Recovery Rates of Diagnostic Cardiac Procedural Volume in Oceania 1 Year Into COVID-19: The IAEA Non-Invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID 2).

AIM: The aim of this study was to assess the recovery rates of diagnostic cardiac procedure volumes in the Oceania Region, midway through the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A survey was performed comparing procedure volumes between March 2019 (pre-pandemic), April 2020 (during first wave of COVID-19 pandemic), and April 2021 (1 year into the COVID-19 pandemic). A total of 31 health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, as well as teaching and non-teaching hospitals. A comparison was made with 549 centres in 96 countries in the rest of the world (RoW) outside of Oceania. The total number and median percentage change in procedure volume were measured between the three timepoints, compared by test type and by facility. RESULTS: A total of 11,902 cardiac diagnostic procedures were performed in Oceania in April 2021 as compared with 11,835 pre-pandemic in March 2019 and 5,986 in April 2020; whereas, in the RoW, 499,079 procedures were performed in April 2021 compared with 497,615 pre-pandemic in March 2019 and 179,014 in April 2020. There was no significant difference in the median recovery rates for total procedure volumes between Oceania (-6%) and the RoW (-3%) (p=0.81). While there was no statistically significant difference in percentage recovery been functional ischaemia testing and anatomical coronary testing in Oceania as compared with the RoW, there was, however, a suggestion of poorer recovery in anatomical coronary testing in Oceania as compared with the RoW (CT coronary angiography -16% in Oceania vs -1% in RoW, and invasive coronary angiography -20% in Oceania vs -9% in RoW). There was no statistically significant difference in recovery rates in procedure volume between metropolitan vs regional (p=0.44), public vs private (p=0.92), hospital vs outpatient (p=0.79), or teaching vs non-teaching centres (p=0.73). CONCLUSIONS: Total cardiology procedure volumes in Oceania normalised 1 year post-pandemic compared to pre-pandemic levels, with no significant difference compared with the RoW and between the different types of health care facilities.

Cardiac metastases from neuroendocrine neoplasms: complementary role of SSTR PET/CT and cardiac MRI.

BACKGROUND: Cardiac metastases from neuroendocrine neoplasms (NENs) are being detected with increasing frequency, although the optimal imaging strategy remains unclear. We performed a single-center retrospective study to explore the role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) and cardiac magnetic resonance imaging (CMR) in NEN cardiac metastases, determine the degree of concordance between the findings of these imaging modalities, and examine the advantages and disadvantages of each imaging technique. A secondary aim was to determine if cardiac metastases were associated with adverse cardiac events during peptide receptor radionuclide therapy (PRRT). METHODS AND RESULTS: 19 patients with NEN cardiac metastases were identified. A retrospective review of electronic medical records was performed, and if available SSTR PET/CT and CMR were blindly re-reviewed by imaging specialists, documenting the number and location of cardiac metastases. All 19 patients had SSTR PET/CT, and 10/19 patients had CMR. SSTR PET/CT identified more metastases than CMR. When identified on CMR, metastases were more accurately localized. 12/19 patients received PRRT, with no cardiac adverse effects. CONCLUSION: SSTR PET/CT and CMR are complementary investigations in the imaging of NEN cardiac metastases. SSTR PET/CT appears more sensitive for lesion detection, and CMR offers better lesion characterization. Both investigations present useful information for the planning of treatment including PRRT, which was administered safely.

Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

Comparison of Adjusted Fluoride Concentrations Between Water Treatment Facilities and Endpoints in Alberta, Canada.

OBJECTIVES: This investigation aimed to determine whether fluoride concentration in water at the user endpoint remains the same as at the adjusted source, i.e., water treatment facilities. METHODS: Daycares in Alberta, Canada, were used as the endpoint to measure fluoride concentration. They were randomly selected from a list of 400 licensed daycares provided by the Ministry of Children's Services. All water samples collected from the daycares were sent to the accredited Alberta Centre for Toxicology (ACFT) for analysis within 7 days of collection. ACFT used ion chromatography to determine fluoride concentration levels. Statistics analyses were conducted using the software SPSS 25. RESULTS: Water samples were collected from 141 daycares in 35 municipalities. In municipalities that adjust fluoride content, public water is supplied by 8 Alberta Environment & Parks regulated water systems. Fluoride concentration in water samples examined at the endpoint ranged from 0.58 mg/L to 0.79 mg/L. The differences between fluoride concentration at the water treatment facilities and the daycares ranged from -0.03 to 0.22 mg/L. CONCLUSIONS: This study confirms that the concentration of fluoride adjusted at water treatment facilities in Alberta is maintained at endpoints at the approximate optimal level of 0.7 mg/L.

