The effect of taurolidine on the time-to-positivity of blood cultures.

Background: Taurolidine containing lock solutions (TL) are a promising method for the prevention of central line associated bloodstream infections. Per accident, the TL may not always be aspirated from the central venous catheter (CVC) before blood cultures are obtained. The TL could, unintentionally, end up in a blood culture vial, possibly altering the results. The aim of this study was to investigate the effect of the TLs on the detection of microbial growth in blood culture vials. Methods: Different lock solutions (taurolidine-citrate-heparin (TCHL), taurolidine, heparin, citrate or NaCl) were added to BD BACTECTM blood culture vials (Plus Aerobic/F, Lytic/10 Anaerobic/F or Peds Plus/F) before spiking with Staphylococcus aureus (ATCC 29213 or a clinical strain) or Escherichia coli (ATCC 25922 or a clinical strain) in the presence and absence of blood. Subsequently, blood culture vials were incubated in the BD BACTEC FX instrument with Time-to-positivity (TTP) as primary outcome. In addition, the effect of the TCHL on a variety of other micro-organisms was tested. Discussion: In the presence of taurolidine, the TTP was considerably delayed or vials even remained negative as compared to vials containing heparin, citrate or NaCl. This effect was dose-dependent. The delayed TTP was much less pronounced in the presence of blood, but still notable. Conclusion: This study stresses the clinical importance of discarding TLs from the CVC before obtaining a blood culture.

Depletion of CLL cells by venetoclax treatment reverses oxidative stress and impaired glycolysis in CD4 T cells.

Acquired T-cell dysfunction is characteristic of chronic lymphocytic leukemia (CLL) and is associated with reduced efficacy of T cell-based therapies. A recently described feature of dysfunctional CLL-derived CD8 T cells is reduced metabolic plasticity. To what extend CD4 T cells are affected and whether CD4 T-cell metabolism and function can be restored upon clinical depletion of CLL cells are currently unknown. We address these unresolved issues by comprehensive phenotypic, metabolic, transcriptomic, and functional analysis of CD4 T cells of untreated patients with CLL and by analysis of the effects of venetoclax plus obinutuzumab on the CD4 population. Resting CD4 T cells derived from patients with CLL expressed lower levels of GLUT-1 and displayed deteriorated oxidative phosphorylation (OXPHOS) and overall reduced mitochondrial fitness. Upon T-cell stimulation, CLL T cells were unable to initiate glycolysis. Transcriptome analysis revealed that depletion of CLL cells in vitro resulted in upregulation of OXPHOS and glycolysis pathways and restored T-cell function in vitro. Analysis of CD4 T cells from patients with CLL before and after venetoclax plus obinutuzumab treatment, which led to effective clearance of CLL in blood and bone marrow, revealed recovery of T-cell activation and restoration of the switch to glycolysis, as well as improved T-cell proliferation. Collectively, these data demonstrate that CLL cells impose metabolic restrictions on CD4 T cells, which leads to reduced CD4 T-cell functionality. This trial was registered in the Netherlands Trial Registry as #NTR6043.

The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis.

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing <10 patients and studies using TLs as treatment. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A random effects model was used to pool individual study incidence rate ratios (IRRs). Subgroup analyses were performed based on the following factors: CVC indication, comparator lock and bacterial isolates cultured. A total of 14 articles were included in the qualitative synthesis describing 1219 haemodialysis, total parenteral nutrition and oncology patients. The pooled IRR estimated for all patient groups together (nine studies; 918 patients) was 0.30 (95% confidence interval 0.19-0.46), favouring the TLs. Adverse events (10 studies; 867 patients) were mild and scarce. The quality of the evidence was limited due to a high risk of bias and indirectness of evidence. The use of TLs might be promising for the prevention of CVC-related bloodstream infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of TLs.

The GI Simulated Clinic in the Era of COVID-19: a Comparison of Virtual to In-Person Delivery.

