The effect of number of clusters and magnitude of within-cluster homogeneity in outcomes on the performance of four variance estimators for a marginal multivariable Cox regression model fit to clustered data in the context of observational research.

Researchers often estimate the association between the hazard of a time-to-event outcome and the characteristics of individuals and the clusters in which individuals are nested. Lin and Wei's robust variance estimator is often used with a Cox regression model fit to clustered data. Recently, alternative variance estimators have been proposed: the Fay-Graubard estimator, the Kauermann-Carroll estimator, and the Mancl-DeRouen estimator. Using Monte Carlo simulations, we found that, when fitting a marginal Cox regression model with both individual-level and cluster-level covariates: (i) in the presence of weak to moderate within-cluster homogeneity of outcomes, the Lin-Wei variance estimator can result in estimates of the SE with moderate bias when the number of clusters is fewer than 20-30, while in the presence of strong within-cluster homogeneity, it can result in biased estimation even when the number of clusters is as large as 100; (ii) when the number of clusters was less than approximately 20, the Fay-Graubard variance estimator tended to result in estimates of SE with the lowest bias; (iii) when the number of clusters exceeded approximately 20, the Mancl-DeRouen estimator tended to result in estimated standard errors with the lowest bias; (iv) the Mancl-DeRouen estimator used with a t-distribution tended to result in 95% confidence that had the best performance of the estimators; (v) when the magnitude of within-cluster homogeneity in outcomes was strong or very strong, all methods resulted in confidence intervals with lower than advertised coverage rates even when the number of clusters was very large.

Derivation and internal validation of the multivariate toxigenic C. difficile diarrhea model and risk score for emergency room and hospitalized patients with diarrhea.

Background: Many factors have been associated with the risk of toxigenic C. difficile diarrhea (TCdD). This study derived and internally validated a multivariate model for estimating the risk of TCdD in patients with diarrhea using readily available clinical factors. Methods: A random sample of 3,050 symptomatic emergency department or hospitalized patients undergoing testing for toxigenic C. difficile at a single teaching hospital between 2014 and 2018 was created. Unformed stool samples positive for both glutamate dehydrogenase antigen by enzyme immunoassay and tcdB gene by polymerase chain reaction were classified as TCdD positive. The TCdD Model was created using logistic regression and was modified to the TCdD Risk Score to facilitate its use. Results: 8.1% of patients were TCdD positive. TCdD risk increased with abdominal pain (adjusted odds ratio 1.3; 95% CI, 1.0-1.8), previous C. difficile diarrhea (2.5, 1.1-6.1), and prior antibiotic exposure, especially when sampled in the emergency department (4.2, 2.5-7.0) versus the hospital (1.7, 1.3-2.3). TCdD risk also increased when testing occurred earlier during the hospitalization encounter, when age and white cell count increased concurrently, and with decreased eosinophil count. In internal validation, the TCdD Model had moderate discrimination (optimism-corrected C-statistic 0.65, 0.62-0.68) and good calibration (optimism-corrected Integrated Calibration Index [ICI] 0.017, 0.001-0.022). Performance decreased slightly for the TCdD Risk Score (C-statistic 0.63, 0.62-0.63; ICI 0.038, 0.004-0.038). Conclusions: TCdD risk can be predicted using readily available clinical risk factors with modest accuracy.

Ambulatory Cardiology or General Internal Medicine Assessment Prior to Scheduled Major Vascular Surgery is Associated with Improved Outcomes.

OBJECTIVE: To characterize the association between ambulatory cardiology or general internal medicine (GIM) assessment prior to surgery and outcomes following scheduled major vascular surgery. BACKGROUND: Cardiovascular risk assessment and management prior to high-risk surgery remains an evolving area of care. METHODS: This is population-based retrospective cohort study of all adults who underwent scheduled major vascular surgery in Ontario, Canada, April 1, 2004-March 31, 2019. Patients who had an ambulatory cardiology and/or GIM assessment within 6 months prior to surgery were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes included: composite of 30-day mortality, myocardial infarction or stroke; 30-day cardiovascular death; 1-year mortality; composite of 1-year mortality, myocardial infarction or stroke; and 1-year cardiovascular death. Cox proportional hazard regression using inverse probability of treatment weighting (IPTW) was used to mitigate confounding by indication. RESULTS: Among 50,228 patients, 20,484 (40.8%) underwent an ambulatory assessment prior to surgery: 11,074 (54.1%) with cardiology, 8,071 (39.4%) with GIM and 1,339 (6.5%) with both. Compared to patients who did not, those who underwent an assessment had a higher Revised Cardiac Risk Index (N with Index over 2= 4,989[24.4%] vs. 4,587[15.4%], P<0.001) and more frequent pre-operative cardiac testing (N=7,772[37.9%] vs. 6,113[20.6%], P<0.001) but, lower 30-day mortality (N=551[2.7%] vs. 970[3.3%], P<0.001). After application of IPTW, cardiology or GIM assessment prior to surgery remained associated with a lower 30-day mortality (weighted Hazard Ratio [95%CI] = 0.73 [0.65-0.82]) and a lower rate of all secondary outcomes. CONCLUSIONS: Major vascular surgery patients assessed by a cardiology or GIM physician prior to surgery have better outcomes than those who are not. Further research is needed to better understand potential mechanisms of benefit.