Cost-Effectiveness of Cardiovascular Magnetic Resonance in Diagnosing Coronary Artery Disease in the Australian Health Care System.

BACKGROUND: Coronary artery disease (CAD) remains a major public health problem in Australia and globally. A variety of imaging techniques allow for both anatomical and functional assessment of CAD and selection of the optimal investigation pathway is challenging. Cardiovascular magnetic resonance (CMR) is not widely used in Australia, partly due to perceived cost and lack of Federal Government reimbursement compared to the alternative techniques. The aim of this study was to estimate the cost-effectiveness of different diagnostic strategies in identifying significant CAD in patients with chest pain suggestive of angina using the evidence gathered in the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC trial), analysed from the Australian health care perspective. METHODS: A decision analytic model coupled with three distinct Markov models allowed eight potential clinical investigation strategies to be considered; combinations of exercise electrocardiogram stress testing (EST), single-photon emission computed tomography (SPECT), stress CMR, and invasive coronary angiography (ICA). Costs were from the Australian health care system in Australian dollars, and outcomes were measured in terms of quality-adjusted life-years. Parameter estimates were derived from the CE-MARC and EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease (EUROPA) trials, and from reviews of the published literature. RESULTS: The most cost-effective diagnostic strategy, based on a cost-effectiveness threshold of $45,000 to $75,000 per QALY gained, was EST, followed by stress CMR if the EST was positive or inconclusive, followed by ICA if the stress CMR was positive or inconclusive; this held true in the base case and the majority of scenario analyses. CONCLUSIONS: This economic evaluation shows that an investigative strategy of stress CMR if EST is inconclusive or positive is the most cost-effective approach for diagnosing significant coronary disease in chest pain patients within the Australian health care system.

Impact of COVID-19 on Diagnostic Cardiac Procedural Volume in Oceania: The IAEA Non-Invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID).

OBJECTIVES: The INCAPS COVID Oceania study aimed to assess the impact caused by the COVID-19 pandemic on cardiac procedure volume provided in the Oceania region. METHODS: A retrospective survey was performed comparing procedure volumes within March 2019 (pre-COVID-19) with April 2020 (during first wave of COVID-19 pandemic). Sixty-three (63) health care facilities within Oceania that perform cardiac diagnostic procedures were surveyed, including a mixture of metropolitan and regional, hospital and outpatient, public and private sites, and 846 facilities outside of Oceania. The percentage change in procedure volume was measured between March 2019 and April 2020, compared by test type and by facility. RESULTS: In Oceania, the total cardiac diagnostic procedure volume was reduced by 52.2% from March 2019 to April 2020, compared to a reduction of 75.9% seen in the rest of the world (p<0.001). Within Oceania sites, this reduction varied significantly between procedure types, but not between types of health care facility. All procedure types (other than stress cardiac magnetic resonance [CMR] and positron emission tomography [PET]) saw significant reductions in volume over this time period (p<0.001). In Oceania, transthoracic echocardiography (TTE) decreased by 51.6%, transoesophageal echocardiography (TOE) by 74.0%, and stress tests by 65% overall, which was more pronounced for stress electrocardiograph (ECG) (81.8%) and stress echocardiography (76.7%) compared to stress single-photon emission computerised tomography (SPECT) (44.3%). Invasive coronary angiography decreased by 36.7% in Oceania. CONCLUSION: A significant reduction in cardiac diagnostic procedure volume was seen across all facility types in Oceania and was likely a function of recommendations from cardiac societies and directives from government to minimise spread of COVID-19 amongst patients and staff. Longer term evaluation is important to assess for negative patient outcomes which may relate to deferral of usual models of care within cardiology.

Hypertrophic Cardiomyopathy: Challenging the Status Quo?

Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular genetic disorder. While our mechanistic understanding has been informed by elegant gene discovery studies that led to the term "disease of the sarcomere", more recent investigations have challenged the single-gene hypothesis. Multimodality imaging has allowed better phenotyping to facilitate early diagnosis, identify treatable phenocopies, and guide management. While HCM remains an important cause of sudden death, recent studies have reported a substantial cumulative burden of heart failure and atrial fibrillation in middle-aged and older individuals. Nonetheless, improvements in risk stratification have allowed early intervention to transition HCM from being a common cause of sudden death in the young to a treatable chronic disease.

Determinants of Diastolic Dysfunction Following Myocardial Infarction: Evidence for Causation Beyond Infarct Size.

BACKGROUND: The determinants of severe diastolic dysfunction (DD) following myocardial infarction (MI) are not well defined. This study sought to define the determinants of severe DD (restrictive mitral inflow pattern on Doppler echocardiography [RFP]) in patients with a first-ever MI, with particular emphasis on the impact of infarct size. METHODS: Retrospective single-centre study including consecutive patients admitted to a tertiary referral centre with a first-ever non-ST-elevation-MI (NSTEMI) or ST-elevation-MI (STEMI) (n=477). Peak troponin-I (Peak-TnI) was used as the principal measure of infarct size, whilst left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were regarded as surrogate measures. Echocardiography was performed within 24 hours of admission for all patients. RFP was defined as E/A ratio >2.0 or E/A ratio >1.5 and E-wave deceleration time <140 ms. RESULTS: A total of 69 patients (14.5%) had RFP. Peak-TnI levels were higher in the RFP group (32.6±32.7 versus 16.9±25.2 µg/L, p<0.001). In sequential multivariable models incorporating significant clinical, angiographic and left ventricular (LV) size-related variables, Peak-TnI (OR 1.98, p=0.001), WMSI (OR 2.34, p=0.048) and LVEF (OR 0.97, p=0.044) were independent predictors of RFP. Presence of diabetes was also an independent predictor in all the models constructed. When patients were stratified according to an LVEF of 50%, 39% of RFP patients had a preserved LVEF (RFP/preserved EF group), and these patients had lower Peak-TnI levels compared to the RFP/reduced EF group (14.4±18.7 vs 44.5±35.5 µg/L). CONCLUSIONS: Whilst infarct size is a major determinant of severe diastolic dysfunction after MI, a significant subset of patients develop severe diastolic dysfunction despite a small infarct size and preserved LVEF, highlighting that other factors such as pre-existing diastolic dysfunction due to risk factors such as diabetes have an important role in causation.

Making Improvements in the ED: Does ED Busyness Affect Time to Antibiotics in Febrile Pediatric Oncology Patients Presenting to the Emergency Department?

OBJECTIVES: Febrile neutropenic pediatric patients are at heightened risk for serious bacterial infections, and rapid antibiotic administration (in <60 minutes) improves survival. Our objectives were to reduce the time-to-antibiotic (TTA) administration and to evaluate the effect of overall emergency department (ED) busyness on TTA. METHODS: This study was a quality improvement initiative with retrospective chart review to reduce TTA in febrile children with underlying diagnosis of cancer or hematologic immunodeficiency who visited the pediatric ED. A multidisciplinary clinical practice guideline (CPG) was implemented to improve TTA. The CPG's main focus was delivery of antibiotics before availability of laboratory data. We collected data on TTA during baseline and intervention periods. Concurrent patient arrivals to the ED per hour served as a proxy of busyness. Time to antibiotic was compared with the number of concurrent arrivals per hour. Analyses included scatter plot and regression analysis. RESULTS: There were 253 visits from October 1, 2010 to March 30, 2012. Median TTA administration dropped from 207 to 89 minutes (P < 0.001). Eight months after completing all intervention periods, the median had dropped again to 44 minutes with 70% of patients receiving antibiotics within 60 minutes of ED arrival. There was no correlation between concurrent patient arrivals and TTA administration during the historical or intervention periods. CONCLUSIONS: Implementation of a CPG and process improvements significantly reduced median TTA administration. Total patient arrivals per hour as a proxy of ED crowding did not affect TTA administration. Our data suggest that positive improvements in clinical care can be successful despite fluctuations in ED patient volume.

Effect of Antimicrobial and Physical Treatments on Growth of Multispecies Staphylococcal Biofilms.

