John L Moran

University of Adelaide, Tarndarnya, South Australia, Australia

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Publications (109)570.93 Total impact

  • Jessica Kasza · John L. Moran · Patricia J. Solomon
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    ABSTRACT: In recent years, the evaluation of healthcare provider performance has become standard for governments, insurance companies, and other stakeholders. Often, performance is compared across providers using indicators in one time period, for example a year. However it is often important to assess changes in the performance of individual providers over time. Such analyses can be used to determine if any providers have significant improvements, deteriorations, unusual patterns or systematic changes in performance. Studies which monitor healthcare provider performance in this way have to date typically been limited to comparing performance in the most recent period with performance in a previous period. It is also important to consider a longer-term view of performance and assess changes over more than two periods. In this paper, we develop test statistics that account for variable numbers of prior performance indicators, and show that these are particularly useful for assessing consecutive improvements or deteriorations in performance. We apply the tests to coronary artery bypass graft mortality rates in New York State hospitals, and mortality data from Australian and New Zealand intensive care units. Although our applications are to medical data, the new tests have broad application in other areas.
    Biometrical Journal 12/2014; 57(2). DOI:10.1002/bimj.201400105 · 1.24 Impact Factor
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    ABSTRACT: The typical toxidrome in organophosphate (OP) poisoning comprises of the Salivation, Lacrimation, Urination, Defecation, Gastric cramps, Emesis (SLUDGE) symptoms. However, several other manifestations are described. We review the spectrum of symptoms and signs in OP poisoning as well as the different approaches to clinical features in these patients. Articles were obtained by electronic search of PubMed(®) between 1966 and April 2014 using the search terms organophosphorus compounds or phosphoric acid esters AND poison or poisoning AND manifestations. Of the 5026 articles on OP poisoning, 2584 articles pertained to human poisoning; 452 articles focusing on clinical manifestations in human OP poisoning were retrieved for detailed evaluation. In addition to the traditional approach of symptoms and signs of OP poisoning as peripheral (muscarinic, nicotinic) and central nervous system receptor stimulation, symptoms were alternatively approached using a time-based classification. In this, symptom onset was categorized as acute (within 24-h), delayed (24-h to 2-week) or late (beyond 2-week). Although most symptoms occur with minutes or hours following acute exposure, delayed onset symptoms occurring after a period of minimal or mild symptoms, may impact treatment and timing of the discharge following acute exposure. Symptoms and signs were also viewed as an organ specific as cardiovascular, respiratory or neurological manifestations. An organ specific approach enables focused management of individual organ dysfunction that may vary with different OP compounds. Different approaches to the symptoms and signs in OP poisoning may better our understanding of the underlying mechanism that in turn may assist with the management of acutely poisoned patients.
    Indian Journal of Critical Care Medicine 11/2014; 18(11):735-745. DOI:10.4103/0972-5229.144017
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    John L Moran · Patricia J Solomon
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    ABSTRACT: Background Risk adjusted mortality for intensive care units (ICU) is usually estimated via logistic regression. Random effects (RE) or hierarchical models have been advocated to estimate provider risk-adjusted mortality on the basis that standard estimators increase false outlier classification. The utility of fixed effects (FE) estimators (separate ICU-specific intercepts) has not been fully explored. Methods Using a cohort from the Australian and New Zealand Intensive Care Society Adult Patient Database, 2009–2010, the model fit of different logistic estimators (FE, random-intercept and random-coefficient) was characterised: Bayesian Information Criterion (BIC; lower values better), receiver-operator characteristic curve area (AUC) and Hosmer-Lemeshow (H-L) statistic. ICU standardised hospital mortality ratios (SMR) and 95%CI were compared between models. ICU site performance (FE), relative to the grand observation-weighted mean (GO-WM) on odds ratio (OR), risk ratio (RR) and probability scales were assessed using model-based average marginal effects (AME). Results The data set consisted of 145355 patients in 128 ICUs, years 2009 (47.5%) & 2010 (52.5%), with mean(SD) age 60.9(18.8) years, 56% male and ICU and hospital mortalities of 7.0% and 10.9% respectively. The FE model had a BIC = 64058, AUC = 0.90 and an H-L statistic P-value = 0.22. The best-fitting random-intercept model had a BIC = 64457, AUC = 0.90 and H-L statistic P-value = 0.32 and random-coefficient model, BIC = 64556, AUC = 0.90 and H-L statistic P-value = 0.28. Across ICUs and over years no outliers (SMR 95% CI excluding null-value = 1) were identified and no model difference in SMR spread or 95%CI span was demonstrated. Using AME (OR and RR scale), ICU site-specific estimates diverged from the GO-WM, and the effect spread decreased over calendar years. On the probability scale, a majority of ICUs demonstrated calendar year decrease, but in the for-profit sector, this trend was reversed. Conclusions The FE estimator had model advantage compared with conventional RE models. Using AME, between and over-year ICU site-effects were easily characterised.
