Effect of non-vitamin-K oral anticoagulants on stroke severity compared to warfarin: a meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: In addition to lowering stroke risk, warfarin use is also associated with reduced stroke severity in patients with atrial fibrillation and acute ischaemic stroke. It was sought to determine whether the effect of non-vitamin-K oral anticoagulants (NOACs), compared to warfarin, differed by stroke severity. METHODS: Phase III randomized controlled trials with participants who were randomized to receive NOACs or warfarin for stroke prevention in the setting of non-valvular atrial fibrillation were identified. Stroke was classified into two categories, fatal or disabling stroke and non-disabling stroke, and meta-analyses were completed for both outcomes and for comparative case fatality of stroke amongst trials. RESULTS: Five randomized controlled trials met our inclusion criteria. In clinical trials evaluating the NOACs usually prescribed in clinical practice (four trials), acute stroke was reported in 1403 (1.86%) participants, 787 (1.04%) in the NOAC group [386 (0.51%) fatal or disabling, 401 (0.53%) non-disabling] and 616 (0.82%) in the warfarin group [367 (0.49%) fatal or disabling, 249 (0.33%) non-disabling]. On meta-analysis NOACs were significantly superior to warfarin for fatal or disabling stroke (odds ratio [OR] 0.77; 95% confidence interval [CI] 0.66-0.89, I2  = 21%) and non-disabling stroke (OR 0.85; 95% CI 0.73-0.98, I2  = 2%). The case fatality of stroke was no different between groups (OR 0.90, 95% CI 0.75-1.13, I2  = 0%), but the point estimate favoured NOACs. CONCLUSION: In phase III trials of NOACs, for prevention of stroke in atrial fibrillation, NOACs are associated with a lower risk of both fatal/disabling and non-disabling stroke compared to warfarin.

How repeatable is CTmax within individual brook trout over short- and long-time intervals?

As stream temperatures increase due to factors such as heated runoff from impervious surfaces, deforestation, and climate change, fish species adapted to cold water streams are forced to move to more suitable habitat, acclimate or adapt to increased thermal regimes, or die. To estimate the potential for adaptation, a (within individual) repeatable metric of thermal tolerance is imperative. Critical thermal maximum (CTmax) is a dynamic test that is widely used to measure thermal tolerance across many taxa and has been used in fishes for decades, but its repeatability in most species is unknown. CTmax tests increase water temperature steadily over time until loss of equilibrium (LOE) is achieved. To determine if CTmax is a consistent metric within individual fish, we measured CTmax on the same lab-held individually-marked adult brook trout Salvelinus fontinalis at three different times (August & September 2016, September 2017). We found that CTmax is a repeatable trait (Repeatability ±â€¯S.E.: 0.48 ±â€¯0.14). CTmax of individuals males was consistent over time, but the CTmax of females increased slightly over time. This result indicates that CTmax is a robust, repeatable estimate of thermal tolerance in a cold-water adapted fish.

Salt intake and cardiovascular disease: why are the data inconsistent?

Effective population-based interventions are required to reduce the global burden of cardiovascular disease (CVD). Reducing salt intake has emerged as a leading target, with many guidelines recommending sodium intakes of 2.3 g/day or lower. These guideline thresholds are based largely on clinical trials reporting a reduction in blood pressure with low, compared with moderate, intake. However, no large-scale randomized trials have been conducted to determine the effect of low sodium intake on CV events. Prospective cohort studies evaluating the association between sodium intake and CV outcomes have been inconsistent and a number of recent studies have reported an association between low sodium intake (in the range recommended by current guidelines) and an increased risk of CV death. In the largest of these studies, a J-shaped association between sodium intake and CV death and heart failure was found. Despite a large body of research in this area, there are divergent interpretations of these data, with some advocating a re-evaluation of the current guideline recommendations. In this article, we explore potential reasons for the differing interpretations of existing evidence on the association between sodium intake and CVD. Similar to other areas in prevention, the controversy is likely to remain unresolved until large-scale definitive randomized controlled trials are conducted to determine the effect of low sodium intake (compared to moderate intake) on CVD incidence.

