Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

BACKGROUND: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. AIM: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). METHODS: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. RESULTS: A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CONCLUSIONS: CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

[Should every doctor be allowed to use ultrasound? Dilemmas surrounding broad application of ultrasound in clinical practice]. / Mag iedere arts zonder meer echo's maken?

Ultrasound is rapidly gaining ground in clinical medicine. This offers distinct advantages for diagnosis and treatment. This is notably the case when moving images are created by the treating physician, who can integrate them immediately with all other clinical information. The downside of a broad application of ultrasound is an increase in the number of incidental findings and missed diagnoses. This is amplified by the frequent lack of formal requirements for training and skills. Storage of ultrasound images may furthermore lead to verifiable misinterpretations. We are of the opinion that responsible integration of ultrasound in clinical practice requires clear peer agreements without sectarian thinking. To illustrate this, we discuss the dilemmas surrounding increased use of ultrasound from a medicolegal perspective.

Screening regional management options for their impact on climate resilience: an approach and case study in the Venen-Vechtstreek wetlands in the Netherlands.

Freshwater systems provide various resources and services. These are often vulnerable to climate change and other pressures. Therefore, enhancing resilience to climate change is important for their long term viability. This paper explores how management options can be evaluated on their resilience implications. The approach included five steps: (1) characterizing the system, (2) characterizing the impacts of climate change and other disturbances, (3) inventorying management options, (4) assessing the impacts of these on climate resilience, and (5) follow-up analysis. For the resilience assessment, we used a set of 'resilience principles': homeostasis, omnivory, high flux, flatness, buffering, and redundancy. We applied the approach in a case study in a Dutch wetlands region. Many options in the region's management plan contribute to resilience, however, the plan underutilised several principles, particularly flatness, but also redundancy and omnivory for agriculture, and high flux for nature. Co-benefits was identified as an important additional criterion to obtain support for adaptation from local stakeholders, such as farmers. The approach provided a relatively quick and participatory way to screen options. It allowed us to consider multiple impacts and sectors, multiple dimensions of resilience, and stakeholder perspectives. The results can be used to identify gaps or pitfalls, and set priorities for follow-up analyses.

Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.

Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time-depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

Effects of neonicotinoids and fipronil on non-target invertebrates.

We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section "other invertebrates" review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.

Adoption and implementation of the original strict glycemic control guideline is feasible and safe in adult critically ill patients.

BACKGROUND: Three trials of tight glucose control (TGC) found clinical benefit of normalization of blood glucose levels in the intensive care unit (ICU). Implementation of TGC was imperfect in subsequent trials, since attained blood glucose levels (BGLs) never reached the targets as in the original trials of TGC. We investigated whether implementation of the TGC guideline as used in the original trials of TGC is feasible and safe. METHODS: In this study 3 ICUs adopted and implemented the TGC guideline as used in the original trials of TGC using a multifaceted practice change strategy; 3 ICUs that did not change their blood glucose control guideline served as controls. TGC was practiced by physicians and nurses during the first 12-month (period-2), thereafter exclusively by nurses (period-3). Blood glucose metrics 12-month before (period-1) and 24-month after implementation of the guideline were compared. RESULTS: The analysis included 1321 in period-1, 1169 and 1006 patients in period-2, and -3, respectively, in the intervention ICUs, and 3110 patients in the control ICUs. After implementation of the new TGC guideline, patients in intervention ICUs had lower median BGLs (105 [IQR: 85-130] mg/dL vs. 119 [99-150] mg/dL in period-1, P<0.001; and vs. 113 [95-141] mg/dL in control ICUs, P<0.001). The incidence of severe hypoglycemia initially increased, but again decreased when exclusively nurses practiced TGC, and was not associated with increased mortality or morbidity. CONCLUSIONS: Implementation of the original TGC guideline is feasible and safe. Our study suggests a learning effect over time.

Survey into blood glucose control in critically ill adult patients in the Netherlands.

