Variations in Long-term Opioid Therapy Definitions: A Systematic Review of Observational Studies Using Routinely Collected Data (2000-2019).

Routinely collected data have been increasingly used to assess long-term opioid therapy (LTOT) patterns, with very little guidance on how to measure LTOT from these data sources. We conducted a systematic review of studies published between January 2000 and July 2019 to catalogue LTOT definitions, the rationale for definitions and LTOT rates in observational research using routinely collected data in nonsurgical settings. We screened 4056 abstracts, 210 full-text manuscripts and included 128 studies, mostly from the United States (81%) and published between 2015 and 2019 (69%). We identified 78 definitions of LTOT, commonly operationalised as 90 days of use within a year (23%). Studies often used multiple criteria to derive definitions (60%), mostly based on measures of duration, such as supply days/days of use (66%), episode length (21%) or prescription fills within specified time periods (12%). Definitions were based on previous publications (63%), clinical judgment (16%) or empirical data (3%); 10% of studies applied more than one definition. LTOT definition was not provided with enough details for replication in 14 studies and 38 studies did not specify the opioids evaluated. Rates of LTOT within study populations ranged from 0.2% to 57% according to study design and definition used. We observed a substantial rise in the last 5 years in studies evaluating LTOT with large variability in the definitions used and poor reporting of the rationale and implementation of definitions. This variation impacts on research reproducibility, comparability of findings and the development of strategies aiming to curb therapy that is not guideline-recommended.

Interrupted time series analysis using autoregressive integrated moving average (ARIMA) models: a guide for evaluating large-scale health interventions.

BACKGROUND: Interrupted time series analysis is increasingly used to evaluate the impact of large-scale health interventions. While segmented regression is a common approach, it is not always adequate, especially in the presence of seasonality and autocorrelation. An Autoregressive Integrated Moving Average (ARIMA) model is an alternative method that can accommodate these issues. METHODS: We describe the underlying theory behind ARIMA models and how they can be used to evaluate population-level interventions, such as the introduction of health policies. We discuss how to select the shape of the impact, the model selection process, transfer functions, checking model fit, and interpretation of findings. We also provide R and SAS code to replicate our results. RESULTS: We illustrate ARIMA modelling using the example of a policy intervention to reduce inappropriate prescribing. In January 2014, the Australian government eliminated prescription refills for the 25 mg tablet strength of quetiapine, an antipsychotic, to deter its prescribing for non-approved indications. We examine the impact of this policy intervention on dispensing of quetiapine using dispensing claims data. CONCLUSIONS: ARIMA modelling is a useful tool to evaluate the impact of large-scale interventions when other approaches are not suitable, as it can account for underlying trends, autocorrelation and seasonality and allows for flexible modelling of different types of impacts.

Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia.

BACKGROUND: Australia introduced tamper-resistant controlled-release (CR) oxycodone in April 2014. We quantified the impact of the reformulation on dispensing, switching and poisonings. METHODS: We performed interrupted time-series analyses using population-representative national dispensing data from 2012 to 2016. We measured dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids and switching to other strong opioids after the reformulation compared with a historical control period. Similarly, we compared calls about intentional opioid poisoning using data from a regional poisons information centre. RESULTS: After the reformulation, dispensing decreased for 10-30 mg (total level shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%) and 40-80 mg oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in participants less than 65 years of age but was unchanged in people 65 years of age or older. Compared with the previous year, discontinuation of use of strong opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79). Switching to morphine varied by age (p < 0.001), and the greatest increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80). Participants switching after the reformulation were more likely to be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone taken orally increased immediately after the reformulation (incidence rate ratio (IRR) 1.31, 95% CI 1.05-1.64), but there was no change for injected oxycodone. INTERPRETATION: The reformulation had a greater impact on opioid access patterns of people less than 65 years of age who were using higher strengths of oxycodone CR. This group has been identified as having an increased risk of problematic opioid use and warrants closer monitoring in clinical practice.

