Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO): rationale and design.

BACKGROUND: More than 6200 End Stage Renal Disease patients in the Netherlands are dependent on dialysis, either performed at home or in a dialysis centre. Visiting a dialysis centre three times a week is considered a large burden by many patients. However, recent data regarding the effects of dialysis at home on quality of life, clinical outcomes, and costs compared with in-centre haemodialysis are lacking. METHODS: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO) is a nationwide, prospective, observational cohort study that will include adult patients starting with a form of dialysis. Health-related quality of life, as the primary outcome, clinical outcomes and costs, as secondary outcomes, will be measured every 3-6 months in patients on home dialysis, and compared with a control group consisting of in-centre haemodialysis patients. During a 3-year period 800 home dialysis patients (600 peritoneal dialysis and 200 home haemodialysis patients) and a comparison group of 800 in-centre haemodialysis patients will be included from 53 Dutch dialysis centres (covering 96% of Dutch centres) and 1 Belgian dialysis centre (covering 4% of Flemish centres). DISCUSSION: DOMESTICO will prospectively investigate the effect of home dialysis therapies on health-related quality of life, clinical outcomes and costs, in comparison with in-centre haemodialysis. The findings of this study are expected to ameliorate the shared decision-making process and give more guidance to healthcare professionals, in particular to assess which type of patients may benefit most from home dialysis. TRIAL REGISTRATION: The DOMESTICO study is registered with the National Trial Register on (number: NL6519 , date of registration: 22 August 2017) and the Central Committee on Research Involving Human Subjects (CCMO) (number: NL63277.029.17).

Duplex real-time PCR for rapid simultaneous detection of Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans in Amphibian samples.

Chytridiomycosis is a lethal fungal disease contributing to declines and extinctions of amphibian species worldwide. The currently used molecular screening tests for chytridiomycosis fail to detect the recently described species Batrachochytrium salamandrivorans. In this study, we present a duplex real-time PCR that allows the simultaneous detection of B. salamandrivorans and Batrachochytrium dendrobatidis. With B. dendrobatidis- and B. salamandrivorans-specific primers and probes, detection of the two pathogens in amphibian samples is possible, with a detection limit of 0.1 genomic equivalent of zoospores of both pathogens per PCR. The developed real-time PCR shows high degrees of specificity and sensitivity, high linear correlations (r(2) > 0.995), and high amplification efficiencies (>94%) for B. dendrobatidis and B. salamandrivorans. In conclusion, the described duplex real-time PCR can be used to detect DNA of B. dendrobatidis and B. salamandrivorans with highly reproducible and reliable results.

Bacteremic complications of intravascular catheter tip colonization with Gram-negative micro-organisms in patients without preceding bacteremia.

Although Gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with Gram-negative micro-organisms without preceding bacteremia remains unclear. We determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent Gram-negative bacteremia. All patients with positive intravascular catheter tip cultures with Gram-negative micro-organisms at the University Medical Center, Utrecht, The Netherlands, between 2005 and 2009, were retrospectively studied. Patients with Gram-negative bacteremia within 48 h before catheter removal were excluded. The main outcome measure was bacteremia with Gram-negative micro-organisms. Other endpoints were length of the hospital stay, in-hospital mortality, secondary complications of Gram-negative bacteremia, and duration of intensive care admission. A total of 280 catheters from 248 patients were colonized with Gram-negative micro-organisms. Sixty-seven cases were excluded because of preceding positive blood cultures, leaving 213 catheter tips from 181 patients for analysis. In 40 (19%) cases, subsequent Gram-negative bacteremia developed. In multivariate analysis, arterial catheters were independently associated with subsequent Gram-negative bacteremia (odds ratio [OR] = 5.00, 95% confidence interval [CI]: 1.20-20.92), as was selective decontamination of the digestive tract (SDD) (OR = 2.47, 95% CI: 1.07-5.69). Gram-negative bacteremia in patients who received SDD was predominantly caused by cefotaxime (part of the SDD)-resistant organisms. Mortality was significantly higher in the group with subsequent Gram-negative bacteremia (35% versus 20%, OR = 2.12, 95% CI: 1.00-4.49). Patients with a catheter tip colonized with Gram-negative micro-organisms had a high chance of subsequent Gram-negative bacteremia from any cause. This may be clinically relevant, as starting antibiotic treatment pre-emptively in high-risk patients with Gram-negative micro-organisms cultured from arterial intravenous catheters may be beneficial.

Widespread Warming Before and Elevated Barium Burial During the Paleocene-Eocene Thermal Maximum: Evidence for Methane Hydrate Release?

Current climate change may induce positive carbon cycle feedbacks that amplify anthropogenic warming on time scales of centuries to millennia. Similar feedbacks might have been active during a phase of carbon cycle perturbation and global warming, termed the Paleocene-Eocene Thermal Maximum (PETM, 56 million years ago). The PETM may help constrain these feedbacks and their sensitivity to warming. We present new high-resolution carbon isotope and sea surface temperature data from Ocean Drilling Program Site 959 in the Equatorial Atlantic. With these and existing data from the New Jersey Shelf and Maud Rise, Southern Ocean, we quantify the lead-lag relation between PETM warming and the carbon input that caused the carbon isotope excursion (CIE). We show ~2 °C of global warming preceded the CIE by millennia, strongly implicating CO2-driven warming triggered a positive carbon cycle feedback. We further compile new and published barium (Ba) records encompassing continental shelf, slope, and deep ocean settings. Based on this compilation, we calculate that average Ba burial rates approximately tripled during the PETM, which may require an additional source of Ba to the ocean. Although the precipitation pathway is not well constrained, dissolved Ba stored in sulfate-depleted pore waters below methane hydrates could represent an additional source. We speculate the most complete explanation for early warming and rise in Ba supply is that hydrate dissociation acted as a positive feedback and caused the CIE. These results imply hydrates are more temperature sensitive than previously considered, and may warrant reconsideration of the political assignment of 2 °C warming as a safe future scenario.

