Statins and prevention of infections: systematic review and meta-analysis of data from large randomised placebo controlled trials

Objective To evaluate whether the potential of statins to lower the risk of infections as published in observational studies is causal

Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans

Abstract High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced expression of immune and inflammatory genes, which was not attenuated by Ex. Conversely, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed a significant association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle

Modeling healthcare authorization and claim submissions using the openEHR dual-model approach

<p>Abstract</p> <p>Background</p> <p>The TISS standard is a set of mandatory forms and electronic messages for healthcare authorization and claim submissions among healthcare plans and providers in Brazil. It is not based on formal models as the new generation of health informatics standards suggests. The objective of this paper is to model the TISS in terms of the openEHR archetype-based approach and integrate it into a patient-centered EHR architecture.</p> <p>Methods</p> <p>Three approaches were adopted to model TISS. In the first approach, a set of archetypes was designed using ENTRY subclasses. In the second one, a set of archetypes was designed using exclusively ADMIN_ENTRY and CLUSTERs as their root classes. In the third approach, the openEHR ADMIN_ENTRY is extended with classes designed for authorization and claim submissions, and an ISM_TRANSITION attribute is added to the COMPOSITION class. Another set of archetypes was designed based on this model. For all three approaches, templates were designed to represent the TISS forms.</p> <p>Results</p> <p>The archetypes based on the openEHR RM (Reference Model) can represent all TISS data structures. The extended model adds subclasses and an attribute to the COMPOSITION class to represent information on authorization and claim submissions. The archetypes based on all three approaches have similar structures, although rooted in different classes. The extended openEHR RM model is more semantically aligned with the concepts involved in a claim submission, but may disrupt interoperability with other systems and the current tools must be adapted to deal with it.</p> <p>Conclusions</p> <p>Modeling the TISS standard by means of the openEHR approach makes it aligned with ISO recommendations and provides a solid foundation on which the TISS can evolve. Although there are few administrative archetypes available, the openEHR RM is expressive enough to represent the TISS standard. This paper focuses on the TISS but its results may be extended to other billing processes. A complete communication architecture to simulate the exchange of TISS data between systems according to the openEHR approach still needs to be designed and implemented.</p

The Influence of Long-Acting Somatostatin Analogs on 68 Ga-DOTATATE Uptake in Patients With Neuroendocrine Tumors

Purpose A high SUVmax tumor-to-liver ratio (TLR) of 68Ga-DOTATATE can be used to select patients with neuroendocrine tumors (NETs) for peptide receptor radionuclide therapy (PRRT). In addition, an SUVmax TLR ≥ 8.1 is associated with increased progression-free survival in NET patients treated with somatostatin analogs (SSAs). To avoid a theoretical interaction, several guidelines recommend performing PET/CT just before the monthly administration of long-acting SSAs. We aimed to investigate the effect of SSA on the SUVmax of 68Ga-DOTATATE in patients with NET and to identify independent predictors for high SUVmax TLR. Patients and Methods For this retrospective study, 192 68Ga-DOTATATE PET/CT scans of 165 patients without (n = 115) and with (n = 77) SSA (octreotide or lanreotide) in the 3 months before PET/CT were collected and reviewed. The effect of SSA on SUVmax values was analyzed by a maximum likelihood mixed model. Results Patients with SSA had a significantly higher median SUVmax TLR than patients without SSA (4.7 [IQR], 3.1-7.7) versus 3.2 [IQR, 2.0-5.4]; P < 0.001). Multivariable logistic regression analysis showed that SSA use was an independent predictor for SUVmax TLR ≥ 8.1 (odds ratio, 2.91; 95% confidence interval, 1.26-6.72; P = 0.012). Conclusions Our data suggest that higher SSA concentrations do not have a negative effect on 68Ga-DOTATATE uptake in tumor lesions. In addition, we found that only SSA use was associated with SUVmax TLR ≥ 8.1. Our results are consistent with previously conducted studies and in line with the recently published guideline that suggests that the relatively recent use of SSA does not necessitate any delay in 68Ga-DOTATATE PET/CT imaging

Cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands in different age groups

OBJECTIVE: We aimed to assess the cost-effectiveness of screening smokers and ex-smokers for lung cancer in the Netherlands. METHODS: A Markov model was used to evaluate the health effects and costs of lung cancer screening from the healthcare perspective. The effects and costs of ten screening scenarios with different start and stop ages of screening were examined across a lifetime horizon in a cohort of 100,000 smokers and ex- smokers 50 years and older. RESULTS: The incremental cost-effectiveness ratios (ICERs) of screening smokers and ex-smokers aged 50-60 years, 50-70 years, and 50 years and older are below the cost-effectiveness threshold of € 20,000 per quality adjusted life year (QALY) gained. Screening 50-60-year-old smokers and ex-smokers was the most cost-effective scenario with an ICER of € 14,094 per QALY gained. However, screening smokers and ex-smokers 50 years and older yielded the highest QALYs and resulted in an ICER of € 16,594 per QALY, which is below the threshold of € 20,000 per QALY. All screening scenarios compared to no screening resulted in CERs between the € 14,000 and € 16,000 per QALY gained. The efficiency frontier showed that screening smokers and ex-smokers in the age groups 70 years and older, 60-70 years, 60 years and older are excluded by extended dominance by no screening, screening smokers and ex-smokers aged 50-60 years and 50-70 years. CONCLUSION: This study showed that lung cancer screening is cost-effective in the Netherlands

