High count rate {\gamma}-ray spectroscopy with LaBr3:Ce scintillation detectors

The applicability of LaBr3:Ce detectors for high count rate {\gamma}-ray spectroscopy is investigated. A 3"x3" LaBr3:Ce detector is used in a test setup with radioactive sources to study the dependence of energy resolution and photo peak efficiency on the overall count rate in the detector. Digitized traces were recorded using a 500 MHz FADC and analysed with digital signal processing methods. In addition to standard techniques a pile-up correction method is applied to the data in order to further improve the high-rate capabilities and to reduce the losses in efficiency due to signal pile-up. It is shown, that {\gamma}-ray spectroscopy can be performed with high resolution at count rates even above 1 MHz and that the performance can be enhanced in the region between 500 kHz and 10 MHz by using pile-up correction techniques

Searching for real-world effectiveness versus efficacy of healthcare innovations: the case of social prescribing for diabetes

Background: Social prescribing is a process whereby primary care patients are linked or referred to nonmedical sources of support in the community and voluntary sector. It is a concept that has arisen in practice and implemented widely in the United Kingdom and has been evaluated by various organizations. Objective: The aim of our study was to characterize, collate, and analyze the evidence from evaluation of social prescribing for type 2 diabetes in the United Kingdom and Ireland, comparing information available on publicly available websites with the published literature. Methods: We used a broad, pragmatic definition of social prescribing and conducted Web-based searches for websites of organizations providing potentially relevant services. We also explored linked information. In parallel, we searched Medline, PubMed, Cochrane Library, Google Scholar, and reference lists for relevant studies published in peer-reviewed journals. We extracted the data systematically on the characteristics, any reported evaluation, outcomes measured and results, and terminology used to describe each service. Results: We identified 40 UK- or Ireland-based projects that referred people with type 2 diabetes and prediabetes to nonmedical interventions or services provided in the community. We located evaluations of 24 projects; 11 as published papers, 12 as Web-based reports, and 1 as both a paper and a Web-based report. The interventions and services identified included structured group educational programs, exercise referral schemes, and individualized advice and support with signposting of health-related activities in the community. Although specific interventions such as community-based group educational programs and exercise referral have been evaluated in randomized controlled trials, evaluation of individualized social prescribing services involving people with type 2 diabetes has, in most cases, used pre-post and mixed methods approaches. These evaluations report generic improvement in a broad range of outcomes and provide an insight into the criteria for the success of social prescribing services. Conclusions: Our study revealed the varied models of social prescribing and nonmedical, community-based services available to people with type 2 diabetes and the extent of evaluation of these, which would not have been achieved by searching databases alone. The findings of this scoping study do not prove that social prescribing is an effective measure for people with type 2 diabetes in the United Kingdom, but can be used to inform future evaluation and contribute to the development of the evidence base for social prescribing. Accessing Web-based information provides a potential method for investigating how specific innovative health concepts, such as social prescribing, have been translated, implemented, and evaluated in practice. Several challenges were encountered including defining the concept, focusing on process plus intervention, and searching diverse, evolving Web-based sources. Further exploration of this approach will inform future research on the application of innovative health care concepts into practice

Nebulized heparin in burn patients with inhalation trauma : safety and feasibility

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients

Insight in the role of lipids and other systemic factors in hand and knee osteoarthritis: lessons from clinical studies

Osteoarthritis is one of the most common musculoskeletal disorders. Despite its high prevalence, the pathogenesis of osteoarthritis is incompletely understood. A major risk factor for osteoarthritis is obesity. Not only due to increased mechanical stress, but also due to systemic factors such as lipids. Our knowledge on how lipids are involved in osteoarthritis is limited. Therefore, this thesis focusses on the association of lipids with hand and knee osteoarthritis. Firstly, we investigated the reproducibility of lipid measurements to guide future lipidomic research. Subsequently, comparison of the lipid profile of osteoarthritis patients in different disease stages showed that the lipid profile explained disease severity to a limited extent. We observed the strongest association of the lipid profile with hand pain, and no association with knee osteoarthritis. This suggests that lipotoxicity may play a larger role in the hand, while in the knee mechanical stress is more relevant. In addition, treatment with anti-inflammatory medication resulted in a change in lipid concentrations in patients with hand osteoarthritis, suggesting that lipids are involved in inflammation and/or pain processes. These insights may increase our understanding of osteoarthritis pathophysiology and lead to new targets for future development of disease modifying osteoarthritis medication.LUMC / Geneeskund

Lifestyle index for mortality prediction using multiple ageing cohorts in the USA, UK and Europe

Current mortality prediction indexes are mainly based on functional morbidity and comorbidity, with limited information for risk prevention. This study aimed to develop and validate a modifiable lifestyle-based mortality predication index for older adults. Data from 51,688 participants (56% women) aged ≥50 years in 2002 Health and Retirement Study, 2002 English Longitudinal Study of Ageing and 2004 Survey of Health Ageing and Retirement in Europe were used to estimate coefficients of the index with cohort-stratified Cox regression. Models were validated across studies and compared to the Lee index (having comorbid and morbidity predictors). Over an average of 11-year follow-up, 10,240 participants died. The lifestyle index includes smoking, drinking, exercising, sleep quality, BMI, sex and age; showing adequate model performance in internal validation (C-statistic 0.79; D-statistic 1.94; calibration slope 1.13) and in all combinations of internal-external cross-validation. It outperformed Lee index (e.g. differences in C-statistic = 0.01, D-statistic = 0.17, P < 0.001) consistently across health status. The lifestyle index stratified participants into varying mortality risk groups, with those in the top quintile having 13.5% excess absolute mortality risk over 10 years than those in the bottom 50th centile. Our lifestyle index with easy-assessable behavioural factors and improved generalizability may maximize its usability for personalized risk management

International criteria for acute kidney injury: advantages and remaining challenges

• Acute Kidney Injury (AKI) is defined using widely accepted international criteria that are based on changes in serum creatinine concentration and degree of oliguria. • AKI, when defined in this way, has a strong association with poor patient outcomes, including high mortality rates and longer hospital admissions with increased resource utilisation and subsequent chronic kidney disease. • The detection of AKI using current criteria can assist with AKI diagnosis and stratification of individual patient risk. • The diagnosis of AKI requires clinical judgement to integrate the definition of AKI with the clinical situation, to determine underlying cause of AKI, and to take account of factors that may affect performance of current definitions

The additional value of TGF beta 1 and IL-7 to predict the course of prostate cancer progression

Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGF beta 1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-specific survival. Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989-2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGF beta 1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their confidence intervals were estimated, and Akaike's information criterio The predictive ability of a model for prostate cancer survival more than doubled when TGF beta 1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively). IL-7 and TGF beta 1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy