93 research outputs found
Stratified breast cancer follow-up using a continuous state partially observable Markov decision process
Frequency and duration of follow-up for breast cancer patients is still under discussion. Currently, in the Netherlands follow-up consists of annual mammography for the first five years after treatment and does not depend on the personal risk of developing a locoregional recurrence or a second primary tumor. The aim of this study is to gain insight in how to allocate resources for optimal and personalized follow-up. We formulate a discrete-time Partially Observable Markov Decision Process (POMDP) over a finite horizon with both discrete and continuous states, in which the size of the tumor is modeled as a continuous state. Transition probabilities are obtained from data of the Netherlands Cancer Registry. We show that the optimal value function of the POMDP is piecewise linear and convex and provide an alternative representation for it. Under some reasonable conditions on the dynamics of the POMDP, the optimal value function can be obtained from the parameters of the underlying probability distributions only. Finally, we present results for a stratification of the patients based on their age to show how this model can be applied in practice
Environmental aspects of tensile membrane enclosed spaces
Buildings enclosed by fabric membranes are very sensitive to changes in environmental conditions as a result of their low mass and low thermal insulation values. Development in material technology and the understanding of the structural behaviour of tensile membrane structures along with the vast progress in computer formfinding software, has made it possible for structural design of tensile membrane structures to be approached with almost total confidence. On the contrary, understanding of the environmental behaviour in the spaces enclosed by fabric membrane and their thermal performance is still in its infancy, which to some extent has hindered their wide acceptance by the building industry. The environmental behaviour of tensile membrane structures is outlined and the possible use of the fabric’s topology and geometry particularly to enhance ventilation rates and airflow velocities within the enclosed space is discussed. A need for further research in this area is identified in order to fully realise the potential benefits offered by these structures
Trauma team activation varies across Dutch emergency departments: a national survey
Background
Tiered trauma team response may contribute to efficient in-hospital trauma triage by reducing the amount of resources required and by improving health outcomes. This study evaluates current practice of trauma team activation (TTA) in Dutch emergency departments (EDs).
Methods
A survey was conducted among managers of all 102 EDs in the Netherlands, using a semi-structured online questionnaire.
Results
Seventy-two questionnaires were analysed. Most EDs use a one-team system (68 %). EDs with a tiered-response receive more multi trauma patients (p < 0.01) and have more trauma team alerts per year (p < 0.05) than one-team EDs. The number of trauma team members varies from three to 16 professionals. The ED nurse usually receives the pre-notification (97 %), whereas the decision to activate a team is made by an ED nurse (46 %), ED physician (30 %), by multiple professionals (20 %) or other (4 %). Information in the pre-notification mostly used for trauma team activation are Airway-Breathing-Circulation (87 %), Glasgow Coma Score (90 %), and Revised Trauma Score (85 %) or Paediatric Trauma Score (86 %). However, this information is only available for 75 % of the patients or less. Only 56 % of the respondents were satisfied with their current in-hospital trauma triage system.
