The diagnostic accuracy of 18F-FDG PET/CT in diagnosing fracture-related infections.

PURPOSE: 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) is frequently used to diagnose fracture-related infections (FRIs), but its diagnostic performance in this field is still unknown. The aims of this study were: (1) to assess the diagnostic performance of qualitative assessment of 18F-FDG PET/CT scans in diagnosing FRI, (2) to establish the diagnostic performance of standardized uptake values (SUVs) extracted from 18F-FDG PET/CT scans and to determine their associated optimal cut-off values, and (3) to identify variables that predict a false-positive (FP) or false-negative (FN) 18F-FDG PET/CT result. METHODS: This retrospective cohort study included all patients with suspected FRI undergoing 18F-FDG PET/CT between 2011 and 2017 in two level-1 trauma centres. Two nuclear medicine physicians independently reassessed all 18F-FDG PET/CT scans. The reference standard consisted of the result of at least two deep, representative microbiological cultures or the presence/absence of clinical confirmatory signs of FRI (AO/EBJIS consensus definition) during a follow-up of at least 6 months. Diagnostic performance in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was calculated. Additionally, SUVs were measured on 18F-FDG PET/CT scans. Volumes of interest were drawn around the suspected and corresponding contralateral areas to obtain absolute values and ratios between suspected and contralateral areas. A multivariable logistic regression analysis was also performed to identify the most important predictor(s) of FP or FN 18F-FDG PET/CT results. RESULTS: The study included 156 18F-FDG PET/CT scans in 135 patients. Qualitative assessment of 18F-FDG PET/CT scans showed a sensitivity of 0.89, specificity of 0.80, PPV of 0.74, NPV of 0.91 and diagnostic accuracy of 0.83. SUVs on their own resulted in lower diagnostic performance, but combining them with qualitative assessments yielded an AUC of 0.89 compared to an AUC of 0.84 when considering only the qualitative assessment results (p = 0.007). 18F-FDG PET/CT performed <1 month after surgery was found to be the independent variable with the highest predictive value for a false test result, with an absolute risk of 46% (95% CI 27-66%), compared with 7% (95% CI 4-12%) in patients with 18F-FDG PET/CT performed 1-6 months after surgery. CONCLUSION: Qualitative assessment of 18F-FDG PET/CT scans had a diagnostic accuracy of 0.83 and an excellent NPV of 0.91 in diagnosing FRI. Adding SUV measurements to qualitative assessment provided additional accuracy in comparison to qualitative assessment alone. An interval between surgery and 18F-FDG PET/CT of <1 month was associated with a sharp increase in false test results.

Incorporating repeated measurements into prediction models in the critical care setting: a framework, systematic review and meta-analysis.

BACKGROUND: The incorporation of repeated measurements into multivariable prediction research may greatly enhance predictive performance. However, the methodological possibilities vary widely and a structured overview of the possible and utilized approaches lacks. Therefore, we [1] propose a structured framework for these approaches, [2] determine what methods are currently used to incorporate repeated measurements in prediction research in the critical care setting and, where possible, [3] assess the added discriminative value of incorporating repeated measurements. METHODS: The proposed framework consists of three domains: the observation window (static or dynamic), the processing of the raw data (raw data modelling, feature extraction and reduction) and the type of modelling. A systematic review was performed to identify studies which incorporate repeated measurements to predict (e.g. mortality) in the critical care setting. The within-study difference in c-statistics between models with versus without repeated measurements were obtained and pooled in a meta-analysis. RESULTS: From the 2618 studies found, 29 studies incorporated multiple repeated measurements. The annual number of studies with repeated measurements increased from 2.8/year (2000-2005) to 16.0/year (2016-2018). The majority of studies that incorporated repeated measurements for prediction research used a dynamic observation window, and extracted features directly from the data. Differences in c statistics ranged from - 0.048 to 0.217 in favour of models that utilize repeated measurements. CONCLUSIONS: Repeated measurements are increasingly common to predict events in the critical care domain, but their incorporation is lagging. A framework of possible approaches could aid researchers to optimize future prediction models.

The ClearSight System for Postoperative Arterial Blood Pressure Monitoring After Carotid Endarterectomy: A Validation Study.

BACKGROUND: The majority of postoperative events in patients undergoing carotid endarterectomy (CEA) are of hemodynamic origin, requiring preventive strict postoperative arterial blood pressure (BP) control. This study aimed to assess whether BP monitoring with noninvasive beat-to-beat ClearSight finger BP (BPCS) can replace invasive beat-to-beat radial artery BP (BPRAD) in the postoperative phase. METHODS: This study was a single-center clinical validation study using a prespecified study protocol. In 48 patients with symptomatic carotid artery stenosis, BPCS and BPRAD were monitored ipsilateral in a simultaneous manner during a 6-hour period on the recovery unit following CEA. Primary endpoints were accuracy and precision of BP derived by ClearSight (Edward Lifesciences, Irvine, CA) vs. the reference standard (Arbocath 20 G, Hospira, Lake Forest, IL) to investigate if BPCS is a reliable noninvasive alternative for BP monitoring postoperatively in CEA patients. Validation was guided by the standard set by the Association for Advancement of Medical Instrumentation (AAMI), considering a BP-monitor adequate when bias (precision) is <5 (8) mm Hg. Secondary endpoint was percentage under- and overtreatment, defined as exceedance of individual postoperative systolic BP threshold by BPRAD or BPCS in contrast to BPCS or BPRAD, respectively. RESULTS: The bias (precision) of BPCS compared to BPRAD was -10 (13.6), 8 (7.2) and 4 (7.8) mm Hg for systolic, diastolic and mean arterial pressure (MAP), respectively. Based on BPCS, undertreatment was 5.6% and overtreatment was 2.4%; however, percentages of undertreatment quadrupled for lower systolic BP thresholds. CONCLUSIONS: Noninvasive MAP, but not systolic and diastolic BP, was similar to invasive BPRAD during postoperative observation following CEA, based on AAMI criteria. However, as systolic BP is currently leading in postoperative monitoring to adjust BP therapy on, BPCS is not a reliable alternative for BPRAD.

Perinatal thalamic injury: MRI predictors of electrical status epilepticus in sleep and long-term neurodevelopment.

OBJECTIVE: Perinatal thalamic injury is associated with epilepsy with electrical status epilepticus in sleep (ESES). The aim of this study was to prospectively quantify the risk of ESES and to assess neuroimaging predictors of neurodevelopment. METHODS: We included patients with perinatal thalamic injury. MRI scans were obtained in the neonatal period, around three months of age and during childhood. Thalamic and total brain volumes were obtained from the three months MRI. Diffusion characteristics were assessed. Sleep EEGs distinguished patients into ESES (spike-wave index (SWI) >85%), ESES-spectrum (SWI 50-85%) or no ESES (SWI < 50%). Serial Intelligence Quotient (IQ)/Developmental Quotient (DQ) scores were obtained during follow-up. Imaging and EEG findings were correlated to neurodevelopmental outcome. RESULTS: Thirty patients were included. Mean thalamic volume at three months was 8.11 (±1.67) ml and mean total brain volume 526.45 (±88.99) ml. In the prospective cohort (n = 23) 19 patients (83%) developed ESES (-spectrum) abnormalities after a mean follow-up of 96 months. In the univariate analysis, larger thalamic volume, larger total brain volume and lower SWI correlated with higher mean IQ/DQ after 2 years (Pearson's r = 0.74, p = 0.001; Pearson's r = 0.64, p = 0.005; and Spearman's rho -0.44, p = 0.03). In a multivariable mixed model analysis, thalamic volume was a significant predictor of IQ/DQ (coefficient 9.60 [p < 0.001], i.e., corrected for total brain volume and SWI and accounting for repeated measures within patients, a 1 ml higher thalamic volume was associated with a 9.6 points higher IQ). Diffusion characteristics during childhood correlated with IQ/DQ after 2 years. SIGNIFICANCE: Perinatal thalamic injury is followed by electrical status epilepticus in sleep in the majority of patients. Thalamic volume and diffusion characteristics correlate to neurodevelopmental outcome.

Sleep slow-wave homeostasis and cognitive functioning in children with electrical status epilepticus in sleep.

STUDY OBJECTIVES: Encephalopathy with electrical status epilepticus in sleep (ESES) is characterized by non-rapid eye movement (non-REM)-sleep-induced epileptiform activity and acquired cognitive deficits. The synaptic homeostasis hypothesis describes the process of daytime synaptic potentiation balanced by synaptic downscaling in non-REM-sleep and is considered crucial to retain an efficient cortical network. We aimed to study the overnight decline of slow waves, an indirect marker of synaptic downscaling, in patients with ESES and explore whether altered downscaling relates to neurodevelopmental and behavioral problems. METHODS: Retrospective study of patients with ESES with at least one whole-night electroencephalogram (EEG) and neuropsychological assessment (NPA) within 4 months. Slow waves in the first and last hour of non-REM-sleep were analyzed. Differences in slow-wave slope (SWS) and overnight slope course between the epileptic focus and non-focus electrodes and relations to neurodevelopment and behavior were analyzed. RESULTS: A total of 29 patients with 44 EEG ~ NPA combinations were included. Mean SWS decreased from 357 to 327 µV/s (-8%, p < 0.001) across the night and the overnight decrease was less pronounced in epileptic focus than in non-focus electrodes (-5.6% vs. -8.7%, p = 0.003). We found no relation between SWS and neurodevelopmental test results in cross-sectional and longitudinal analyses. Patients with behavioral problems showed less SWS decline than patients without and the difference was most striking in the epileptic focus (-0.9% vs. -8.8%, p = 0.006). CONCLUSIONS: Slow-wave homeostasis-a marker of synaptic homeostasis-is disturbed by epileptiform activity in ESES. Behavioral problems, but not neurodevelopmental test results, were related to severity of this disturbance.

The intermediate care unit as a cost-reducing critical care facility in tertiary referral hospitals: a single-centre observational study.

OBJECTIVES: To determine whether and to what extent the surgical intermediate care unit (IMCU) reduces healthcare costs. DESIGN: Retrospective cohort study. SETTING: The mixed-surgical IMCU of a tertiary academic referral hospital. PARTICIPANTS: All admissions (n=2577) from 2012 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was the hypothetical cost savings due to the presence of the IMCU. For this, each admission day was classified as either low-acuity or high-acuity, based on the Therapeutic Intervention Scoring System-28, the required specific nursing interventions and the indication for admission at the IMCU. Costs (2018) used were €463 per hospital ward, €1307 per IMCU and €2224 per intensive care unit (ICU) admission day. Savings were calculated by subtracting the actual IMCU costs from the hypothetical costs in the absence of the IMCU. RESULTS: There were 9037 admission days (n=2577 admissions) at the IMCU. The proportion of high-acuity admissions was 87.6%. Total costs at the IMCU were €11.808 888. Total hypothetical costs in absence of the IMCU were €18.115 284. Total cost savings were thus €6.306 395, or €1.576 599, per year. CONCLUSIONS: The surgical IMCU may substantially reduce societal healthcare costs, making it a cost saving alternative to ICU care. Constant adequate triage is essential to optimise its potential.

Optimizing critical care of the trauma patient at the intermediate care unit: a cost-efficient approach.

