% CI 0.64-1.88) with partial coverage and (AOR 1.63, 95% CI 0.81-3.3) inadequate coverage. Time to antibiotics was not significantly associated with the risk of mortality/ICU admission. This inference remained the same when analysis was restricted to cases with adequate antibiotic coverage. CONCLUSIONS: In a large multicentre sample of patients with culture-positive sepsis, inadequacy of antibiotics was associated with higher risk of in-hospital mortality or ICU admission.

Computerized Clinical Decision Support Systems for the Early Detection of Sepsis Among Pediatric, Neonatal, and Maternal Inpatients: Scoping Review.

BACKGROUND: Sepsis is a severe condition associated with extensive morbidity and mortality worldwide. Pediatric, neonatal, and maternal patients represent a considerable proportion of the sepsis burden. Identifying sepsis cases as early as possible is a key pillar of sepsis management and has prompted the development of sepsis identification rules and algorithms that are embedded in computerized clinical decision support (CCDS) systems. OBJECTIVE: This scoping review aimed to systematically describe studies reporting on the use and evaluation of CCDS systems for the early detection of pediatric, neonatal, and maternal inpatients at risk of sepsis. METHODS: MEDLINE, Embase, CINAHL, Cochrane, Latin American and Caribbean Health Sciences Literature (LILACS), Scopus, Web of Science, OpenGrey, ClinicalTrials.gov, and ProQuest Dissertations and Theses Global (PQDT) were searched by using a search strategy that incorporated terms for sepsis, clinical decision support, and early detection. Title, abstract, and full-text screening was performed by 2 independent reviewers, who consulted a third reviewer as needed. One reviewer performed data charting with a sample of data. This was checked by a second reviewer and via discussions with the review team, as necessary. RESULTS: A total of 33 studies were included in this review-13 (39%) pediatric studies, 18 (55%) neonatal studies, and 2 (6%) maternal studies. All studies were published after 2011, and 27 (82%) were published from 2017 onward. The most common outcome investigated in pediatric studies was the accuracy of sepsis identification (9/13, 69%). Pediatric CCDS systems used different combinations of 18 diverse clinical criteria to detect sepsis across the 13 identified studies. In neonatal studies, 78% (14/18) of the studies investigated the Kaiser Permanente early-onset sepsis risk calculator. All studies investigated sepsis treatment and management outcomes, with 83% (15/18) reporting on antibiotics-related outcomes. Usability and cost-related outcomes were each reported in only 2 (6%) of the 31 pediatric or neonatal studies. Both studies on maternal populations were short abstracts. CONCLUSIONS: This review found limited research investigating CCDS systems to support the early detection of sepsis among pediatric, neonatal, and maternal patients, despite the high burden of sepsis in these vulnerable populations. We have highlighted the need for a consensus definition for pediatric and neonatal sepsis and the study of usability and cost-related outcomes as critical areas for future research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/24899.

Computerized Clinical Decision Support Systems for the Early Detection of Sepsis Among Adult Inpatients: Scoping Review.

BACKGROUND: Sepsis is a significant cause of morbidity and mortality worldwide. Early detection of sepsis followed promptly by treatment initiation improves patient outcomes and saves lives. Hospitals are increasingly using computerized clinical decision support (CCDS) systems for the rapid identification of adult patients with sepsis. OBJECTIVE: This scoping review aims to systematically describe studies reporting on the use and evaluation of CCDS systems for the early detection of adult inpatients with sepsis. METHODS: The protocol for this scoping review was previously published. A total of 10 electronic databases (MEDLINE, Embase, CINAHL, the Cochrane database, LILACS [Latin American and Caribbean Health Sciences Literature], Scopus, Web of Science, OpenGrey, ClinicalTrials.gov, and PQDT [ProQuest Dissertations and Theses]) were comprehensively searched using terms for sepsis, CCDS, and detection to identify relevant studies. Title, abstract, and full-text screening were performed by 2 independent reviewers using predefined eligibility criteria. Data charting was performed by 1 reviewer with a second reviewer checking a random sample of studies. Any disagreements were discussed with input from a third reviewer. In this review, we present the results for adult inpatients, including studies that do not specify patient age. RESULTS: A search of the electronic databases retrieved 12,139 studies following duplicate removal. We identified 124 studies for inclusion after title, abstract, full-text screening, and hand searching were complete. Nearly all studies (121/124, 97.6%) were published after 2009. Half of the studies were journal articles (65/124, 52.4%), and the remainder were conference abstracts (54/124, 43.5%) and theses (5/124, 4%). Most studies used a single cohort (54/124, 43.5%) or before-after (42/124, 33.9%) approach. Across all 124 included studies, patient outcomes were the most frequently reported outcomes (107/124, 86.3%), followed by sepsis treatment and management (75/124, 60.5%), CCDS usability (14/124, 11.3%), and cost outcomes (9/124, 7.3%). For sepsis identification, the systemic inflammatory response syndrome criteria were the most commonly used, alone (50/124, 40.3%), combined with organ dysfunction (28/124, 22.6%), or combined with other criteria (23/124, 18.5%). Over half of the CCDS systems (68/124, 54.8%) were implemented alongside other sepsis-related interventions. CONCLUSIONS: The current body of literature investigating the implementation of CCDS systems for the early detection of adult inpatients with sepsis is extremely diverse. There is substantial variability in study design, CCDS criteria and characteristics, and outcomes measured across the identified literature. Future research on CCDS system usability, cost, and impact on sepsis morbidity is needed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/24899.

Use and Evaluation of Computerized Clinical Decision Support Systems for Early Detection of Sepsis in Hospitals: Protocol for a Scoping Review.

BACKGROUND: Sepsis is a leading cause of death in hospitals, with high associated costs for both patients and health care systems worldwide. Early detection followed by timely intervention is critical for successful sepsis management and, hence, can save lives. Health care institutions are increasingly leveraging clinical data captured in electronic health records for the development of computerized clinical decision support (CCDS) systems aimed at enhancing the early detection of sepsis. However, a comprehensive evidence base regarding sepsis CCDS systems to inform clinical practice, research, and policy is currently lacking. OBJECTIVE: This scoping review aims to systematically describe studies reporting on the use and evaluation of CCDS systems for early detection of sepsis in hospitals. METHODS: The methodology for conducting scoping reviews presented by the Joanna Briggs Institute Reviewer's Manual and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) will be used and adapted as guides. A comprehensive literature search of 10 electronic databases will be conducted to identify all empirical quantitative and qualitative studies that investigate the use of CCDS systems for early detection of sepsis in hospitals. Detailed inclusion and exclusion criteria have been developed. Two reviewers will independently screen all articles based on these criteria. Any discrepancies will be resolved through discussion and further review by a third researcher if required. RESULTS: Electronic database searches have retrieved 12,139 references after removing 10,051 duplicates. As of the submission date of this protocol, we have completed the title and abstract screening. A total of 372 references will be included for full-text screening. Only 15.9% (59/372) of these studies were focused on children: 11.0% (41/372) for pediatric and 4.8% (18/372) for neonatal patients. The scoping review and the manuscript will be completed by December 2020. CONCLUSIONS: Results of this review will guide researchers in determining gaps and shortcomings in the current evidence base for CCDS system use and evaluation in the early detection of sepsis. The findings will be shared with key stakeholders in clinical care, research, policy, and patient advocacy. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/24899.

GP services in Australia: presentation profiles during usual practice hours and after-hours periods.

After-hours general practitioner (GP) services can reduce emergency department demand, which is currently increasing in Australia. Understanding GP after-hours care may assist in service planning. From April 2014 to March 2015, 986 GPs recorded 38275 consultations with start and finish times in the Bettering the Evaluation and Care of Health (BEACH) study, a national, cross-sectional, representative study of GP activity. GP and patient characteristics and the content of encounters in usual-hours and after-hours were compared. Significantly more after-hours than usual-hours encounters were with: GPs aged 60+ years; in metropolitan practices; and practices with 10+ GPs. Patients seen after-hours were more often: male; aged 15-64 years; new to practice; and less likely to hold a Commonwealth Concession Card. They were more likely to be prescribed antibiotics and less likely to: have chronic problems managed; be referred; receive psycholeptic or psychoanaleptic prescription; and undergo a procedure. Throat symptoms, fever and injury were more common reasons for encounter, while infections and injury were more frequently managed problems after-hours. The patient mix, GP characteristics, problems managed and management actions in after-hours care differ from those in usual-hours care in Australia. This greater understanding of after-hours care is the first step to informed resource allocation to improve the delivery of after-hours primary care.