Implications of Five Different Risk Models In Primary Prevention Guidelines.

BACKGROUND: A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Our objective was to determine potential improvements in the number needed to treat (NNT) and number of events prevented (NEP) using different risk models in patients eligible for risk stratification. METHODS: A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). RESULTS: The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%). Accordingly, the NEP was highest for the FRS at 406 and lowest for SCORE2 at 156. CONCLUSIONS: Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT but prevent fewer events at the population level.

Accounting for Competing Risks in Clinical Research.

This JAMA Guide to Statistics and Methods article discusses accounting for competing risks in clinical research.

Population Trends of New Prescriptions for Antihyperglycemics and Antihypertensives Between 2014 and 2022.

BACKGROUND: In the wake of pandemic-related health decline and health care disruptions, there are concerns that previous gains for cardiovascular risk factors may have stalled or reversed. Population-level excess burden of drug-treated diabetes and hypertension during the pandemic compared with baseline is not well characterized. We evaluated the change in incident prescription claims for antihyperglycemics and antihypertensives before versus during the pandemic. METHODS AND RESULTS: In this retrospective, serial, cross-sectional, population-based study, we used interrupted time series analyses to examine changes in the age- and sex-standardized monthly rate of incident prescriptions for antihyperglycemics and antihypertensives in patients aged ≥66 years in Ontario, Canada, before the pandemic (April 2014 to March 2020) compared with during the pandemic (July 2020 to November 2022). Incident claim was defined as the first prescription filled for any medication in these classes. The characteristics of patients with incident prescriptions of antihyperglycemics (n=151 888) or antihypertensives (n=368 123) before the pandemic were comparable with their pandemic counterparts (antihyperglycemics, n=97 015; antihypertensives, n=146 524). Before the pandemic, monthly rates of incident prescriptions were decreasing (-0.03 per 10 000 individuals [95% CI, -0.04 to -0.01] for antihyperglycemics; -0.14 [95% CI, -0.18 to -0.10] for antihypertensives). After July 2020, monthly rates increased (postinterruption trend 0.31 per 10 000 individuals [95% CI, 0.28-0.34] for antihyperglycemics; 0.19 [95% CI, 0.14-0.23] for antihypertensives). CONCLUSIONS: Population-level increases in new antihyperglycemic and antihypertensive prescriptions during the pandemic reversed prepandemic declines and were sustained for >2 years. Our findings are concerning for current and future cardiovascular health.

Days alive and out of hospital for adult female and male cardiac surgery patients: a population-based cohort study.

BACKGROUND: Research shows women experience higher mortality than men after cardiac surgery but information on sex-differences during postoperative recovery is limited. Days alive and out of hospital (DAH) combines death, readmission and length of stay, and may better quantify sex-differences during recovery. This main objective is to evaluate (i) how DAH at 30-days varies between sex and surgical procedure, (ii) DAH responsiveness to patient and surgical complexity, and (iii) longer-term prognostic value of DAH. METHODS: We evaluated 111,430 patients (26% female) who underwent one of three types of cardiac surgery (isolated coronary artery bypass [CABG], isolated non-CABG, combination procedures) between 2009 - 2019. Primary outcome was DAH at 30 days (DAH30), secondary outcomes were DAH at 90 days (DAH90) and 180 days (DAH180). Data were stratified by sex and surgical group. Unadjusted and risk-adjusted analyses were conducted to determine the association of DAH with patient-, surgery-, and hospital-level characteristics. Patients were divided into two groups (below and above the 10th percentile) based on the number of days at DAH30. Proportion of patients below the 10th percentile at DAH30 that remained in this group at DAH90 and DAH180 were determined. RESULTS: DAH30 were lower for women compared to men (22 vs. 23 days), and seen across all surgical groups (isolated CABG 23 vs. 24, isolated non-CABG 22 vs. 23, combined surgeries 19 vs. 21 days). Clinical risk factors including multimorbidity, socioeconomic status and surgical complexity were associated with lower DAH30 values, but women showed lower values of DAH30 compared to men for many factors. Among patients in the lowest 10th percentile at DAH30, 80% of both females and males remained in the lowest 10th percentile at 90 days, while 72% of females and 76% males remained in that percentile at 180 days. CONCLUSION: DAH is a responsive outcome to differences in patient and surgical risk factors. Further research is needed to identify new care pathways to reduce disparities in outcomes between male and female patients.

The performance of marginal structural models for estimating risk differences and relative risks using weighted univariate generalized linear models.

We used Monte Carlo simulations to compare the performance of marginal structural models (MSMs) based on weighted univariate generalized linear models (GLMs) to estimate risk differences and relative risks for binary outcomes in observational studies. We considered four different sets of weights based on the propensity score: inverse probability of treatment weights with the average treatment effect as the target estimand, weights for estimating the average treatment effect in the treated, matching weights and overlap weights. We considered sample sizes ranging from 500 to 10,000 and allowed the prevalence of treatment to range from 0.1 to 0.9. We examined both the robust variance estimator when using generalized estimating equations with an independent working correlation matrix and a bootstrap variance estimator for estimating the standard error of the risk difference and the log-relative risk. The performance of these methods was compared with that of direct weighting. Both the direct weighting approach and MSMs based on weighted univariate GLMs resulted in the identical estimates of risk differences and relative risks. When sample sizes were small to moderate, the use of an MSM with a bootstrap variance estimator tended to result in the most accurate estimates of standard errors. When sample sizes were large, the direct weighting approach and an MSM with a bootstrap variance estimator tended to produce estimates of standard error with similar accuracy. When using a MSM to estimate risk differences and relative risks, in general it is preferable to use a bootstrap variance estimator than the robust variance estimator. We illustrate the application of the different methods for estimating risks differences and relative risks using an observational study on the effect on mortality of discharge prescribing of a beta-blocker in patients hospitalized with acute myocardial infarction.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

Validation of the Passive Surveillance Stroke Severity Score in Three Canadian Provinces.

BACKGROUND: Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada. METHODS: We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models' discriminative values using Uno's c-statistic, comparing models with versus without PaSSV. RESULTS: We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable. CONCLUSION: PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Teen Pregnancy and Risk of Premature Mortality.

Importance: Unintentional injury, suicide, and homicide are leading causes of death among young females. Teen pregnancy may be a marker of adverse life experiences. Objective: To evaluate the risk of premature mortality from 12 years of age onward in association with number of teen pregnancies and age at pregnancy. Design, Setting, and Participants: This population-based cohort study was conducted among all females alive at 12 years of age from April 1, 1991, to March 31, 2021, in Ontario, Canada (the most populous province, which has universal health care and data collection). The study period ended March 31, 2022. Exposures: The main exposure was number of teen pregnancies between 12 and 19 years of age (0, 1, or ≥2). Secondary exposures included how the teen pregnancy ended (birth or miscarriage vs induced abortion) and age at first teen pregnancy. Main Outcomes and Measures: The main outcome was all-cause mortality starting at 12 years of age. Hazard ratios (HRs) were adjusted for year of birth, comorbidities at 9 to 11 years of age, and area-level education, income level, and rurality. Results: Of 2 242 929 teenagers, 163 124 (7.3%) experienced a pregnancy at a median age of 18 years (IQR, 17-19 years). Of those with a teen pregnancy, 60 037 (36.8%) ended in a birth (of which 59 485 [99.1%] were live births), and 106 135 (65.1%) ended in induced abortion. The median age at the end of follow-up was 25 years (IQR, 18-32 years) for those without a teen pregnancy and 31 years (IQR, 25-36 years) for those with a teen pregnancy. There were 6030 deaths (1.9 per 10 000 person-years [95% CI, 1.9-2.0 per 10 000 person-years]) among those without a teen pregnancy, 701 deaths (4.1 per 10 000 person-years [95% CI, 3.8-4.5 per 10 000 person-years]) among those with 1 teen pregnancy, and 345 deaths (6.1 per 10 000 person-years [95% CI, 5.5-6.8 per 10 000 person-years]) among those with 2 or more teen pregnancies; adjusted HRs (AHRs) were 1.51 (95% CI, 1.39-1.63) for those with 1 pregnancy and 2.14 (95% CI, 1.92-2.39) for those with 2 or more pregnancies. Comparing those with vs without a teen pregnancy, the AHR for premature death was 1.25 (95% CI, 1.12-1.40) from noninjury, 2.06 (95% CI, 1.75-2.43) from unintentional injury, and 2.02 (95% CI, 1.54-2.65) from intentional injury. Conclusions and Relevance: In this population-based cohort study of 2.2 million female teenagers, teen pregnancy was associated with future premature mortality. It should be assessed whether supports for female teenagers who experience a pregnancy can enhance the prevention of subsequent premature mortality in young and middle adulthood.

