A systematic scoping review of early interventions for parents of deaf infants.

BACKGROUND: Over 90% of the 50,000 deaf children in the UK have hearing parents, many of whom were not expecting a deaf child and may require specialist support. Deaf children can experience poorer long-term outcomes than hearing children across a range of domains. After early detection by the Universal Newborn Hearing Screening Programme, parents in the UK receive support from Qualified Teachers of the Deaf and audiologists but resources are tight and intervention support can vary by locality. There are challenges faced due to a lack of clarity around what specific parenting support interventions are most helpful. METHODS: The aim of this research was to complete a systematic scoping review of the evidence to identify early support interventions for parents of deaf infants. From 5577 identified records, 54 met inclusion criteria. Two reviewers screened papers through three rounds before completing data extraction and quality assessment. RESULTS: Identified parent support interventions included both group and individual sessions in various settings (including online). They were led by a range of professionals and targeted various outcomes. Internationally there were only five randomised controlled trials. Other designs included non-randomised comparison groups, pre / post and other designs e.g. longitudinal, qualitative and case studies. Quality assessment showed few high quality studies with most having some concerns over risk of bias. CONCLUSION: Interventions commonly focused on infant language and communication followed by parental knowledge and skills; parent wellbeing and empowerment; and parent/child relationship. There were no interventions that focused specifically on parent support to understand or nurture child socio-emotional development despite this being a well-established area of poor outcome for deaf children. There were few UK studies and research generally was not of high quality. Many studies were not recent and so not in the context of recent healthcare advances. Further research in this area is urgently needed to help develop evidence based early interventions.

Inferior vena cava branch variations in C57BL/6 mice have an impact on thrombus size in an IVC ligation (stasis) model.

BACKGROUND: Animal models of venous thrombosis (VT) are critical tools for those investigating the VT mechanism. Recently, inferior vena cava (IVC) branches have been subject to debate, causing controversy in the field. OBJECTIVES: To understand how the variability of IVC branches, in commonly used C57BL/6 mice, have an impact on thrombus formation in the IVC ligation model. METHODS: C57BL/6 male mice (n = 46), 20-25 g, were subjected to the IVC ligation model with various interruptions of the IVC branches. Control animals (n = 50) had all branches interrupted. Two days after IVC ligation, thrombus weight (TW), as a parameter of thrombus size, was assessed. RESULTS: We found four different anatomical patterns. Side branches were more prevalent on the mouse's right side (34%) compared with the left (20%). In mice where side branches were absent (21%), back branches appeared larger. Also, 25% of mice had both side branches. Controls that had all IVC branches interrupted had the most consistent and largest TW (32.6 mg to 34.7 mg) while groups that had no back branches interrupted had the smallest TW (3.6-9.7 mg), a 4 to 9-fold decrease. All groups with open back branches had significantly smaller TW (P < 0.05) than controls. CONCLUSIONS: Variations in TW were observed based on different branch interruption patterns, compared with the fully ligated controls. Having two back branches was the most consistent anatomy and open back branches had the largest negative impact on thrombus size. This work confirms that the IVC branches significantly affect thrombus burden in C57BL/6 mice and further studies should be conducted in order to standardize this and other animal models of VT.

Plasminogen activator-1 overexpression decreases experimental postthrombotic vein wall fibrosis by a non-vitronectin-dependent mechanism.

BACKGROUND: Factors associated with postthrombotic syndrome are known clinically, but the underlying cellular processes at the vein wall are not well delineated. Prior work suggests that vein wall damage does not correlate with thrombus resolution but rather with plasminogen activator-1 (PAI-1) and matrix metalloproteinase (MMP) activity. OBJECTIVE: We hypothesized that PAI-1 would confer post venous thrombosis (VT) vein wall protection via a vitronectin (Vn)-dependent mechanism. METHODS: A stasis model of VT was used with harvest over 2 weeks, in wild-type, Vn(-/-) , and PAI-1-overexpressing mice (PAI-1 Tg). RESULTS: PAI-1 Tg mice had larger VT at 6 and 14 days, compared to controls, but Vn(-/-) mice had no alteration of VT resolution. Gene deletion of Vn resulted in an increase in, rather than the expected decrease in, circulating PAI-1 activity. While both Vn(-/-) and PAI-1 Tg had attenuated intimal fibrosis, PAI-1 Tg had significantly less vein wall collagen and a compensatory increase in collagen III gene expression. Both Vn(-/-) and PAI-1 Tg vein wall had less monocyte chemotactic factor-1 and fewer macrophages (F4/80), with significantly less MMP-2 activity and decreased TIMP-1 antigen. Ex vivo assessment of transforming growth factor ß-mediated fibrotic response showed that PAI-1 Tg vein walls had increased profibrotic gene expression (collagens I and III, MMP-2, and α-smooth muscle actin) compared with controls, opposite of the in vivo response. CONCLUSIONS: The absence of Vn increases circulating PAI-1, which positively modulates vein wall fibrosis in a dose-dependent manner. Translationally, PAI-1 elevation may decrease vein wall damage after deep vein thrombosis, perhaps by decreasing macrophage-mediated activities.