    PLoS ONE 07/2014; 9(7):e102297. DOI:10.1371/journal.pone.0102297 · 3.23 Impact Factor
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    ABSTRACT: TARGET Investigators and the ANZICS Clinical Trials Group, Sandra L . Active Reviews Reviewer Area and click on , and log in to your account. Enter the http://submit.ajcn.org view, go to available in the Full MS Info view of the manuscript. To reach this manuscript link [Download Supplemental Files] additional materials, click on the This paper includes additional materials for review purposes. To view
    American Journal of Clinical Nutrition 07/2014; DOI:10.3945/ajcn.114.086322 · 6.92 Impact Factor
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    ABSTRACT: Recent studies have suggested that circulating levels of the tumor necrosis factor α receptor 1 (sTNFαR1) may be a useful predictor for the risk of end-stage renal disease (ESRD) in patients with diabetes. However, its potential utility as a biomarker has not been formally quantified.RESEARCH DESIGN AND METHODS: Circulating levels of sTNFαR1 were assessed in 429 patients with type 1 diabetes and overt nephropathy from the Finnish Diabetic Nephropathy (FinnDiane) cohort study. Predictors of incident ESRD over a median of 9.4 years of follow-up were determined by Cox regression and Fine-Gray competing risk analyses. The added value of sTNFαR1 was estimated via time-dependent receiver operating characteristic curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) for survival data.RESULTS: A total of 130 individuals developed ESRD (28%; ESRD incidence rate of 3.4% per year). In cause-specific modeling, after adjusting for baseline renal status, predictors of increased incidence of ESRD in patients with overt nephropathy were an elevated HbA1c, shorter duration of diabetes, and circulating levels of sTNFαR1. Notably, sTNFαR1 outperformed estimated glomerular filtration rate in terms of R(2). Circulating levels of the sTNFαR1 also remained associated with ESRD after adjusting for the competing risk of death. A prediction model including sTNFαR1 (as a -0.5 fractional polynomial) was superior to a model without it, as demonstrated by better global fit, an increment of R(2), the C index, and area under the curve. Estimates of IDI and NRI(>0) were 0.22 (95% CI 0.16-0.28; P < 0.0001) and 0.98 (0.78-1.23; P < 0.0001), respectively. The median increment in the risk score after including sTNFαR1 in the prediction model was 0.18 (0.12-0.30; P < 0.0001).CONCLUSIONS: Circulating levels of sTNFαR1 are independently associated with the cumulative incidence of ESRD. This association is both significant and biologically plausible and appears to provide added value as a biomarker, based on the absolute values of NRI and IDI.
