Between-centre differences in care for in-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Survival after in-hospital cardiac arrest is poor, but current literature shows substantial heterogeneity in reported survival rates. This study aims to evaluate care for patients suffering in-hospital cardiac arrest (IHCA) in the Netherlands by assessing between-hospital heterogeneity in outcomes and to explain this heterogeneity stemming from differences in case-mix or differences in quality of care. METHODS: A prospective multicentre study was conducted comprising 14 centres. All IHCA patients were included. The adjusted variation in structure and process indicators of quality of care and outcomes (in-hospital mortality and cerebral performance category [CPC] scale) was assessed with mixed effects regression with centre as random intercept. Variation was quantified using the median odds ratio (MOR), representing the expected odds ratio for poor outcome between two randomly picked centres. RESULTS: After excluding centres with less than 10 inclusions (2 centres), 701 patients were included of whom, 218 (32%) survived to hospital discharge. The unadjusted and case-mix adjusted MOR for mortality was 1.19 and 1.05, respectively. The unadjusted and adjusted MOR for CPC score was 1.24 and 1.19, respectively. In hospitals where personnel received cardiopulmonary resuscitation (CPR) training twice per year, 183 (64.7%) versus 290 (71.4%) patients died or were in a vegetative state, and 59 (20.8%) versus 68 (16.7%) patients showed full recovery (p < 0.001). CONCLUSION: In the Netherlands, survival after IHCA is relatively high and between-centre differences in outcomes are small. The existing differences in survival are mainly attributable to differences in case-mix. Variation in neurological outcome is less attributable to case-mix.

The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. METHODS: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. DISCUSSION: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? TRIAL REGISTRATION: EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

Post COVID-19 Pandemic Increased Detection of Mycoplasma Pneumoniae in Adults Admitted to the Intensive Care.

Background: Mycoplasma pneumoniae (M. pneumoniae) infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for timely diagnosis, given potential diagnostic method limitations. Methods: A retrospective case series analysis was conducted on M. pneumonia PCR-positive patients admitted to two Dutch secondary hospitals' ICUs between January 2023 and February 2024. Clinical presentations, treatments, outcomes, and mechanical ventilation data were assessed. Results: Seventeen ICU-admitted patients were identified, with a median age of 44 years, primarily due to hypoxia. Non-invasive ventilation was effective for most, while five required invasive mechanical ventilation. None of the patients required extracorporeal membrane oxygenation. No fatalities occurred. Post-PCR, treatment was adjusted to doxycycline or azithromycin; seven received steroid treatment. Discussion: Increased ICU admissions for M. pneumoniae infection were observed. Diverse clinical and radiological findings emphasize heightened clinical awareness. Early molecular diagnostics and tailored antibiotic regimens are crucial since beta-lactam antibiotics are ineffective. Conclusion: This study highlights the escalating challenge of severe M. pneumoniae infections in ICUs, necessitating a multifaceted approach involving accurate diagnostics, vigilant monitoring, and adaptable treatment strategies for optimal patient outcomes.

Presence of procoagulant peripheral blood mononuclear cells in severe COVID-19 patients relate to ventilation perfusion mismatch and precede pulmonary embolism.

PURPOSE: Pulmonary emboli (PE) contribute substantially to coronavirus disease 2019 (COVID-19) related mortality and morbidity. Immune cell-mediated hyperinflammation drives the procoagulant state in COVID-19 patients, resulting in immunothrombosis. To study the role of peripheral blood mononuclear cells (PBMC) in the procoagulant state of COVID-19 patients, we performed a functional bioassay and related outcomes to the occurrence of PE. Secondary aims were to relate this functional assay to plasma D-dimer levels, ventilation perfusion mismatch and TF expression on monocyte subsets. METHODS: PBMC from an ICU biobank were obtained from 20 patients with a computed tomography angiograph (CTA) proven PE and compared to 15 COVID-19 controls without a proven PE. Functional procoagulant properties of PBMC were measured using a modified fibrin generation time (MC-FGT) assay. Tissue factor (TF) expression on monocyte subsets were measured by flow cytometry. Additional clinical data were obtained from patient records including end-tidal to arterial carbon dioxide gradient. RESULTS: MC-FGT levels were highest in the samples taken closest to the PE detection, similar to the end-tidal to arterial carbon dioxide gradient (ETCO2 - PaCO2), a measurement to quantify ventilation-perfusion mismatch. In patients without proven PE, peak MC-FGT relates to an increase in end-tidal to arterial carbon dioxide gradient. We identified non-classical, CD16 positive monocytes as the subset with increased TF expression. CONCLUSION: We show that the procoagulant state of PBMC could aid in early detection of PE in COVID-19 ICU patients. Combined with end-tidal to ETCO2 - PaCO2 gradient, these tests could improve early detection of PE on the ICU.

