Rural Clinical School - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 13
-
ItemRecommended pre-analytical plasma glucose sampling methodology may distort gestational diabetes mellitus prevalence: implications for diagnostic thresholds(WILEY, 2019-10)AIM: Current International Association of the Diabetes and Pregnancy Study Groups/World Health Organization gestational diabetes mellitus (GDM) diagnostic thresholds are based on a landmark study in which the pre-analytical plasma glucose sampling methodology is unclear. Worldwide, plasma glucose pre-analytical sampling methodology practices are divergent. We considered the effects of pre-analytical plasma glucose sampling methodology on GDM prevalence and gestational outcomes. METHODS: This is a retrospective observational cohort study of 1178 pregnant women undergoing an oral glucose tolerance test (OGTT). Of the 1178 pregnant women, a subset of 892 non-GDM women with singleton births undergoing OGTT between 24 and 28 weeks' gestation were investigated for large for gestation age (LGA) outcomes. OGTT were determined using traditional methods (sodium fluoride tubes batched at roomed temperature). We modelled the potential effects of using a recommended pre-analytical plasma glucose methodology (lyophilized citrate tubes) on GDM prevalence. RESULTS: The GDM prevalence in our cohort was 13.5%. The incidence of LGA showed a linear association with maternal plasma glucose that was similar to the association observed in the Hyperglycemia and Adverse Pregnancy Outcome study. Frequency of LGA exceeded 10% at HAPO glucose category 4 (fasting, 4.8 to 4.9 mmol/l; 1-h, 8.7 to 9.5 mmol/l) for fasting and 1-h plasma glucose. The use of a recommended pre-analytical method is projected to increase the prevalence of GDM to 39.2%. CONCLUSION: We challenge the consensus that recommended pre-analytical plasma glucose methodologies are optimal for the accurate diagnosis of GDM. Recommended pre-analytical plasma glucose methods may profoundly over-diagnose GDM. Centres using recommended pre-analytical plasma glucose methodologies may need to reappraise their diagnostic thresholds.
-
ItemNon-invasive ventilation of patients with acute asthma(WILEY, 2019-02)A retrospective observational study of 21 patients admitted to the Intensive Care Unit (ICU) of Frankston Hospital with acute asthma between 2011 and 2014 was undertaken. We report the outcomes for three groups of patients; those that did (n = 7) or did not (n = 6) receive initial therapy with non-invasive ventilation (NIV) together with those that received invasive ventilation (n = 8). Patients successfully managed with NIV alone experienced a shorter ICU and hospital stay versus those who required invasive ventilation.
-
ItemEndotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders(BMC, 2012)INTRODUCTION: The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship. METHODS: Published studies with ≥ 10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥ 1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots. RESULTS: Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal. CONCLUSIONS: The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies.
-
ItemParadoxical ventilator associated pneumonia incidences among selective digestive decontamination studies versus other studies of mechanically ventilated patients: benchmarking the evidence base(BMC, 2011)INTRODUCTION: Selective digestive decontamination (SDD) appears to have a more compelling evidence base than non-antimicrobial methods for the prevention of ventilator associated pneumonia (VAP). However, the striking variability in ventilator associated pneumonia-incidence proportion (VAP-IP) among the SDD studies remains unexplained and a postulated contextual effect remains untested for. METHODS: Nine reviews were used to source 45 observational (benchmark) groups and 137 component (control and intervention) groups of studies of SDD and studies of three non-antimicrobial methods of VAP prevention. The logit VAP-IP data were summarized by meta-analysis using random effects methods and the associated heterogeneity (tau2) was measured. As group level predictors of logit VAP-IP, the mode of VAP diagnosis, proportion of trauma admissions, the proportion receiving prolonged ventilation and the intervention method under study were examined in meta-regression models containing the benchmark groups together with either the control (models 1 to 3) or intervention (models 4 to 6) groups of the prevention studies. RESULTS: The VAP-IP benchmark derived here is 22.1% (95% confidence interval; 95% CI; 19.2 to 25.5; tau2 0.34) whereas the mean VAP-IP of control groups from studies of SDD and of non-antimicrobial methods, is 35.7 (29.7 to 41.8; tau2 0.63) versus 20.4 (17.2 to 24.0; tau2 0.41), respectively (P < 0.001). The disparity between the benchmark groups and the control groups of the SDD studies, which was most apparent for the highest quality studies, could not be explained in the meta-regression models after adjusting for various group level factors. The mean VAP-IP (95% CI) of intervention groups is 16.0 (12.6 to 20.3; tau2 0.59) and 17.1 (14.2 to 20.3; tau2 0.35) for SDD studies versus studies of non-antimicrobial methods, respectively. CONCLUSIONS: The VAP-IP among the intervention groups within the SDD evidence base is less variable and more similar to the benchmark than among the control groups. These paradoxical observations cannot readily be explained. The interpretation of the SDD evidence base cannot proceed without further consideration of this contextual effect.
-
Item
-
ItemTowards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect(MDPI, 2013-12)Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged.
-
ItemUnusually High Incidences of Staphylococcus aureus Infection within Studies of Ventilator Associated Pneumonia Prevention Using Topical Antibiotics: Benchmarking the Evidence Base(MDPI, 2018-03)Selective digestive decontamination (SDD, topical antibiotic regimens applied to the respiratory tract) appears effective for preventing ventilator associated pneumonia (VAP) in intensive care unit (ICU) patients. However, potential contextual effects of SDD on Staphylococcus aureus infections in the ICU remain unclear. The S. aureus ventilator associated pneumonia (S. aureus VAP), VAP overall and S. aureus bacteremia incidences within component (control and intervention) groups within 27 SDD studies were benchmarked against 115 observational groups. Component groups from 66 studies of various interventions other than SDD provided additional points of reference. In 27 SDD study control groups, the mean S. aureus VAP incidence is 9.6% (95% CI; 6.9-13.2) versus a benchmark derived from 115 observational groups being 4.8% (95% CI; 4.2-5.6). In nine SDD study control groups the mean S. aureus bacteremia incidence is 3.8% (95% CI; 2.1-5.7) versus a benchmark derived from 10 observational groups being 2.1% (95% CI; 1.1-4.1). The incidences of S. aureus VAP and S. aureus bacteremia within the control groups of SDD studies are each higher than literature derived benchmarks. Paradoxically, within the SDD intervention groups, the incidences of both S. aureus VAP and VAP overall are more similar to the benchmarks.