The Dynamic Nature of the Socioeconomic Determinants of Cardiovascular Health: A Narrative Review.

Despite decades of social epidemiologic research, health inequities remain pervasive and ubiquitous in Canada and elsewhere. One reason may be our use of socioeconomic measurement, which has often relied on single point-in-time exposures. To explore the extent to which researchers have incorporated dynamic socioeconomic measurement into cardiovascular health outcome evaluations, we performed a narrative review. We estimated the prevalence of socioeconomic longitudinal cardiovascular research studies that identified socioeconomic exposures at 2 or more points in time between the years of 2019 and 2023. We defined cardiovascular outcome studies as those that examined coronary artery disease, myocardial infarction, acute coronary syndrome, stroke, heart failure, cardiac arrhythmias, cardiac death, cardiometabolic factors, transient ischemic attacks, peripheral artery disease, or hypertension. Socioeconomic exposures included individual income, neighbourhood income, intergenerational social mobility, education, occupation, insurance status, and economic security. Seven percent of socioeconomic cardiovascular outcome studies have measured socioeconomic status at 2 or more points in time throughout the follow-up period, hypothesized mechanisms by which dynamic socioeconomic measures affected outcome focused on social mobility, accumulation, and critical period theories. Insights, implications, and future directions are discussed, in which we highlight ways in which postal code data can be better used methodologically as a dynamic socioeconomic measure. Future research must incorporate dynamic socioeconomic measurement to better inform root causes, interventions, and health-system designs if health equity is to be improved.

ESPEN practical guideline: Nutritional support for polymorbid medical inpatients.

BACKGROUND: Disease-related malnutrition in polymorbid medical inpatients is a highly prevalent syndrome associated with significantly increased morbidity, disability, short- and long-term mortality, impaired recovery from illness, and healthcare costs. AIM: As there are uncertainties in applying disease-specific guidelines to patients with multiple conditions, our aim was to provide evidence-based recommendations on nutritional support for the polymorbid patient population hospitalized in medical wards. METHODS: The 2023 update adheres to the standard operating procedures for ESPEN guidelines. We undertook a systematic literature search for 15 clinical questions in three different databases (Medline, Embase and the Cochrane Library), as well as in secondary sources (e.g., published guidelines), until July 12th, 2022. Retrieved abstracts were screened to identify relevant studies that were used to develop recommendations (including SIGN grading), which was followed by submission to Delphi voting. Here, the practical version of the guideline is presented which has been shortened and equipped with flow charts for patients care. RESULTS: 32 recommendations (7× A, 11× B, 10× O and 4× GPP), which encompass different aspects of nutritional support were included from the scientific guideline including indication, route of feeding, energy and protein requirements, micronutrient requirements, disease-specific nutrients, timing, monitoring and procedure of intervention. Here, the practical version of the guideline is presented which has been shortened and equipped with flow charts for patients care. CONCLUSIONS: Recent high-quality trials have provided increasing evidence that nutritional support can reduce morbidity and other complications associated with malnutrition in polymorbid patients. The timely screening of patients for risk of malnutrition at hospital admission followed by individualized nutritional support interventions for at-risk patients should be part of routine clinical care and multimodal treatment in hospitals worldwide. Use of this updated practical guideline offers an evidence-based nutritional approach to polymorbid medical inpatients and may improve their outcomes.

Bacterial isolates from positive paired venous catheter and peripheral blood cultures taken during parenteral nutrition were the same species but different strains: A case report.

