Detailed assessment of benefits and risks of retrievable inferior vena cava filters on patients with complicated injuries: the da Vinci multicentre randomised controlled trial study protocol

Introduction Retrievable inferior vena cava (IVC) filters have been increasingly used in patients with major trauma who have contraindications to anticoagulant prophylaxis as a primary prophylactic measure against venous thromboembolism (VTE). The benefits, risks and cost-effectiveness of such strategy are uncertain. Methods and analysis Patients with major trauma, defined by an estimated Injury Severity Score >15, who have contraindications to anticoagulant VTE prophylaxis within 72 hours of hospitalisation to the study centre will be eligible for this randomised multicentre controlled trial. After obtaining consent from patients, or the persons responsible for the patients, study patients are randomly allocated to either control or IVC filter, within 72 hours of trauma admission, in a 1:1 ratio by permuted blocks stratified by study centre. The primary outcomes are (1) the composite endpoint of (A) pulmonary embolism (PE) as demonstrated by CT pulmonary angiography, high probability ventilation/perfusion scan, transoesophageal echocardiography (by showing clots within pulmonary arterial trunk), pulmonary angiography or postmortem examination during the same hospitalisation or 90-day after trauma whichever is earlier and (B) hospital mortality; and (2) the total cost of treatment including the costs of an IVC filter, total number of CT and ultrasound scans required, length of intensive care unit and hospital stay, procedures and drugs required to treat PE or complications related to the IVC filters. The study started in June 2015 and the final enrolment target is 240 patients. No interim analysis is planned; incidence of fatal PE is used as safety stopping rule for the trial. Ethics and dissemination Ethics approval was obtained in all four participating centres in Australia. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN12614000963628; Pre-results

Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

Evaluation of long-term clinical and health service outcomes following coronary artery revascularisation in Western Australia (WACARP): a population-based cohort study protocol

Introduction: Coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) are procedures commonly performed on patients with significant obstructive coronary artery disease to relieve symptoms of ischaemia, improve survival or both. Although the efficacy of both procedures at the individual level has been established, the impact of advances in coronary artery revascularisation procedures (CARP) on long-term outcomes and cost-effectiveness at the population level are yet to be assessed. Our aim is to evaluate a minimum of 6-year outcomes and costs for the total population of patients who had CARP in Western Australia (WA) in 2000–2005. Methods and analysis This retrospective population cohort study will link clinical and administrative health data for a previously defined cohort including all patients in WA who had a CARP in the period 2000–2005. The cohort consists of 19 014 patients who had 21 175 procedures (15 429 PCI and 5746 CABG). We are now collecting a minimum of 6 years follow-up of morbidity and mortality data for the cohort using the WA Data Linkage System, clinical registries and hospital records, with 12 years follow-up for cases in the year 2000. Comparison of long-term outcomes for different CARP will be reported (PCI vs CABG; bare metal stents vs drug-eluting stents vs CABG). Cost-effectiveness analysis of CARP from the perspective of the healthcare sector will be performed using individual level cost data and average costs from Australian Refined Diagnosis Related Groups. Ethics and dissemination This study has received ethics approval from the University of Western Australia, the Western Australian Department of Health and all participating hospitals. Being a large population cohort study, approval included a waiver of informed consent. All findings will be presented at local, national and international healthcare/academic conferences and published in peer-reviewed journals

Biogeochemical impacts of fish farming on coastal sediments: Insights into the functional role of cable bacteria

Fish farming in sea cages is a growing component of the global food industry. A prominent ecosystem impact of this industry is the increase in the downward flux of organic matter, which stimulates anaerobic mineralization and sulfide production in underlying sediments. When free sulfide is released to the overlying water, this can have a toxic effect on local marine ecosystems. The microbially-mediated process of sulfide oxidation has the potential to be an important natural mitigation and prevention strategy that has not been studied in fish farm sediments. We examined the microbial community composition (DNA-based 16S rRNA gene) underneath two active fish farms on the Southwestern coast of Iceland and performed laboratory incubations of resident sediment. Field observations confirmed the strong geochemical impact of fish farming on the sediment (up to 150 m away from cages). Sulfide accumulation was evidenced under the cages congruent with a higher supply of degradable organic matter from the cages. Phylogenetically diverse microbes capable of sulfide detoxification were present in the field sediment as well as in lab incubations, including cable bacteria (Candidatus Electrothrix), which display a unique metabolism based on long-distance electron transport. Microsensor profiling revealed that the activity of cable bacteria did not exert a dominant impact on the geochemistry of fish farm sediment at the time of sampling. However, laboratory incubations that mimic the recovery process during fallowing, revealed successful enrichment of cable bacteria within weeks, with concomitant high sulfur-oxidizing activity. Overall our results give insight into the role of microbially-mediated sulfide detoxification in aquaculture impacted sediments.publishedVersio

Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure : a Mendelian randomization study in the FINRISK cohort

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide poly-morphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N= 6669), B-type natriuretic peptide (BNP) (N= 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N= 6813) were measured in the FINRISK 1997 cohort. N=30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.Peer reviewe

Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes

INTRODUCTION: This study aimed to assess the association between fasting serum C-peptide levels and the presence of impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We performed a cross-sectional study among 509 individuals with type 1 diabetes (diabetes duration 5-65 years). Extensive clinical data and fasting serum C-peptide concentrations were collected and related to the presence or absence of IAH, which was evaluated using the validated Dutch version of the Clarke questionnaire. A multivariable logistic regression model was constructed to investigate the association of C-peptide and other clinical variables with IAH. RESULTS: In 129 (25%) individuals, residual C-peptide secretion was detected, while 75 (15%) individuals reported IAH. The median (IQR) C-peptide concentration among all participants was 0.0 (0.0-3.9) pmol/L. The prevalence of severe hypoglycemia was lower in people with demonstrable C-peptide versus those with absent C-peptide (30% vs 41%, p=0.025). Individuals with IAH were older, had longer diabetes duration, more frequently had macrovascular and microvascular complications, and more often used antihypertensive drugs, antiplatelet agents and cholesterol-lowering medication. There was a strong association between IAH and having a severe hypoglycemia in the preceding year. In multivariable regression analysis, residual C-peptide, either continuously or dichotomous, was associated with lower prevalence of IAH (p=0.040-0.042), while age at diabetes onset (p=0.001), presence of microvascular complications (p=0.003) and body mass index (BMI) (p=0.003) were also independently associated with the presence of IAH. CONCLUSIONS: Higher BMI, the presence of microvascular complications and higher age at diabetes onset were independent risk factors for IAH in people with type 1 diabetes, while residual C-peptide secretion was associated with lower risk of this complication

Chromium Remediation or Release? Effect of Iron(II) Sulfate Addition on Chromium(VI) Leaching from Columns of Chromite Ore Processing Residue

Chromite ore processing residue (COPR), derived from the so-called high lime processing of chromite ore, contains high levels of Cr(III) and Cr(VI) and has a pH between 11 and 12. Ferrous sulfate, which is used for remediation of Cr(VI) contamination in wastewater and soils via reduction to Cr(III) and subsequent precipitation of iron(III)/chromium- (III) hydroxide, has also been proposed for remediation of Cr(VI) in COPR. Instead, however, addition of FeSO4 to the infiltrating solution in column experiments with COPR greatly increased leaching of Cr(VI). Leached Cr(VI) increased from 3.8 to 12.3 mmol kg-1 COPR in 25 pore volumes with 20 mM FeSO4, reaching solution concentrations as high as 1.6 mM. Fe(II) was ineffective in reducing Cr(VI) to Cr(III) because it precipitated when it entered the column due to the high pH of COPR, while Cr(VI) in solution was transported away with the infiltrating solution. The large increase in leaching of Cr(VI) upon infiltration of sulfate, either as FeSO4 or Na2SO4, was caused by anion exchange of sulfate for chromate in the layered double hydroxide mineral hydrocalumite, a process for which scanning electron microscopy with energy-dispersive X-ray microanalysis provided direct evidence

Genetic risk prediction of atrial fibrillation

Background—Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods—To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10-3 to <1x10-8 in a prior independent genetic association study. Results—Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10-4) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10-3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). Conclusions—Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms

A novel method for engineering autologous non-thrombogenic in situ tissue-engineered blood vessels for arteriovenous grafting

The durability of prosthetic arteriovenous (AV) grafts for hemodialysis access is low, predominantly due to stenotic lesions in the venous outflow tract and infectious complications. Tissue engineered blood vessels (TEBVs) might offer a tailor-made autologous alternative for prosthetic grafts. We have designed a method in which TEBVs are grown in vivo, by utilizing the foreign body response to subcutaneously implanted polymeric rods in goats, resulting in the formation of an autologous fibrocellular tissue capsule (TC). One month after implantation, the polymeric rod is extracted, whereupon TCs (length 6 cm, diameter 6.8 mm) were grafted as arteriovenous conduit between the carotid artery and jugular vein of the same goats. At time of grafting, the TCs were shown to have sufficient mechanical strength in terms of bursting pressure (2382 +/- 129 mmHg), and suture retention strength (SRS: 1.97 +/- 0.49 N). The AV grafts were harvested at 1 or 2 months after grafting. In an ex vivo whole blood perfusion system, the lumen of the vascular grafts was shown to be less thrombogenic compared to the initial TCs and ePTFE grafts. At 8 weeks after grafting, the entire graft was covered with an endothelial layer and abundant elastin expression was present throughout the graft. Patency at 1 and 2 months was comparable with ePTFE AV-grafts. In conclusion, we demonstrate the remodeling capacity of cellularized in vivo engineered TEBVs, and their potential as autologous alternative for prosthetic vascular grafts.Vascular Surger

Effect of an Injury Awareness Education Program on Risk-Taking Behaviors and Injuries in Juvenile Justice Offenders: A Retrospective Cohort Study

Background Risk-taking behavior is a leading cause of injury and death amongst young people. Methodology and Principal Findings This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%–25.8%; number needed to benefit = 4.3, 95%CI 3.9–5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%–2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%–2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05–0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93–0.99) were associated with a lower risk of subsequent traffic or violence-related offences. Significance Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders