Incidence of venous thromboembolic events not related to vascular catheters in a prospective cohort of critically ill children.

The risk for venous thromboembolism (VTE) is considered to be low in the general paediatric intensive care unit (PICU) population, and pharmacological thromboprophylaxis is not routinely used. PICU patients considered at high-risk of VTE could possibly benefit from pharmacological thromboprophylaxis, but the incidence of VTE in this group of patients is unclear. This was an observational, prospective study at a tertiary multi-disciplinary paediatric hospital. We used comprehensive ultrasonography screening for VTE in critically ill children with multiple risk factors for VTE. Patients admitted to PICU ≥ 72 h and with ≥ two risk factors for VTE were included. Patients receiving pharmacological thromboprophylaxis during their entire PICU stay were excluded. The primary outcome of the study was VTEs not related to the use of a CVC. Ultrasonography screening of the great veins was performed at PICU discharge. Seventy patients with median (interquartile range) 3 (2-4) risk factors for VTE were evaluated. Median age was 0.3 years (0.03-4.3) and median PICU length of stay 9 days (5-17). Regarding the primary outcome, no symptomatic VTEs occurred and no asymptomatic VTEs were found on ultrasonography screening, resulting in an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). CONCLUSION: Our results indicate that VTEs not related to a vascular catheter are a rare event even in a selected group of severely ill small children considered to be at high risk of VTE. WHAT IS KNOWN: • Children in the PICU often have several risk factors for venous thromboembolism (VTE). • The incidence of VTE in PICU patients is highly uncertain, and there are no evidence-based guidelines regarding VTE prophylaxis. WHAT IS NEW: • This study found an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). • This indicates that such VTE events are rare even in PICU patients with multiple risk factors for VTE.

Complications of Pediatric Midline Catheters: A Prospective Observational Pilot Study.

BACKGROUND: Midline catheters are peripheral intravenous (IV) catheters in which the tip of the catheter does not reach the central circulation. In children, the use of midline catheters could lead to decreased complications from central venous catheters. To validate the safety of midline catheter use in children, we aimed to describe the complications and dwell time of pediatric midline catheters. The primary outcome was the incidence of catheter-related venous thromboembolism (VTE). METHODS: We conducted an observational, prospective study including consecutive patients at a tertiary multidisciplinary pediatric hospital. One hundred pediatric midline catheters were followed for thrombotic, infectious, and mechanical complications. After catheter removal, Doppler ultrasonography was performed to detect asymptomatic VTE. RESULTS: The mean age was 6.0 years (standard deviation [SD], 4.7), and median catheter dwell time was 6 (4-8) days. Most midline catheters were inserted in arm veins, most commonly in the basilic vein (56%). Catheter-related VTE was diagnosed in 30 (30%; 95% confidence interval [CI], 21%-40%) cases, corresponding to an incidence rate of 39 (95% CI, 26-55) cases per 1000 catheter days. Eight of 14 saphenous vein catheters were complicated by VTE compared to 22 of 86 arm vein catheters, suggesting an imbalance in favor of arm vein insertion site. Two patients needed anticoagulation therapy due to catheter-related VTE. Thirty (30%) catheters were removed unintentionally or due to complications, 22 of these needed additional IV access to complete the intended therapy. No catheter-related bloodstream infection (95% CI, 0%-4%) occurred. Mechanical complications occurred in 33 (33%; 95% CI, 24%-43%) midline catheters. CONCLUSIONS: In children, thrombotic and mechanical complications of midline catheters are common, but only few VTEs are severe enough to warrant anticoagulation therapy. Systemic infectious complications are rare. Seventy-eight percent of patients did not need additional venous access to complete short-term IV therapy. Considering the rate of clinically relevant complications and the catheter dwell time, pediatric midline catheters could be an alternative to central venous access for short-term (5-10 days) IV therapy.

Thromboembolic Complications of Vascular Catheters Used for Pediatric Continuous Renal Replacement Therapy: Prevalence in a Single-Center, Retrospective Cohort.