BACKGROUND: The aim of this study was to describe the case load, safety, and cost savings of critical care of the trauma patient provided at the surgical intermediate care unit (IMCU). METHODS: This cohort study included all trauma admissions between January 1, 2011 and January 7, 2015 at the general intensive care unit (ICU), stand-alone neuro(surgical) IMCU, and stand-alone (trauma) surgical IMCU. Trauma mechanism, Abbreviated Injury Scale score and Injury Severity Score (ISS), vital signs, laboratory parameters, admission duration, intubation duration, ICU transfer, and in-hospital mortality were prospectively collected. Hypothetical cost savings were calculated using the fixed cost price per IMCU (US$1500) and ICU (US$2500) admission day. RESULTS: A total of 1320 admissions were included, 675 (51.1%) at the IMCU and 645 (48.9%) at the ICU. Patients admitted at the IMCU had a median ISS of 17 (11, 22). Their median duration of admission was 32.8 hours (18.8, 62.5). At the IMCU, one patient died due to aneurogenic shock. A subsequent ICU transfer was required in 38 (5.6%) IMCU admissions. Of these transfers, four patients died due to neurological deterioration. At the ICU, the median ISS was 22 (14, 30). Nearly all (n=620, 96.3%) ICU trauma patients required mechanical ventilation. Expected total cost savings due to the presence of the IMCU were US$1 772 785. DISCUSSION: A substantial amount of trauma patients in need of critical care can safely be admitted at the IMCU, without the need for further mechanical ventilation. Thereby, the IMCU could fulfill an essential cost-saving role in the management of severely injured trauma patients. LEVEL OF EVIDENCE: Level IV.

Predicting early deterioration of admitted patients at the Intermediate Care Unit.

PURPOSE: Under-triage is a major threat when admitting patients at the Intermediate Care Unit (IMCU). This study aims to identify risk factors and predict early deterioration of IMCU admissions, to reduce the risk of under-triage. MATERIALS AND METHODS: This retrospective cohort study included all admissions to the mixed-surgical stand-alone IMCU of a tertiary referral hospital (2001-2015). Variables included were age, sex, admission indication, admitting specialty, re-admission, and nursing interventions. Early clinical deterioration was defined as ICU transfer or death ≤24 h of admission. Multinomial and logistic regression analyses were performed to identify risk factors and obtain predictions, for several frequently encountered subgroups. RESULTS: A total of 9103 admissions were included, of which 350 (3.8%) early deteriorated. Patients admitted for hemodynamic and respiratory instability had a high risk of early deterioration (OR 16.3 (CI 4.5-59.1)), probability 47.1%. Patients admitted with respiratory insufficiency and active diuresis or complicated sepsis had a high probability of early deterioration (≥29% and ≥26% respectively). The model had an optimism-corrected c-statistic of 0.79 (IQR 0.78-0.80). CONCLUSIONS: Patients with combined hemodynamic and respiratory instability should not be admitted to the IMCU. Patients with respiratory insufficiency and active diuresis, or complicated sepsis require close monitoring.

Joint management format at the mixed-surgical intermediate care unit: an interrupted time series analysis.

BACKGROUND: The management format of the mixed-surgical intermediate care unit (IMCU) affects its performance. A format of combined supervision of surgeons with additional critical care certifications and admitting specialists, named the "joint format", may herein be a promising new model of specialized critical care. This study aims to assess the performance of the joint management format. METHODS: This observational cohort study compared three IMCU management formats at the stand-alone, mixed-surgical IMCU of a tertiary referral hospital using interrupted time series analyses. All admissions from 2001 until 2015 were included. Predetermined criteria for performance (utilization, efficiency, and safety) were applied to three different management format periods: open (2001-2006), closed (2006-2011), and joint (2011-2015) formats. RESULTS: A total of 8894 admissions were analyzed. In terms of case load (utilization), there was an overall increase in the number of surgical patients (0.25%/year) (p<0.001), age (0.38/year) (p<0.001), and readmissions from the ward (0.16%/year) (p<0.001) and from the intensive care unit (ICU) (0.17%/year) (p=0.014). In terms of efficiency, the admission duration decreased (1.58 hours/year) (p<0.001). Transfer to the ICU within 24 hours, readmission within 24 hours from the ward, and unplanned mortality (eg, safety) did not change over time. DISCUSSION: At a time of increasingly complex case load, the joint format at the mixed-surgical IMCU is an efficient and safe management format in which the admitting specialist continues to provide specialized care. Specialty-specific supervision at IMCUs is a safe option which should be considered in healthcare policy decisions. LEVEL OF EVIDENCE: Level IV.

A Proposal for an Intermediate Care Unit-Quality Measurement Framework.