    Diabetes Care 05/2014; 37(8). DOI:10.2337/dc14-0225 · 8.57 Impact Factor
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    Patricia J Solomon · John L Moran · Jessica Kasza
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    ABSTRACT: The Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD) collects voluntary data on patient admissions to Australian and New Zealand intensive care units (ICUs). This paper presents an in-depth statistical analysis of risk-adjusted mortality of ICU admissions from 2000 to 2010 for the purpose of identifying ICUs with unusual performance. A cohort of 523, 462 patients from 144 ICUs was analysed. For each ICU, the natural logarithm of the standardised mortality ratio (log-SMR) was estimated from a risk-adjusted, three-level hierarchical model. This is the first time a three-level model has been fitted to such a large ICU database anywhere. The analysis was conducted in three stages which included the estimation of a null distribution to describe usual ICU performance. Log-SMRs with appropriate estimates of standard errors are presented in a funnel plot using 5% false discovery rate thresholds. False coverage-statement rate confidence intervals are also presented. The observed numbers of deaths for ICUs identified as unusual are compared to the predicted true worst numbers of deaths under the model for usual ICU performance. Seven ICUs were identified as performing unusually over the period 2000 to 2010, in particular, demonstrating high risk-adjusted mortality compared to the majority of ICUs. Four of the seven were ICUs in private hospitals. Our three-stage approach to the analysis detected outlying ICUs which were not identified in a conventional (single) risk-adjusted model for mortality using SMRs to compare ICUs. We also observed a significant linear decline in mortality over the decade. Distinct yearly and weekly respiratory seasonal effects were observed across regions of Australia and New Zealand for the first time. The statistical approach proposed in this paper is intended to be used for the review of observed ICU and hospital mortality. Two important messages from our study are firstly, that comprehensive riskadjustment is essential in modelling patient mortality for comparing performance, and secondly, that the appropriate statistical analysis is complicated.
    BMC Medical Research Methodology 04/2014; 14(1):53. DOI:10.1186/1471-2288-14-53 · 2.17 Impact Factor
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    Diabetes care 04/2014; 37(4):e62-3. DOI:10.2337/dc13-1947 · 8.57 Impact Factor
  • Bhuvana Krishna · Sriram Sampath · John L Moran
    Indian Journal of Critical Care Medicine 01/2014; 18(1):51. DOI:10.4103/0972-5229.125445
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    ABSTRACT: Introduction. Clinical scoring systems are used to predict mortality rate in hospitalized patients. Their utility in organophosphate (OP) poisoning has not been well studied. Methods. In this retrospective study of 396 patients, we evaluated the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Simplified Acute Physiology Score (SAPS) II, Mortality Prediction Model (MPM) II, and the Poisoning Severity Score (PSS). Demographic, laboratory, and survival data were recorded. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated to study the relationship between individual scores and mortality rate. Results. The mean (standard deviation) age of the patients was 31.4 (12.7) years, and at admission, their pseudocholinesterase (median, interquartile) level was 317 (222-635) U/L. Mechanical ventilation was required in 65.7% of the patients and the overall mortality rate was 13.1%. The mean (95% confidence interval) scores were as follows: APACHE-II score, 16.4 (15.5-17.3); SAPS-II, 34.4 (32.5-36.2); MPM-II score, 28.6 (25.7-31.5); and PSS, 2.4 (2.3-2.5). Overall, the AUC for mortality was significantly higher for APACHE-II (0.77) and SAPS-II (0.77) than the PSS (0.67). When patients were categorized, the AUCs were better for WHO Class II (0.71-0.82) than that for Class I compounds (0.60-0.66). For individual compounds, the AUC for APACHE-II was highest in quinalphos (0.93, n = 46) and chlorpyrifos (0.86, n = 38) and lowest in monocrotophos (0.60, n = 63). AUCs for SAPS-II and MPM-II were marginally but not significantly lower than those for APACHE-II. The PSS was generally a poorer discriminator compared to the other scoring systems across all categories. Conclusions. In acute OP poisoning, the generic scoring systems APACHE-II and SAPS-II outperform the PSS. These tools may be used to predict the mortality rate in OP poisoning.
