Rural Clinical School - Research Publications
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ItemDiscrepancies in Control Group Mortality Rates Within Studies Assessing Topical Antibiotic Strategies to Prevent Ventilator-Associated Pneumonia: An Umbrella Review.(Ovid Technologies (Wolters Kluwer Health), 2020-01)OBJECTIVES: To test the postulate that concurrent control patients within ICUs studying topical oropharyngeal antibiotics to prevent ventilator-associated pneumonia and mortality would experience spillover effects from the intervention. DATA SOURCES: Studies cited in 15 systematic reviews of various topical antibiotic and other infection prevention interventions among ICU patients. STUDY SELECTION: Studies of topical antibiotics, stratified into concurrent control versus nonconcurrent control designs. Studies of nondecontamination-based infection prevention interventions provide additional points of reference. Studies with no infection prevention intervention provide the mortality benchmark. Data from additional studies and data reported as intention to treat were used within sensitivity tests. DATA EXTRACTION: Mortality incidence proportion data, mortality census, study characteristics, group mean age, ICU type, and study publication year. DATA SYNTHESIS: Two-hundred six studies were included. The summary effect sizes for ventilator-associated pneumonia and mortality prevention derived in the 15 systematic reviews were replicated. The mean ICU mortality incidence for concurrent control groups of topical antibiotic studies (28.5%; 95% CI, 25.0-32.3; n = 41) is higher versus the benchmark (23.7%; 19.2-28.5%; n = 34), versus nonconcurrent control groups (23.5%; 19.3-28.3; n = 14), and versus intervention groups (24.4%; 22.1-26.9; n = 62) of topical antibiotic studies. In meta-regression models adjusted for group-level characteristics such as group mean age and publication year, concurrent control group membership within a topical antibiotic study remains associated with higher mortality (p = 0.027), whereas other group memberships, including membership within an antiseptic study, are each neutral (p = not significant). CONCLUSIONS: Within topical antibiotic studies, the concurrent control group mortality incidence proportions are inexplicably high, whereas the intervention group mortality proportions are paradoxically similar to a literature-derived benchmark. The unexplained ventilator-associated pneumonia and mortality excess in the concurrent control groups implicates spillover effects within studies of topical antibiotics. The apparent ventilator-associated pneumonia and mortality prevention effects require cautious interpretation.
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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.
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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.
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ItemForrest plots or caterpillar plots?(ELSEVIER SCIENCE INC, 2020-05)
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ItemCandida-Acinetobacter-Pseudomonas Interaction Modelled within 286 ICU Infection Prevention Studies(MDPI, 2020-12)BACKGROUND: Whether Candida interacts to enhance the invasive potential of Acinetobacter and Pseudomonas bacteria cannot be resolved within individual studies. There are several anti-septic, antibiotic, anti-fungal, and non-decontamination-based interventions to prevent ICU acquired infection. These effective prevention interventions would be expected to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies simulates a multi-centre natural experiment with which to evaluate Candida, Acinetobacter and Pseudomonas interaction (CAPI). METHODS: Eight Candidate-generalized structural equation models (GSEM), with Candida, Pseudomonas and Acinetobacter colonization as latent variables, were confronted with blood culture and respiratory tract isolate data derived from >400 groups derived from 286 infection prevention studies. RESULTS: Introducing an interaction term between Candida colonization and each of Pseudomonas and Acinetobacter colonization improved model fit in each case. The size of the coefficients (and 95% confidence intervals) for these interaction terms in the optimal Pseudomonas (+0.33; 0.22 to 0.45) and Acinetobacter models (+0.32; 0.01 to 0.5) were similar to each other and similar in magnitude, but contrary in direction, to the coefficient for exposure to topical antibiotic prophylaxis (TAP) on Pseudomonas colonization (-0.45; -0.71 to -0.2). The coefficient for exposure to topical antibiotic prophylaxis on Acinetobacter colonization was not significant. CONCLUSIONS: GSEM modelling of published ICU infection prevention data supports the CAPI concept. The CAPI model could account for some paradoxically high Acinetobacter and Pseudomonas infection incidences, most apparent among the concurrent control groups of TAP studies.
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ItemNo Preview AvailableIncidence of coagulase-negative staphylococcal bacteremia among ICU patients: decontamination studies as a natural experiment(SPRINGER, 2020-04)The epidemiology of coagulase-negative staphylococcal (CNS) bacteremia among adult ICU patients remains unclear. Decontamination studies among ICU patients provide a unique opportunity to study the impacts of different diagnostic criteria, exposure to various decontamination interventions, and various other factors, on its incidence over three decades. Decontamination studies among ICU patients reporting CNS bacteremia incidence data were obtained mostly from recent systematic reviews. The CNS bacteremia incidence within component (control and intervention) groups of decontamination studies was benchmarked versus studies without intervention (observational groups). The impacts of antibiotic versus chlorhexidine decontamination interventions, control group concurrency, publication year, and diagnostic criteria were examined in meta-regression models. Among non-intervention (observational) studies which did versus did not specify stringent (≥ 2 positive blood cultures) diagnostic criteria, the mean CNS bacteremia incidence per 100 patients (and 95% CI; n) is 1.3 (0.9-2.0; n = 23) versus 3.6 (1.8-6.9; n = 8), respectively, giving an overall benchmark of 1.8 (1.2-2.4; n = 31). Versus the benchmark incidence, the mean incidence is high among concurrent control (5.7; 3.6-9.1%) and intervention (5.2; 3.6-6.9%), but not non-concurrent control (1.0; 0.4-3.9%) groups of 21 antibiotic studies, nor among eleven component groups of chlorhexidine studies. This high incidence remained apparent (p < 0.01) in meta-regression models adjusting for group wide factors such as diagnostic criteria and publication year. The incidence of CNS bacteremia within both intervention and concurrent (but not non-concurrent) control groups of antibiotic-based decontamination studies are unusually high even accounting for variable diagnostic criteria and other factors.
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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.
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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.
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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.