The prevalence and structure of Staphylococcus aureus and Staphylococcus epidermidis within multispecies biofilms were found to depend sensitively on physical environment and antibiotic dosage. Although these species commonly infect similar sites, such as orthopedic implants, little is known about their behavior in multispecies communities, particularly in response to treatment. This research establishes that S. aureus is much more prevalent than S. epidermidis when simultaneously seeded and grown under unstressed conditions (pH 7, 37°C) in both laboratory and clinical strains. In multispecies communities, S. epidermidis is capable of growing a more confluent biofilm when the addition of S. aureus is delayed 4 to 6 h during 18 h of growth. Different vancomycin dosages generate various behaviors: S. epidermidis is more prevalent at a dose of 1.0 µg/ml vancomycin, but reduced growth of both species occurs at 1.9 µg/ml vancomycin. This variability is consistent with the different MICs of S. aureus and S. epidermidis Growth at higher temperature (45°C) results in an environment where S. aureus forms porous biofilms. This porosity allows S. epidermidis to colonize more of the surface, resulting in detectable S. epidermidis biomass. Variations in pH result in increased prevalence of S. epidermidis at low pH (pH 5 and 6), while S. aureus remains dominant at high pH (pH 8 and 9). This work establishes the structural variability of multispecies staphylococcal biofilms as they undergo physical and antimicrobial treatments. It provides a basis for understanding the structure of these communities at infection sites and how treatments disrupt their multispecies behaviors.IMPORTANCEStaphylococcus aureus and Staphylococcus epidermidis are two species of bacteria that are commonly responsible for biofilm infections on medical devices. Biofilms are structured communities of bacteria surrounded by polysaccharides, proteins, and DNA; bacteria are more resistant to antimicrobials as part of a biofilm than as individual cells. This work investigates the structure and prevalence of these two organisms when grown together in multispecies biofilms and shows shifts in the behavior of the polymicrobial community when grown in various concentrations of vancomycin (an antibiotic commonly used to treat staphylococcal infections), in a high-temperature environment (a condition previously shown to lead to cell disruption and death), and at low and high pH (a change that has been previously shown to soften the mechanical properties of staphylococcal biofilms). These shifts in community structure demonstrate the effect such treatments may have on multispecies staphylococcal infections.

Cardiac Society of Australia and New Zealand position statement executive summary: coronary artery calcium scoring.

Introduction This article summarises the Cardiac Society of Australia and New Zealand position statement on coronary artery calcium (CAC) scoring. CAC scoring is a non-invasive method for quantifying coronary artery calcification using computed tomography. It is a marker of atherosclerotic plaque burden and the strongest independent predictor of future myocardial infarction and mortality. CAC scoring provides incremental risk information beyond traditional risk calculators such as the Framingham Risk Score. Its use for risk stratification is confined to primary prevention of cardiovascular events, and can be considered as individualised coronary risk scoring for intermediate risk patients, allowing reclassification to low or high risk based on the score. Medical practitioners should carefully counsel patients before CAC testing, which should only be undertaken if an alteration in therapy, including embarking on pharmacotherapy, is being considered based on the test result. Main recommendations CAC scoring should primarily be performed on individuals without coronary disease aged 45-75 years (absolute 5-year cardiovascular risk of 10-15%) who are asymptomatic. CAC scoring is also reasonable in lower risk groups (absolute 5-year cardiovascular risk, < 10%) where risk scores traditionally underestimate risk (eg, family history of premature CVD) and in patients with diabetes aged 40-60 years. We recommend aspirin and a high efficacy statin in high risk patients, defined as those with a CAC score ≥ 400, or a CAC score of 100-399 and above the 75th percentile for age and sex. It is reasonable to treat patients with CAC scores ≥ 100 with aspirin and a statin. It is reasonable not to treat asymptomatic patients with a CAC score of zero. Changes in management as a result of this statement Cardiovascular risk is reclassified according to CAC score. High risk patients are treated with a high efficacy statin and aspirin. Very low risk patients (ie, CAC score of zero) do not benefit from treatment.

Cardiac Society of Australia and New Zealand Position Statement: Coronary Artery Calcium Scoring.