BACKGROUND: To study current clinical practice in blood glucose (BG) control in adult intensive care units (ICUs) in the Netherlands. METHODS: We performed a national survey focusing on blood glucose targets, insulin administration, BG control guidelines, and opinions regarding BG control aiming for normoglycaemia (known as intensive insulin therapy, IIT). RESULTS: The completed questionnaire was returned by 88/113 (78%) of the participating centres. In 98% (86/88) of the ICUs some sort of BG control was being practised. Half of the ICUs (42/86, 48%) used tight BG targets as with IIT; 28/86 (33%) and 13/86 (15%) used more liberal targets of 4.4 to 7.0 mmol/l and 4.4 to 8.0 mmol/l, respectively. Eighty-two (93%) reported having a local guideline on BG control (or IIT). The BG threshold to start insulin was 7.0+/-1.3 mmol/l vs 7.8+/-1.3 mmol/l in ICUs that practised IIT vs ICUs that practised less tight BG control, respectively (p=0.005). In 28/86 (33%) measurement of the BG values was done according to a strict time schedule (i.e., BG values were measured on predefined time points). While respondents were fairly agreed on the benefits of IIT, opinions regarding ease of implementation and time needed to apply this strategy varied. In addition, severe hypoglycaemia was considered a serious side effect of IIT. CONCLUSION: Approximately half of the ICUs in the Netherlands reported having implemented IIT. However, the full guideline as used in the original studies on IIT was hardly ever implemented. Concerns about severe hypoglycaemia, at least in part, hampers implementation of IIT.

A guidance for assessing and communicating uncertainties.

In the daily practice of science for policy, as experienced by governmental agencies which inform the policy and the public on the state and outlook of the environment, there is a pressing need for guidance in assessing and communicating uncertainties. This need extends beyond the quantitative assessment of uncertainties in model results, and focuses on the entire process of environmental assessment, running from problem framing towards reporting the results of the study. Using the Netherlands Environmental Assessment Agency (RIVM/MNP) as a case, the development, structure and content of such a guidance system is highlighted. Conditions for a successful implementation of the guidance system are discussed, and some prospects for future work are outlined.

Closure of Disputes in Assessments of Climate Change in The Netherlands

/ This paper presents an analysis of the closure of visible disputes in the assessments of climate change in the Netherlands. We focus primarily on two key constituents of the assessments: the estimate of climate sensitivity and the inclusion of non-CO2 greenhouse gases in assessment studies. For the cases studied, we identify variability in the assessment reports in the Netherlands during the pre-IPCC period. In the Netherlands arena, the assessments in this period can be seen as exponents of two different lines, a Netherlands line and an international line. We seek to identify what factors were decisive in the selection processes that resulted in the closure of visible disputes (visible in or across the assessment reports) for both cases. Our analysis reveals a remarkable difference in the adoption behavior of two Dutch assessment groups despite a large overlap in membership. We provide evidence that it is not the paradigmatic predisposition of the experts in the committee that was decisive for the closure of visible disputes, but it was the context in which the experts operated and the commitments they had made in each setting.

Differential adherence of murine hematopoietic stem cell subsets to fibronectin.

Growth and differentiation of hematopoietic stem cells occur in close contact with the cells and extracellular-matrix (ECM) proteins of the hematopoietic microenvironment. We observed the role of fibronectin, a matrix glycoprotein proposed to be involved in the attachment of hematopoietic cells and in the binding of stem cell subsets to bone marrow stroma, for this study. Murine bone marrow cells (BMC) were allowed to adhere to surfaces coated with human plasma fibronectin. Using the cobblestone-area-forming cells (CAFC) assay, adherent and nonadherent cell fractions were tested for their quantity of primitive and less primitive stem cell subsets. The CAFC assay is based on a time-dependent clone formation in pre-established, bone marrow-derived, irradiated stromal layers under limiting dilution conditions, and it allows in vitro enumeration of day-12 colony-forming unit-spleen (CFU-S12) (CAFC-10) and more primitive cells with long-term repopulating abilities (LTRA) (CAFC-28/35). We observed that the majority of primitive CAFC-28/35 adhered to fibronectin, while only a minority of CFU-S-like CAFC-10 did. The adherence of primitive stem cells to fibronectin could partially be blocked by high molar concentrations of oligopeptides containing the essential amino acid sequence of the central cell-binding domain of fibronectin, RGD. Adherence of the small subpopulation of CAFC-10 to fibronectin could almost entirely be prevented by oligopeptides organized in a specific fashion. These data suggest a role for RGD-binding integrins in the adherence of hematopoietic stem cells.