Water chemistry in the microenvironment of rainbow trout Oncorhynchus mykiss embryos is affected by development, the egg capsule and crowding.

The hypothesis tested was that embryonic metabolism affects the water chemistry in the boundary layer. In addition, embryo crowding would further compound the metabolic effect on the water chemistry in the boundary layer. As development progressed, the magnitude of the boundary layer gradients for O(2) and pH, but not for NH4(+), increased. The presence of the egg capsule hindered the diffusion of O(2) into and H(+) and NH4(+) out of the embryo. The magnitude of the O(2), pH and NH4(+) boundary layer gradient was significantly increased when embryos were surrounded by either sham embryos or live embryos. The majority of this crowding effect on embryo boundary layers was due to changes in water flow rather than due to metabolism directly. These results clearly show that the microenvironment adjacent to the developing rainbow trout Oncorhynchus mykiss embryo becomes more stagnant as development progresses in the presence of the egg capsule and is further intensified with embryo crowding.

Effective cleaning and decontamination of the internal air and water channels, heads and head-gears of multiple contra-angle dental handpieces using an enzymatic detergent and automated washer-disinfection in a dental hospital setting.

BACKGROUND: Dental handpieces (DHPs) are reusable invasive medical devices that must be cleaned, decontaminated, lubricated and steam sterilized after use. DHPs have a complex internal design including narrow channels, contamination of which can compromise sterilization. DHPs are not designed for routine disassembly, making cleaning/decontamination efficacy difficult to monitor. Washer-disinfection is the preferred method of decontaminating DHPs, but few studies have investigated its direct effectiveness at reducing microbial contamination internally. AIMS: To use contra-angle DHPs as a model system to investigate the effectiveness of washer-disinfection at reducing microbial contamination of internal components of multiple DHPs. METHODS: The air and water channels and heads of 10 disassembled contra-angle DHPs (BienAir, Biel/Bienne, Switzerland) were inoculated separately with 108 colony forming units (cfu) of Pseudomanas aeruginosa, Staphylococcus aureus, Enterococcus hirae or Candida albicans in the presence of 0.3% bovine serum albumin (BSA) (clean conditions), 3.0% BSA or 10% artificial test soil (dirty conditions). After reassembly, all 10 DHPs underwent washer-disinfection simultaneously in a Míele (Míele Ireland Ltd., Dublin, Ireland) PG8528 washer-disinfector and were tested for reductions in micro-organisms and protein. Additional experiments were undertaken with three lubricated DHPs inoculated with S. aureus and 10% test soil. All experiments were repeated in triplicate. FINDINGS: On average, an approximate 5 log or greater reduction in microbial cfu and a >93% reduction in protein from DHP heads and channels was consistently recorded following washer-disinfection for all DHPs under all conditions tested. CONCLUSIONS: The internal components of multiple DHPs can be effectively cleaned and decontaminated by washer-disinfection.

Stabilization and swelling of hagfish slime mucin vesicles.

When agitated, Atlantic hagfish (Myxine glutinosa) produce large quantities of slime that consists of hydrated bundles of protein filaments and membrane-bound mucin vesicles from numerous slime glands. When the slime exudate contacts seawater, the thread bundles unravel and the mucin vesicles swell and rupture. Little is known about the mechanisms of vesicle rupture in seawater and stabilization within the gland, although it is believed that the vesicle membrane is permeable to most ions except polyvalent anions. We hypothesized that the most abundant compounds within the slime gland exudate have a stabilizing effect on the mucin vesicles. To test this hypothesis, we measured the chemical composition of the fluid component of hagfish slime exudate and conducted functional assays with these solutes to test their ability to keep the vesicles in a condensed state. We found K(+) concentrations that were elevated relative to plasma, and Na(+), Cl(-) and Ca(2+) concentrations that were considerably lower. Our analysis also revealed high levels of methylamines such as trimethylamine oxide (TMAO), betaine and dimethylglycine, which had a combined concentration of 388 mmol l(-1) in the glandular fluid. In vitro rupture assays demonstrated that both TMAO and betaine had a significant effect on rupture, but neither was capable of completely abolishing mucin swelling and rupture, even at high concentrations. This suggests that some other mechanism such as the chemical microenvironment within gland mucous cells, or hydrostatic pressure is responsible for stabilization of the vesicles within the gland.