Соціальний капітал у формуванні екстерналій освітньої сфери

У статті аналізується передавальний механізм імпульсу, який одержує економіка від зміни рівня освіти. Виходячи із припущення про прискорення (уповільнення) економічного зростання як одну із можливих екстерналій освіти, автори досліджують опосередкований вплив соціального капіталу на формування цієї екстерналії.В статье анализируется передаточный механизм импульса, полученного экономикой от изменения уровня образования. Исходя из предположения об ускорении (замедлении) экономического роста как о возможной экстерналии образования, авторы исследуют опосредованное влияние социального капитала на формирование этой экстерналии.The article under consideration analyzes the intermediary mechanism of impulse which results in economics due to education level change. In terms of assumption as regards economic growth acceleration (impairment) as one of possible education externalities the authors are researching the indirect social capital influence upon this externality formation

Microbial aetiology, outcomes, and costs of hospitalisation for community-acquired pneumonia; an observational analysis

BACKGROUND: The aim of this study was to investigate the clinical outcome and especially costs of hospitalisation for community-acquired pneumonia (CAP) in relation to microbial aetiology. This knowledge is indispensable to estimate cost-effectiveness of new strategies aiming to prevent and/or improve clinical outcome of CAP. METHODS: We performed our observational analysis in a cohort of 505 patients hospitalised with confirmed CAP between 2004 and 2010. Hospital administrative databases were extracted for all resource utilisation on a patient level. Resource items were grouped in seven categories: general ward nursing, nursing on ICU, clinical chemistry laboratory tests, microbiology exams, radiology exams, medication drugs, and other.linear regression analyses were conducted to identify variables predicting costs of hospitalisation for CAP. RESULTS: Streptococcus pneumoniae was the most identified causative pathogen (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%). Overall median length of hospital stay was 8.5 days, in-hospital mortality rate was 4.8%. Total median hospital costs per patient were €3,899 (IQR 2,911-5,684). General ward nursing costs represented the largest share (57%), followed by nursing on the intensive care unit (16%) and diagnostic microbiological tests (9%). In multivariate regression analysis, class IV-V Pneumonia Severity Index (indicative for severe disease), Staphylococcus aureus, or Streptococcus pneumonia as causative pathogen, were independent cost driving factors. Coxiella burnetii was a cost-limiting factor. CONCLUSIONS: Median costs of hospitalisation for CAP are almost €4,000 per patient. Nursing costs are the main cause of these costs.. Apart from prevention, low-cost interventions aimed at reducing length of hospital stay therefore will most likely be cost-effective

Real-world treatment patterns and outcomes of patients with extensive disease small cell lung cancer

Objective: Clinical outcome data on patients with extensive disease small cell lung cancer (ED SCLC) treated in routine practice is limited. The aim of this retrospective study is to present data on treatment patterns and survival in an unselected patient population with ED SCLC. Methods: All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were included. We collected data on patient characteristics, systemic treatments, overall survival (OS), dose reductions ('80% of initial dose) and early discontinuation ('4 cycles). Results: From 792 diagnosed patients, 568 (72%) started with first-line treatment. Of these patients, 41% received second-line treatment. Only 68 patients received third-line treatment. For all treated patients, the mean age was 66 years. The majority (72%) had a performance status (ECOG) of 0 or 1 at diagnosis. Median OS of treated patients was 7.4 months. Of all patients with first-line treatment, 26% received '4 cycles and dose reductions were observed in 29%. Conclusion: After first-line systemic treatment in ED SCLC the fraction of patients receiving subsequent lines of treatment is rapidly decreasing. This information is necessary as background for evaluation of the added value of future drugs under study for ED SCLC

Origin of entropy convergence in hydrophobic hydration and protein folding

An information theory model is used to construct a molecular explanation why hydrophobic solvation entropies measured in calorimetry of protein unfolding converge at a common temperature. The entropy convergence follows from the weak temperature dependence of occupancy fluctuations for molecular-scale volumes in water. The macroscopic expression of the contrasting entropic behavior between water and common organic solvents is the relative temperature insensitivity of the water isothermal compressibility. The information theory model provides a quantitative description of small molecule hydration and predicts a negative entropy at convergence. Interpretations of entropic contributions to protein folding should account for this result.Comment: Phys. Rev. Letts. (in press 1996), 3 pages, 3 figure