The crux of the matter: Did the ABC's Catalyst program change statin use in Australia?

OBJECTIVES: To examine the impact of a two-part special edition of the Australian Broadcasting Corporation's science journalism program Catalyst (titled Heart of the matter), aired in October 2013, that was critical of HMG-CoA reductase inhibitors ("statins"). DESIGN, SETTING AND PARTICIPANTS: Population-based interrupted time-series analysis of a 10% sample of Australian long-term concessional beneficiaries who were dispensed statins under the Pharmaceutical Benefits Scheme (about 51% of all people who were dispensed a statin between 1 July 2009 and 30 June 2014); dispensing of proton pump inhibitors (PPIs) was used as a comparator. MAIN OUTCOME MEASURES: Change in weekly dispensings and discontinuation of use of statins and PPIs, adjusting for seasonal and long-term trends, overall and (for statins only) stratified by the use of cardiovascular and diabetes medicines. RESULTS: In our sample, 191 833 people were dispensed an average of 26 946 statins weekly. Following the Catalyst program, there was a 2.60% (95% CI, 1.40%-3.77%; P < 0.001) reduction in statin dispensing, equivalent to 14 005 fewer dispensings Australia-wide every week. Dispensing decreased by 6.03% (95% CI, 3.73%-8.28%; P < 0.001) for people not dispensed other cardiovascular and diabetes medicines and 1.94% (0.42%-3.45%; P = 0.01) for those dispensed diabetes medicines. In the week the Catalyst program aired, there was a 28.8% (95% CI, 15.4%-43.7%; P < 0.001) increase in discontinuation of statin use, which decayed by 9% per week. An estimated 28 784 additional Australians ceased statin treatment. Discontinuation occurred regardless of the use of other cardiovascular and diabetes medicines. There were no significant changes in PPI use after the Catalyst program. CONCLUSIONS: Following airing of the Catalyst program, there was a temporary increase in discontinuation and a sustained decrease in overall statin dispensing. Up until 30 June 2014, there were 504 180 fewer dispensings of statins, and we estimate this to have affected 60 897 people.

Assessing measures of comorbidity and functional status for risk adjustment to compare hospital performance for colorectal cancer surgery: a retrospective data-linkage study.

BACKGROUND: Comparing outcomes between hospitals requires consideration of patient factors that could account for any observed differences. Adjusting for comorbid conditions is common when studying outcomes following cancer surgery, and a commonly used measure is the Charlson comorbidity index. Other measures of patient health include the ECOG performance status and the ASA physical status score. This study aimed to ascertain how frequently ECOG and ASA scores are recorded in population-based administrative data collections in New South Wales, Australia and to assess the contribution each makes in addition to the Charlson comorbidity index in risk adjustment models for comparative assessment of colorectal cancer surgery outcomes between hospitals. METHODS: We used linked administrative data to identify 6964 patients receiving surgery for colorectal cancer in 2007 and 2008. We summarised the frequency of missing data for Charlson comorbidity index, ECOG and ASA scores, and compared patient characteristics between those with and without these measures. The performance of ASA and ECOG in risk adjustment models that also included Charlson index was assessed for three binary outcomes: 12-month mortality, extended length of stay and 28-day readmission. Patient outcomes were compared between hospital peer groups using multilevel logistic regression analysis. RESULTS: The Charlson comorbidity index could be derived for all patients, ASA score was recorded for 78 % of patients and ECOG performance status recorded for only 24 % of eligible patients. Including ASA or ECOG improved the predictive ability of models, but there was no consistently best combination. The addition of ASA or ECOG did not substantially change parameter estimates for hospital peer group after adjusting for Charlson comorbidity index. CONCLUSIONS: While predictive ability of regression models is maximised by inclusion of one or both of ASA score and ECOG performance status, there is little to be gained by adding ASA or ECOG to models containing the Charlson comorbidity index to address confounding. The Charlson comorbidity index has good performance and is an appropriate measure to use in risk adjustment to compare outcomes between hospitals.

