Clinical decision making in spinal fusion for chronic low back pain. Results of a nationwide survey among spine surgeons

OBJECTIVES: To assess the use of prognostic patient factors and predictive tests in clinical decision making for spinal fusion in patients with chronic low back pain. DESIGN AND SETTING: Nationwide survey among spine surgeons. PARTICIPANTS: Surgeon members of the Dutch Spine Society were questioned on their treatment strategy for chronic low back pain. PRIMARY AND SECONDARY OUTCOME MEASURES: The surgeons’ opinion on the use of prognostic factors and tests for patient selection were addressed, and the degree of uniformity was assessed. In addition, the influence of surgeon specific factors, such as clinical experience and training, was determined. RESULTS: The comments from 62 surgeons (70% response rate) were analysed. Forty-four surgeons (71%) had extensive clinical experience. There was a statistically significant lack of uniformity of opinion in 7 of the 11 items on prognostic factors and 8 of the 11 items on predictive tests, respectively. Imaging was valued much higher than predictive tests, psychological screening, or patient preferences (all p<0.01). Apart from the use of discography and long multi-segment fusions, differences in training or clinical experience did not appear to be of significant influence on treatment strategy. CONCLUSIONS: The present survey showed a lack of consensus among spine surgeons on the use of predictive tests for patient selection. Prognostic patient factors were not consistently incorporated in their treatment strategy. Clinical decision making for spinal fusion to treat chronic low back pain does not have a uniform evidence base in practice. Future research should focus on identifying subgroups of patients for whom spinal fusion is an effective treatment. Only a reliable prediction of surgical outcome, combined with the implementation of individual patient factors, may enable the instalment of consensus guidelines in surgical decision making for chronic low back pain

Within-Host Evolution of the Dutch High-Prevalent<i> Pseudomonas aeruginosa</i> Clone ST406 during Chronic Colonization of a Patient with Cystic Fibrosis

This study investigates adaptation of ST406, a prevalent P. aeruginosa clone, present in 15% of chronically infected cystic fibrosis (CF) patients in the Netherlands, in a newly infected CF patient during three years using whole genome sequencing (WGS), transcriptomics, and phenotypic assays, including biofilm formation. WGS-based phylogeny demonstrates that ST406 is genetically distinct from other reported CF related strains or epidemic clones. Comparative genomic analysis of the early (S1) and late (S2) isolate yielded 42 single nucleotide polymorphisms (SNPs) and 10 indels and a single 7 kb genomic fragment only found in S2. Most SNPs and differentially expressed genes encoded proteins involved in metabolism, secretion and signal transduction or transcription. SNPs were identified in regulator genes mexT and exsA and coincided with differential gene expression of mexE and mexF, encoding the MexE/F efflux pump, genes encoding the type six secretion system (T6SS) and type three secretion system (T3SS), which have also been previously implicated in adaptation of other P. aeruginosa strains during chronic infection of CF lungs. The observation that genetically different strains from different patients have accumulated similar genetic adaptations supports the concept of adaptive parallel evolution of P. aeruginosa in chronically infected CF patients. Phenotypically, there was loss of biofilm maturation coinciding with a significant lower level of transcription of both bfmR and bfmS during chronic colonization. These data suggest that the high-prevalent Dutch CF clone ST406 displays adaptation to the CF lung niche, which involves a limited number of mutations affecting regulators controlling biofilm formation and secretion and genes involved in metabolism. These genes could provide good targets for anti-pseudomonal therapy

Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals

Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations. Methods We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012-2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination. Results On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination. Conclusions In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance.Peer reviewe

