BACKGROUND:Timely active empirical therapy (AET) may improve outcomes following bloodstream infection. In high-income settings, low pediatric mortality following gram-negative bloodstream infection (GNBSI) limits its value as a sole endpoint. Composite measures that incorporate multiple clinically relevant outcomes may detect differences more readily. We assessed the effect of AET on clinical outcomes in pediatric GNBSI. METHODS:We analyzed data from a prospective surveillance study of hospitalized Australian children with GNBSI. A ranked composite endpoint included 30-day all-cause mortality (30D ACM), time to death, intensive care unit (ICU) admission, relapse, and hospitalization duration. Baseline differences were adjusted using inverse probability of treatment weighting. Generalized pairwise comparison (GPC) generated win statistics. Analyses were stratified by comorbidity, acquisition setting, and organism. RESULTS:Active empirical therapy occurred in 597 episodes and inactive empirical therapy (IET) in 62. Median treatment duration was similar (AET 10 vs IET 11 days, P = .44). Generalized pairwise comparison analysis showed an adjusted win ratio of 1.04 (95% CI .72-1.52, P = .83), indicating no significant difference. Contributions from each composite component (AET vs IET) were the following: 30D ACM (2.2% vs 1.3%), time to death (0.02% vs 0.01%), ICU admission (7.5% vs 9.1%), relapse (2.6% vs 1.4%), and hospitalization duration (37.3% vs 36.0%). Stratified estimates were similar for comorbidity and acquisition. CONCLUSIONS:In this large multicenter pediatric GNBSI cohort, AET was not associated with improved outcomes. In high-resource settings, the impact of initial antibiotic activity may be smaller than traditionally assumed, though timely effective therapy remains essential for severe illness and low-resource settings.

BACKGROUND:Infants born very preterm frequently experience neurodevelopmental challenges. Early detection enables provision of targeted interventions to improve outcomes. Early neonatal and term-equivalent age (TEA) MRI and 3-5-month corrected age (CA) Prechtl Motor Optimality Score - revised (MOS-R) are useful prognostic tools, however structure-function relationships between them are not well established. METHODS:Infants born <31 weeks' gestation underwent MRI at 32-weeks postmenstrual age and TEA. Modified Kidokoro MRI scoring generated white matter, cortical grey matter, deep grey matter and cerebellar scores which were summed to produce a global score. Infant MOS-R was assessed from videos recorded at 3-4 months' CA. Relationships between MRI abnormality scores and MOS-R and absent fidgety general movements were modelled using regression analysis. RESULTS:Brain MRI was performed at 32-weeks in 249 infants, of whom 221 had TEA MRI and 225 had a MOS-R. For 32-week MRI, white matter, deep grey matter and global scores were related to MOS-R (global βMOS-R = -0.27, 95% confidence interval [CI] -0.46, -0.08; p = 0.006) and absent fidgety movements (global odds ratio = 1.23, 95%CI 1.07, 1.40; p = 0.003). For TEA MRI, white matter and global scores were related to MOS-R (global βMOS-R = -0.26, 95%CI -0.47, -0.06; p = 0.01) and absent fidgety movements (global odds ratio = 1.23, 95%CI 1.05, 1.42; p = 0.008). In multivariable model including global scores from both timepoints, term equivalent MRI scores remained related to MOS-R (βMOS-R = -0.41, 95%CI -0.72, 0.10; p = 0.009). CONCLUSION:Early and TEA MRI are related to MOS-R and general movements assessment. Term MRI global scores are independently related to MOS-R at 3-4 months' corrected age. This has implications for prioritising infants with poorer MRI scores for early assessment and that poorer MOS-R scores may be a manifestation of changes to brain structure and due to preterm birth.