Mechanisms of transport of H+, Na+ and K+, across the distal gastric caecum of larval Aedes aegypti.

Measured changes in ion fluxes, transepithelial potential (TEP) and basolateral membrane potential (Vb) in response to ion transporter inhibitors were used to assess the mechanisms of transport of H+, Na+ and K+, across the distal gastric caecum of larval Aedes aegypti, a vector of yellow fever. Preparations were stimulated with 5-hydroxytryptamine (5-HT, 10-6 M) in order to maintain stable rates of H+, Na+, and K+ transport across the distal caecum. Transepithelial potential (TEP), basolateral membrane potential (Vb), and H+, Na+ and K+ fluxes all declined after the addition of a vacuolar-type H+-ATPase (VA) inhibitor, n-ethlymaleimide (NEM), consistent with a primary role for VA in energizing ion transport across the distal gastric caecum. Amiloride also inhibited H+, Na+, and K+ fluxes, consistent with an apically expressed VA that is coupled to a cation:H+ antiporter (AeNHE8), analogous to the coupling of apical VA and cation:nH+ antiporter in Malpighian tubules. A working model of transport of H+, Na+ and K+ across the distal gastric caecum proposes that coupling of VA and AeNHE8 in the apical membrane leads to the removal of intracellular Na+ or K+, thus creating favourable ion gradients to promote the activity of two transporters in the basal membrane, cation:H+ antiporter (AeNHE3) and a bumetanide-sensitive cation chloride cotransporter (CCC).

Whole-genome sequencing identifies highly related Pseudomonas aeruginosa strains in multiple washbasin U-bends at several locations in one hospital: evidence for trafficking of potential pathogens via wastewater pipes.

BACKGROUND: Hand washbasin U-bends have increasingly been associated with nosocomial outbreaks by Gram-negative bacteria, including Pseudomonas aeruginosa which is virtually ubiquitous in U-bends. Wastewater networks servicing U-bends are potential highways for trafficking pathogenic bacteria. AIM: To use P. aeruginosa to investigate trafficking of bacteria between hospital washbasin U-bends. METHODS: Twenty-five washbasin U-bends in five locations in Dublin Dental University Hospital (DDUH) were investigated for trafficking of P. aeruginosa: 10 in Clinic 2 (C2), 10 in the Accident & Emergency Department (A&E) and five in three other locations. In addition, washbasin tap samples (N=80) and mains and tap water samples (N=72) were cultured for P. aeruginosa. Selected P. aeruginosa isolates recovered over 29 months underwent whole-genome sequencing, and relatedness was interpreted using whole-genome multi-locus sequence typing and pairwise single nucleotide polymorphism (SNP) analysis. FINDINGS: P. aeruginosa was recovered from all U-bends but not from taps or water. Eighty-three U-bend isolates yielded 10 sequence types (STs), with ST560 and ST179 from A&E, C2 and two other locations predominating (70%). ST560 was also recovered from a common downstream pipe. Isolates within ST560 and ST179 were highly related regardless of source. ST560 was divided into Cluster I (N=25) and Cluster II (N=2) with average allelic differences and SNPs of three and zero, and two and five, respectively. The 31 ST179 isolates exhibited an average allelic difference and SNPs of three and 12, respectively. CONCLUSION: Highly related P. aeruginosa strains were identified in multiple U-bends in several DDUH locations, indicating trafficking via the wastewater network.

Risk factors for posterior compared to anterior ischemic stroke: an observational study of the Registry of the Canadian Stroke Network.