The COVID-19 pandemic has significantly impacted medical education; thus, there is a need to better understand the effectiveness of virtual learning compared to in-person learning. This is a single-center, cross-sectional study of first-year medical students who attended a gastroenterology simulated clinic activity in person in 2018 and 2019 or virtually in 2020. Participants were surveyed on the activity's relevance and effectiveness. Students' assessment of the virtual clinic's effectiveness and relevance was not significantly different from the in-person version of the activity. In addition, most students rated the virtual clinic as effective for learning about telemedicine.

[The influence of corona related factors on acute psychiatric admissions]. / De invloed van coronagerelateerde factoren op acute psychiatrische opnames.

BACKGROUND: Since the COVID-19 outbreak there are warnings for an increase of psychological complaints in the general population and in psychiatric patients. AIM: To gain insight in corona associated factors that can provoke psychiatric decompensation, wherefore admission in our psychiatric clinic was necessary. To investigate if the admission rate of our clinic increased since the start of the quarantine measures. METHOD: From the 16th of March until the 1st of June 2020 we collected data in our psychiatric acute admission clinic in Amsterdam of patients with a corona associated triggering factor for the current psychiatric decompensation. Additionally, the admission rates between the 16th of March and the 1st of June 2020 were compared with the admission rates in the same period in 2019. RESULTS: In 25 of 120 admitted patients there was a corona associated triggering factor. The disruption of daily routine and increased stress due to corona were mentioned most often. In the studied period there were significantly more admissions in 2020 compared to 2019. CONCLUSION: The corona crisis can contribute to psychiatric decompensation. In a fifth of the admitted patients a corona associated triggering factor was mentioned. Furthermore we observed a higher demand for psychiatric admissions since the start of the quarantine measures in comparison with 2019.

Incidence, severity and outcome of central line related complications in pediatric oncology patients; A single center study.

BACKGROUND: Central venous access device (CVAD)-related complications are associated with high morbidity rates. This study was performed to underline the importance of CVAD-complication prevention and treatment. METHODS: An audit of practice of CVAD-related complications in pediatric oncology patients receiving a CVAD between January 2015 and June 2017 was performed. CVADs included were totally implantable venous access ports (TIVAPs), Hickman-Broviac® (HB), nontunneled, and peripherally inserted CVADs. RESULTS: A total of 201 children, with 307 CVADs, were analyzed. The incidence rates per 1000 CVAD-days for the most common complications were 1.66 for malfunctions, and 1.51 for central line-associated bloodstream infections (CLABSIs). Of all CVADs inserted, 37.1% were removed owing to complications, of which 45.6% were owing to CLABSIs. In 42% of the CLABSIs, the CLABSI could be successfully cured with systemic antibiotic treatment only. Of all included patients, 5.0% were admitted to the intensive care unit owing to CLABSI. The HB-CVAD compared to the TIVAP was a risk factor for CVAD-related complications, CLABSIs and dislocations in particular. CONCLUSIONS: The incidence of CVAD-related complications is high. Research on the prevention and treatment of CVAD-related complications in pediatric oncology patients should be a high priority for all health care professionals. TYPE OF STUDY: Prognosis study (retrospective). LEVEL OF EVIDENCE: Level II.

Performance evaluation of duplex constructed wetlands for the treatment of diesel contaminated wastewater.

A duplex constructed wetland (duplex-CW) is a hybrid system that combines a vertical flow (VF) CW as a first stage with a horizontal flow filter (HFF) as a second stage for a more efficient wastewater treatment as compared to traditional constructed wetlands. This study evaluated the potential of the hybrid CW system to treat influent wastewater containing diesel range organic compounds varying from C7 - C40 using a series of 12-week practical and numerical experiments under controlled conditions in a greenhouse (pH was kept at 7.0 ±â€¯0.2, temperature between 20 and 23° C and light intensity between 85 and 100-µmol photons m-2 sec-1 for 16 h d-1). The VF CWs were planted with Phragmites australis and were spiked with different concentrations of NH4+-N (10, 30 and 60 mg/L) and PO43--P (3, 6 and 12 mg/L) to analyse their effects on the degradation of the supplied petroleum hydrocarbons. The removal rate of the diesel range organics considering the different NH4+-N and PO43--P concentrations were simulated using Monod degradation kinetics. The simulated results compared well with the observed database. The results showed that the model can effectively be used to predict biochemical transformation and degradation of diesel range organic compounds along with nutrient amendment in duplex constructed wetlands.