Rationale, Aims, and Objectives. The Intermediate Care Unit (IMCU) is a hospital unit which is logistically situated between the hospital ward and the Intensive Care Unit (ICU). There is debate regarding the value of the IMCU. Understanding its value is compromised by the lack of adequate quality indicators. Therefore, this study identifies currently used IMCU indicators and evaluates their usefulness. Methods. Through a systematic literature search, currently used quality indicators were identified and evaluated for their importance using a proposed IMCU-specific quality measurement framework. Results. From 4034 titles and abstracts, 168 articles were selected for full-text review. Of these, 22 articles were included, which reported IMCU quality at the level of the IMCU (n = 12), the ICU (n = 5), both IMCU and ICU (n = 3) or hospital level (n = 2). At the IMCU, the IMCU mortality (n = 16), discharge-to-ICU rate (n = 7), in-hospital IMCU mortality (n = 7), and length of stay (n = 6) were most frequently reported. Three studies compared the effect of different structures of the IMCU on its utilization or hospital outcome. Conclusions. Current focus in IMCU quality research is towards measuring quality at the IMCU itself. Since the influence of the structure of IMCUs on its utilization and its effects on hospital outcome are only rarely investigated, attention should shift towards these important issues in further research. The proposed IMCU quality measurement framework can thereby serve as a helpful tool.

Introducing high-flow nasal cannula oxygen therapy at the intermediate care unit: expanding the range of supportive pulmonary care.

BACKGROUND: Non-invasive respiratory support is a frequent indication for intermediate care unit (IMCU) admission. Extending the possibilities of respiratory support at the IMCU with high-flow nasal cannula oxygen therapy (HFNC) may prevent intensive care unit (ICU) transfer and invasive ventilation. However, the safety and limitations of HFNC administration in the stand-alone IMCU setting are not yet studied. This study therefore aims to investigate to what extent and in which patients HFNC can safely be administered at a stand-alone mixed surgical IMCU. METHODS: A case series, using retrospectively collected data, was performed after the first year of introducing HFNC at a stand-alone IMCU. The following variables were collected: indication to start HFNC, vital parameters and arterial blood gas measurements. Primary outcome was 30-day mortality. Secondary outcome was transfer to the ICU. RESULTS: A total of 96 admissions were included. The indications to start HFNC at the IMCU were predominantly pathologies of pulmonary origin (n=67, 69.8%). Less frequent indications were prolonged support postweaning (n=15), non-pulmonary sepsis (n=7) and post-trauma resuscitation (n=6). The average PaO2/FiO2ratio at start of HFNC was 152 (95% CI 139 to 165). 30-day mortality was 7, of which 5 were admitted with treatment restrictions (no ICU policy) and 2 deaths were unrelated to HFNC. Transfer to the ICU occurred in 18 (18.8%) admissions, of which 12 received invasive mechanical ventilation. Reason for ICU transfer was mainly PaO2/FiO2 ratio<100 under maximum non-invasive treatment (n=12, 66.7%). Application of HFNC at the IMCU prevented 162 days of ICU admission. DISCUSSION: Administration of HFNC at a stand-alone surgical IMCU may be safe as it expands the range of supportive possibilities and thereby reduces the need for ICU admissions. Pulmonary indications to start HFNC increase the risk of ICU transfer and mechanical ventilation. LEVEL OF EVIDENCE: Level VI.

Assessment of the intermediate care unit triage system.

BACKGROUND: An important critique with respect to the utilization of intermediate care units (IMCU) is that they potentially admit patients who would otherwise be cared for on the regular ward. This would lead to an undesired waste of critical care resources. This article aims to (1) describe the caseload at the IMCU and (2) to assess the triage system at the IMCU to determine potentially unnecessary admissions. METHODS: This cohort study included all admissions at the mixed-surgical IMCU from 2001 to 2015. The Therapeutic Intervention Scoring System-28 (TISS-28) was prospectively collected for all admissions to describe the caseload at the IMCU and to identify medical criteria for admission. These were combined with logistical criteria to assess the IMCU triage system. RESULTS: A total of 8816 admissions were included in the study. The average TISS-28 was 20.19 (95% CI 18.05 to 22.33), corresponding with 3.57 (95% CI 3.19 to 3.94) hours of direct patient-related work per patient per nursing shift. Over time, this increased by an average of 0.27 points/year (p<0.001). Of all admissions, 6539 (74.2%) were medically considered to be justly admitted, and 7093 (80.4%) were logistically considered to be justly admitted. With these criteria combined, a total of 8324 (94.4%) were correctly admitted. DISCUSSION: Most admissions to the IMCU are medically and/or logistically necessary, as the majority of admitted patients demand a higher level of nursing care than available on the general ward. Continuous triage is thereby essential. These findings support further utilization of the IMCU in our current healthcare system and has important implications for IMCU-related management decisions. LEVEL OF EVIDENCE: Level VI.