OBJECTIVES: Pediatric venous thromboembolic events are commonly associated with in situ central venous catheters. The risk for severe venous thromboembolism increases if a larger portion of the vessel lumen is occupied by the central venous catheter. A functioning vascular catheter is required when the continuous renal replacement therapy is used in critically ill children. Due to the high blood flow required for continuous renal replacement therapy, the external diameter of the catheter needs to be larger than a conventional central venous catheter used for venous access, potentially increasing the risk of venous thromboembolism. However, children on continuous renal replacement therapy often receive systemic anticoagulation to prevent filter clotting, possibly also preventing venous thromboembolism. The frequency of catheter-related venous thromboembolic events in this setting has not been described. Our main objective was to determine the prevalence of catheter-related venous thromboembolism in pediatric continuous renal replacement therapy. DESIGN: Retrospective cohort study. SETTING: Tertiary multidisciplinary academic pediatric hospital. PATIENTS: Patients 0-18 years old with a vascular catheter used for continuous renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In our series of 80 patients, we used 105 vascular catheters. The median age of the patients was 10 months and PICU mortality rate was 21%. Venous thromboembolic events were considered to be catheter related if located in the same vein as the vascular catheter and radiologically verified. Six (5.7%) catheter-related venous thromboembolic events were found. The clinically relevant complications of venous thromboembolism included superior vena cava syndrome and catheter dysfunction. In one patient, severe and life-threatening pulmonary embolism occurred. In comparison with patients without venous thromboembolism, venous thromboembolic events were associated with lower body weight (p = 0.03) and longer durations of continuous renal replacement therapy (p < 0.01), mechanical ventilation (p = 0.03), and PICU stay (p < 0.01). Five out of six venous thromboembolisms appeared in neonates. CONCLUSIONS: Catheter-related venous thromboembolism is a clinically relevant complication of pediatric continuous renal replacement therapy, with a prevalence of 5.7% in our cohort. Clinicians involved in pediatric continuous renal replacement therapy need to be vigilant for symptoms of venous thromboembolisms and initiate appropriate treatment as soon as possible.

Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters.

BACKGROUND: Venous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort. METHODS: Observational, prospective study enrolling consecutive patients at a tertiary multi-disciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVC-related VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT. RESULTS: Overall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5-36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVC-related VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive. CONCLUSIONS: Paediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass. CLINICAL TRIAL REGISTRATION: ACTRN12615000442505.

Molecular Insights into Covalently Stained Carious Dentine Using Solid-State NMR and ToF-SIMS.

Dyes currently used to stain carious dentine have a limited capacity to discriminate normal dentine from carious dentine, which may result in overexcavation. Consequently, finding a selective dye is still a challenge. However, there is evidence that hydrazine-based dyes, via covalent bonds to functional groups, bind specifically to carious dentine. The aim of this study was to investigate the possible formation of covalent bonds between carious dentine and 15N2-hydrazine and the hydrazine-based dye, 15N2-labelled Lucifer Yellow, respectively. Powdered dentine from extracted carious and normal teeth was exposed to the dyes, and the staining reactions were analysed using time-of-flight secondary ion mass spectrometry (ToF-SIMS), solid-state 13C-labelled nuclear magnetic resonance (NMR) and 15N-NMR spectroscopy. The results showed that 15N2-hydrazine and 15N2-labelled Lucifer Yellow both bind to carious dentine but not to normal dentine. It can thus be concluded that hydrazine-based dyes can be used to stain carious dentine and leave normal dentine unstained.

Ionization of Cellobiose in Aqueous Alkali and the Mechanism of Cellulose Dissolution.

Cellulose, one of the most abundant renewable resources, is insoluble in most common solvents but dissolves in aqueous alkali under a narrow range of conditions. To elucidate the solubilization mechanism, we performed electrophoretic NMR on cellobiose, a subunit of cellulose, showing that cellobiose acts as an acid with two dissociation steps at pH 12 and 13.5. Chemical shift differences between cellobiose in NaOH and NaCl were estimated using 2D NMR and compared to DFT shift differences upon deprotonation. The dissociation steps are the deprotonation of the hemiacetal OH group and the deprotonation of one of four OH groups on the nonreducing anhydroglucose unit. MD simulations reveal that aggregation is suppressed upon charging cellulose chains in solution. Our findings strongly suggest that cellulose is to a large extent charged in concentrated aqueous alkali, a seemingly crucial factor for solubilization. This insight, overlooked in the current literature, is important for understanding cellulose dissolution and for synthesis of new sustainable materials.

Adsorption of arabinoxylan on cellulosic surfaces: influence of degree of substitution and substitution pattern on adsorption characteristics.

This study presents results that show that the fine structure of arabinoxylan affects its interaction with cellulosic surfaces, an important understanding when designing and evaluating properties of xylan-cellulose-based materials. Arabinoxylan samples, with well-defined structures, were prepared from a wheat flour arabinoxylan with targeted enzymatic hydrolysis. Turbidity measurements and analyses using NMR diffusometry showed that the solubility and the hydrodynamic properties of arabinoxylan are determined not only by the degree of substitution but also by the substitution pattern. On the basis of results obtained from adsorption experiments on microcrystalline cellulose particles and on cellulosic model surfaces investigated with quartz crystal microbalance with dissipation monitoring, it was also found that arabinoxylan adsorbs irreversibly on cellulosic surfaces and that the adsorption characteristics, as well as the properties of the adsorbed layer, are controlled by the fine structure of the xylan molecule.

Breastfeeding in preterm and term twins--maternal factors associated with early cessation: a population-based study.