BACKGROUND:Gram-negative bacterial bloodstream infections (BSI) cause substantial mortality and morbidity. The GAME CHANGER trial compared cefiderocol with standard of care (SOC) for Gram-negative BSI, with 14-day all-cause mortality (ACM) as the primary endpoint. We evaluated cefiderocol versus SOC integrating efficacy and safety outcomes using desirability of outcome ranking (DOOR) and generalized pairwise comparisons (GPC). METHODS:Composite endpoints were prespecified prior to data review. The DOOR endpoint included treatment failure, infectious complications, serious adverse events (SAEs) and 90-day ACM, with functional improvement as a tiebreaker. The GPC approach included ACM at 30-days, clinical failure, SAEs, functional improvement and hospitalization duration. Analyses were conducted in the main population and carbapenem-resistant subset. RESULTS:The DOOR composite in the main population resulted in a probability of a more desirable outcome with cefiderocol of 50.4% (95% CI 45.6, 55.1). The analysis with GPC resulted in a win ratio and win odds of 1.04 (95% CI: 0.85, 1.28) and net treatment benefit (NTB) of 2.1% (95% CI: -8.0%, 12.2%). In the carbapenem-resistant subset, the DOOR probability with cefiderocol was 46.8% (95% CI 37.4%, 56.1%). The analysis with GPC resulted in a win ratio and win odds of 0.90 (95% CI: 0.60, 1.34) and NTB of -5.4% (95% CI: -25.3%, 14.5%). CONCLUSIONS:In adults with Gram-negative bacterial BSI, cefiderocol was not superior to SOC based on DOOR or GPC analyses in both the main population and carbapenem-resistant subset. Integrating efficacy, safety and functional outcomes using these approaches provides a more comprehensive assessment than mortality alone.

In random-effects meta-analysis, the between-study heterogeneity variance, $\tau <^>2$ , is often reported but is not easy to interpret. For meta-analyses of differences (such as mean differences, standardized mean differences, or risk differences), the standard deviation (SD), $\tau $ , indicates the extent to which studies' true effects vary about their average. For meta-analyses of (natural) log-transformed measures of effect (such as log risk ratios [RRs]), we explain how the geometric SD, $\exp (\tau )$ , is helpful to understand how untransformed measures (such as RRs) vary multiplicatively about their average. We recommend that authors and software developers report $\tau $ for differences and $\exp (\tau )$ for ratios, rather than $\tau <^>2$ . This will facilitate the interpretation of the magnitude of heterogeneity values, for example, the interpretation of heterogeneity estimates and confidence intervals beyond simple binary statements about the presence or absence of heterogeneity.

BACKGROUND:Bloodstream infections caused by bacteria with carbapenem resistance are associated with high mortality. Cefiderocol has broad in vitro activity against carbapenem-resistant Gram-negative bacilli. We aimed to assess whether cefiderocol was non-inferior or superior to standard-of-care antibiotics in preventing mortality in patients with bloodstream infection caused by Gram-negative bacilli. METHODS:The GAME CHANGER trial was an open-label, parallel-group, randomised clinical trial in which patients with health-care-associated or hospital-acquired Gram-negative bloodstream infection were recruited from 17 tertiary hospitals with more than 500 beds in Australia, Malaysia, Singapore, Taiwan, Thailand, and Türkiye. Adult patients (aged ≥21 years in Singapore or ≥18 years elsewhere) with positive blood cultures and Gram-negative bacilli seen on Gram stain were eligible. Participants were randomly assigned in a 1:1 ratio to cefiderocol (2 g intravenously every 8 h) or standard of care (chosen by the patient's clinical team) using an online randomisation tool with strata defined by severity of comorbidities and region, with random permuted blocks of unequal size. Patients, treating clinicians, and site investigators were not masked to treatment. The primary outcome was all-cause mortality at 14 days after randomisation. All outcomes were analysed in participants who received at least one dose of assigned antibiotic, grew an aerobic Gram-negative bacillus from the index blood culture, and did not withdraw consent before day 14. The non-inferiority margin was 10%; superiority was to be assessed if non-inferiority was shown, and was evaluated in both the main analysis population and in patients with at least one carbapenem-resistant organism causing bloodstream infection. Missing data were handled by imputing data. The trial was registered on ClinicalTrials.gov (NCT03869437) and is closed to new participants. FINDINGS:513 participants were enrolled between Nov 12, 2019, and Oct 31, 2023 (210 [42%] female and 294 [58%] male). 256 patients were randomly assigned to cefiderocol and 257 were assigned to standard of care. Nine patients (six in the cefiderocol group and three in the standard-of-care group) were excluded from further analysis because they withdrew consent or their blood cultures did not grow an aerobic Gram-negative bacillus. Thus, 504 participants were included in the main analysis population. 20 (8%) of 250 patients in the cefiderocol group had died at 14 days compared with 17 (7%) of 254 patients in the standard-of-care group (absolute risk difference 1%, 95% CI -3 to 6). 127 (25%) of 504 patients had an infection with a carbapenem-resistant organism; at 14 days, nine (14%) of 64 patients in the cefiderocol group had died compared with six (10%) of 63 patients in the standard-of-care group (5%, -7 to 16). There were five treatment-emergent serious adverse events that were either probably or possibly related to the study drug (all in the cefiderocol group): delirium, stupor, rigors, abnormal liver chemistry, and rash, all of which resolved without treatment (except for the rash, which required hydrocortisone and anti-histamines). INTERPRETATION:Among patients with a hospital-acquired or health-care-associated Gram-negative bloodstream infection, cefiderocol resulted in non-inferior 14-day mortality compared with standard of care. Adverse events were similar between groups, although those thought to be related to the study drug only occurred in the cefiderocol group. In both the main analysis population and the carbapenem-resistant subset, cefiderocol was not superior to standard of care. This evidence suggests that cefiderocol is efficacious in patients with health-care-associated Gram-negative bloodstream infection who are at high risk of antibiotic resistance, but more evidence is required to define its efficacy when carbapenem-resistant organisms are the cause. FUNDING:The University of Queensland, Shionogi, The Henderson Foundation, and the National Medical Research Council (Singapore).

AIM:To compare active upper-limb therapies for children with cerebral palsy using a network meta-analysis. METHOD:For this systematic review, five electronic databases were searched up to 2nd September 2024. Outcomes pertaining to improved hand use (Assisting Hand Assessment, AHA), goal attainment (Canadian Occupational Performance Measure, COPM), and self-care were analysed with therapies classified into 15 discrete categories. RESULTS:Quantitative analysis of 48 randomized controlled trials (n = 1629) was performed. Compared with control, treatment effect on hand function (AHA mean difference, standard error) was greater for bimanual therapy (BiM: 4.6, 1.0), modified constraint-induced movement therapy (mCIMT; 4.0, 1.0), goal-directed therapy (GDT; 3.8, 1.6), action observation (4.9, 1.1), and mCIMT + intensive (7.4, 2.5). For COPM performance, treatment effect was greater for cognitive orientation to occupational performance (CO-OP; 5.9, 1.4), BiM (3.3, 0.4), mCIMT (2.5, 0.5), GDT (2.3, 0.7), mirror therapy (2.6, 1.2), and mCIMT + GDT (4.2, 1.1). For self-care, treatment effect (standardized mean difference, standard error) was greater for BiM (0.39, 0.10), mCIMT (0.37, 0.08), and mCIMT + GDT (0.43, 0.32). INTERPRETATION:BiM and mCIMT were confirmed as effective interventions for hand function, self-care, and individual goal achievement. Mirror therapy, CO-OP, and four different combination approaches feature single studies, small sample sizes, and high risk of bias, requiring further clinical trials to confirm efficacy.

Maternal and early childhood nutrition is foundational in setting the course for lifetime metabolic and disease outcomes. Food security influences the achievement of optimal diets; however, little is known about how traditional food intake may influence this dynamic for Aboriginal and Torres Strait Islander people living in remote communities. This study describes diets and food security status of Aboriginal and Torres Strait Islander pregnant and breastfeeding women and children 6 months to 5 years in remote communities in Australia, and explores interactions between diet quality, food security and traditional food consumption. Baseline data from a trial testing a discount on healthy foods and drinks were used. Participants from eight communities (four each in coastal Cape York, Queensland and desert Central Australia, Northern Territory) participated in June–September 2021. A validated food frequency questionnaire was used to assess usual intake and calculate a diet quality score. A modified version of the United States Department of Agriculture 18-item Household Food Security Scale Module measured food security status. A model was fitted to explore the interactions between diet quality, food security and traditional food consumption. Complete dietary data were available for 471 participants from 294 households. Average reported food group intakes of children were similar to recommended patterns, however except for adequate meat intakes those of women were not; mean diet quality scores were 23