Conclusions
Trauma team activation varies across Dutch EDs and there is room for improvement in the trauma triage system used, size of the teams and the professionals involved. More direct communication and more uniform criteria could be used to efficiently and safely activate a specific trauma team. Therefore, the implementation of a revised national consensus guideline is recommende
Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens
Although GH treatment for short stature in Turner syndrome is an accepted
treatment in many countries, which GH dosage to use and which age to start
puberty induction are issues of debate. This study shows final height (FH)
in 60 girls with Turner syndrome treated in a randomized dose-response
trial, combining GH treatment with low dose estrogens at a relatively
young age. Girls were randomly assigned to group A (4 IU/m(2).d;
approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter
6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6
IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH
treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized
17beta-estradiol was given orally. After a mean duration of GH treatment
of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH,
expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in
group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or
-0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected
for height SD score and age at start of treatment, was significant between
groups A and B [regression coefficient, 4.1; 95% confidence interval (CI),
1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3,
7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI,
-1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD
score, more than -2). After starting estrogen treatment, the decrease in
height velocity (HV) changed significantly to a stable HV, without
affecting bone maturation (change in bone age/change in chronological
age). The following variables contributed significantly to predicting FH
SD score: GH dose, height SD score (ref. normal girls), chronological age
at start of treatment, and HV in the first year of GH treatment. GH
treatment was well tolerated. In conclusion, GH treatment leads to a
normalization of FH in most girls, even when puberty is induced at a
normal pubertal age. The optimal GH dosage depends on height and age at
the start of treatment and first year HV
Microarray testing in patients with systemic lupus erythematosus identifies a high prevalence of CpG DNA-binding antibodies
OBJECTIVE: Many autoantibodies are known to be associated with SLE, although their role in clinical practice is limited because of low sensitivity and weak associations with clinical manifestations. There has been great interest in the discovery of new autoantibodies to use in clinical practice. In this study, we investigated 57 new and known antibodies and their potential for diagnostics or risk stratification. METHODS: Between 2014 and 2017, residual sera of all anti-dsDNA tests in the UMC Utrecht were stored in a biobank. This included sera of patients with SLE, patients with a diagnosis of another immune-mediated inflammatory disease (IMID), patients with low (non-IMID) or medium levels of clinical suspicion of SLE but no IMID diagnosis (Rest), and self-reported healthy blood bank donors. Diagnosis and (presence of) symptoms at each blood draw were retrospectively assessed in the patient records with the Utrecht Patient-Oriented Database using a newly developed text mining algorithm. Sera of patients were analysed for the presence of 57 autoantibodies with a custom-made immunofluorescent microarray. Signal intensity cut-offs for all antigens on the microarray were set to the 95th percentile of the non-IMID control group. Differences in prevalence of autoantibodies between patients with SLE and control groups were assessed. RESULTS: Autoantibody profiles of 483 patients with SLE were compared with autoantibody profiles of 1397 patients from 4 different control groups. Anti-dsDNA was the most distinguishing feature between patients with SLE and other patients, followed by antibodies against Cytosine-phosphate-Guanine (anti-CpG) DNA motifs (p<0.0001). Antibodies against CMV (cytomegalovirus) and ASCA (anti-Saccharomyces cerevisiae antibodies) were more prevalent in patients with SLE with (a history of) lupus nephritis than patients with SLE without nephritis. CONCLUSION: Antibodies against CpG DNA motifs are prevalent in patients with SLE. Anti-CMV antibodies are associated with lupus nephritis
Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE. Methods: We performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity. Results: We observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = −0.530; p = 0.007) and anti-PmScl100 (r = −0.445; p = 0.03). Conclusion: We identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature
Microarray analysis of autoantibodies can identify future Systemic Lupus Erythematosus patients
OBJECTIVE: Reliable early ascertainment in patients with SLE is important to prevent the accumulation of irreversible organ damage. Autoantibodies are often present in the serum of patients before the first symptoms arise, therefore they are of potential use as early diagnostic tools. METHODS: We used a custom-made antibody microarray containing 57 autoantigens to analyze serum samples of 1519 patients previously tested for anti-dsDNA and 361 samples of self-reported healthy blood bank donors (BBD). The 1519 patients included 483 patients with SLE, 346 patients with other immune mediated inflammatory diseases (IMID), 218 patient controls without relevant clinical symptoms (Non-IMID), and 472 patients that did not fit in any of the previous groups (Rest). The Non-IMID and BBD groups were used individually to create multivariable prediction models to distinguish samples of patients with SLE from these control groups. We subsequently used these models to predict the outcome for samples of patients who developed SLE while in follow-up (pre-SLE). RESULTS: Out of 1036 patients with no diagnosis of SLE at the moment of sample collection, 17 patients developed SLE while in follow-up (mean time to diagnosis 7.2 months). The best performing model (AUC 0.83) identified 9 out of 17 (53%) pre-SLE samples as SLE, with a specificity of 94%. CONCLUSION: Serum samples of patients who will develop SLE in the future already show a shift of the autoantibody profile prior to diagnosis. In this study, we show that these autoantibody profiles can be used to identify these future SLE patients
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