Fate of heavy metals in vertical subsurface flow constructed wetlands treating secondary treated petroleum refinery wastewater in Kaduna, Nigeria.

This study examined the performance of pilot-scale vertical subsurface flow constructed wetlands (VSF-CWs) planted with three indigenous plants, i.e. Typha latifolia, Cyperus alternifolius, and Cynodon dactylon, in removing heavy metals from secondary treated refinery wastewater under tropical conditions. The T. latifolia-planted VSF-CW had the best heavy metal removal performance, followed by the Cyperus alternifolius-planted VSF-CW and then the Cynodon dactylon-planted VSF-CW. The data indicated that Cu, Cr, Zn, Pb, Cd, and Fe were accumulated in the plants at all the three VSF-CWs. However, the accumulation of the heavy metals in the plants accounted for only a rather small fraction (0.09-16%) of the overall heavy metal removal by the wetlands. The plant roots accumulated the highest amount of heavy metals, followed by the leaves, and then the stem. Cr and Fe were mainly retained in the roots of T. latifolia, Cyperus alternifolius, and Cynodon dactylon (TF < 1), meaning that Cr and Fe were only partially transported to the leaves of these plants. This study showed that VSF-CWs planted with T. latifolia, Cyperus Alternifolius, and Cynodon dactylon can be used for the large-scale removal of heavy metals from secondary refinery wastewater.

Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein.

Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells.

The effect of aeration and recirculation on a sand-based hybrid constructed wetland treating low-strength domestic wastewater.

The Duplex-constructed wetland (CW) is a hybrid system composed of a vertical flow (VF) CW on top of a horizontal flow filter (HFF). Each compartment is designed to play a different role: aerobic treatment in the VF CW due to intermittent feeding and anoxic treatment in the HFF due to saturated conditions. Three Duplex-CWs were used in this study: Control, Aerated and Recirculating. The role of each compartment was tested for pollutant removal and micro-invertebrate abundance. In all systems, the VF CW removed mainly organic matter, solids and NH4(+)-N. Pathogens were removed in both compartments. Likewise, total nitrogen removal occurred in both compartments, only the Recirculating HFF was not able to denitrify the nitrogen due to the slightly more oxic conditions as compared to the other systems. All systems met discharge guidelines for organic matter, but only the Control and Aerated systems met those for total nitrogen. At the applied loading rates, the pollutant removal was not significantly enhanced by the use of aeration and recirculation. Therefore, operation as in the Control system, without aeration or recirculation, is recommended for the tested Duplex-CWs. If artificial aeration will be used in CWs, the support material should be carefully selected to allow a proper air distribution.

[Referral for mammography often not according to guideline]. / Verwijzing voor mammogram vaak niet volgens richtlijn.

OBJECTIVE: To analyse the percentage of women with a family history of breast cancer referred by general practitioners (GPs) for a screening mammography in accordance with the Dutch Breast Cancer Guideline produced by the Netherlands Comprehensive Cancer Centre (IKNL). DESIGN: Prospective cohort study. METHOD: Women referred by their GP between December 2011 and December 2012 for mammography, with the indication "family history of breast cancer", were invited to take part in this study. A trained radiology laboratory assistant carried out a structured questionnaire to assess their risk on the basis of the categories of the 2008 IKNL guideline "Family history of breast/ovarian cancer". Based on the presence of certain risk factors, the women were allocated to one of the following groups: "referral for mammography", "referral to a clinical geneticist" or "no referral indicated". RESULTS: 242 women were referred by their GPs to the Radiology Department for mammography on the basis of family history; we included 210 women in our study. Their ages ranged from 25 to 77 years (mean age: 48 years). Forty-five patients (21%) were referred for mammography in accordance with the guideline. Twenty-two patients (10%) should have been referred to a clinical geneticist according to the guideline, whereas 143 patients (68%) did not meet the criteria for a screening mammography outside the screening programme. CONCLUSION: In only 21% of patients referred by their GPs for a screening mammography, with "family history" given as the reason, this referral was in accordance with the standard of the Dutch College of General Practitioners (NHG) or the IKNL guideline. Screening outside the breast cancer screening programme was not indicated according to the guideline for the majority of the women. Referral of 10% of the women referred should have been to a clinical geneticist; this figure rises to as many as 20% using the 2012 IKNL guideline.