Background:Healthy Stores 2020 tested a co-designed strategy restricting retailer merchandising of unhealthy foods in a community-level pragmatic, partially randomised, parallel group trial in 20 remote Australian Aboriginal and Torres Strait Islander community stores. We aimed to evaluate the impact of Healthy Stores 2020 on free sugar sales 24-weeks post-trial. Methods:Twenty stores were randomly assigned by a statistician using a single sequence of random assignments to the intervention group, in which a strategy restricted merchandising of unhealthy food (either six or seven strategy components), or to a control group of usual retail practice. The trial was done in partnership with an Indigenous organisation operating in remote Australia. In the post-trial period (24 weeks), immediately following the 25-week RCT, intervention stores (n = 10) continued the strategy but with no external implementation support, and control stores (n = 10) continued usual practice. The primary outcome was impact on purchases (weekly sales data) of free sugars from all foods and beverages (g/MJ) using mixed models. Secondary outcomes included total food and beverage dollars and gross profit (AUD$) and strategy implementation (number of strategies with full implementation assessed via photographic data collected). Trial registration, ACTRN12618001588280. Findings:We observed a difference in sales of total free sugars to energy between the treatment and control groups post-trial (-4.6%, 95% CI -7.1, -1.9). Between group differences in total food and beverage and gross profit dollars were 7.0% (0.9, 13.5) and 11.4% (4.6, 18.6), respectively. Two intervention stores had full implementation of all strategy components and eight intervention stores had compliance with at least four of the seven strategy components at post-trial end. Interpretation:A health-enabling retail intervention showed an effect on sugar reduction in the post-trial period without adversely impacting profit. Funding:Australian National Health and Medical Research Council.

Statistics on the natural log scale, such as differences, regression coefficients, and standard deviations, frequently arise when analyzing log-transformed data or modeling binary, count, or time-to-event data. The statistical properties of log-transformed estimators (for example, log odds ratio estimators) frequently appear in statistical articles. Understanding the magnitude of these quantities can be useful. Remarkably, many can be readily interpreted, without exponentiation. In this note, we introduce four new interpretations. While a log-scale standard deviation can be interpreted as an approximate coefficient of variation describing variation about an arithmetic mean, we argue it can be more useful to interpret it exactly as a "standard relative deviation" describing variation about a geometric mean. For positive-valued estimators, we show how the standard error of a log-transformed estimator can be interpreted as the "standard relative error" describing the precision of the untransformed estimator. We also show how the bias and root mean squared error of a the log-transformed estimator can be interpreted as the "mean relative error" and "root mean squared relative error" of the untransformed estimator. We illustrate the usefulness of our interpretations for (i) the usual scale parameter of a lognormal distribution, (ii) statistical properties of a log odds ratio estimator, and (iii) a single measure of the precision of an odds ratio estimator which agrees with its usual, asymmetric 95% confidence interval.

BACKGROUND:Infants born very preterm (VPT) are at increased risk of neurodevelopmental impairments. The Test of Infant Motor Performance (TIMP) is an assessment used to evaluate an infant's gross motor skills, however, understanding of its predictive accuracy in VPT infants is limited. AIMS:To determine the accuracy of the TIMP assessed at term equivalent age (TEA), and 3 months corrected age (CA), to identify motor or cognitive impairment at 12 months CA in VPT infants. METHOD:This prospective observational cohort study recruited 202 infants born at <31wks gestational age (GA). At TEA and 3 months CA the TIMP was performed. At 12 months CA the following neurodevelopmental assessments were conducted; Alberta Infant Motor Scale (AIMS), Neurological Sensory Motor Development Assessment (NSMDA) and Bayley Scale of Infant and Toddler Development 3rd edition (Bayley III). RESULTS:The TIMP had higher specificity than sensitivity across all four outcome measures. Using a cut off-of ≤ -0.5 at TEA, TIMP z-scores demonstrated low sensitivity and specificity for motor outcomes on the NSMDA (sensitivity 61 %, specificity 50 %), AIMS (sensitivity 59 %, specificity 50 %) and Bayley III (sensitivity 56 %, specificity 51 %). Area under the curve analyses showed that the TIMP assessed at 3 months had greater accuracy than at TEA in identifying neurodevelopmental impairments at 12 months CA. CONCLUSIONS:The TIMP assessed at TEA and 3 months CA correctly identified the majority of VPT infants without motor and cognitive impairments. However, it missed VPT infants who developed adverse neurodevelopmental outcomes by 12 months CA.

In this article, I review Create and Export Tables Using Stata, by Michael N. Mitchell (2025, Stata Press).

Introduction Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2–49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention.Methods and analysis We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function.Ethics and dissemination The Human Research Ethics Committees (HREC) of Children’s Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke’s Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations.Trial registration number ACTRN12621000315819.