    Clinical Toxicology 09/2013; 51(9). DOI:10.3109/15563650.2013.841181 · 3.12 Impact Factor
  • J Kasza · J L Moran · P J Solomon
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    ABSTRACT: The Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS APD) is one of the largest databases of its kind in the world and collects individual admissions' data from intensive care units (ICUs) around Australia and New Zealand. Use of this database for monitoring and comparing the performance of ICUs, quantified by the standardised mortality ratio, poses several theoretical and computational challenges, which are addressed in this paper. In particular, the expected number of deaths must be appropriately estimated, the ICU casemix adjustment must be adequate, statistical variation must be fully accounted for, and appropriate adjustment for multiple comparisons must be made. Typically, one or more of these issues have been neglected in ICU comparison studies. Our approach to the analysis proceeds by fitting a random coefficient hierarchical logistic regression model for the inhospital death of each patient, with patients clustered within ICUs. We anticipate the majority of ICUs will be estimated as performing 'usually' after adjusting for important clinical covariates. We take as a starting point the ideas in Ohlssen et al and estimate an appropriate null model that we expect these ICUs to follow, taking a frequentist rather than a Bayesian approach. This methodology allows us to rigorously account for the aforementioned statistical issues and to determine if there are any ICUs contributing to the Australian and New Zealand Intensive Care Society database that have comparatively unusual performance. In addition to investigating the yearly performance of the ICUs, we also estimate changes in individual ICU performance between 2009 and 2010 by adjusting for regression-to-the-mean. Copyright © 2013 John Wiley & Sons, Ltd.
    Statistics in Medicine 09/2013; 32(21). DOI:10.1002/sim.5779 · 2.04 Impact Factor
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    ABSTRACT: Aims: Whilst low dietary salt intake has beneficial effects on blood pressure (BP), low 24h urinary sodium excretion (24hUNa), the most accurate estimate of dietary salt intake, is associated with increased mortality in people with diabetes. In the non diabetic population, low salt intake is associated with increased renin angiotensin aldosterone system (RAAS) activity. In this study cross-sectional study, we examined the relationship between 24hUNa, plasma renin activity (PRA), serum aldosterone, and B-type natriuretic peptide (BNP) in patients with diabetes. Methods: Clinical characteristics, 24hUNa, PRA, serum aldosterone, and BNP were recorded in 222 consecutive patients (77% with type 2 diabetes) attending a diabetes clinic at a tertiary hospital. The relationship between 24hUNa, serum aldosterone, PRA, BNP, urinary potassium excretion, serum potassium, serum sodium, estimated glomerular filtration rate (eGFR), urinary albumin excretion and HbA1c was examined by a multivariable regression model. Results: 24hUNa significantly predicted serum aldosterone in a linear fashion (R2=0.20, p=0.002). In the subgroup of patients (n=46) not taking RAAS modifying agents, this relationship was also observed (R2=0.10, p=0.03), and the effect of 24hUNa on serum aldosterone was found to be more pronounced than in the whole cohort (coefficient = -0.0014, vs. -0.0008). There was no demonstrable relationship between 24hUNa and PRA or BNP. Conclusions: Low 24hUNa is associated with increased serum aldosterone in people with diabetes, in the presence and absence of RAAS modifying agents. This raises the possibility that stimulation of the RAAS may be a mechanism which contributes to adverse outcomes observed in patients with low 24hUNa.
    Clinical Science 07/2013; 126(1-2). DOI:10.1042/CS20130128 · 5.63 Impact Factor
  • Bhuvana Krishna · Sriram Sampath · John L Moran
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    ABSTRACT: The use of non-invasive positive pressure ventilation (NIPPV) in post-extubation respiratory failure is not well-established. Meta-analytic techniques were used to assess the effects of prophylactic application of NIPPV (prior to the development of respiratory failure) and therapeutic application of NIPPV (subsequent to the development of respiratory failure). Randomized controlled trials (RCTs) from 1966 to May 2010 were identified using electronic databases. RCTs, which reported the use of NIPPV in post-extubation respiratory failure with defined assessable endpoints: reintubation, mortality and length of stay, were included. Reintubation was the primary outcome, mortality and lengths of stay were the secondary outcomes. Risk ratios (RR) were calculated for discrete outcomes and weighted mean differences (WMD) for continuous measures. There were 13 trials with 1420 patients; 9 prophylactic with 861 patients and 4 therapeutic with 559 patients. In the prophylactic group, NIPPV was associated with lower rates of reintubation: RR 0.53 (95% confidence interval [CI], 0.28-0.98), P = 0.04. In the therapeutic group, NIPPV showed a null effect on reintubation: RR 0.79 (95% CI, 0.50-1.25), P = 0.31. The analysis on the secondary outcomes suggested significant reduction of hospital mortality with prophylactic application of NIPPV: RR 0.62 (95% CI 0.4-0.97), P = 0.03, with no effect on the other outcomes. Therapeutic application of NIPPV reduced intensive care unit length of stay: WMD -1.17 (95% CI -2.82 to -0.33), P = 0.006, but no effect on the other secondary outcomes. The results of this review suggested prophylactic NIPPV was beneficial with respect to reintubation and the therapeutic use of NIPPV showed a null effect.
