147 research outputs found

    Universal screening or a universal risk assessment combined with risk-based screening for multidrug-resistant microorganisms upon admission:Comparing strategies

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    OBJECTIVE: Timely identification of patients who carry multidrug-resistant microorganisms (MDRO) is needed to prevent nosocomial spread to other patients and to the hospital environment. We aimed to compare the yield of a universal screening strategy upon admission to the currently installed universal risk assessment combined with risk-based screening upon admission. METHODS: This observational study was conducted within a prospective cohort study. From January 1, 2018, until September 1, 2019, patients admitted to our hospital were asked to participate. Nasal and perianal samples were taken upon admission and checked for the presence of MDRO. The results of the universal risk assessment and risk-based screening were collected retrospectively from electronic health records. RESULTS: In total, 1017 patients with 1069 separate hospital admissions participated in the study. Universal screening identified 38 (3.6%) unknown MDRO carriers upon admission (37 individual patients), all carrying extended-spectrum beta-lactamase-producing Enterobacterales. For 946 of 1069 (88.5%) patients, both the universal risk assessment and universal screening were performed. For 19 (2.0%) admissions, ≥1 risk factor was identified. The universal risk assessment identified one (0.1%) unknown carrier, compared to 37 out of 946 carriers for the universal screening (P&lt;0.001). Of the 37 carriers identified through the universal screening, 35 (94.6%) reported no risk factors. CONCLUSIONS: Our results show that in our low endemic setting, a universal screening strategy identified significantly more MDRO carriers than the currently implemented universal risk-assessment. When implementing a universal risk-assessment, risk factors should be carefully selected to be able to identify ESBL-E carriers. While the universal screening identified more MDRO carriers, further research is needed to determine the cost-effectiveness of this strategy.</p

    Dynamics of Staphylococcus aureus in patients and the hospital environment in a tertiary care hospital in the Netherlands

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    Background: The dynamics of Staphylococcus aureus in patients and the hospital environment are relatively unknown. We studied these dynamics in a tertiary care hospital in the Netherlands. Methods: Nasal samples were taken from adult patients at admission and discharge. Isolates cultured from clinical samples taken before and during hospitalization from these patients were included. Environmental samples of patient rooms were taken over a three-year period. Finally, isolates from clinical samples from patients with an epidemiological link to S. aureus positive rooms were included. Staphylococcal protein A (spa) typing was performed. Results: Nasal samples were taken from 673 patients. One hundred eighteen (17.5%) were positive at admission and discharge, 15 (2.2%) patients acquired S. aureus during hospitalization. Nineteen patients had a positive clinical sample during hospitalization, 15.9% of the S. aureus were considered as from an exogenous source. One hundred and forty (2.8%) environmental samples were S. aureus positive. No persistent contamination of surfaces was observed. Isolates were highly diverse: spa typing was performed for 893 isolates, identifying 278 different spa types, 161 of these spa types were observed only once. Conclusion: Limited transmission could be identified between patients and the hospital environment, and from patient-to-patient. Exogenous acquisition was assumed to occur in 15% of clinical samples. Environmental contamination was infrequent, temporarily, and coincided with the strain from the patient admitted to the room at that time. MRSA was rare and not found in the environment.</p

    Exposome-Wide Association Study of Body Mass Index Using a Novel Meta-Analytical Approach for Random Forest Models

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    BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688-141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in formula presented buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to formula presented . The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. https://doi.org/10.1289/EHP13393.</p

    Optimal Use of Vitamin D When Treating Osteoporosis

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    Inadequate serum 25-hydroxyvitamin D (25[OH]D) concentrations are associated with muscle weakness, decreased physical performance, and increased propensity in falls and fractures. This paper discusses several aspects with regard to vitamin D status and supplementation when treating patients with osteoporosis in relation to risks and prevention of falls and fractures. Based on evidence from literature, adequate supplementation with at least 700 IU of vitamin D, preferably cholecalciferol, is required for improving physical function and prevention of falls and fractures. Additional calcium supplementation may be considered when dietary calcium intake is below 700 mg/day. For optimal bone mineral density response in patients treated with antiresorptive or anabolic therapy, adequate vitamin D and calcium supplementation is also necessary. Monitoring of 25(OH)D levels during follow-up and adjustment of vitamin D supplementation should be considered to reach and maintain adequate serum 25(OH)D levels of at least 50 nmol/L, preferably greater than 75 nmol/L in all patients

    Increasingly strong reduction in breast cancer mortality due to screening

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    Item does not contain fulltextBACKGROUND: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. METHODS: In Nijmegen, the Netherlands, 55,529 women received an invitation for screening between 1975 and 2008. We designed a case-referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50-69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. RESULTS: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49-0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975-1991 (OR=0.72; 95% CI=0.47-1.09) to 65% in the period 1992-2008 (OR=0.35; 95% CI=0.19-0.64). CONCLUSION: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening

    Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

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    Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

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    Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.Peer reviewe

    Rare and low-frequency coding variants alter human adult height

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    Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

    Diminishing benefits of urban living for children and adolescents’ growth and development

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    Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income&nbsp;countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of&nbsp;countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
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