Material selection for a constructed wetroof receiving pre-treated high strength domestic wastewater.

A constructed wetroof (CWR) is defined in this study as the combination of a green roof and a constructed wetland: a shallow wastewater treatment system placed on the roof of a building. The foremost challenge of such CWRs, and the main aim of this investigation, is the selection of an appropriate matrix capable of assuring the required hydraulic retention time, the long-term stability and the roof load-bearing capacity. Six substrata were subjected to water dynamics and destructive tests in two testing-tables. Among all the materials tested, the substratum configuration composed of sand, light expanded clay aggregates, biodegradable polylactic acid beads together with stabilization plates and a turf mat is capable of retaining the water for approximately 3.8 days and of providing stability (stabilization plates) and an immediate protection (turf mat) to the system. Based on those results, a full-scale CWR was built, which did not show any physical deterioration after 1 year of operation. Preliminary wastewater treatment results on the full-scale CWR suggest that it can highly remove main wastewater pollutants (e.g. chemical oxygen demand, PO4(3-)-P and NH4(+)-N). The results of these tests and practical design considerations of the CWR are discussed in this paper.

Reactive transport simulation in a tropical horizontal subsurface flow constructed wetland treating domestic wastewater.

A promising approach to the simulation of flow and conversions in the complex environment of horizontal subsurface flow constructed wetlands (HSSF-CWs) is the use of reactive transport models, in which the transport equation is solved together with microbial growth and mass-balance equations for substrate transformation and degradation. In this study, a tropical pilot scale HSSF-CW is simulated in the recently developed CWM1-RETRASO mechanistic model. The model predicts organic matter, nitrogen and sulfur effluent concentrations and their reaction rates within the HSSF-CW. Simulations demonstrated that these reactions took place simultaneously in the same (fermentation, methanogenesis and sulfate reduction) or at different (aerobic, anoxic and anaerobic) locations. Anaerobic reactions occurred over large areas of the simulated HSSF-CW and contributed (on average) to the majority (68%) of the COD removal, compared to aerobic (38%) and anoxic (1%) reactions. To understand the effort and compare computing resources needed for the application of a mechanistic model, the CWM1-RETRASO simulation is compared to a process-based, semi-mechanistic model, run with the same data. CWM1-RETRASO demonstrated the interaction of components within the wetland in a better way, i.e. concentrations of microbial functional groups, their competition for substrates and the formation of intermediary products within the wetland. The CWM1-RETRASO model is thus suitable for simulations aimed at a better understanding of the CW system transformation and degradation processes. However, the model does not support biofilm-based modeling, and it is expensive in computing and time resources required to perform the simulations.

[Antibiotic prophylaxis not indicated in dental procedures in patients with a joint prosthesis]. / Antibioticaprofylaxe niet geïndiceerd bij tandheelkundige ingrepen bij patiënten met een gewrichtsprothese.

Antibiotic prophylaxis is suggested for high-risk patients undergoing dental procedures to prevent haematogenous infection of the artificial joint. However, randomised placebo-controlled trials are lacking. Case reports are difficult to interpret, because bacteraemias are very common after chewing and tooth brushing anyway. Widespread use of antibiotics has serious downsides. Therefore, more convincing data are needed to support the use of antibiotic prophylaxis for high-risk patients.

Shared and delegated systems are not quick remedies for improving diabetes care: a systematic review.