-
ItemUnusually High Incidences of Pseudomonas Bacteremias Within Topical Polymyxin-Based Decolonization Studies of Mechanically Ventilated Patients: Benchmarking the Literature(OXFORD UNIV PRESS INC, 2018-11)BACKGROUND: Topical polymyxin (PM)-based regimens to decolonize patients receiving prolonged mechanical ventilation (MV) have been widely studied. However, paradoxical bacteremia incidences remain unexplained. METHODS: The literature was searched for studies of topical PM-based regimens used to decontaminate MV patients reporting incidences of overall and Pseudomonas bacteremia data. In addition, observational groups without any intervention and trials of various interventions other than topical PM (non-PM studies) served to provide external benchmarks and additional points of reference, respectively. The bacteremia incidences were extracted from the control and intervention (component) groups of these studies and compared with metaregression using generalized estimating equation methods. RESULTS: The summary odds ratio derived from studies of topical PM-based interventions against overall bacteremia was 0.60 (95% confidence interval [CI], 0.53-0.69). Benchmark incidences per 100 MV patients for overall (mean, 8.9%; 95% CI, 6.9% to 10.9%) and Pseudomonas (mean, 0.7%; 95% CI, 0.5% to 1.1%) bacteremia were derived from 16 observational studies. By contrast, among 17 studies of topical PM, the mean incidences among control groups for overall (mean, 15.3%; 95% CI, 11.5% to 20.3%) and Pseudomonas (mean, 1.6%; 95% CI, 0.9% to 3.1%) bacteremia were both higher, whereas these incidences in the intervention groups for both topical PM and non-PM studies were in each case more similar to the respective benchmarks. These paradoxical incidences cannot readily be explained in metaregression models. CONCLUSIONS: Paradoxically, despite an apparent prevention effect of topical PM-based methods against bacteremia overall, the incidences of Pseudomonas bacteremia within the component groups of these studies are unusually high vs literature-derived benchmarks.
-
ItemWorld-Wide Variation in Incidence of Staphylococcus aureus Associated Ventilator-Associated Pneumonia: A Meta-Regression(MDPI, 2018-03)Staphylococcus aureus (S. aureus) is a common Ventilator-Associated Pneumonia (VAP) isolate. The objective here is to define the extent and possible reasons for geographic variation in the incidences of S. aureus-associated VAP, MRSA-VAP and overall VAP. A meta-regression model of S. aureus-associated VAP incidence per 1000 Mechanical Ventilation Days (MVD) was undertaken using random effects methods among publications obtained from a search of the English language literature. This model incorporated group level factors such as admission to a trauma ICU, year of publication and use of bronchoscopic sampling towards VAP diagnosis. The search identified 133 publications from seven worldwide regions published over three decades. The summary S. aureus-associated VAP incidence was 4.5 (3.9-5.3) per 1000 MVD. The highest S. aureus-associated VAP incidence is amongst reports from the Mediterranean (mean; 95% confidence interval; 6.1; 4.1-8.5) versus that from Asian ICUs (2.1; 1.5-3.0). The incidence of S. aureus-associated VAP varies by up to three-fold (for the lowest versus highest incidence) among seven geographic regions worldwide, whereas the incidence of VAP varies by less than two-fold. Admission to a trauma unit is the most important group level correlate for S. aureus-associated VAP.
-
ItemTopical antibiotics as a major contextual hazard toward bacteremia within selective digestive decontamination studies: a meta-analysis(BMC, 2014-12-31)BACKGROUND: Among methods for preventing pneumonia and possibly also bacteremia in intensive care unit (ICU) patients, Selective Digestive Decontamination (SDD) appears most effective within randomized concurrent controlled trials (RCCT's) although more recent trials have been cluster randomized. However, of the SDD components, whether protocolized parenteral antibiotic prophylaxis (PPAP) is required, and whether the topical antibiotic actually presents a contextual hazard, remain unresolved. The objective here is to compare the bacteremia rates and patterns of isolates in SDD-RCCT's versus the broader evidence base. METHODS: Bacteremia incidence proportion data were extracted from component (control and intervention) groups decanted from studies investigating antibiotic (SDD) or non-antibiotic methods of VAP prevention and summarized using random effects meta-analysis of study and group level data. A reference category of groups derived from purely observational studies without any prevention method under study provided a benchmark incidence. RESULTS: Within SDD RCCTs, the mean bacteremia incidence among concurrent component groups not exposed to PPAP (27 control; 17.1%; 13.1-22.1% and 12 intervention groups; 16.2%; 9.1-27.3%) is double that of the benchmark bacteremia incidence derived from 39 benchmark groups (8.3; 6.8-10.2%) and also 20 control groups from studies of non-antibiotic methods (7.1%; 4.8 - 10.5). There is a selective increase in coagulase negative staphylococci (CNS) but not in Pseudomonas aeruginosa among bacteremia isolates within control groups of SDD-RCCT's versus benchmark groups with data available. CONCLUSIONS: The topical antibiotic component of SDD presents a major contextual hazard toward bacteremia against which the PPAP component partially mitigates.