BACKGROUND: Traditional vascular risk factors appear to exert varying magnitudes of risk for different major vascular events. For example, hypercholesterolemia is a much stronger risk factor for myocardial infarction than ischemic stroke. Limited evidence also suggests that vascular risk factors may exert differing magnitudes of risk for ischemic stroke within different cerebral arterial territories. We sought to determine the association between traditional vascular risk factors and the location of ischemic stroke (posterior versus anterior). METHODS: Consecutive patients with acute ischemic stroke who were admitted to 11 regional stroke centers within the Registry of the Canadian Stroke Network were included in the study sample. The Oxfordshire Community Stroke Project classification was used to distinguish posterior from anterior circulation ischemic stroke. Multivariable logistic regression was applied to determine the association between risk factors (age, gender, diabetes mellitus, hypercholesterolemia, hypertension, atrial fibrillation and smoking history) and posterior (compared to anterior) circulation ischemic stroke. RESULTS: In total, 8,489 patients with acute ischemic stroke were included. On multivariable analysis, diabetes mellitus (OR = 1.14; 95% CI = 1.02-1.27) was associated with an increased odds of posterior circulation ischemic stroke, whereas age (OR = 0.86; 95% CI = 0.83-0.90), female sex (OR = 0.84; 95% CI = 0.76-0.93), atrial fibrillation (OR = 0.83; 95% CI = 0.74-0.94) and pulmonary edema (OR = 0.74; 95% CI = 0.62-0.88) were related to a reduced odds of posterior compared with anterior circulation ischemic stroke. CONCLUSIONS: Some traditional vascular risk factors for ischemic stroke appear to exert different magnitudes of risk for posterior compared to anterior circulation ischemic stroke.

In-hospital myocardial infarction following acute ischaemic stroke: an observational study.

BACKGROUND AND PURPOSE: Acute myocardial infarction is expected to be an important medical complication following ischaemic stroke. We sought to describe the frequency and clinical impact of in-hospital myocardial infarction following acute ischaemic stroke. METHODS: Consecutive patients with acute ischaemic stroke were identified from the Registry of the Canadian Stroke Network (2003-2006). Stroke severity was measured using the Canadian Neurological Scale (CNS). Functional status at discharge was measured with the modified-Rankin Scale, and categorized into strokes with no or mild-moderate dependency (m-Rankin 0-3) and those with severe dependence or death (m-Rankin 4-6). Multivariable logistic regression was used to determine the association between myocardial infarction and clinical outcome (death or severe dependence at hospital discharge and 1 year mortality), independent of co-morbidities and in-hospital medical complications. RESULTS: In total, 9180 patients with acute ischaemic stroke were included. The mean age was 72 years (SD 13.9) and 48% were female. Overall, 211 (2.3%) patients were reported to have myocardial infarction during hospitalization. At hospital discharge, 64.9% of patients with in-hospital myocardial infarction had died or were severely disabled, compared with 35.8% in the entire cohort. Mortality at 1 year after ischaemic stroke was 56.4% in patients with myocardial infarction and 21.9% in the entire cohort. On multivariable analyses, myocardial infarction was also associated with death or severe dependence at discharge (OR 2.51; 95%CI 1.75-3.59) and mortality within 1 year (HR 1.83; 95%CI 1.51-2.23). Previous history of myocardial infarction (OR 1.50; 95%CI 1.05-2.15), diabetes mellitus (OR 1.55; 95%CI 1.42-2.10), stroke severity (OR 1.13; 95% CI 1.09-1.17) and peripheral vascular disease (OR 1.61; 95%CI 1.04-2.49) were independently associated with myocardial infarction during hospitalization. CONCLUSIONS: Myocardial infarction is an important medical complication after acute ischaemic stroke.

Biofilm problems in dental unit water systems and its practical control.