    Indian Journal of Critical Care Medicine 07/2013; 17(4):253-61. DOI:10.4103/0972-5229.118477
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    John L Moran · Patricia J Solomon
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    ABSTRACT: Background Statistical process control (SPC), an industrial sphere initiative, has recently been applied in health care and public health surveillance. SPC methods assume independent observations and process autocorrelation has been associated with increase in false alarm frequency. Methods Monthly mean raw mortality (at hospital discharge) time series, 1995–2009, at the individual Intensive Care unit (ICU) level, were generated from the Australia and New Zealand Intensive Care Society adult patient database. Evidence for series (i) autocorrelation and seasonality was demonstrated using (partial)-autocorrelation ((P)ACF) function displays and classical series decomposition and (ii) “in-control” status was sought using risk-adjusted (RA) exponentially weighted moving average (EWMA) control limits (3 sigma). Risk adjustment was achieved using a random coefficient (intercept as ICU site and slope as APACHE III score) logistic regression model, generating an expected mortality series. Application of time-series to an exemplar complete ICU series (1995-(end)2009) was via Box-Jenkins methodology: autoregressive moving average (ARMA) and (G)ARCH ((Generalised) Autoregressive Conditional Heteroscedasticity) models, the latter addressing volatility of the series variance. Results The overall data set, 1995-2009, consisted of 491324 records from 137 ICU sites; average raw mortality was 14.07%; average(SD) raw and expected mortalities ranged from 0.012(0.113) and 0.013(0.045) to 0.296(0.457) and 0.278(0.247) respectively. For the raw mortality series: 71 sites had continuous data for assessment up to or beyond lag40 and 35% had autocorrelation through to lag40; and of 36 sites with continuous data for ≥ 72 months, all demonstrated marked seasonality. Similar numbers and percentages were seen with the expected series. Out-of-control signalling was evident for the raw mortality series with respect to RA-EWMA control limits; a seasonal ARMA model, with GARCH effects, displayed white-noise residuals which were in-control with respect to EWMA control limits and one-step prediction error limits (3SE). The expected series was modelled with a multiplicative seasonal autoregressive model. Conclusions The data generating process of monthly raw mortality series at the ICU level displayed autocorrelation, seasonality and volatility. False-positive signalling of the raw mortality series was evident with respect to RA-EWMA control limits. A time series approach using residual control charts resolved these issues.
    BMC Medical Research Methodology 05/2013; 13(1):66. DOI:10.1186/1471-2288-13-66 · 2.17 Impact Factor
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    ABSTRACT: AIMS: It is recommended that individuals with diabetes restrict their dietary sodium intake. But while salt intake is correlated with blood pressure, it also partly determines the activation state of renin-angiotensin-aldosterone-system (RAAS), a key mediator of diabetes-associated atherosclerosis. METHODS: ApolipoproteinE KO mice were allocated for the induction of diabetes with streptozotocin or citrate-buffer (controls) and further randomized to isocaloric diets containing (0.05%, 0.3%, or 3.1% sodium with or without the ACE inhibitor, perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis assessed using RT-PCR and ELISA. The association of sodium intake and adverse cardiovascular and mortality outcomes were explored in 2648 adults with type 1 diabetes without prior cardiovascular disease from the FinnDiane study. RESULTS: A 0.05% sodium diet was associated with increased plaque accumulation in diabetic apoE KO mice, associated with activation of the RAAS. By contrast, a diet containing 3.1% sodium suppressed atherogenesis associated with suppression of the RAAS, with an efficacy comparable to ACE inhibition. In adults with type 1 diabetes, low sodium intake was also associated with an increased risk of all-cause mortality and new-onset cardiovascular events. However, high sodium intake was also associated with adverse outcomes, leading to a J-shaped relationship overall. CONCLUSIONS: While blood pressure lowering is an important goal for the management of diabetes, off-target actions to activate the RAAS may contribute to an observed lack of protection from cardiovascular complications in patients with type 1 diabetes with low sodium intake.