Home haemodialysis in the Netherlands: State of the art.

Home haemodialysis (HHD) has gained popularity in recent years, due to improved clinical outcomes associated with frequent or prolonged haemodialysis sessions, best achievable at home. However, several barriers to HHD are perceived by the physician and patient, among which lack of experience and education, logistic difficulties and reimbursement issues seem to be the most important ones. HHD, in particular when performed with intensified frequency or duration, is associated with improved quality of life, blood pressure control and survival. Serious adverse events are rare; however, more vascular access complications arise due to frequent needling. This emphasises the importance of comprehensive education and training. This review aims to provide the physician with a detailed state of the art overview on HHD in the Netherlands, discussing potential barriers and benefits, and offering practical advice.

Wildlife disease. Recent introduction of a chytrid fungus endangers Western Palearctic salamanders.

Emerging infectious diseases are reducing biodiversity on a global scale. Recently, the emergence of the chytrid fungus Batrachochytrium salamandrivorans resulted in rapid declines in populations of European fire salamanders. Here, we screened more than 5000 amphibians from across four continents and combined experimental assessment of pathogenicity with phylogenetic methods to estimate the threat that this infection poses to amphibian diversity. Results show that B. salamandrivorans is restricted to, but highly pathogenic for, salamanders and newts (Urodela). The pathogen likely originated and remained in coexistence with a clade of salamander hosts for millions of years in Asia. As a result of globalization and lack of biosecurity, it has recently been introduced into naïve European amphibian populations, where it is currently causing biodiversity loss.

Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins in leukemia patients.

BCR-ABL fusion proteins show increased signaling through their ABL tyrosine kinase domain, which can be blocked by specific inhibitors, thereby providing effective treatment. This makes detection of BCR-ABL aberrations of utmost importance for diagnosis, classification and treatment of leukemia patients. BCR-ABL aberrations are currently detected by karyotyping, fluorescence in situ hybridization (FISH) or PCR techniques, which are time consuming and require specialized facilities. We developed a simple flow cytometric immunobead assay for detection of BCR-ABL fusion proteins in cell lysates, using a bead-bound anti-BCR catching antibody and a fluorochrome-conjugated anti-ABL detection antibody. We noticed protein stability problems in lysates caused by proteases from mature myeloid cells. This problem could largely be solved by adding protease inhibitors in several steps of the immunobead assay. Testing of 145 patient samples showed fully concordant results between the BCR-ABL immunobead assay and reverse transcriptase PCR of fusion gene transcripts. Dilution experiments with BCR-ABL positive cell lines revealed sensitivities of at least 1%. We conclude that the BCR-ABL immunobead assay detects all types of BCR-ABL proteins in leukemic cells with high specificity and sensitivity. The assay does not need specialized laboratory facilities other than a flow cytometer, provides results within approximately 4 h, and can be run in parallel to routine immunophenotyping.

Breath hydrogen and methane expiration in men and women after oat extract consumption.

Oat extract has been shown to modify blood glucose response and fasting lipids after dietary incorporation although some abdominal discomfort and increased flatulence were noted. To determine the extent of gas production, hydrogen and methane were determined after tolerance tests containing cooked and uncooked oat extract and after dietary incorporation. Breath gases were determined before and periodically after tolerance tests. Study 1: While consuming a maintenance diet, 24 subjects (55.3-112.5 kg body weight) underwent a tolerance test (1 g carbohydrate/kg body wt) of glucose (GTT, 1700 kJ/100 g) or uncooked, baked, or boiled pudding [2191 kJ/100 g carbohydrate, (0.67 glucose and 0.33 oat extract containing 10 g/100 g beta-glucan)]. Hydrogen and methane expiration after all tolerance tests with the oat extract puddings, regardless of cooking method, was significantly higher than expirations after the GTT. Cooking the oat extract did not significantly change hydrogen or methane expiration. Study 2: Twenty-three subjects consumed a maintenance diet followed by the incorporation of oat extracts (50 g/8.33 MJ, 1 or 10 g/100 g beta-glucan) to the diet in a crossover pattern. A GTT and a tolerance test containing 0.67 g glucose and 0.33 g of the respective oat extract/kg body weight were consumed after the maintenance and oat extract diet periods. Breath hydrogen was significantly higher after both oat extract tolerance tests than after the GTT. Hydrogen excretion after the 10% beta-glucan oat extract was higher at 4, 5 and 6 h than after the 1% beta-glucan oat extract; breath methane was not significantly different. These data indicate that cooking did not alter the influence of oat extracts on intestinal function, and increased beta-glucan marginally increased hydrogen expiration.