Multicenter evaluation of the Sepsityper™ extraction kit and MALDI-TOF MS for direct identification of positive blood culture isolates using the BD BACTEC™ FX and VersaTREK(®) diagnostic blood culture systems.

AIMS: (i) Evaluation of delayed time to blood culture extraction by the Sepsityper kit and impact of shipping pellets off-site for MALDI-TOF MS analysis. (ii) Comparison of Sepsityper and laboratory-developed extraction methods from a literature review. METHODS AND RESULTS: Using two blood culture systems (BD BACTEC and VersaTREK), we extracted 411 positive blood cultures using the Sepsityper kit to mimic a potential protocol for institutions without a MALDI-TOF MS. Extracted pellets were shipped and analysed on the Bruker UltraflexIII. Successful extraction of 358 (87·1%) samples was determined by the presence of detectable proteins. MALDI-TOF MS correctly identified 332 (80·8%) samples. CONCLUSIONS: Delayed time to extraction did not affect Sepsityper extraction or MALDI-TOF MS accuracy. The extracted pellets remain stable and provide accurate results by MALDI-TOF MS when shipped at room temperature to off-site reference laboratories. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to show that institutions without a MALDI-TOF MS can take advantage of this innovative technology by shipping a volume of blood to an off-site laboratory for extraction and MALDI-TOF MS analysis. We also performed a literature review to compare various extraction methods.

Plasma DNA is Elevated in Patients with Deep Vein Thrombosis.

OBJECTIVE: To investigate if plasma DNA is elevated in patients with deep vein thrombosis (DVT) and to determine whether there is a correlation with other biomarkers of DVT. BACKGROUND: Leukocytes release DNA to form extracellular traps (ETs), which have recently been linked to experimental DVT. In baboons and mice, extracellular DNA co-localized with von Willebrand factor (VWF) in the thrombus and DNA appeared in circulation at the time of thrombus formation. ETs have not been associated with clinical DVT. SETTING: From December 2008 to August 2010, patients were screened through the University of Michigan Diagnostic Vascular Unit and were divided into three distinct groups: 1) the DVT positive group, consisting of patients who were symptomatic for DVT, which was confirmed by compression duplex ultrasound (n=47); 2) the DVT negative group, consisting of patients that present with swelling and leg pain but had a negative compression duplex ultrasound, (n=28); and 3) a control group of healthy non-pregnant volunteers without signs or symptoms of active or previous DVT (n=19). Patients were excluded if they were less than 18 years of age, unwillingness to consent, pregnant, on an anticoagulant therapy, or diagnosed with isolated calf vein thrombosis. METHODS: Blood was collected for circulating DNA, CRP, D-dimer, VWF activity, myeloperoxidase (MPO), ADAMTS13 and VWF. The Wells score for a patient's risk of DVT was assessed. The Receiver Operating Characteristic (ROC) curve was generated to determine the strength of the relationship between circulating DNA levels and the presence of DVT. A Spearman correlation was performed to determine the relationship between the DNA levels and the biomarkers and the Wells score. Additionally the ratio of ADAMTS13/VWF was assessed. RESULTS: Our results showed that circulating DNA (a surrogate marker for NETs) was significantly elevated in DVT patients, compared to both DVT negative patients (57.7±6.3 vs. 17.9±3.5ng/mL, P<.01) and controls (57.7±6.3 vs. 23.9±2.1ng/mL, P<.01). There was a strong positive correlation with CRP (P<.01), D-dimer (P<.01), VWF (P<.01), Wells score (P<.01) and myeloperoxidase (MPO) (P<.01), along with a strong negative correlation with ADAMTS13 (P<.01) and the ADAMTS13/VWF ratio. The logistic regression model showed a strong association between plasma DNA and the presence of DVT (ROC curve was determined to be 0.814). CONCLUSIONS: Plasma DNA is elevated in patients with deep vein thrombosis and correlates with biomarkers of DVT. A strong correlation between circulating DNA and MPO suggests that neutrophils may be a source of plasma DNA in patients with DVT.

Rosuvastatin reduced deep vein thrombosis in ApoE gene deleted mice with hyperlipidemia through non-lipid lowering effects.

INTRODUCTION: Statins, particularly rosuvastatin, have recently become relevant in the setting of venous thrombosis. The objective of this study was to study the non-lipid lowering effects of rosuvastatin in venous thrombosis in mice with hyperlipidemia. MATERIALS AND METHODS: An inferior vena cava ligation model of venous thrombosis in mice was utilized. Saline or 5mg/kg of rosuvastatin was administered by gavage 48hs previous to thrombosis. Blood, the inferior vena cava, thrombus, and liver were harvested 3, 6hours, and 2days post-thrombosis. Thrombus weight, inflammatory markers, and plasminogen activator inhibitor-1 expression and plasma levels were measured. Also, neutrophil migration to the IVC was assessed. RESULTS: Rosuvastatin significantly decreased thrombus weight, plasminogen activator inhibitor-1 expression and plasma levels, expression of molecules related to the interleukin-6 pathway, and neutrophil migration into the vein wall. CONCLUSIONS: This work supports the beneficial effects of rosuvastatin on venous thrombosis in mice with hyperlipidemia, due to its non-lipid lowering effects.

Novel anticoagulants: a discussion of clinical use in the treatment and prevention of venous thromboembolism.

Traditional therapeutic oral anticoagulation strategies often require invasive dosing or monitoring. Vitamin K antagonists (VKAs) have a large number of interactions, delayed onset requires frequent dose monitoring, and they have a small margin between therapeutic dose and bleeding complications. Novel oral anticoagulants, such as dabigatran, rivaroxaban and apixaban, are being developed to prevent those VKAs drawbacks. Besides oral bioavailability, those compounds are designed to require minimal to no monitoring and have a favourable safety profile. This review reports efficacy and safety data of these compounds throughout clinical development, as well as new approaches for oral pharmacological management of venous thromboembolism.

Decrease in fibrin content of venous thrombi in selectin-deficient mice.

The purpose of this study was to quantify the fibrin content of thrombi produced in a mouse model of venous thrombosis and correlate this to thrombus mass. The role of P-selectin, E-selectin, and IL-10 on thrombus fibrin content was analyzed using knockout (KO) mice. Five groups of mice were evaluated: control (N = 10), P-selectin KO (N = 7), E-selectin KO (N = 5), combined E-/P-selectin KO (N = 12), and IL-10 KO (N = 10). Venous thrombosis was induced by ligation of the infrarenal IVC. Mice were sacrificed on postoperative days (POD) 2 and 6. Thrombus mass was calculated. Sections of IVC were stained with an antibody that cross reacts with mouse fibrin. The distribution of RGB color pixels was generated from digitized micrographs of the thrombus of each animal. The mean pixel value for each group was compiled and analyzed using 2-way ANOVA. Mean pixel value per group was correlated with the mean thrombus mass per group. Color analysis demonstrated significant decreases in the analyzed fibrin content on POD-2 between the control vs E-/P-selectin KO (P < 0.05) and control vs IL-10 KO (P < 0.05) groups. In addition, significantly less fibrin staining was noted on POD-6 between the control vs E-selectin KO (P = 0.03), control vs P-selectin KO (P = 0.01), and control vs E-/P-selectin KO (P < 0.01). There was a strong overall correlation between the mean pixel value for each group and the thrombus mass (R = 0.964; P < 0.01). This study demonstrates a difference in fibrin content of thrombi produced in animals deficient in E-selectin, P-selectin, and IL-10, supporting their importance in thrombus amplification, fibrin formation, and the mass of thrombus formed.

Triplex ultrasound: elasticity imaging to age deep venous thrombosis.

Deep venous thrombosis (DVT), and its sequela, pulmonary embolism (PE), is the leading cause of preventable in-hospital mortality in the USA and other developed countries. After it is detected, acute clots must be differentiated from chronic DVT for appropriate treatment. However, there are no reliable thrombus staging methods presently available in clinical practice. In this study, we tested the hypothesis that blood clots can be detected and staged using a triplex ultrasound (US) test. Triplex US is based on a "gold standard" duplex US technique augmented by US-based reconstructive elasticity imaging. Fibrin-composed blood clots harden with development and organization. By imaging clot elasticity, it may be possible to both detect and differentiate clots and, therefore, provide an urgently needed noninvasive means of DVT staging.

Venous thrombosis incidence in burn patients: preliminary results of a prospective study.

There are few prospective data on the incidence of deep venous thrombosis (DVT) in burn patients. In an on-going prospective study, hospitalized burn patients 18 years or older with an expected hospital length of stay more than 72 hours were imaged with baseline venous duplex ultrasound of all extremities within the first 48 hours after admission and weekly until discharge. Patient demographics and clinical risk factors for DVT were assessed. At the time of submission, 40 patients met screening criteria, and 30 were enrolled. Ultrasound diagnosed seven patients with 11 acute DVT for an incidence of 23%. One pulmonary embolism was documented. DVT patients had a mean age of 49 +/- 23 years with an average TBSA burn of 15 +/- 4% compared with those without thrombosis with a mean age of 44 +/- 17 years (P = NS) and TBSA burn of 18 +/- 25% (P = NS). There were no statistically significant differences for DVT patients in terms of age, number of central line days, hospital length of stay, or TBSA burned. Given the preliminary findings of this small study, we believe that all hospitalized burn patients are at risk for DVT. On-going investigation will be helpful in defining level of risk and improved prevention strategies for thromboembolic complications in burn patients.