Coronary Artery Calcium Scoring (CAC) is a non-invasive quantitation of coronary artery calcification using computed tomography (CT). It is a marker of atherosclerotic plaque burden and an independent predictor of future myocardial infarction and mortality. Coronary Artery Calcium Scoring provides incremental risk information beyond traditional risk calculators (eg. Framingham Risk Score). Its use for risk stratification is confined to primary prevention of cardiovascular events, and can be considered as "individualised coronary risk scoring" for those not considered to be of high or low risk. Medical practitioners should carefully counsel patients prior to CAC. Coronary Artery Calcium Scoring should only be undertaken if an alteration in therapy including embarking on pharmacotherapy is being considered based on the test result. Patient Groups to Consider Coronary Calcium Scoring: Patient Groups in Whom Coronary Calcium Scoring Should Not be Considered: Coronary Artery Calcium Scoring is not recommended for patients who are: Interpretation of CAC CAC=0 A zero score confers a very low risk of death, <1% at 10 years. CAC=1-100 Low risk, <10% CAC=101-400 Intermediate risk, 10-20% CAC=101-400 & >75th centile. Moderately high risk, 15-20% CAC >400 High risk, >20% Management Recommendations Based on CAC Optimal diet and lifestyle measures are encouraged in all risk groups and form the basis of primary prevention strategies. Patients with moderately-high or high risk based on CAC score are recommended to receive preventative medical therapy such as aspirin and statins. The evidence for pharmacotherapy is less robust in patients at intermediate levels of CAC 100-400, with modest benefit for aspirin use; though statins may be reasonable if they are above 75th centile. Aspirin and statins are generally not recommended in patients with CAC <100. Repeat CAC Testing In patients with a CAC of 0, a repeat CAC may be considered in 5 years but not sooner. In patients with positive calcium score, routine re-scanning is not currently recommended. However, an annual increase in CAC of >15% or annual increase of CAC >100 units are predictive of future myocardial infarction and mortality. Cost Effectiveness of CAC Based Primary Prevention Recommendations: There is currently no data in Australia and New Zealand that CAC is cost-effective in informing primary prevention decisions. Given the cost of testing is currently borne entirely by the patient, discussion regarding the implications of CAC results should occur before CAC is recommended and undertaken.

Zinc oxide nanoparticle suspensions and layer-by-layer coatings inhibit staphylococcal growth.

Despite a decade of engineering and process improvements, bacterial infection remains the primary threat to implanted medical devices. Zinc oxide nanoparticles (ZnO-NPs) have demonstrated antimicrobial properties. Their microbial selectivity, stability, ease of production, and low cost make them attractive alternatives to silver NPs or antimicrobial peptides. Here we sought to (1) determine the relative efficacy of ZnO-NPs on planktonic growth of medically relevant pathogens; (2) establish the role of bacterial surface chemistry on ZnO-NP effectiveness; (3) evaluate NP shape as a factor in the dose-response; and (4) evaluate layer-by-layer (LBL) ZnO-NP surface coatings on biofilm growth. ZnO-NPs inhibited bacterial growth in a shape-dependent manner not previously seen or predicted. Pyramid shaped particles were the most effective and contrary to previous work, larger particles were more effective than smaller particles. Differential susceptibility of pathogens may be related to their surface hydrophobicity. LBL ZnO-NO coatings reduced staphylococcal biofilm burden by >95%. From the Clinical Editor: The use of medical implants is widespread. However, bacterial colonization remains a major concern. In this article, the authors investigated the use of zinc oxide nanoparticles (ZnO-NPs) to prevent bacterial infection. They showed in their experiments that ZnO-NPs significantly inhibited bacterial growth. This work may present a new alternative in using ZnO-NPs in medical devices.

Effects of temperature on the morphological, polymeric, and mechanical properties of Staphylococcus epidermidis bacterial biofilms.

Changes in temperature were found to affect the morphology, cell viability, and mechanical properties of Staphylococcus epidermidis bacterial biofilms. S. epidermidis biofilms are commonly associated with hospital-acquired medical device infections. We observed the effect of heat treatment on three physical properties of the biofilms: the bacterial cell morphology and viability, the polymeric properties of the extracellular polymeric substance (EPS), and the rheological properties of the bulk biofilm. After application of a 1 h heat treatment at 45 °C, cell reproduction had ceased, and at 60 °C, cell viability was significantly reduced. Size exclusion chromatography was used to fractionate the extracellular polymeric substance (EPS) based on size. Chemical analysis of each fraction showed that the relative concentrations of the polysaccharide, protein, and DNA components of the EPS were unchanged by the heat treatment at 45 and 60 °C. The results suggest that the EPS molecular constituents are not significantly degraded by the temperature treatment. However, some aggregation on the scale of 100 nm was found by dynamic light scattering at 60 °C. Finally, relative to control biofilms maintained at 37 °C, we observed an order of magnitude reduction in the biofilm yield stress after 60 °C temperature treatment. No such difference was found for treatment at 45 °C. From these results, we conclude that the yield stress of bacterial biofilms is temperature-sensitive and that this sensitivity is correlated with cell viability. The observed significant decrease in yield stress with temperature suggests a means to weaken the mechanical integrity of S. epidermidis biofilms with applications in areas such as the treatment of biofilm-infected medical devices.

Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial.

BACKGROUND: In patients with suspected coronary heart disease, single-photon emission computed tomography (SPECT) is the most widely used test for the assessment of myocardial ischaemia, but its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation. The aim of this study was to establish the diagnostic accuracy of a multiparametric cardiovascular magnetic resonance (CMR) protocol with x-ray coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease. METHODS: In this prospective trial patients with suspected angina pectoris and at least one cardiovascular risk factor were scheduled for CMR, SPECT, and invasive x-ray coronary angiography. CMR consisted of rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement, and MR coronary angiography. Gated adenosine stress and rest SPECT used (99m)Tc tetrofosmin. The primary outcome was diagnostic accuracy of CMR. This trial is registered at controlled-trials.com, number ISRCTN77246133. FINDINGS: In the 752 recruited patients, 39% had significant CHD as identified by x-ray angiography. For multiparametric CMR the sensitivity was 86·5% (95% CI 81·8-90·1), specificity 83·4% (79·5-86·7), positive predictive value 77·2%, (72·1-81·6) and negative predictive value 90·5% (87·1-93·0). The sensitivity of SPECT was 66·5% (95% CI 60·4-72·1), specificity 82·6% (78·5-86·1), positive predictive value 71·4% (65·3-76·9), and negative predictive value 79·1% (74·8-82·8). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p<0·0001 for both) but specificity and positive predictive value did not (p=0·916 and p=0·061, respectively). INTERPRETATION: CE-MARC is the largest, prospective, real world evaluation of CMR and has established CMR's high diagnostic accuracy in coronary heart disease and CMR's superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease. FUNDING: British Heart Foundation.

Impact of hourly emergency department patient volume on blood culture contamination and diagnostic yield.

Emergency departments (EDs) are an important diagnostic site for outpatients with potentially serious infections. EDs frequently experience high patient volumes, and crowding has been shown to negatively impact the delivery of early care for serious infections, such as pneumonia. Here, we hypothesized that other important factors in the early care of infectious diseases, the rate of blood culture contamination and the accurate detection of pathogens, would be sensitive to ED operational stress, as proper collection requires fastidious attention to technique and timing. We related all blood samples collected over 1 year and their rates of recovery of likely contaminants and pathogens to the number of patients being cared for in the ED at the time of sample collection. Likely pathogens and contaminants were classified through combined microbiological and manual chart review criteria. Zero-inflated Poisson regression was used to relate crowding to culture results. Blood samples were obtained from 7,586 patients over 82,521 adult and pediatric patient visits. The unadjusted rates of recovering a likely pathogen or a likely contaminant were 8.0% and 3.7%, respectively. Periods of increased crowding (3rd and 4th quartiles of hourly occupancy) were significantly associated (P < 0.01) with increased rates of contamination (relative risk, 1.23 compared to the least busy quartile). Collecting samples for culture during busy times was also associated with a reduced likelihood of recovering a likely pathogen (relative risk, 0.93 compared to the least busy quartile). ED crowding was associated with degraded performance of blood cultures, both increasing the rate of contamination and decreasing the diagnostic yield.

Role of environmental and antibiotic stress on Staphylococcus epidermidis biofilm microstructure.