Objectives Randomised controlled trials in serious infections typically use a single primary endpoint such as mortality. Ordinal or rank-based composite endpoints that evaluate mortality and other measures are a novel approach in clinical trials. Desirability of outcome ranking (DOOR) has been increasingly used in infectious disease trials and generalised pairwise comparisons (GPC) in cardiovascular trials. Methods We undertook a post hoc analysis of the MERINO trial, comparing piperacillin-tazobactam (PTZ) with meropenem in bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp. to demonstrate and compare the DOOR and GPC approaches. The primary composite endpoint included mortality, microbiological relapse and secondary infection. A further analysis was performed by adding length of stay as a tiebreaker. We applied DOOR to evaluate the DOOR distribution, probability and conducted partial credit analyses. We applied GPC to estimate the win statistics: win ratio, win odds and net benefit. A secondary analysis with both approaches was conducted with trial participants with PTZ susceptible isolates only as recorded by a central laboratory. Results The DOOR probability was 44.3 % (95 % CI: 40.8 %, 47.9 %), indicating superiority of meropenem. Partial credit analyses demonstrated similar conclusions across different patient preferences. The win ratio, win odds and net benefit were 0.40 (95 % CI: 0.23, 0.70; p = 0.001), 0.80 (95 % CI: 0.69, 0.92; p = 0.002) and −11.3 % (95 % CI:18.7 %, −4.0 %; p = 0.003), also indicating superiority of meropenem. With the addition of length of stay, the DOOR probability was 43.7 % (95 % CI: 37.9 %, 49.6 %) and the win ratio, win odds and net benefit were 0.77 (95 % CI: 0.60, 0.99; p = 0.04), 0.78 (95 % CI: 0.62, 0.99; p = 0.04), −12.1 % (95 % CI:23.8 %, −0.3 %; p = 0.04). Superiority of meropenem was not able to be demonstrated in the secondary analysis where only patients with PTZ susceptible isolates were assessed. Conclusions Though the functionality and interpretation of DOOR and GPC differ, both approaches can enhance the overall understanding of treatment effect in survivors beyond a single endpoint such as mortality.

BackgroundAboriginal and Torres Strait Islander communities in remote Australia have initiated bold policies for health-enabling stores. Benchmarking, a data-driven and facilitated 'audit and feedback' with action planning process, provides a potential strategy to strengthen and scale health-enabling best-practice adoption by remote community store directors/owners. We aim to co-design a benchmarking model with five partner organisations and test its effectiveness with Aboriginal and Torres Strait Islander community stores in remote Australia.MethodsStudy design is a pragmatic randomised controlled trial with consenting eligible stores (located in very remote Northern Territory (NT) of Australia, primary grocery store for an Aboriginal community, and serviced by a Nutrition Practitioner with a study partner organisation). The Benchmarking model is informed by research evidence, purpose-built best-practice audit and feedback tools, and co-designed with partner organisation and community representatives. The intervention comprises two full benchmarking cycles (one per year, 2022/23 and 2023/24) of assessment, feedback, action planning and action implementation. Assessment of stores includes i adoption status of 21 evidence-and industry-informed health-enabling policies for remote stores, ii implementation of health-enabling best-practice using a purpose-built Store Scout App, iii price of a standardised healthy diet using the Aboriginal and Torres Strait Islander Healthy Diets ASAP protocol; and, iv healthiness of food purchasing using sales data indicators. Partner organisations feedback reports and co-design action plans with stores. Control stores receive assessments and continue with usual retail practice. All stores provide weekly electronic sales data to assess the primary outcome, change in free sugars (g) to energy (MJ) from all food and drinks purchased, baseline (July-December 2021) vs July-December 2023.DiscussionWe hypothesise that the benchmarking intervention can improve the adoption of health-enabling store policy and practice and reduce sales of unhealthy foods and drinks in remote community stores of Australia. This innovative research with remote Aboriginal and Torres Strait Islander communities can inform effective implementation strategies for healthy food retail more broadly.Trial registrationACTRN12622000596707, Protocol version 1.