Uptake and outcomes of laparoscopically assisted resection for colon and rectal cancer in Australia: a population-based study.

BACKGROUND: Meta-analyses of randomized controlled trials support the use of laparoscopically assisted resection for colon cancer. The evidence supporting its use in rectal cancer is weak. OBJECTIVE: The purpose of this work was to investigate the uptake of laparoscopically assisted resection for colon and rectal cancer and to compare short- and long-term outcomes using population data. DESIGN: This was a retrospective cohort study using linked administrative health data. SETTINGS: The study encompassed all of the public and private hospitals in New South Wales, Australia, between 2000 and 2008. PATIENTS: A total of 27,947 patients with colon or rectal cancer undergoing surgery with curative intent were included in the study. MAIN OUTCOME MEASURES: We summarized the proportion of resections performed laparoscopically. Short-term outcomes were extended stay, 28-day readmission, 28-day emergency readmission, 30- and 90-day mortality, and 90-day readmission with pulmonary embolism or deep-vein thrombosis. Long-term outcomes were all-cause and cancer-specific death and admission with obstruction or incisional hernia repair. RESULTS: Laparoscopic procedures increased between 2000 and 2008 for colon (1.5%-20.7%) and rectal cancer (0.6%-15.5%). Laparoscopic procedures reduced rates of extended stay (OR, 0.60; 95% CI, 0.49-0.72) and 28-day readmission (OR, 0.86; 95% CI, 0.74-0.99) for colon cancer. For rectal cancer, laparoscopic procedures had lower rates of 28-day readmission (OR, 0.58; 95% CI, 0.42-0.78) and 28-day emergency readmission (OR, 0.54; 95% CI, 0.34-0.85). Laparoscopic procedures improved cancer-specific survival for rectal cancer (HR, 0.71; 95% CI, 0.51-1.00). Survival benefits were observed for laparoscopically assisted colon resection in higher-caseload hospitals but not lower-caseload hospitals. LIMITATIONS: It was not possible to identify laparoscopically assisted resections converted to open procedures because of the claims-based nature of the data. CONCLUSIONS: Despite increases in laparoscopically assisted resections for colon and rectal cancer, the majority of resections are still treated by open procedures. Our data suggest that laparoscopic resection reduces the lengths of stay and rates of readmission and may result in improved cancer-specific survival for both colon and rectal resections.

Predictors of variation in colorectal cancer care and outcomes in New South Wales: a population-based health data linkage study.

OBJECTIVE: To identify predictors of variation in colorectal cancer care and outcomes in New South Wales. DESIGN, SETTING AND PATIENTS: Multilevel logistic regression analysis using a linked population-based dataset based on the records of patients with cancer of the colon, rectosigmoid junction or rectum who were registered in 2007 and 2008 by the NSW Central Cancer Registry and treated in 105 hospitals in NSW. MAIN OUTCOME MEASURES: Six outcome measures (30-day mortality, 28-day emergency readmission, prolonged length of stay, 30-day wound infection, 90-day venous thromboembolism, 1-year mortality) and five care process measures (discussion at multidisciplinary team [MDT] meeting, documented cancer stage, recorded pathological stage, treatment within 31 days of decision to treat, treatment within 62 days of referral). RESULTS: We analysed data for 6890 people. There was wide variation between hospitals in care process measures, even after adjusting for patient and hospital factors. Older adults were less likely to be discussed at an MDT meeting and receive treatment within suggested time frames (all P < 0.001 for colon cancer). Increasing patient age, greater extent of disease, higher Charlson comorbidity score and resection after emergency admission consistently showed strong evidence of an association with poor outcomes. Much of the variation between hospitals in outcome measures was accounted for by patient characteristics. CONCLUSIONS: Patient characteristics should be included in risk-adjustment models for comparing outcomes between hospitals and for quantifying hospital variation. Further exploration of the reasons why certain hospitals and patients appear to be at risk of poorer care is needed.

Association between tobacco plain packaging and Quitline calls: a population-based, interrupted time-series analysis.

OBJECTIVES: To investigate whether the introduction of tobacco plain packaging in Australia from 1 October 2012 was associated with a change in the number of calls to the smoking cessation helpline, Quitline, and to compare this with the impact of the introduction of graphic health warnings from 1 March 2006. DESIGN AND SETTING: Whole-of-population interrupted time-series analysis in New South Wales and the Australian Capital Territory between 1 March 2005 and October 2006 for the comparator, graphic health warnings, and October 2011 and April 2013 for the intervention of interest, tobacco plain packaging. MAIN OUTCOME MEASURE: Weekly number of calls to the Quitline, after adjusting for seasonal trends, anti-tobacco advertising, cigarette costliness and the number of smokers in the community. RESULTS: There was a 78% increase in the number of calls to the Quitline associated with the introduction of plain packaging (baseline, 363/week; peak, 651/week [95% CI, 523-780/week; P < 0.001]). This peak occurred 4 weeks after the initial appearance of plain packaging and has been prolonged. The 2006 introduction of graphic health warnings had the same relative increase in calls (84%; baseline, 910/week; peak, 1673/week [95% CI, 1383-1963/week; P < 0.001]) but the impact of plain packaging has continued for longer. CONCLUSIONS: There has been a sustained increase in calls to the Quitline after the introduction of tobacco plain packaging. This increase is not attributable to anti-tobacco advertising activity, cigarette price increases nor other identifiable causes. This is an important incremental step in comprehensive tobacco control.

Opioid prescribing patterns among medical practitioners in New South Wales, Australia.

INTRODUCTION: Prescriber behaviour is important for understanding opioid use patterns. We described variations in practitioner-level opioid prescribing in New South Wales, Australia (2013-2018). METHODS: We quantified opioid prescribing patterns among medical practitioners using population-level dispensing claims data, and used partitioning around medoids to identify clusters of practitioners who prescribe opioids based on prescribing patterns and patient characteristics identified from linked dispensing claims, hospitalisations and mortality data. RESULTS: The number of opioid prescribers ranged from 20,179 in 2013 to 23,408 in 2018. The top 1% of practitioners prescribed 15% of all oral morphine equivalent (OME) milligrams dispensed annually, with a median of 1382 OME grams (interquartile range [IQR], 1234-1654) per practitioner; the bottom 50% prescribed 1% of OMEs dispensed, with a median of 0.9 OME grams (IQR 0.2-2.6). Based on 63.6% of practitioners with ≥10 patients filling opioid prescriptions in 2018, we identified four distinct practitioner clusters. The largest cluster prescribed multiple analgesic medicines for older patients (23.7% of practitioners) accounted for 76.7% of all OMEs dispensed and comprised 93.0% of the top 1% of practitioners by opioid volume dispensed. The cluster prescribing analgesics for younger patients with high rates of surgery (18.7% of practitioners) prescribed only 1.6% of OMEs. The remaining two clusters comprised 21.2% of prescribers and 20.9% of OMEs dispensed. DISCUSSION AND CONCLUSION: We observed substantial variation in opioid prescribing among practitioners, clustered around four general patterns. We did not assess appropriateness but some prescribing patterns are concerning. Our findings provide insights for targeted interventions to curb potentially harmful practices.

Australian national birthweight percentiles by sex and gestational age, 1998-2007.

OBJECTIVE: To present updated national birthweight percentiles by gestational age for male and female singleton infants born in Australia. DESIGN AND SETTING: Cross-sectional population-based study of 2.53 million singleton live births in Australia between 1998 and 2007. MAIN OUTCOME MEASURES: Birthweight percentiles by gestational age and sex. RESULTS: Between 1998 and 2007, women in Australia gave birth to 2 539 237 live singleton infants. Of these, 2 537 627 had a gestational age between 20 and 44 weeks, and sex and birthweight data were available. Birthweight percentiles are presented by sex and gestational age for a total of 2 528 641 births, after excluding 8986 infants with outlying birthweights. Since the publication of the previous Australian birthweight percentiles in 1999, median birthweight for term babies has increased between 0 and 25 g for boys and between 5 g and 45 g for girls. CONCLUSIONS: There has been only a small increase in birthweight percentiles for babies of both sexes and most gestational ages since 1991-1994. These national percentiles provide a current Australian reference for clinicians and researchers assessing weight at birth.