Cellular clustering and separation of Staphylococcus epidermidis surface adherent biofilms were found to depend significantly on both antibiotic and environmental stress present during growth under steady flow. Image analysis techniques common to colloidal science were applied to image volumes acquired with high-resolution confocal laser scanning microscopy to extract spatial positions of individual bacteria in volumes of size ~30 × 30 × 15 µm(3). The local number density, cluster distribution, and radial distribution function were determined at each condition by analyzing the statistics of the bacterial spatial positions. Environmental stressors of high osmotic pressure (776 mM NaCl) and sublethal antibiotic dose (1.9 µg/mL vancomycin) decreased the average bacterial local number density 10-fold. Device-associated bacterial biofilms are frequently exposed to these environmental and antibiotic stressors while undergoing flow in the bloodstream. Characteristic density phenotypes associated with low, medium, and high local number densities were identified in unstressed S. epidermidis biofilms, while stressed biofilms contained medium- and low-density phenotypes. All biofilms exhibited clustering at length scales commensurate with cell division (~1.0 µm). However, density phenotypes differed in cellular connectivity at the scale of ~6 µm. On this scale, nearly all cells in the high- and medium-density phenotypes were connected into a single cluster with a structure characteristic of a densely packed disordered fluid. However, in the low-density phenotype, the number of clusters was greater, equal to 4% of the total number of cells, and structures were fractal in nature with d(f) =1.7 ± 0.1. The work advances the understanding of biofilm growth, informs the development of predictive models of transport and mechanical properties of biofilms, and provides a method for quantifying the kinetics of bacterial surface colonization as well as biofilm fracture and fragmentation.

Molar mass, entanglement, and associations of the biofilm polysaccharide of Staphylococcus epidermidis.

Biofilms are microbial communities that are characterized by the presence of a viscoelastic extracellular polymeric substance (EPS). Studies have shown that polysaccharides, along with proteins and DNA, are a major constituent of the EPS and play a dominant role in mediating its microstructure and rheological properties. Here, we investigate the possibility of entanglements and associative complexes in solutions of extracellular polysaccharide intercellular adhesin (PIA) extracted from Staphylococcus epidermidis biofilms. We report that the weight average molar mass and radius of gyration of PIA isolates are 2.01×10(5)±1200 g/mol and 29.2±1.2 nm, respectively. The coil overlap concentration, c*, was thus determined to be (32±4)×10(-4) g/mL. Measurements of the in situ concentration of PIA (cPIA,biofilm) was found to be (10±2)×10(-4) g/mL.Thus, cPIA,biofilm

In situ rheology of Staphylococcus epidermidis bacterial biofilms.

We developed a method to grow Staphylococcus epidermidis bacterial biofilms and characterize their rheological properties in situ in a continuously fed bioreactor incorporated into a parallel plate rheometer. The temperature and shear rates of growth modeled bloodstream conditions, a common site of S. epidermidis infection. We measured the linear elastic (G') and viscous moduli (G″) of the material using small-amplitude oscillatory rheology and the yield stress using non-linear creep rheology. We found that the elastic and viscous moduli of the S. epidermidis biofilm were 11 ± 3 Pa and 1.9 ± 0.5 Pa at a frequency of 1 Hz (6.283 rad per s) and that the yield stress was approximately 20 Pa. We modeled the linear creep response of the biofilm using a Jeffreys model and found that S. epidermidis has a characteristic relaxation time of approximately 750 seconds and a linear creep viscosity of 3000 Pa s. The effects on the linear viscoelastic moduli of environmental stressors, such as NaCl concentration and extremes of temperature, were also studied. We found a non-monotonic relationship between moduli and NaCl concentrations, with the stiffest material properties found at human physiological concentrations (135 mM). Temperature dependent rheology showed hysteresis in the moduli when heated and cooled between 5 °C and 60 °C. Through these experiments, we demonstrated that biofilms are rheologically complex materials that can be characterized by a combination of low modulus (~10 Pa), long relaxation time (~103 seconds), and a finite yield stress (20 Pa). This suggests that biofilms should be viewed as soft viscoelastic solids whose properties are determined in part by local environmental conditions. The in situ growth method introduced here can be adapted to a wide range of biofilm systems and applied over a broad spectrum of rheological and environmental conditions because the technique minimizes the risk of irreversible, non-linear deformation of the microbial specimen before analysis.