Selective advantage of normal erythrocyte production after bone marrow transplantation of alpha-thalassemic mice.

Anemia resulting from alpha-thalassemia in mice was corrected by transplantation of normal bone marrow cells following sublethal total body irradiation, resulting in partial hematopoietic chimerism with a preponderance of normal peripheral blood red cells. Peripheral blood red cell chimerism in recipients of graded numbers of bone marrow cells from sex-mismatched donors, determined by cytometric analysis, was directly compared with immature hematopoietic cell (CFU-S) chimerism and peripheral blood white cell chimerism. The latter two were assessed by fluorescent in situ hybridization with a murine Y-chromosome-specific probe. Peripheral blood white cell chimerism consistently corresponded with immature hematopoietic cell chimerism, emphasizing the selective advantage of normal red cell production in partially chimeric alpha-thalassemic mice.

Loss of long-term repopulating ability in long-term bone marrow culture.

We have studied the maintenance of stem cells with long-term multilineage repopulating ability from murine bone marrow, cultured on a pre-established bone marrow-derived stromal cell layer, both in a qualitative and quantitative way. Female bone marrow cells were cultured for a period of 1-4 weeks and compared with uncultured cells for their ability to establish and maintain a level of 50% chimerism in a sex-mismatched bone marrow transplantation model. Chimerism was determined in nucleated cells using fluorescence in situ hybridization with a murine Y-chromosome-specific probe. We observed a rapid decline in the ability of cultured marrow cells to repopulate the blood, bone marrow, spleen, and thymus of sublethally irradiated male recipients. After 4 weeks of culture only 5% of the long-term repopulating ability of the inoculated bone marrow cells remained. The remaining long-term repopulating cells, however, had similar qualities to establish and maintain long-term engraftment compared to fresh bone marrow, as judged from their ability to give stable chimerism over a period of 6 months. These observations are relevant for the therapeutic applications of long-term bone marrow cultures in purging protocols prior to autologous bone marrow transplantation of acute and chronic myeloid leukemic patients, and for the use of long-term marrow cultures when introducing foreign genetic material in hematopoietic stem cells.

Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrow-repopulating and spleen colony-forming hematopoietic stem cells in the mouse.

We have developed an in vitro clonal assay of murine hematopoietic precursor cells that form spleen colonies (CFU-S day 12) or produce in vitro clonable progenitors in the marrow (MRA cells) of lethally irradiated mice. The assay is essentially a long-term bone marrow culture in microtiter wells containing marrow-derived stromal "feeders" depleted for hematopoietic activity by irradiation. To test the validity of the assay as a quantitative in vitro stem cell assay, a series of unsorted and physically sorted bone marrow cells were simultaneously assayed in vivo and overlaid on the feeders in a range of concentrations, while frequencies of cells forming hematopoietic clones (cobblestone area forming cells, CAFC) were calculated by means of Poisson statistics. Linear regression analysis of the data showed high correlations between the frequency of CFU-S day 12 and CAFC day 10, and between MRA cells and CAFC day 28. A majority of MRA activity and CAFC day 28 was separable from CFU-S day 12 and CAFC day 10. This correlation study validates the CAFC system as a clonal assay facilitation both the quantitative assessment of a series of subsets in the hematopoietic stem cell hierarchy and the study of single long-term repopulating cells in vitro.