New methods to analyse microarray data that partially lack a reference signal

BACKGROUND: Microarray-based Comparative Genomic Hybridisation (CGH) has been used to assess genetic variability between bacterial strains. Crucial for interpretation of microarray data is the availability of a reference to compare signal intensities to reliably determine presence or divergence each DNA fragment. However, the production of a good reference becomes unfeasible when microarrays are based on pan-genomes.When only a single strain is used as a reference for a multistrain array, the accessory gene pool will be partially represented by reference DNA, although these genes represent the genomic repertoire that can explain differences in virulence, pathogenicity or transmissibility between strains. The lack of a reference makes interpretation of the data for these genes difficult and, if the test signal is low, they are often deleted from the analysis. We aimed to develop novel methods to determine the presence or divergence of genes in a Staphylococcus aureus multistrain PCR product microarray-based CGH approach for which reference DNA was not available for some probes. RESULTS: In this study we have developed 6 new methods to predict divergence and presence of all genes spotted on a multistrain Staphylococcus aureus DNA microarray, published previously, including those gene spots that lack reference signals. When considering specificity and PPV (i.e. the false-positive rate) as the most important criteria for evaluating these methods, the method that defined gene presence based on a signal at least twice as high as the background and higher than the reference signal (method 4) had the best test characteristics. For this method specificity was 100% and 82% for MRSA252 (compared to the GACK method) and all spots (compared to sequence data), respectively, and PPV were 100% and 76% for MRSA252 (compared to the GACK method) and all spots (compared to sequence data), respectively. CONCLUSION: A definition of gene presence based on signal at least twice as high as the background and higher than the reference signal (method 4) had the best test characteristics, allowing the analysis of 6-17% more of the genes not present in the reference strain. This method is recommended to analyse microarray data that partially lack a reference signal

Array Configuration Effect on the Spatial Correlation of MU-MIMO Channels in NLoS Environments

In this paper, three different base-station antenna (BSA) configurations are compared in terms of inter-user spatial correlation in a two dimensional (2D) non-line-of-sight (NLoS) environment. The three configurations are: (i) a regular uniform linear array (ULA); (ii) a periodic sparse array; and (iii) an aperiodic sparse array. Electromagnetic modeling of the NLoS channel is proposed where scatterers are considered as resonant dipoles confined in clusters of scatterers (CoSs). While the probability of facing highly correlated user-equipments (UEs) in a multi-user multiple-input multiple-output (MU-MIMO) system is decreasing as the richness of mutipath increases, the sparsity (increased inter-element spacing) is seen to be capable of reducing this probability as well. This is due to the larger spatial variations experienced by the sparse array. Moreover, the results show that further improvement can be achieved by deploying an aperiodic distribution of antenna elements into the sparse antenna aperture

Enterococcus faecium:from microbiological insights to practical recommendations for infection control and diagnostics

Early in its evolution, Enterococcus faecium acquired traits that allowed it to become a successful nosocomial pathogen. E. faecium inherent tenacity to build resistance to antibiotics and environmental stressors that allows the species to thrive in hospital environments. The continual wide use of antibiotics in medicine has been an important driver in the evolution of E. faecium becoming a highly proficient hospital pathogen.For successful prevention and reduction of nosocomial infections with vancomycin resistant E. faecium (VREfm), it is essential to focus on reducing VREfm carriage and spread. The aim of this review is to incorporate microbiological insights of E. faecium into practical infection control recommendations, to reduce the spread of hospital-acquired VREfm (carriage and infections). The spread of VREfm can be controlled by intensified cleaning procedures, antibiotic stewardship, rapid screening of VREfm carriage focused on high-risk populations, and identification of transmission routes through accurate detection and typing methods in outbreak situations. Further, for successful management of E. faecium, continual innovation in the fields of diagnostics, treatment, and eradication is necessary

Game on! Lessons learned from joint development and production of health games

In September 2010, Hanze University of Applied Sciences in Groningen (the Netherlands) started a 20-week international program titled GameOn! The object of this program is for students to develop serious games, that aim to help the youth become aware of social and/or health related issues. Since the start of GameOn! students have worked on a number of different projects, all related to education through the use of interactive media. Topics were malaria, hiv/aids and personal hygiene. In all these projects, specific knowledge about the target region, domain knowledge of the subject of the game, and the target group was brought in by specialists and local representatives. The lessons drawn, in development and production, from these projects are: 1. The importance of an agile game development method that allows for regular testing, feedback moments and changes. 2. The importance of a user/player centred design and the context of playful experiences. 3. Cultural awareness in game design and development: consider and adapt to the values and beliefs of the target audience. 4. Collaboration and co-creation with local representatives in game development adds to game acceptance. 5. A very positive attitude towards the use of computers in education in the targeted areas. Addressing and incorporating these aspects into projects may contribute in more effective and adequate (social) health games or, in a broader sense, more effective interactive media applications aimed at facilitating educational learning