    Clinical Science 12/2012; 124(9-10). DOI:10.1042/CS20120352 · 5.63 Impact Factor
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    ABSTRACT: Enteral nutrition (EN) is widely accepted as the preferred method for providing nutrition therapy to critically ill patients. However, optimal energy goals and the best way to achieve those goals are ill defined. To determine the type and energy concentration of commonly prescribed EN formulations and whether energy-dense formulations (> 1 kcal/mL) are used. Prospective, observational, multicentre, single-day, point-prevalence study. All patients present in 38 Australian and New Zealand intensive care units at 10:00 on 17 November 2010. Demographic data, admission diagnosis and information on EN administration were collected. 522 patients were enrolled. Mean age was 58.7 (SD, 17.3) years, 65% were male and 79% were mechanically ventilated. On study day, 220/522 patients received EN (43%; 95% CI, 39%-48%). ICU admission source, Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic category, APACHE II score and ventilation on study day predicted receipt of EN. Of those receiving EN, 111/220 (51%; 95% CI, 44%-57%) received a 1 kcal/mL formulation and the remainder received an energy-dense formulation - 2 kcal/mL, 39/220 (18%; 95% CI, 13%-23%); and 1.5 kcal/mL, 32/220 (15%; 95% CI, 10%-20%). There were no significant predictors for receipt of energy-dense versus 1 kcal/mL EN. 1 kcal/mL and energy-dense formulations are administered with about equal frequency in Australian and New Zealand ICUs. This finding supports future research into the evaluation of optimal nutritional delivery amounts using EN formulations with differing energy concentrations.
    Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine 06/2012; 14(2):148-53. · 2.15 Impact Factor
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    John L Moran · Patricia J Solomon
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    ABSTRACT: Background For the analysis of length-of-stay (LOS) data, which is characteristically right-skewed, a number of statistical estimators have been proposed as alternatives to the traditional ordinary least squares (OLS) regression with log dependent variable. Methods Using a cohort of patients identified in the Australian and New Zealand Intensive Care Society Adult Patient Database, 2008–2009, 12 different methods were used for estimation of intensive care (ICU) length of stay. These encompassed risk-adjusted regression analysis of firstly: log LOS using OLS, linear mixed model [LMM], treatment effects, skew-normal and skew-t models; and secondly: unmodified (raw) LOS via OLS, generalised linear models [GLMs] with log-link and 4 different distributions [Poisson, gamma, negative binomial and inverse-Gaussian], extended estimating equations [EEE] and a finite mixture model including a gamma distribution. A fixed covariate list and ICU-site clustering with robust variance were utilised for model fitting with split-sample determination (80%) and validation (20%) data sets, and model simulation was undertaken to establish over-fitting (Copas test). Indices of model specification using Bayesian information criterion [BIC: lower values preferred] and residual analysis as well as predictive performance (R2, concordance correlation coefficient (CCC), mean absolute error [MAE]) were established for each estimator. Results The data-set consisted of 111663 patients from 131 ICUs; with mean(SD) age 60.6(18.8) years, 43.0% were female, 40.7% were mechanically ventilated and ICU mortality was 7.8%. ICU length-of-stay was 3.4(5.1) (median 1.8, range (0.17-60)) days and demonstrated marked kurtosis and right skew (29.4 and 4.4 respectively). BIC showed considerable spread, from a maximum of 509801 (OLS-raw scale) to a minimum of 210286 (LMM). R2 ranged from 0.22 (LMM) to 0.17 and the CCC from 0.334 (LMM) to 0.149, with MAE 2.2-2.4. Superior residual behaviour was established for the log-scale estimators. There was a general tendency for over-prediction (negative residuals) and for over-fitting, the exception being the GLM negative binomial estimator. The mean-variance function was best approximated by a quadratic function, consistent with log-scale estimation; the link function was estimated (EEE) as 0.152(0.019, 0.285), consistent with a fractional-root function. Conclusions For ICU length of stay, log-scale estimation, in particular the LMM, appeared to be the most consistently performing estimator(s). Neither the GLM variants nor the skew-regression estimators dominated.
    BMC Medical Research Methodology 05/2012; 12(1):68. DOI:10.1186/1471-2288-12-68 · 2.17 Impact Factor
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    ABSTRACT: Hypokalaemia is a common problem in critically ill patients, which if untreated, can result in dysrhythmia or another adverse outcome. We assessed the safety and efficacy of a continuous infusion of potassium chloride versus an existing intermittent infusion regimen. In this open-label randomised parallel-arm active-controlled pilot study, critically ill adults with plasma potassium concentration between 2.5 and 3.8 mmol/l were randomised to receive either a continuous infusion or intermittent infusions of potassium chloride for establishment and maintenance of normokalaemia. The primary outcome was the mean difference in plasma potassium concentration over time between the two study arms as assessed by a linear mixed-effects model. Although a statistically significant difference was observed (0.22 mmol/l; 95% confidence interval 0.17, 0.27; P <0.0001), this did not reach the pre-determined level indicative of a treatment effect (0.5 mmol/l). The continuous group demonstrated less variance in (mean) plasma potassium as reflected in narrower confidence intervals in a prediction-by-time model. The incidence rate ratio of dysrhythmia, assessed by a mixed-effects Poisson model, was similar in each group (0.62; 95% confidence interval 0.32, 1.21; P=0.16). We recorded no adverse events directly attributable to infusion of potassium chloride in either study arm. Although titrated continuous infusion did not demonstrate a clinically important difference by comparison with intermittent infusions for the maintenance of normokalaemia, there was more consistent control of plasma potassium with no observed complications or adverse events. Therefore, this trial showed an acceptable efficacy and safety profile for the continuous infusion regimen, suggesting scope for further study.
    Anaesthesia and intensive care 05/2012; 40(3):433-41. · 1.47 Impact Factor
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    ABSTRACT: Hyperfiltration is widely regarded as a contributing factor to the development of microalbuminuria and progressive nephropathy in type 1 diabetes. However, recent studies have questioned this conclusion. To address this conflicting evidence, we examined the association between hyperfiltration and progression to microalbuminuria in 2,318 adults with type 1 diabetes. We also compared the estimated GFR in our diabetic patients with rates observed in 6,247 adults from the Finnish general population, using age- and sex-specific z scores. The distribution of estimated GFR in adults with type 1 diabetes and normoalbuminuria was not significantly different from that expected in the general population (p = 0.51, Mann-Whitney test). Type 1 diabetic patients with a higher estimated GFR were also no more likely to develop microalbuminuria over a median of 5.2 years of follow-up than those with normal estimated GFR. This was the case regardless of whether hyperfiltration was defined by an absolute threshold, deciles of estimated GFR or a z score, using creatinine- or cystatin-based clearance formulas in men or in women. Together with other studies, these data suggest that creatinine- or cystatin-based estimates of GFR do not predict the development of microalbuminuria in patients with type 1 diabetes. Moreover, in the absence of incipient or overt nephropathy, conventionally determined renal function in patients with type 1 diabetes appears no different from that in the general population. This is hardly surprising, given that these individuals, by all definitions, do not have kidney disease.