OBJECTIVE: The same microbial species isolated from blood simultaneously drawn from a central venous catheter hub and a peripheral vein (paired blood cultures) during parenteral nutrition may be assumed to represent the same strain. This case report provides an example of this assumption being incorrect along with a comparator example of it being correct. This has implications for interpretation of differential time to positivity and differential quantitative blood cultures during investigation of suspected intraluminal intravascular catheter or cannula bloodstream infection. CASE DESCRIPTION: Two patients ages ≥18 y prescribed parenteral nutrition each had positive paired blood cultures that had been taken for suspected catheter bloodstream infection because of temperature spikes ≥38°C. The paired Staphylococcus epidermidis isolates from the first patient and the paired Enterococcus faecium isolates from the second patient were each tested beyond routine clinical care to establish if they could be different strains. The central and peripheral isolates of Staphylococcus epidermidis from the first patient were different strains based on hospital-reported antibiograms, genomic DNA profiles, thermograms, and weaker growth and different sizes of colonies of the central strain compared with the peripheral strain. There were no such differences for the isolates of Enterococcus faecium from the second patient. RESULTS: The central and peripheral isolates of Staphylococcus epidermidis from the first patient were different strains based on hospital-reported antibiograms, genomic DNA profiles, thermograms, and weaker growth and different sizes of colonies of the central strain compared with the peripheral strain. There were no such differences for the isolates of Enterococcus faecium from the second patient. CONCLUSION: This case report indicates consideration should be given to reporting whether bacteria have been identified at either species or strain level if differential time to positivity or differential quantitative blood cultures are used to define catheter or cannula bloodstream infection.

Transcatheter Aortic Valve Implantation Wait-Time Management: Derivation and Validation of the Canadian TAVI Triage Tool (CAN3T).

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has seen indication expansion and thus exponential growth in demand over the past decade. In many jurisdictions, the growing demand has outpaced capacity, increasing wait times and preprocedural adverse events. In this study, we derived prediction models that estimate the risk of adverse events on the waitlist and developed a triage tool to identify patients who should be prioritized for TAVI. METHODS AND RESULTS: We included adult patients in Ontario, Canada referred for TAVI and followed up until one of the following events first occurred: death, TAVI procedure, removal from waitlist, or end of the observation period. We used subdistribution hazards models to find significant predictors for each of the following outcomes: (1) all-cause death while on the waitlist; (2) all-cause hospitalization while on the waitlist; (3) receipt of urgent TAVI; and (4) a composite outcome. The median predicted risk at 12 weeks was chosen as a threshold for a maximum acceptable risk while on the waitlist and incorporated in the triage tool to recommend individualized wait times. Of 13 128 patients, 586 died while on the waitlist, and 4343 had at least 1 hospitalization. A total of 6854 TAVIs were completed, of which 1135 were urgent procedures. We were able to create parsimonious models for each outcome that included clinically relevant predictors. CONCLUSIONS: The Canadian TAVI Triage Tool (CAN3T) is a triage tool to assist clinicians in the prioritization of patients who should have timely access to TAVI. We anticipate that the CAN3T will be a valuable tool as it may improve equity in access to care, reduce preventable adverse events, and improve system efficiency.

The potential for isothermal microcalorimetry to detect venous catheter infection isolates and establish antibiograms.

OBJECTIVES: Because bloodstream infection and venous catheter (or cannula) bloodstream infection are associated with high morbidity and cost, early identification and treatment are important. Isothermal microcalorimetry can detect microbial growth using thermal power (heat flow), essentially in real time. The aim of this study was to examine the potential of this technique in clinical practice. METHODS: Thermal power of wild-type bacteria (Escherichia coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Enterococcus faecium) isolated from blood cultures of adult inpatients receiving parenteral nutrition in routine clinical practice was measured at 37°C every 10s using a Thermometric 2277 instrument. Temporal patterns of heat flow were used to detect the presence of bacteria, differentiate between them, and test their antibiotic sensitivity. Within and between batch reproducibility (% coefficient of variation [%CV]) was also established. RESULTS: Isothermal microcalorimetry always correctly detected the absence or presence of wild-type bacteria. Thermograms differed distinctly between species. Key thermographic features, such as peak heights, timing of peak heights, and interval between peak heights, were highly reproducible within each species (within-batch %CV usually about ≤1%, although between-batch %CV was usually higher). The antibiotic sensitivities (tested only for S. epidermidis and K. pneumoniae) confirmed the results obtained from the hospital laboratory. CONCLUSIONS: Isothermal microcalorimetry is a promising and highly reproducible real-time measurement technique with potential application to the investigation, species identification, and targeted antibiotic treatment of bloodstream infection and venous catheter (or cannula) bloodstream infection.