Dental chair units (DCUs) contain integrated systems that provide the instruments and services for a wide range of dental procedures. DCUs use water to cool and irrigate DCU-supplied instruments and tooth surfaces during dental treatment. Water is supplied to these instruments by a network of interconnected narrow-bore (2-3 mm) plastic tubes called dental unit waterlines (DUWLs). Many studies over the last 40 years demonstrated that DUWL output water is often contaminated with high densities of micro-organisms, predominantly Gram-negative aerobic heterotropic environmental bacteria, including Legionella and Pseudomonas species. Untreated DUWLs host biofilms that permit micro-organisms to multiply and disperse through the water network and which are aerosolized by DCU instrument use, thus exposing patients and staff to these micro-organisms, to fragments of biofilm and bacterial endotoxins. This review concentrates on how practical developments and innovations in specific areas can contribute to effective DUWL biofilm control. These include the use of effective DUWL treatment agents, improvements to DCU supply water quality, DCU design changes, development of automated DUWL treatment procedures that are effective at controlling biofilm in the long-term and require minimal human intervention, are safe for patients and staff, and which do not cause deterioration of DCU components following prolonged use.

Minimizing microbial contamination risk simultaneously from multiple hospital washbasins by automated cleaning and disinfection of U-bends with electrochemically activated solutions.

BACKGROUND: Outbreaks of infection associated with microbial biofilm in hospital hand washbasin U-bends are being reported increasingly. In a previous study, the efficacy of a prototype automated U-bend decontamination method was demonstrated for a single non-hospital pattern washbasin. It used two electrochemically activated solutions (ECA) generated from brine: catholyte with detergent properties and anolyte with disinfectant properties. AIM: To develop and test a large-scale automated ECA treatment system to decontaminate 10 hospital pattern washbasin U-bends simultaneously in a busy hospital clinic. METHODS: A programmable system was developed whereby the washbasin drain outlets, U-bends and proximal wastewater pipework automatically underwent 10-min treatments with catholyte followed by anolyte, three times weekly, over five months. Six untreated washbasins served as controls. Quantitative bacterial counts from U-bends were determined on Columbia blood agar, Reasoner's 2A agar and Pseudomonas aeruginosa selective agar following treatment and 24 h later. FINDINGS: The average bacterial densities in colony-forming units/swab from treated U-bends showed a >3 log reduction compared with controls, and reductions were highly significant (P<0.0001) on all media. There was no significant increase in average bacterial counts from treated U-bends 24 h later on all media (P>0.1). P. aeruginosa was the most prevalent organism recovered throughout the study. Internal examination of untreated U-bends using electron microscopy showed dense biofilm extending to the washbasin drain outlet junction, whereas treated U-bends were free from biofilm. CONCLUSION: Simultaneous automated treatment of multiple hospital washbasin U-bends with ECA consistently minimizes microbial contamination and thus the associated risk of infection.

Sequencing exons 5 to 8 of the p53 gene by MALDI-TOF mass spectrometry.

Matrix-assisted laser desorption ionization time of flight mass spectrometry was used to sequence exons 5 to 8 of the human p53 gene. A single tube procedure was established for target amplification and mass spectrometric (MS) sequencing. The MS sequencing scheme is designed for high throughput and parallel sample processing, and is amenable to full automation. Reliable sequencing data were obtained using fmol sample amounts. The high resolution and accuracy of MS sequencing was demonstrated by direct sequencing of a heterozygous template.

The role of manufacturers in reducing biofilms in dental chair waterlines.

OBJECTIVES: This paper reviews how dental chair unit (DCU) manufacturers can contribute practically to resolving the problem of biofilm formation in dental unit waterlines (DUWs). STUDY SELECTION: The review concentrates on how novel developments and changes in a range of specific areas have, and might contribute to DUW biofilm control. These include (i) DCU engineering and design changes; (ii) improvements to DCU supply water quality; (iii) development of automated DUW treatment procedures that are effective at controlling biofilm in the long-term, safe for patients and dental staff, environmentally friendly and which do not exhibit adverse effects on DCU components after prolonged use. SOURCES: The majority of the material contained in this review is based on, or supported by the peer-reviewed literature. DATA: The current consensus from the literature reveals that the emphasis on DUW biofilm and its control has focused on describing the problem and its control using a range of periodic and residual DUW treatment agents. Unfortunately, until recently, DCU manufacturers have provided very little specific guidance in this regard. Indeed, ensuring that DCUs provide good quality output water has generally been regarded to be the responsibility of dental practitioners. Some recent studies have shown that novel DCUs with integral semi-automated or automated DUW cleaning systems can effectively control DUW biofilm in the long-term. However, there are other potential DCU engineering and design changes that DCU manufacturers could undertake to further improve DUW biofilm control. CONCLUSIONS: DCU manufacturers can significantly contribute to controlling the problem of DUW biofilm.