Limited Predictive Value of Serum Inflammatory Markers for Diagnosing Fracture-Related Infections: results of a large retrospective multicenter cohort study.

Introduction: Diagnosing Fracture-Related Infections (FRI) based on clinical symptoms alone can be challenging and additional diagnostic tools such as serum inflammatory markers are often utilized. The aims of this study were 1) to determine the individual diagnostic performance of three commonly used serum inflammatory markers: C-Reactive Protein (CRP), Leukocyte Count (LC) and Erythrocyte Sedimentation Rate (ESR), and 2) to determine the diagnostic performance of a combination of these markers, and the additional value of including clinical parameters predictive of FRI. Methods: This cohort study included patients who presented with a suspected FRI at two participating level I academic trauma centers between February 1st 2009 and December 31st 2017. The parameters CRP, LC and ESR, determined at diagnostic work-up of the suspected FRI, were retrieved from hospital records. The gold standard for diagnosing or ruling out FRI was defined as: positive microbiology results of surgically obtained tissue samples, or absence of FRI at a clinical follow-up of at least six months. The diagnostic accuracy of the individual serum inflammatory markers was assessed. Analyses were done with both dichotomized values using hospital thresholds as well as with continuous values. Multivariable logistic regression analyses were performed to obtain the discriminative performance (Area Under the Receiver Operating Characteristic, AUROC) of (1) the combined inflammatory markers, and (2) the added value of these markers to clinical parameters. Results: A total of 168 patients met the inclusion criteria and were included for analysis. CRP had a 38% sensitivity, 34% specificity, 42% positive predictive value (PPV) and 78% negative predictive value (NPV). For LC this was 39%, 74%, 46% and 67% and for ESR 62%, 64%, 45% and 76% respectively. The diagnostic accuracy was 52%, 61% and 80% respectively. The AUROC was 0.64 for CRP, 0.60 for LC and 0.58 for ESR. The AUROC of the combined inflammatory markers was 0.63. Serum inflammatory markers combined with clinical parameters resulted in AUROC of 0.66 as opposed to 0.62 for clinical parameters alone. Conclusion: The added value of CRP, LC and ESR for diagnosing FRI is limited. Clinicians should be cautious when interpreting the results of these tests in patients with suspected FRI.

Utilisation of Intermediate Care Units: A Systematic Review.

Background. The diversity in formats of Intermediate Care Units (IMCUs) makes it difficult to compare data from different settings. The purpose of this article was to describe and quantify these different formations and utilisation. Methods. We performed a systematic review extracting geographic location, nomenclature used, admitting specialties, open (admitting specialist in charge) or closed (intensivist/generalist in charge) management format, location in hospital, number of beds, nursing workload, medical staff to patient ratios, and modalities-possibilities and limitations-implemented. Results. Nomenclature used was High Dependency Unit (56.8%) or Intermediate Care Unit (24.3%), with the latter one increasingly being used recently. The median number of beds was 6 (IQR 4-10). Location (p < 0.001) and admitting specialties (p = 0.03) were related to the management format. IMCUs integrated or adjacent to Intensive Care Units were more often capable of using single vasoactive medication (p = 0.025). The mean nurse to patient ratio was 1 to 2.5. Conclusions. IMCUs often have a specific task in a hospital, which is reflected in location, format, and utilisation. The management format depends on location and admitting specialist while incorporated supportive treatment modules reflect its function. Common IMCU denominators are continuous monitoring and respiratory support, without mechanical ventilation and multiple vasoactive medications.