Using Residual Blood from the Arterial Blood Gas Test to Perform Therapeutic Drug Monitoring of Vancomycin: An Example of Good Clinical Practice Moving towards a Sustainable Intensive Care Unit.

Background: Regarding sustainability in the intensive care unit (ICU), there is increasing interest in reducing material waste and avoiding unnecessary procedures. Therapeutic drug monitoring (TDM) of vancomycin, using a dedicated tube, is standard clinical care during treatment with vancomycin. Furthermore, in the ICU, on a daily basis, arterial blood gas (ABG) tests are frequently performed throughout the day. After analysis, a variable volume of blood is discarded. Lithium heparin (LiHep) syringes for ABG tests differ from normally used dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The primary objective was to compare both containers and validate the use of LiHep syringes. Secondary objectives were to evaluate the potential impact on saving materials, nursing time, and costs when implementing vancomycin TDM via LiHep syringes. Methods: Vancomycin analysis from sampling in lithium heparin (LiHep) syringes for ABG tests was validated and compared with the concentrations from conventional sampling in K2EDTA tubes. For method comparison, a Bland-Altman plot and Deming regression analysis were performed. The method was validated for inter- and intra-day precision and accuracy. Vancomycin was analyzed by means of the validated method using a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) autoanalyzer. Furthermore, an analysis was conducted to evaluate the potential impact of implementing vancomycin sampling via ABG tests on savings in materials, nursing time, and costs. Results: From 18 patients, 24 plasma samples in both K2EDTA tubes and LiHep syringes were obtained and compared. The mean relative difference between the two containers was -2.0% (-3.0 to -0.93%). Both the Deming regression analysis and the Bland-Altman plot met the acceptance criteria. Potentially, over 1000 blood draws and accompanying materials and packaging can be saved when vancomycin samples are obtained by means of scavenged LiHep syringes. The vancomycin analysis for LiHep syringes showed a total interday precision of 1.95% and an accuracy of 99.7%. The total intraday precision was 2.22%, and the accuracy was 99.2%. Accuracy and precision values were within the acceptance criteria of recovery 85 to 115% and ≤15%, respectively. Conclusion: No significant differences were found in vancomycin concentration between the two analyses, and the LiHep analysis was validated for further implementation in clinical care. Residual blood from ABG test samples can be used for TDM of vancomycin, resulting in a potential reduction of materials used and the number of blood draws. These results will contribute to a more sustainable TDM process with benefits for the patient.

In-depth assessment of health-related quality of life after in-hospital cardiac arrest.

INTRODUCTION: Evidence on physical and psychological well-being of in-hospital cardiac arrest (IHCA) survivors is scarce. The aim of this study is to describe long-term health-related quality of life (HRQoL), functional independence and psychological distress 3 and 12 months post-IHCA. METHODS: A multicenter prospective cohort study in 25 hospitals between January 2017 - May 2018. Adult IHCA survivors were included. HRQoL (EQ-5D-5L, SF-12), psychological distress (HADS, CSI) and functional independence (mRS) were assessed at 3 and 12 months post-IHCA. RESULTS: At 3-month follow-up 136 of 212 survivors responded to the questionnaire and at 12 months 110 of 198 responded. The median (IQR) EQ-utility Index score was 0.77 (0.65-0.87) at 3 months and 0.81 (0.70-0.91) at 12 months. At 3 months, patients reported a median SF-12 (IQR) physical component scale (PCS) of 38.9 (32.8-46.5) and mental component scale (MCS) of 43.5 (34.0-39.7) and at 12 months a PCS of 43.1 (34.6-52.3) and MCS 46.9 (38.5-54.5). DISCUSSION: Using various tools most IHCA survivors report an acceptable HRQoL and a substantial part experiences lower HRQoL compared to population norms. Our data suggest that younger (male) patients and those with poor functional status prior to admission are at highest risk of impaired HRQoL.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Systemic cytokine response in patients with community-acquired pneumonia.

The role of individual cytokines and polymorphisms in pneumonia has been described, but the relationship between different cytokines and polymorphisms in relation to causative microorganisms, antibiotics, corticosteroids and clinical course has not. This study questions the relationship between cytokines, polymorphisms and clinical characteristics of pneumonia. Patients diagnosed with pneumonia were included in the study. Serum cytokine levels were measured during hospital stay, genotyping was performed, causative microorganisms were identified and patients were monitored throughout the hospital stay. In 201 patients with pneumonia interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8 and IL-10 acted as acute phase proteins. After admission, the levels of these cytokines decreased rapidly. Single nucleotide polymorphisms did not influence cytokine production and were not associated with clinical outcome. Cytokine serum levels were significantly higher in patients with pneumococcal pneumonia. The decrease in levels of cytokines was independently influenced by the start of corticosteroid therapy. IL-1RA, IL-6, IL-8 and IL-10 are acute phase proteins, independent of genotype. Their levels are influenced by the nature of the causative microorganism and the start of corticosteroids therapy.