To investigate the duration of breastfeeding and the impact of maternal factors for cessation of breastfeeding in twin infants, the authors undertook a population-based cohort study. Breastfeeding data obtained from Child Health Centres were matched with data on infant and maternal demographics from Swedish national registers. A total of 1.657 twins were included, of whom 695 were born preterm. Breastfeeding frequencies in preterm twins were 79% at 2 months, 58% at 4 months, 39% at 6 months, 14% at 9 months, and 6% at 12 months. In term twins, the corresponding frequencies were 84%, 63%, 45%, 18%, and 6%, respectively. In both preterm and term mothers, mothers who had a lower educational level or smoked at first antenatal care visit were subject to earlier cessation of breastfeeding by 6 months of age. In addition, in mothers of term infants, mothers who were < 23 years old or primiparous had a higher risk for cessation of breastfeeding before 6 months. Thus, mothers of twins have a good potential to breastfeed, but additional support is needed for those more susceptible to early cessation of breastfeeding.

Chemical shift imaging NMR to track gel formation.

In this work we have combined (1)H and (19)F NMR chemical shift images to investigate the dynamic processes of gel formation of a cellulose solution. Chemical shift imaging (CSI) NMR is shown to be a valuable technique for studying phase changes in soft materials. The technique provides spatial position of each chemical component, and by repeatedly recording sample images the dynamic rearrangements in the material can be followed in detail. CSI NMR follows the same principles as magnetic resonance imaging, but can be performed on most of the nowadays commercial NMR probes. Position resolution of the chemical shift gives the opportunity to derive diffusion rate data of individual components during the gel formation process. The results suggest that the method can be used for detailed studies of dynamic processes in multi-component systems and to extract diffusion coefficients for the components investigated.

Dissolution and gelation of cellulose in TBAF/DMSO solutions: the roles of fluoride ions and water.

Solutions of cellulose in a mixture of tetrabutylammonium fluoride and dimethyl sulfoxide (TBAF/DMSO) containing small and varying amounts of water were studied by nuclear magnetic resonance (NMR). By measuring the composition dependences of (19)F NMR and (1)H NMR chemical shifts and line widths, details on the dissolution and gelation mechanisms for cellulose in TBAF/DMSO were elucidated. Our results suggest that the strongly electronegative fluoride ions act as hydrogen bond acceptors to cellulose hydroxyl groups, thus dissolving the polymer by breaking the cellulose-cellulose hydrogen bonds and by rendering the chains an effective negative charge. It was found that the fluoride ions also interact strongly with water. Small amounts of water remove the fluoride ions from the cellulose chains and allow reformation of the cellulose-cellulose hydrogen bonds, which leads to formation of highly viscous solutions or gels even at low cellulose concentrations.

Comparison of PEI-PEG and PLL-PEG copolymer coatings on the prevention of protein fouling.

The effect of surface charge on the protein resistance of adsorbed layers of poly(ethylene imine)-[g]-poly(ethylene glycol), PEI-PEG, and poly(L-lysine)-[g]-poly(ethylene glycol), PLL-PEG, was studied. Mixed and monofunctional self-assembled monolayers, SAMs, on gold were obtained by adsorption of 16-mercapto-1-hexadecanoic acid and 16-mercapto-1-hexadecanol. The surface charge was systematically varied by changing the ratio of the two alkanethiols. The graft copolymers PEI-PEG and PLL-PEG were adsorbed at the SAMs and tested for resistance towards human serum albumin and fibrinogen. The adsorbed amount of copolymers increased with increasing negative surface charge. However, the best protein resistance was found at an intermediate surface charge. The PLL-PEG covered surfaces showed better protein resistance than the PEI-PEG covered surfaces. Thus, this work demonstrates that an adsorbed layer of PEG-grafted PEI and, in particular, PEG-grafted PLL is efficient in preventing protein adsorption when there is charge neutralization between the copolymer and the underlying surface.

Single run measurements of drug-protein binding by high-performance frontal analysis capillary electrophoresis and mass spectrometry.

A novel drug-protein binding measurement method based on high-performance frontal analysis and capillary electrophoresis (HPFA/CE) is presented. A single run measurement approach is proposed to circumvent utilization of a calibration curve that is often performed with HPFA. A sensitive mass spectrometer is applied as a detector enabling the measurement of in vitro protein binding at lower drug concentrations. Unbound free fraction and binding constants can be determined by a single run measurement by consecutive injections of an internal drug standard, a buffer plug and a drug-protein mixture. Effects of injection volumes on peak height and plateau profile were investigated in two different separation systems, non-volatile buffer and volatile buffer, with UV and mass spectrometry detection, respectively. A simplified one-to-one binding model is employed to evaluate the proposed method by using both single and multiple drug concentrations to measure the unbound free fraction and calculate the binding constants of some selected compounds. The method is suitable for rapid and direct screening of the binding of a drug to a specific protein or drug-plasma protein binding.