External validation of WGS-based antimicrobial susceptibility prediction tools, KOVER-AMR and ResFinder 4.1, for Escherichia coli clinical isolates

Objective: To externally validate whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 for Escherichia coli clinical isolates from Dutch routine care. Methods: A random sample of 234 E. coli and 283 third generation cephalosporin-resistant E. coli isolates from urine and blood were collected (2014–2017). Culture-antimicrobial susceptibility testing was performed using VITEK 2 and BD Phoenix. Sequences were used as input for KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1. The concordance, major error rate (MER), and very major error rate (VMER) were calculated, with subsequent comparison to U.S. Food and Drug Administration (FDA) criteria (MER ≤3% and VMER with a 95% confidence interval ≤1.5–≤7.5%). Results: ResFinder 4.1 performed better than KOVER-AMR-models; however, neither tool achieved overall (V)MERs below FDA criteria. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1, MER (cumulative all antimicrobials) were: 5.1% (4.4–5.9), 4.3% (3.6–5.0), and 5.1% (4.5–5.8), respectively. MERs ≤3% were achieved for 6 (SCM) and 5 (CART) of the 11 tested antimicrobials for KOVER-AMR-models and for 9/13 antimicrobials tested with ResFinder 4.1. KOVER-AMR-SCM, KOVER-AMR-CART, and ResFinder 4.1 cumulative VMERs were: 26% (24–28), 29% (27–31), and 11% (9.2–12). VMERs with a 95% CI ≤ 1.5–≤7.5 were only achieved for 4/13 tested antimicrobials with ResFinder 4.1. Discussion: In this study, whole genome sequence-antimicrobial susceptibility testing phenotype prediction tools KOVER-AMR and ResFinder 4.1 did not meet the FDA criteria needed for clinical diagnostic use in 517 E. coli clinical isolates from Dutch routine care. The tested tools should be further improved before they can be used for clinical decision making

Eindrapport SD 24/7 project:Smart Diabetes 24/7

mHealth 24/7 is een dienst die diabetespatiënten helpt om op eenvoudige wijze toezicht te houden op hun eigen gezondheid. mDiabetes 24/7 is een prototype app binnen de dienst mHealth 24/7. Op dit moment kunnen patiënten met het prototype van de app hun bloedsuikerwaardes, een eetdagboek en de hoeveelheid toegediende insuline bijhouden. mHealth 24/7 heeft de wens geformuleerd om haar informatievoorziening aan diabetespatiënten verder uit te breiden, door gepersonaliseerd inzicht te geven in de oorzaak van stijgingen en dalingen van hun bloedsuikerwaarden. Meer informatie stelt de patiënt in staat om beter gemotiveerde maatregelen te nemen en stimuleert therapietrouw waarmee later complicaties kunnen worden voorkomen. Dit verbetert de kwaliteit van leven en vermindert kosten. In het project is gerealiseerd dat data uit een activity tracker en omgevingstemperatuur ingelezen wordt in de app en wordt geïntegreerd met bestaande data zoals bloedsuikerwaarde. Daarnaast kunnen patiënten handmatig aangeven hoe ze zich voelen. Patiënten krijgen daarmee inzicht in het effect van activiteit, omgevingstemperatuur en stemming op fluctuaties in bloedsuikerwaardes. In een pilot met 25 proefpersonen is de technische werking van de verrijkte app getest evenals de functionaliteit. Er is aangetoond dat de app werkt en dat voor gebruikers de verrijking van de informatie in de app met hartslag, omgevingstemperatuur en stemming van toegevoegde waarde is. Wel blijkt dat een app zoals deze foutloos en realtime moet werken en de gebruiksinterface dusdanig moet werken, dat de gebruikers er uitsluitend gemak van ondervinden. Diabetes is een arbeidsintensieve ziekte en nog meer werk is ongewenst! Als in een volgende pilot meer data kan worden verzameld, kan worden gewerkt aan het voorspellen van fluctuaties in bloedsuikerwaardes waardoor een patiënt ook voortijdig gewaarschuwd kan worden. Vanuit verschillende marktpartijen zoals ziekenhuizen en zorgverzekeraars is interesse getoond voor het project. Gezamenlijk gaan deze partijen aanspraak doen op tijdelijke financiering vanuit de “Beleidsregel Innovatie Kleinschalige Experimenten