PURPOSE:To determine whether short-term wear of textured insoles alters balance, gait, foot sensation, physical activity, or patient-reported outcomes, in people with diabetic neuropathy. MATERIALS AND METHODS:53 adults with diabetic neuropathy were randomised to wear textured or smooth insoles for 4-weeks. At baseline and post-intervention, balance (foam/firm surface; eyes open/closed) and walking were assessed whilst barefoot, wearing shoes only, and two insoles (textured/smooth). The primary outcome was center of pressure (CoP) total sway velocity. Secondary outcomes included other CoP measures, spatiotemporal gait measures, foot sensation, physical activity, and patient-reported outcomes (foot health, falls efficacy). RESULTS:Wearing textured insoles led to improvements in CoP measures when standing on foam with eyes open, relative to smooth insoles (p ≤ 0.04). The intervention group demonstrated a 5% reduction in total sway velocity, indicative of greater balance. The intervention group also showed a 9-point improvement in self-perceived vigour (p = 0.03). Adjustments for multiple comparisons were not applied. CONCLUSIONS:This study provides weak statistical evidence in favour of textured insoles. Wearing textured insoles may alter measures of balance, suggestive of greater stability, in people with diabetic neuropathy. Plantar stimulation, through textured insoles, may have the capacity to modulate the perception of foot pain, leading to improved well-being.IMPLICATIONS FOR REHABILITATIONShort-term wear of textured insoles can lead to improvements in centre of pressure sway measures when standing on a compliant supporting surface.Wearing textured insoles may have the capacity to help relieve foot pain leading to enhanced self-perceived vitality in people with diabetic peripheral neuropathy.

INTRODUCTION:Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2. METHODS:This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample. RESULTS:10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00-1.00) when candidemia was defined according to both methods. CONCLUSION:Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.

Aim: Pharmacokinetic studies in children are limited, in part due to challenges in blood sampling. We compare the use of capillary microsampling and conventional sampling techniques in pediatric patients to show results that can be used in the pharmacokinetic analysis of Cefazolin. Patients & Methods: Paired blood samples (n = 48) were collected from 12 patients (median age/weight 49 months/18 kg). Results: The United States Federal Drug Administration incurred sample reanalysis acceptance criteria was used and identified 79% of paired samples achieved a difference of less than 20% in magnitude with a capillary microsampling bias of -10% (SD 20%). With exclusion of PK outliers, this rose to 88%. Conclusion: Capillary microsampling is reliable, meets acceptance criteria and can be used in pharmacokinetic studies. Plain language summary: What is this article about?: This study assesses a novel method of blood sample collection (capillary microsampling) for the analysis of a common antibiotic, cefazolin. In this study, we compare the results from samples collected using this method to blood tests taken in the traditional way. Capillary microsampling collects a very small volume of blood (about a drop of blood or 0.05 ml) taken from a skin prick and collected in a capillary tube. Traditional blood sampling collects a larger volume of blood (typically from 1 to 3 ml) taken from an artery or a vein. In this study, the patients (10 male and 2 female) had a mean age of 49 months and a mean weight of 18 kg. The amount of cefazolin in the blood samples were analyzed using the same methodology and results compared with assess the variability and reliability of the capillary microsampling method.What is this article about?This study assesses a novel method of blood sample collection (capillary microsampling) for the analysis of a common antibiotic, cefazolin. In this study, we compare the results from samples collected using this method to blood tests taken in the traditional way. What were the results?: The results showed that difference of the two sample types is within the accepted criteria of the United States Federal Drug Administration and the European Medicines Agency, meaning the results are reliable. What do the results of the study mean?: Blood samples for cefazolin can be small and easily obtained from a skin prick as a capillary microsample and can give reliable results. This greatly aids the ability to study the metabolism of cefazolin in children, particularly those that are not able to give a large amount of blood.

A range of strategies are available that can improve the outcomes of older persons particularly in relation to basic activities of daily living during and after an acute care (AC) episode. This paper outlines the original development of outcome-oriented quality indicators (QIs) in relation to common geriatric syndromes and function for the care of the frail aged hospitalized in acute general medical wards. Design QIs were developed using evidence from literature, expert opinion, field study data and a formal voting process. A systematic literature review of literature identified existing QIs (there were no outcome QIs) and evidence of interventions that improve older persons’ outcomes in AC. Preliminary indicators were developed by two expert panels following consideration of the evidence. After analysis of the data from field testing (indicator prevalence, variability across sites), panel meetings refined the QIs prior to a formal voting process. Data was collected in nine Australian general medical wards. Patients aged 70 years and over, consented within 24 h of admission to the AC ward. The interRAI Acute Care – Comprehensive Geriatric Assessment (interRAI AC-CGA) was administered at admission and discharge; a daily risk assessment in hospital; 28-day phone follow-up and chart audit. Ten outcome QIs were established which focused on common geriatric syndromes and function for the care of the frail aged hospitalized in acute general medical wards. Ten outcome QIs were developed. These QIs can be used to identify areas where specific action will lead to improvements in the quality of care delivered to older persons in hospital.