Microbial evaluation of proton-pump inhibitors and the risk of pneumonia.

Recent initiation of proton-pump inhibitor (PPI) treatment may increase the risk of community-acquired pneumonia (CAP), hypothetically by allowing colonisation of the oropharynx by gastrointestinal bacteria. The aim of this study was to assess the causal pathway by considering microbial aetiology of pneumonia and indications for initiation of PPI treatment. This was a population-based, case-control study with 430 cases with pneumonia and 1,720 matched controls. An elaborate diagnostic protocol was used to identify the causative microorganism of pneumonia. For patients recently starting PPI treatment, indications for treatment were assessed. Recent initiation of PPI treatment (<30 days) was associated with an increased risk of CAP (adjusted OR 3.1, 95% CI 1.4-7.1). Oropharyngeal bacteria were evenly distributed among current users, past users and nonusers of PPIs (p=0.41). Gastrointestinal bacteria were identified in only five (1.2%) patients with pneumonia (two current users and three nonusers). Excluding patients who were possibly prescribed PPI treatment for early symptoms of pneumonia (protopathic bias) did not alter the study findings. This study reaffirmed that use of PPIs is associated with an increased risk of CAP, especially when treatment has recently been started. Neither protopathic bias nor shifts in microbial aetiology seem to explain the association.

Long-term survival and health-related quality of life after in-hospital cardiac arrest.

INTRODUCTION: In-hospital cardiac arrest (IHCA) is an adverse event associated with high mortality. Because of the impact of IHCA more data is needed on incidence, outcomes and associated factors that are present prior to cardiac arrest. The aim was to assess one-year survival, patient-centred outcomes after IHCA and their associated pre-arrest factors. METHODS: A multicentre prospective cohort study in 25 hospitals between January 1st 2017 and May 31st 2018. Patients ≥ 18 years receiving cardiopulmonary resuscitation (CPR) for IHCA were included. Data were collected using Utstein and COSCA-criteria, supplemented by pre-arrest Modified Rankin Scale (MRS, functional status) and morbidity through the Charlson Comorbidity Index (CCI). Main outcomes were survival, health-related quality of life (HRQoL, EuroQoL) and functional status (MRS) after one-year. RESULTS: A total of 713 patients were included, 64.5% was male, median age was 63 years (IQR 52-72) and 72.8% had a non-shockable rhythm, 394 (55.3%) achieved ROSC, 231 (32.4%) survived to hospital discharge and 198 (27.8%) survived one year after cardiac arrest. Higher pre-arrest MRS, age and CCI were associated with mortality. At one year, patients rated HRQoL 72/100 points on the EQ-VAS and 69.7% was functionally independent. CONCLUSION: One-year survival after IHCA in this study is 27.8%, which is relatively high compared to previous studies. Survival is associated with a patient's pre-arrest functional status and morbidity. HRQoL appears acceptable, however functional rehabilitation warrants attention. These findings provide a comprehensive insight in in-hospital cardiac arrest prognosis.

[Communication about in hospital resuscitation orders]. / Communicatie over reanimatiebeleid in het ziekenhuis.

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Incidence of thrombotic complications in critically ill ICU patients with COVID-19.

INTRODUCTION: COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. METHODS: We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. RESULTS: We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. CONCLUSION: The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis.

INTRODUCTION: We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. METHODS: We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. RESULTS: We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8). CONCLUSION: In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals.

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes.

Mannose-binding lectin (MBL) is a pattern recognition receptor of the complement system and plays an important role in innate immunity. Whether or not MBL acts as an acute-phase response protein in infection has been an issue of extensive debate, because MBL responses have shown a high degree of heterogeneity. Single nucleotide polymorphisms (SNPs) in the promoter (wild-type Y versus X) and exon 1 (A versus 0) of the MBL2 gene can lead to MBL deficiency. This study investigated the influence of SNPs in the promoter and exon 1 of the MBL2 gene on the acute-phase responsiveness of MBL in 143 patients with community-acquired pneumonia. Acute-phase reactivity was observed only in MBL-sufficient genotypes (YA/YA, XA/YA, XA/XA and YA/0). In patients with wild-type exon 1 genotype A/A, positive acute-phase responses were associated with the presence of the YA haplotype and negative responses with its absence. Genotypes YA/0 and XA/XA produced equal levels of MBL in convalescence. In the acute phase, however, patients with genotype XA/XA displayed negative acute-phase responses more often than those with genotype YA/0. Correlation of MBL and C-reactive protein levels in the acute phase of pneumonia also depended upon the MBL2 genotype. In conclusion, acute-phase responsiveness of MBL was highly dependent upon the MBL2 genotype. These data suggest that heterogeneity in protein responses in the acute phase of disease should always be viewed in the light of possible influences of genetic differences in both structural and regulatory parts of the gene.