Optimisation of the long-term efficacy of dental chair waterline disinfection by the identification and rectification of factors associated with waterline disinfection failure.

UNLABELLED: Although many studies have highlighted the problem of biofilm growth in dental chair unit waterlines (DUWs), no long-term studies on the efficacy of DUW disinfection using a large number of dental chair units (DCUs) have been reported. OBJECTIVES: To investigate the long-term (21 months) efficacy of the Planmeca Waterline Cleaning System (WCS) to maintain the quality of DUW output water below the American Dental Association (ADA) recommended standard of < or =200cfu/mL of aerobic heterotrophic bacteria using once weekly disinfection with the hydrogen peroxide-and silver ion-containing disinfectant Planosil. METHODS: Microbiological quality of DUW output water was monitored by culture on R2A agar for 10 DCUs fitted with the WCS. The presence of biofilm in DUWs was examined by electron microscopy. RESULTS: During the first 9 months a high prevalence (28/300 disinfection cycles; 9.3%) of intermittent DUW disinfection failure occurred in 8/10 DCUs due to operator omission to disinfect all DUWs (10/28 failed cycles), incorrect compressed air pressure failing to distribute the disinfectant properly (4/28 failed cycles) and physical blockage of disinfectant intake valves due to corrosion effects of Planosil (14/28 failed cycles). On rectification of these faults through engineering redesign and procedural changes, no further cases of intermittent DUW disinfection failure were observed. Independently of these factors, a rapid and consistent decline in efficacy of DUW disinfection occurred in 4/10 DCUs following the initial 9 months of once weekly disinfection. There was a highly significant difference (P<0.0001) in the prevalence of strongly catalase-positive Novosphingobium and Sphingomonas bacterial species (mean average prevalence of 37.1%) in DUW output water from these 4 DCUs compared to the other 6 DCUs and DCU supply water (prevalence <1%), which correlated with biofilm presence in the DUWs and indicated selective pressure for maintenance of these species by prolonged disinfectant usage. Planosil was reformulated to a more concentrated form (Planosil Forte) and when used once weekly was found to maintain bacterial density in output water below the ADA standard for all 10 DCUs. CONCLUSIONS: A variety of factors can contribute to failure of DUW disinfection in the long-term, including human error, disinfectant corrosion of equipment and natural selection of naturally disinfectant-tolerant bacterial species.

Tetraethylammonium and nicotine transport by the Malpighian tubules of insects.

We examined transepithelial transport of the prototypical type I organic cation (OC) tetraethylammonium (TEA) and the plant alkaloid nicotine by the isolated Malpighian tubules (MTs) of nine insect species from six orders. Isolated tubules were exposed to radiolabelled forms of either TEA or nicotine in the bathing (basal) fluid. Luminal (apical) secreted fluid was collected and TEA or nicotine concentration was determined. Active net transport of nicotine from bath to lumen was observed by the MTs of all the insects studied. TEA was also transported from bath to lumen in MTs of all species except Rhodnius prolixus and Aedes aegypti. MTs of both of these blood feeders did not show active transport of TEA under normal physiological conditions. Transport of TEA but not nicotine increased during the moult in the MTs of Rhodnius, but the concentrations of TEA in the secreted fluid were still consistent with passive accumulation in response to the lumen-negative transepithelial potential. Nicotine transport by Rhodnius MTs was inhibited by the type II OC quinidine, a known p-glycoprotein inhibitor, but not by the type I OCs N-methylnicotinamide or cimetidine. Taken together, the results suggest that active transport of OCs by the MTs is common among species from different orders and that transepithelial TEA and nicotine transport occur through separate pathways.