The impact of electronic health record systems on clinical documentation times: A systematic review.

BACKGROUND: Effective management of hospital staff time is crucial to quality patient care. Recent years have seen widespread implementation of electronic health record (EHR) systems but the effect of this on documentation time is unknown. This review compares time spent on documentation tasks by hospital staff (physicians, nurses and interns) before and after EHR implementation. METHODS: A systematic search identified 8153 potentially relevant citations. Studies examining proportion of total workload spent on documentation with ≥40 h of staff observation time were included. Meta-analysis was performed for physicians, nurses and interns comparing pre- and post-EHR results. Studies were weighted by person-hours observation time. RESULTS: Twenty-eight studies met selection criteria. Seventeen were pre-EHR, nine post-EHR and two examined both periods. With implementation of EHR, physicians' documentation time increased from 16% (95% confidence interval (CI) 11-22%) to 28% (95% CI 19-37%), nurses from 9% (95% CI 6-12%) to 23% (95% CI 15-32%) and interns from 20% (95% CI 7-32%) to 26% (95% CI 10-42%). CONCLUSIONS: There is a lack of long-term follow-up on the effects of EHR implementation. Initial adjustment to EHR appears to increase documentation time but there is some evidence that as staff become more familiar with the system, it may ultimately improve work flow.

Health-Related Quality of Life and Function after Paediatric Injuries in India: A Longitudinal Study.

Paediatric injuries can lead to long-term functional impairment and reduced health-related quality of life, and are a growing public health issue in India. To date, however, the burden has been poorly characterized. This study assessed the impact of non-fatal injuries on health-related quality of life in a prospective cohort study of 373 children admitted to three hospitals in Chandigarh and Haryana states in India. The Pediatric Quality of Life Inventory (PedsQL) and King's Outcome Scale for Childhood Head Injury (KOSCHI) were administered at baseline (pre-injury) and at 1, 2, 4, and 12 months post-injury by telephone interview. Follow-up at all-time points was completed for 277 (77%) of all living participants. Less than one percent reported ongoing disability at 4 months, and no disability was reported at 12 months. PedsQL physical health scores were below healthy child norms (83.4) at 1 month in the cohort for ages 8-12 years and 13-16 years. Although injuries are prevalent, ongoing impact on functioning and disability from most childhood injuries at 12 months was reported to be low. The results raise questions about reliability of generic, Western-centric tools in low- and middle-income settings, and highlight the need for local context-specific tools.

Joint modelling of potentially avoidable hospitalisation for five diseases accounting for spatiotemporal effects: A case study in New South Wales, Australia.

BACKGROUND: Three variant formulations of a spatiotemporal shared component model are proposed that allow examination of changes in shared underlying factors over time. METHODS: Models are evaluated within the context of a case study examining hospitalisation rates for five chronic diseases for residents of a regional area in New South Wales: type II diabetes mellitus (DMII), chronic obstructive pulmonary disease (COPD), coronary arterial disease (CAD), hypertension (HT) and congestive heart failure (CHF) between 2001-2006. These represent ambulatory care sensitive (ACS) conditions, often used as a proxy for avoidable hospitalisations. Using a selected model, the effects of socio-economic status (SES) as a shared component are estimated and temporal patterns in the influence of the residual shared spatial component are examined. RESULTS: Choice of model depends upon the application. In the featured application, a model allowing for changing influence of the shared spatial component over time was found to have the best fit and was selected for further analyses. Hospitalisation rates were found to be increasing for COPD and DMII, decreasing for CHF and stable for CAD and HT. SES was substantively associated with hospitalisation rates, with differing degrees of influence for each disease. In general, most of the spatial variation in hospitalisation rates was explained by disease-specific spatial components, followed by the residual shared spatial component. CONCLUSION: Appropriate selection of a joint disease model allows for the examination of temporal patterns of disease outcomes and shared underlying spatial factors, and distinction between different shared spatial factors.

Mediation of improvements in sun protective and skin self-examination behaviours: results from the healthy text study.