Validation and application of a death proxy in adult cancer patients.

PURPOSE: Fact of death is not always available on data sets used for pharmacoepidemiological research. Proxies may be an appropriate substitute in the absence of death data. The purposes of this study were to validate a proxy for death in adult cancer patients and to assess its performance when estimating survival in two cohorts of cancer patients. METHODS: We evaluated 30-, 60-, 90- and 180-day proxies overall and by cancer type using data from 12 394 Australian veterans with lung, colorectal, breast or prostate cancer. The proxy indicated death if the difference between the last dispensing record and the end of the observational period exceeded the proxy cutoff. We then compared actual survival to 90-day proxy estimates in a subset of 4090 veterans with 'full entitlements' for pharmaceutical items and in 3704 Australian women receiving trastuzumab for HER2+ metastatic breast cancer. RESULTS: The 90-day proxy was optimal with an overall sensitivity of 99.3% (95%CI: 98.4-99.7) and a specificity of 97.6% (95%CI: 91.8-99.4). These measures remained high when evaluated by cancer type and spread of disease. The application of the proxy using the most conservative date of death estimate (date of last dispensing) generally underestimated survival, with estimates up to 3 months shorter than survival based on fact of death. CONCLUSIONS: A 90-day death proxy is a robust substitute to identify death in a chronic population when fact of death is not available. The proxy is likely to be valid across a range of chronic diseases as it relies on the presence of 'regular' dispensing records for individual patients. Copyright © 2011 John Wiley & Sons, Ltd.

Effects of service-wide support on regularity of alcohol screening of clients in Australian Aboriginal and Torres Strait Islander Community Controlled Health Services: a cluster randomised trial.

BACKGROUND: We have previously shown that service-wide support can increase the odds of alcohol screening in any 2-month period in a cluster randomized trial of service-wide support to Aboriginal and Torres Strait Islander Community Controlled Health Services (ACCHS). Here we report an exploratory analysis on whether the resulting pattern of screening was appropriate. AIM: we assess whether that increase in screening was associated with: (i) increased first-time screening, (ii) increased annual screening, (iii) whether frequently screened clients fell into one of four risk categories as defined by national guidelines. METHODS: Setting and participants: 22 ACCHS; randomized to receive the support model in the treatment ('early-support') arm over 24-months or to the waitlist control arm. INTERVENTION: eight-component support, including training, sharing of experience, audit-and-feedback and resource support. ANALYSIS: records of clients with visits before and after start of implementation were included. Multilevel logistic modelling was used to compare (i) the odds of previously unscreened clients receiving an AUDIT-C screen, (ii) odds of clients being screened with AUDIT-C at least once annually. We describe the characteristics of a sub-cohort of clients who received four or more screens annually, including if they were in a high-risk category. RESULTS: Of the original trial sample, 43,054 met inclusion criteria, accounting for 81.7% of the screening events in the overall trial. The support did not significantly increase the odds of first-time screening (OR = 1.33, 95% CI 0.81-2.18, p = 0.25) or of annual screening (OR = 0.99, 95% CI 0.42-2.37, p = 0.98). Screening more than once annually occurred in 6240 clients. Of the 841 clients with four or more screens annually, over 50% did not fall into a high-risk category. Females were overrepresented. More males than females fell into high-risk categories. CONCLUSION: The significant increase in odds of screening observed in the main trial did not translate to significant improvement in first-time or annual screening following implementation of support. This appeared to be due to some clients being screened more frequently than annually, while more than half remained unscreened. Further strategies to improve alcohol screening should focus on appropriate screening regularity as well as overall rates, to ensure clinically useful information about alcohol consumption. Trial Registration ACTRN12618001892202, retrospectively registered 16 November 2018 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001892202 .