    Diabetologia 02/2012; 55(5):1505-13. DOI:10.1007/s00125-012-2485-5 · 6.88 Impact Factor
  • Petra L Graham · John L Moran
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    ABSTRACT: Results of meta-analyses typically conclude that future large studies may be mandated. However, the predictive ability of these estimates is deficient. We explored meta-analytic prediction intervals as means for providing a clear and appropriate future treatment summary reflecting current estimates. A meta-epidemiological study of binary outcome critical care meta-analyses published between 2002 and 2010. Computation of 95% DerSimonian-Laird and Bayesian random-effects meta-analytic confidence intervals (CI) and 95% credible intervals (CrI), respectively, and frequentist (PI) and Bayesian (PrI) prediction intervals for odds ratio (OR) and risk ratio (RR) were undertaken. Bayesian calculations included the probability that the OR and RR point estimates ≥1. Seventy-two meta-analyses from 70 articles were identified, containing between three and 80 studies each, with median nine studies. For both frequentist and Bayesian settings, 49-69% of the meta-analyses excluded the null. All significant CrI had high probabilities of efficacy/harm. The number of PI vs. PrI excluding 1 was 25% vs. 3% (OR), 26% vs. 3% (RR) of the total meta-analyses. Unsurprisingly, PI/PrI width was greater than CI/CrI width and increased with increasing heterogeneity and combination of fewer studies. Robust meta-analytic conclusions and determination of studies warranting new large trials may be more appropriately signaled by consideration of initial interval estimates with prediction intervals. Substantial heterogeneity results in exceedingly wide PIs. More caution should be exercised regarding the conclusions of a meta-analysis.
    Journal of clinical epidemiology 01/2012; 65(5):503-10. DOI:10.1016/j.jclinepi.2011.09.012 · 5.48 Impact Factor
  • John L Moran · Patricia J Solomon
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    ABSTRACT: The mortality outcome of mechanical ventilation, a key intervention in the critically ill, has been variously reported to be determined by intensive care patient volume. We determined the volume-(mortality)-outcome relationship of mechanically ventilated patients whose records were contributed to the Australian and New Zealand Intensive Care Society Adult Patient Database. Retrospective cohort study of 208,810 index patient admissions from 136 Australian and New Zealand intensive care units in the same number of hospitals over the course of 1995-2009. The patient-volume effect on hospital mortality, overall and at the level of patient (nonsurgical, elective surgical, and emergency surgical) and intensive care unit (rural/regional, metropolitan, tertiary, and private) descriptors, was determined by random-effects logistic regression adjusting for illness severity and demographic and geographical predictors. Annualized patient volume was modeled both as a categorical (deciles) and, with calendar year, a continuous variable using fractional polynomials. The patients were of mean age of 59 yrs (SD, 19 yrs), Acute Physiology and Chronic Health Evaluation III score 66 (32), and 39.4% female, with a hospital mortality of 22.4%. Overall and at both the patient and intensive care unit descriptor levels, no progressive decline in mortality was demonstrated across the annual patient volume range (12-932). Over the whole database, mortality odds ratio for the last volume decile (801-932 patients) was 1.26 (95% confidence interval, 1.06-1.50; p = .009) compared with the first volume decile (12-101 patients). Calendar year mortality decreases were evident (odds ratio, 0.96; 95% confidence interval, 0.94-0.98; p = .0001). Using fractional polynomials, modest curvilinear mortality increases (range, 5%-8%) across the volume range were noted over the whole database for nonsurgical patients and at the tertiary intensive care unit level. No inverse volume-(mortality)-outcome relationship was apparent for ventilated patients in the Australian and New Zealand Intensive Care Society database. Mechanisms for mortality increments with patient volume were not identified but warrant further study.
    Critical care medicine 11/2011; 40(3):800-12. DOI:10.1097/CCM.0b013e318236f2af · 6.15 Impact Factor

Publication Stats

3k Citations
570.93 Total Impact Points

Institutions

  • 1995–2014
    • University of Adelaide
      • School of Mathematical Sciences
      Tarndarnya, South Australia, Australia
  • 1988–2014
    • The Queen Elizabeth Hospital
      • • Intensive Care Unit
      • • Department of Cardiology
      Tarndarnya, South Australia, Australia
  • 2010
    • National University Health System
      Singapore
  • 2009
    • Royal Adelaide Hospital
      • Intensive Care Unit
      Tarndarnya, South Australia, Australia
  • 2007
    • Christian Medical College Vellore
      • Department of Intensive care medicine
      Vellore, State of Tamil Nadu, India