OBJECTIVE: Melanoma is on the rise, especially in Caucasian populations exposed to high ultraviolet radiation such as in Australia. This paper examined the psychological components facilitating change in skin cancer prevention or early detection behaviours following a text message intervention. METHODS: The Queensland-based participants were 18 to 42 years old, from the Healthy Text study (N = 546). Overall, 512 (94%) participants completed the 12-month follow-up questionnaires. Following the social cognitive model, potential mediators of skin self-examination (SSE) and sun protection behaviour change were examined using stepwise logistic regression models. RESULTS: At 12-month follow-up, odds of performing an SSE in the past 12 months were mediated by baseline confidence in finding time to check skin (an outcome expectation), with a change in odds ratio of 11.9% in the SSE group versus the control group when including the mediator. Odds of greater than average sun protective habits index at 12-month follow-up were mediated by (a) an attempt to get a suntan at baseline (an outcome expectation) and (b) baseline sun protective habits index, with a change in odds ratio of 10.0% and 11.8%, respectively in the SSE group versus the control group. CONCLUSIONS: Few of the suspected mediation pathways were confirmed with the exception of outcome expectations and past behaviours. Future intervention programmes could use alternative theoretical models to elucidate how improvements in health behaviours can optimally be facilitated.

Spatial modelling of type II diabetes outcomes: a systematic review of approaches used.

With the rising incidence of type II diabetes mellitus (DM II) worldwide, methods to identify high-risk geographical areas have become increasingly important. In this comprehensive review following Cochrane Collaboration guidelines, we outline spatial methods, outcomes and covariates used in all spatial studies involving outcomes of DM II. A total of 1894 potentially relevant citations were identified. Studies were included if spatial methods were used to explore outcomes of DM II or type I and 2 diabetes combined. Descriptive tables were used to summarize information from included studies. Ten spatial studies conducted in the USA, UK and Europe met selection criteria. Three studies used Bayesian generalized linear mixed modelling (GLMM), three used classic generalized linear modelling, one used classic GLMM, two used geographic information systems mapping tools and one compared case:provider ratios across regions. Spatial studies have been effective in identifying high-risk areas and spatial factors associated with DM II outcomes in the USA, UK and Europe, and would be useful in other parts of the world for allocation of additional services to detect and manage DM II early.

Quality of life after early enteral feeding versus standard care for proven or suspected advanced epithelial ovarian cancer: Results from a randomised trial.

BACKGROUND: Malnutrition is common in patients with advanced epithelial ovarian cancer (EOC), and is associated with impaired quality of life (QoL), longer hospital stay and higher risk of treatment-related adverse events. This phase III multi-centre randomised clinical trial tested early enteral feeding versus standard care on postoperative QoL. METHODS: From 2009 to 2013, 109 patients requiring surgery for suspected advanced EOC, moderately to severely malnourished were enrolled at five sites across Queensland and randomised to intervention (n=53) or control (n=56) groups. Intervention involved intraoperative nasojejunal tube placement and enteral feeding until adequate oral intake could be maintained. Despite being randomised to intervention, 20 patients did not receive feeds (13 did not receive the feeding tube; 7 had it removed early). Control involved postoperative diet as tolerated. QoL was measured at baseline, 6weeks postoperatively and 30days after the third cycle of chemotherapy. The primary outcome measure was the difference in QoL between the intervention and the control group. Secondary endpoints included treatment-related adverse event occurrence, length of stay, postoperative services use, and nutritional status. RESULTS: Baseline characteristics were comparable between treatment groups. No significant difference in QoL was found between the groups at any time point. There was a trend towards better nutritional status in patients who received the intervention but the differences did not reach statistical significance except for the intention-to-treat analysis at 7days postoperatively (11.8 intervention vs. 13.8 control, p 0.04). CONCLUSION: Early enteral feeding did not significantly improve patients' QoL compared to standard of care but may improve nutritional status.

Lower preoperative quality of life increases postoperative risk of adverse events in women with endometrial cancer: results from the LACE trial.