Support for Aboriginal health services in reducing harms from alcohol: 2-year service provision outcomes in a cluster randomized trial.

BACKGROUND AND AIMS: There is a higher prevalence of unhealthy alcohol use among Indigenous populations, but there have been few studies of the effectiveness of screening and treatment in primary health care. Over 24 months, we tested whether a model of service-wide support could increase screening and any alcohol treatment. DESIGN: Cluster-randomized trial with 24-month implementation (12 months active, 12 months maintenance). SETTING: Australian Aboriginal Community Controlled primary care services. PARTICIPANTS: Twenty-two services (83 032 clients) that use Communicare practice software and see at least 1000 clients annually, randomized to the treatment arm or control arm. INTERVENTION AND COMPARATOR: Multi-faceted early support model versus a comparator of waiting-list control (11 services). MEASUREMENTS: A record (presence = 1, absence = 0) of: (i) Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening (primary outcome), (ii) any-treatment and (iii) brief intervention. We received routinely collected practice data bimonthly over 3 years (1-year baseline, 1-year implementation, 1-year maintenance). Multi-level logistic modelling was used to compare the odds of each outcome before and after implementation. FINDINGS: The odds of being screened within any 2-month reference period increased in both arms post-implementation, but the increase was nearly eight times greater in early-support services [odds ratio (OR) = 7.95, 95% confidence interval (CI) = 4.04-15.63, P < 0.001]. The change in odds of any treatment in early support was nearly double that of waiting-list controls (OR = 1.89, 95% CI = 1.19-2.98, P = 0.01) but was largely driven by decrease in controls. There was no clear evidence of difference between groups in the change in the odds of provision of brief intervention (OR = 1.95, 95% CI = 0.53-7.17, P = 0.32). CONCLUSIONS: An early support model designed to aid routine implementation of alcohol screening and treatment in Aboriginal health services resulted in improvement of Alcohol Use Disorders Identification Test-Consumption screening rates over 24 months of implementation, but the effect on treatment was less clear.

Use of cyclin D1 in conjunction with human papillomavirus status to predict outcome in oropharyngeal cancer.

There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow-up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. The HPV-positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV-positive group, after adjusting for clinicopathological factors, patients with cyclin D1-positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1-negative tumors. However, within the HPV-negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes.

Support can increase use of the AUDIT-C in Australian Aboriginal Community Controlled Health Services: a cluster randomized trial.

BACKGROUND AND AIMS: Unhealthy alcohol consumption is a key concern for Aboriginal and Torres Strait Islander ('Indigenous') communities. It is important to identify and treat at-risk drinkers, to prevent harms to physical or social wellbeing. We aimed to test whether training and support for Aboriginal Community Controlled Health Service (ACCHS) staff would increase rates of alcohol screening and brief intervention. DESIGN: Cluster randomized trial. SETTING: Australia. Cases/Intervention/Measurements Twenty-two ACCHSs that see at least 1000 clients per year and use Communicare as practice management software. The study included data on 70 419 clients, training, regular data feedback, collaborative support and funding for resources ($9000). Blinding was not used. The comparator was waiting-list control (equal allocation). Alcohol Use Disorder Identification Test (AUDIT-C) screening and records of brief interventions were extracted from practice management software at 2-monthly intervals. Observations described the clinical actions taken for clients over each 2-month interval. The baseline period (28 August 2016-28 August 2017) was compared with the post-implementation period (29 August 2017-28 August 2018). We used multi-level logistic regression to test the hypotheses that clients attending a service receiving active support would be more likely to be screened with AUDIT-C (primary outcome) or to receive a brief intervention (secondary outcome). FINDINGS: We observed an increase in the odds of screening with AUDIT-C for both groups, but the increase was 5.52 [95% confidence interval (CI) = 4.31, 7.07] times larger at services receiving support. We found little evidence that the support programme increased the odds of a recorded brief intervention relative to control services (odds ratio = 2.06; 95% CI = 0.90, 4.69). Differences in baseline screening activity between treatment and control reduce the certainty of our findings. CONCLUSIONS: Providing Aboriginal Community Controlled Health Services with training and support can improve alcohol (AUDIT-C) screening rates.

Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting.

OBJECTIVE: To compare the effectiveness of intravenous (IV) morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane when administered by paramedics to patients with moderate to severe pain. METHODS: We conducted a retrospective comparative study of adult patients with moderate to severe pain treated by paramedics from the Ambulance Service of New South Wales who received IV morphine, IN fentanyl, or inhaled methoxyflurane either alone or in combination between January 1, 2004, and November 30, 2006. We used multivariate logistic regression to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of > or = 30% of initial pain score using an 11-point verbal numeric rating scale (VNRS-11). RESULTS: The study population comprised 52,046 patients aged between 16 and 100 years with VNRS-11 scores of > or = 5. All analgesic agents were effective in the majority of patients (81.8%, 80.0%, and 59.1% for morphine, fentanyl, and methoxyflurane, respectively). There was very strong evidence that methoxyflurane was inferior to both morphine and fentanyl (p < 0.0001). There was strong evidence that morphine was more effective than fentanyl (p = 0.002). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. CONCLUSION: Inhaled methoxyflurane, IN fentanyl, and IV morphine are all effective analgesic agents in the out-of-hospital setting. Morphine and fentanyl are significantly more effective analgesic agents than methoxyflurane. Morphine appears to be more effective than IN fentanyl; however, the benefit of IV morphine may be offset to some degree by the ability to administer IN fentanyl without the need for IV access.

Changes in cardiorespiratory fitness among children and adolescents in Australia: 1997 and 2004.

In this paper, we describe changes in cardiorespiratory fitness among children and adolescents in New South Wales, Australia from 1997 to 2004. Altogether, 4363 children and adolescents were surveyed in 1997 and 3720 were surveyed in 2004. Participants were randomly selected from Grades 4 and 6 in primary school and Grades 8 and 10 in high schools. Cardiorespiratory fitness was assessed on both occasions using the 20-m shuttle run test. There was a very small, but statistically significant, increase in the median number of laps completed for primary (P = 0.02) and high school girls (P = 0.02) and high school boys (P = 0.01); however, the prevalence of adequate cardiorespiratory fitness did not change significantly from 1997 to 2004 for primary or high school boys or girls. Cardiorespiratory fitness was higher among the most socially advantaged boys and girls and this tertile also recorded the greatest increases in all but one group. Over the period 1997 to 2004, the prevalence of adequate cardiorespiratory fitness among students rose slightly in general. It is concerning that the gap between low and high socio-economic tertiles appears to have widened.

The relationship between pulmonary artery and pulmonary capillary wedge pressure for the diagnosis of pulmonary vascular disease.

BACKGROUND: Left heart disease and pulmonary vascular disease (PVD) both lead to raised pulmonary artery pressure (PAP) but differ in pathophysiology, prognosis and treatment. There are currently no criteria for diagnosing PVD in the presence of left heart disease. We therefore studied the relationship between PAP and pulmonary capillary wedge pressure (PCWP, a measure of left atrial pressure) to help define when PAP should be considered 'out-of-proportion' to PCWP, thus suggestive of PVD. METHODS: Retrospective analysis of 898 consecutive simultaneous left and right heart catheterisations. Of these, 684 patients (age 63+/-14 years) were classified according to presence of absence of left heart disease. Multilinear regression explored the relationship between mean PAP and PCWP, age, gender, systemic haemodynamics and left heart disease diagnosis. RESULTS: Increasing PCWP, age and heart rate and female gender were associated with higher PAP (p<0.0001, p=0.049, p<0.0001 and p=0.0015, respectively). Thus, in males: (mean PAP)=0.94+[1.15 x (mean PCWP)]+[0.03 x (age)]+[0.07 x (heart rate)] (for females add 1.38 mm Hg). This model accounted for 75% of variability in PAP, with PCWP alone accounting for 74%. CONCLUSIONS: A strong linear relationship exists between PAP and PCWP, which may help identify PAP 'out-of-proportion' to PCWP, facilitating the diagnosis of PVD in patients with pulmonary hypertension and left heart disease.