BACKGROUND: Type 2 diabetes is an important, chronic condition notorious for its costly and disabling complications. Nowadays, enhanced cooperation is expected to improve the quality of diabetes care and reduce risks for chronically ill patients. It is, however, questionable whether this assumption is evidence based. METHODS: Using a structured literature search, we selected systematic reviews, randomised controlled trials (RCTs) and other effect evaluations regarding the sharing and allocation of diabetes care. RESULTS: We selected 22 studies to include in this review. The process of care improved in all studies investigating this quality aspect. HbA1c improved in seven reviews and in five other studies. All included reviews and four RCTs were unable to demonstrate a positive effect on blood pressure. Total cholesterol improved in two reviews and five other studies. CONCLUSIONS: The sharing and allocation of diabetes care leads to significant reduction in HbA1c and improves the process of care. However, this improvement has not as yet led to better cardiovascular risk management. For a number of reasons, a truly accurate estimation of the results of shared and allocated diabetes care within the Dutch diabetes care system is not possible.

[Rivastigmine as adjunctive therapy in the therapeutic dilemma for the treatment of hallucinations due to Parkinson disease]. / Rivastigmine als ondersteuning bij het dilemma van de behandeling van hallucinaties optredend bij ziekte van Parkinson.

We report three cases of patients with Parkinson's disease without dementia, admitted to our hospital because of hallucinations. The anti-Parkinson medication was adapted and the patients started with rivastigmine. As a result, hallucinations no longer occurred. A 79 years old man also required short-term quetiapine because of agitation and anti-Parkinson doses were without side effects, as a result of which mobility improved. An 84 years old woman reported mild side effects of rivastigmine, without consequences, whereas her mobility appeared to be good. A 72 years old woman reported mild memory problems upon admission, which improved during admission, as did her mobility after increasing the anti-Parkinson medication doses. Treatment of rivastigmine can be useful in the therapeutic dilemma in the treatment of hallucinations in patients with Parkinson's disease (start anti-psychotic or reduce anti-Parkinson medication). In addition to adapting anti-Parkinson doses and sometimes short-term treating with an anti-psychotic, treatment with rivastigmine appears to be a quick improvement, without serious side effects. Also, mobility can improve, due to the possibility of increasing the anti-Parkinson doses, if necessary. Because of the many remaining questions, prospective randomised trials are needed.

Bacterial resistance: a sensitive issue complexity of the challenge and containment strategy in Europe.

The development of antimicrobial agents has been a key achievement of modern medicine. However, their overuse has led to an increasing incidence of infections due to antibiotic-resistant microorganisms. Quantitative figures on the current economic and health impact of antimicrobial resistance are scant, but it is clearly a growing challenge that requires timely action. That action should be at the educational, ethical, economic and political level. An important first step would be to increase public awareness and willingness to take the necessary measures to curb resistance. Hence, studies are needed that would provide solid, quantitative data on the societal impact of antibiotic resistance. This review discusses the complexity of resistance, identifies its main drivers and proposes measures to contain it on a European scale.

Priorities for antibiotic resistance surveillance in Europe.

Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitudinal, and cover a sufficiently large and representative population. However, many fall short of these requirements that define good surveillance studies. Moreover, current efforts are dispersed among many, mostly small, initiatives with different objectives. These studies must be tailored to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during the diagnosis of hospitalised patients, and the DANMAP programme, which collects data in the veterinary sector. As already noted by the WHO, genetic studies that include both the typing of isolates and the characterisation of resistance determinants are necessary to understand fully the spread and development of antibiotic resistance.

Potential of a tropical subsurface constructed wetland to remove phenol from pre-treated pulp and papermill wastewater.

The capacity of a pilot project subsurface flow constructed wetland in the tropics to remove phenol from pre-treated pulp and paper mill wastewater was studied under varying hydraulic retention times (HRT) with batch loading. Initial 15 months results indicate that removal efficiencies for phenol were variable but on average reached 60% at 5-day HRT and 77% at 3-day HRT. It was thought that the longer retention time might have caused oxygen and nutrient deficiencies, which may have reduced removal performance. Although phenol was sometimes not detectable in the wetland outflow, on average values over the experimental period did not meet set national guidelines. In the ongoing study, the impact of varying hydraulic retention time and/or loading rate on the removal of phenols will be evaluated and the main removal process established.