Extremely high serum ferritin levels as diagnostic tool in adult-onset Still's disease.

The diagnosis of adult-onset Still's disease (ASD) is difficult to establish due to the nonspecific clinical and laboratory findings. A markedly raised serum ferritin level is a typical finding, although it is not well understood why ferritin levels are extremely high in ASD. We discuss several possible explanations leading to the extremely high levels of ferritin.

The use of ultrasound during and after central venous catheter insertion versus conventional chest X-ray after insertion of a central venous catheter.

BACKGROUND: After insertion of a central venous catheter (CVC) a conventional chest X-ray (CXR) is usually taken to check for complications and correct position. Ultrasound might be equally effective as CXR and is less time consuming. We studied the use of ultrasound versus CXR after insertion of a CVC in general ward patients. METHODS: General ward patients in need of a CVC were included. CVCs were inserted under direct ultrasound guidance. After insertion, ultrasound was performed and compared with CXR to check for complications and position. The waiting time for CXR was noted. RESULTS: In total, 53 patients were included. In 52/53 patients ultrasound was feasible. The results of ultrasound and CXR only differed in 3 of 53 patients. The sensitivity of ultrasound in detecting the correct CVC position was 98% (89.4-100%). No complications were detected (ultrasound or CXR). The median waiting time for CXR was 24.5 minutes. CONCLUSIONS: Our study shows that an integral use of ultrasound during and after CVC insertion is effective in establishing that the CVC is correctly positioned and for identifying post-procedural complications in patients from the general ward when compared with CXR.

Pain measurement in mechanically ventilated critically ill patients: Behavioral Pain Scale versus Critical-Care Pain Observation Tool.

PURPOSE: The Behavioral Pain Scale (BPS) and Critical-Care Pain Observation Tool (CPOT) are behavioral pain assessment tools for uncommunicative and sedated intensive care unit (ICU) patients. This study compares the discriminant validation and reliability of the CPOT and the BPS, simultaneously, in mechanically ventilated patients on a mixed-adult ICU. MATERIALS AND METHODS: This is a prospective observational cohort study in 68 mechanically ventilated medical ICU patients who were unable to report pain. RESULTS: The BPS and CPOT scores showed a significant increase of 2 points between rest and the painful procedure (turning). The median BPS scores between rest and the nonpainful procedure (oral care) showed a significant increase of 1 point, whereas the median CPOT score remained unchanged. The interrater reliability of the BPS and CPOT scores showed a fair to good agreement (0.74 and 0.75, respectively). CONCLUSIONS: This study showed that the BPS and the CPOT are reliable and valid for use in a daily clinical setting. Although both scores increased with a presumed painful stimulus, the discriminant validation of the BPS use was less supported because it increased during a nonpainful stimulus. The CPOT appears preferable in this particular group of patients, especially with regard to its discriminant validation.

Effects of furosemide on biliary secretion, pancreatic blood flow, and pancreatic exocrine secretion.

The effects of furosemide on biliary secretion and on pancreatic hemodynamics and exocrine function were studied by quantitative flowmetry and timed collections of biliary and pancreatic exocrine secretion in the anesthetized dog. Biliary flow and the output of its components (Na+, K+, Ca, Mg, 3-OH bile salts, and bilirubin) increased significantly following a furosemide injection of 0.6 mg/kg and rose progressively to 75-150 per cent above basal levels as the furosemide dose was increased to 9.6 mg/kg. Pretreatment with secretin had no influence on furosemide-induced biliary secretion. Furosemide doses of 4.8 and 9.6 mg/kg increased blood flow in the superior pancreaticoduodenal arterial bed by 30-60 per cent but did not alter flow in the inferior pancreaticoduodenal arterial bed or the pancreatic branch of the splenic artery. However, small increases were seen in flow in the latter two arterial beds after furosemide when secretin administration preceded furosemide. Basal pancreatic secretion was not affected by furosemide, but pretreatment with a submaximal sustaining infusion of secretin uncovered a furosemide action to increase pancreatic exocrine flow and the outputs of Na+, K+, Ca, Mg, and enzymes by 25-35 per cent. These data extend previous studies of the gastrointestinal vasodilator effects of furosemide to the pancreatic circulation and previous data demonstrating furosemide-induced ionic transport in nonrenal systems to biliary, pancreatic acinar, and ductular transport in both organs. Whether the augmentation of pancreatic blood flow is secondary to enhanced ion transport in the exocrine pancreas or to an effect on ionic cotransport in vascular smooth muscle is unknown.