OBJECTIVE: To examine the association between preoperative quality of life (QoL) and postoperative adverse events in women treated for endometrial cancer. METHODS: 760 women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery. This analysis includes women with preoperative QoL measurements, from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, and who were followed up for at least 6 weeks after surgery (n=684). The outcomes for this study were defined as (1) the occurrence of moderate to severe adverse events within 6 months (Common Toxicology Criteria (CTC) grade≥3); and (2) any serious adverse event (SAE). The association between preoperative QoL and the occurrence of AE was examined, after controlling for baseline comorbidity and other factors. RESULTS: After adjusting for other factors, odds of occurrence of AE of CTC grade≥3 were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.00-1.03, p=0.030), which was driven by physical well-being (PWB) (OR=1.09, 95% CI 1.04-1.13, p=0.0002) and functional well-being subscales (FWB) (OR=1.04, 95% CI 1.00-1.07, p=0.035). Similarly, odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.01-1.04, p=0.011), baseline PWB (OR=1.11, 95% CI 1.06-1.16, p<0.0001) or baseline FWB subscales (OR=1.05, 95% CI 1.01-1.10, p=0.0077). CONCLUSION: Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery. FUNDING: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council, Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.

Missing in space: an evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes.

BACKGROUND: Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. METHODS: We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. RESULTS: Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. CONCLUSIONS: Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

Epidural analgesia is associated with an increased incidence of postoperative complications in patients requiring an abdominal hysterectomy for early stage endometrial cancer.

OBJECTIVE: Analgesia and early quality of recovery may be improved by epidural analgesia. We aimed to assess the effect of receiving epidural analgesia on surgical adverse events and quality of life after laparotomy for endometrial cancer. METHODS: Patients were enrolled in an international, multicentre, prospective randomised trial of outcomes for laparoscopic versus open surgical treatment for the management of apparent stage I endometrial cancer (LACE trial). The current analysis focussed on patients who received an open abdominal hysterectomy via vertical midline incision only (n=257), examining outcomes in patients who did (n=108) and did not (n=149) receive epidural analgesia. RESULTS: Baseline characteristics were comparable between patients with or without epidural analgesia. More patients without epidural (34%) ceased opioid analgesia 3-5 days after surgery compared to patients who had an epidural (7%; p<0.01). Postoperative complications (any grade) occurred in 86% of patients with and in 66% of patients without an epidural (p<0.01) but there was no difference in serious adverse events (p=0.19). Epidural analgesia was associated with increased length of stay (up to 48 days compared to up to 34 days in the non-epidural group). There was no difference in postoperative quality of life up to six months after surgery. CONCLUSIONS: Epidural analgesia was associated with an increase in any, but not serious, postoperative complications and length of stay after abdominal hysterectomy. Randomised controlled trials are needed to examine the effect of epidural analgesia on surgical adverse events, especially as the present data do not support a quality of life benefit with epidural analgesia.

Differences in Epidural and Analgesic Use in Patients with Apparent Stage I Endometrial Cancer Treated by Open versus Laparoscopic Surgery: Results from the Randomised LACE Trial.

Objectives. We compared postoperative analgesic requirements between women with early stage endometrial cancer treated by total abdominal hysterectomy (TAH) or total laparoscopic hysterectomy (TLH). Methods. 760 patients with apparent stage I endometrial cancer were treated in the international, multicentre, prospective randomised trial (LACE) by TAH (n = 353) or TLH (n = 407) (2005-2010). Epidural, opioid, and nonopioid analgesic requirements were collected until ten months after surgery. Results. Baseline demographics and analgesic use were comparable between treatment arms. TAH patients were more likely to receive epidural analgesia than TLH patients (33% versus 0.5%, P < 0.001) during the early postoperative phase. Although opioid use was comparable in the TAH versus TLH groups during postoperative 0-2 days (99.7% versus 98.5%, P = 0.09), a significantly higher proportion of TAH patients required opioids 3-5 days (70% versus 22%, P < 0.0001), 6-14 days (35% versus 15%, P < 0.0001), and 15-60 days (15% versus 9%, P = 0.02) after surgery. Mean pain scores were significantly higher in the TAH versus TLH group one (2.48 versus 1.62, P < 0.0001) and four weeks (0.89 versus 0.63, P = 0.01) following surgery. Conclusion. Treatment of early stage endometrial cancer with TLH is associated with less frequent use of epidural, lower post-operative opioid requirements, and better pain scores than TAH.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.