Doppler-derived pulmonary flow reserve detects pulmonary microvascular obstruction in high primates.

BACKGROUND: Despite increasing evidence implicating the pulmonary microcirculation in the pathogenesis of lung conditions such as pulmonary vascular disease, there remain few methods for its evaluation in vivo. We recently demonstrated that the novel index of Doppler-derived pulmonary flow reserve (PFR(dopp)=maximal hyperaemic/basal pulmonary flow) could be reliably measured in high primates. Noting that the microvasculature is the chief regulator of pulmonary blood flow, we hypothesised that PFR(dopp) may detect microcirculatory loss. We therefore studied the relationship between PFR(dopp) and experimentally induced pulmonary microvascular obstruction using microspheres in higher primates. METHODS: Under ketamine anaesthesia, Doppler sensor-guidewires were placed in the segmental pulmonary artery of three adult baboons. Doppler flow velocity and haemodynamics were recorded at rest and during hyperaemia [as induced by intrapulmonary artery adenosine (200 µg/kg/min)]. Serial PFR(dopp) evaluations were made after cumulative intrapulmonary artery ceramic microspheres administration. RESULTS: Cumulative microsphere administration progressively reduced PFR(dopp) (1.54 ± 0.26, 1.48 ± 0.20, 1.12 ± 0.04 and 1.18 ± 0.09; baseline, 10(4), 10(5) and 10(6) microspheres boluses; p<0.02) without affecting pulmonary artery pressure, systemic artery pressure or heart rate. CONCLUSIONS: Doppler-derived PFR can detect partial, progressive pulmonary microvascular obstruction in higher primates. PFR(dopp) may thus have a potential role in the assessment of the pulmonary microcirculation in vivo.

Prognostic significance of vascular endothelial growth factor in squamous cell carcinomas of the tonsil in relation to human papillomavirus status and epidermal growth factor receptor.

BACKGROUND: Angiogenesis markers, vascular endothelial growth factor (VEGF) and microvessel density (MVD) have been associated with prognosis in squamous cell carcinomas (SCCs) of the head and neck. Other prognostic variables such as human papillomavirus (HPV) and epidermal growth factor (EGFR) may also be involved in tumour angiogenesis. This study determined relationships between VEGF, MVD, EGFR, HPV, response to radiotherapy and clinical outcome in 85 tonsillar SCCs. METHODS: HPV status was determined by an HPV multiplex real-time polymerase chain reaction (PCR) assay/p16 immunohistochemistry. Expression of VEGF, CD31 (as marker of MVD) and EGFR was assessed by semiquantitative immunohistochemistry. RESULTS: Strong VEGF expressers were significantly more likely to have higher MVD than were weak expressers. There were no associations between VEGF or MVD and gender, patient age, TNM stage, EGFR expression or HPV status. Tumours with MVD of >15 per high-power field were significantly more likely to be poorly differentiated. There was a significant inverse relationship between EGFR and HPV status. HPV was a strong independent marker of loco-regional recurrence and death. VEGF and EGFR were risk factors for local recurrence and disease-specific death on univariate analysis but the associations weakened after adjustment for HPV. Among patients treated with radiotherapy, VEGF was associated with disease-specific death after adjusting for HPV and TMN stage. High-VEGF-expressing tumours positive for EGFR had a worse prognosis than all other groups combined after adjusting for HPV and TNM stage. CONCLUSIONS: HPV is a stronger prognostic marker than VEGF or EGFR in tonsillar SCCs. VEGF correlates with MVD in these tumours.