What part of the total care consumed by type 2 diabetes patients is directly related to diabetes? Implications for disease management programs

<p><strong>Background</strong>: Disease management programs (DMP) aim at improving coordination and quality of care and reducing healthcare costs for specific chronic diseases. This paper investigates to what extent total healthcare utilization of type 2 diabetes patients is actually related to diabetes and its implications for diabetes management programs.</p><p><strong>Research design and methods:</strong> Healthcare utilization for diabetes patients was analyzed using 2008 self-reported data (N=316) and data from electronic medical records (EMR) (N=9023), and divided whether or not care was described in the Dutch type 2 diabetes multidisciplinary healthcare standard.</p><p><strong>Results:</strong> On average 4.3 different disciplines of healthcare providers were involved in the care for diabetes patients. 96% contacted a GP-practice and 63% an ophthalmologist, 24% an internist, 32% a physiotherapist and 23% a dietician. Diabetes patients had on average 9.3 contacts with GP-practice of which 53% were included in the healthcare standard. Only a limited part of total healthcare utilization of diabetes patients was included in the healthcare standard and therefore theoretically included in DMPs.</p><p><strong>Conclusion:</strong> Organizing the care for diabetics in a DMP might harm the coordination and quality of all healthcare for diabetics. DMPs should be integrated in the overall organization of care.</p

Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children

While the pharmacokinetics of morphine in children have been studied extensively, little is known about the pharmacodynamics of morphine in this population. Here, we quantified the concentration‐effect relationship of morphine for postoperative pain in preverbal children between 0 and 3 years of age. For this, we applied item response theory modeling in the pharmacokinetic/pharmacodynamic analysis of COMFORT‐Behavior (COMFORT‐B) scale data from 2 previous clinical studies. In the model, we identified a sigmoid maximal efficacy model for the effect of morphine and found that in 26% of children, increasing morphine concentrations were not associated with lower pain scores (nonresponders to morphine up‐titration). In responders to morphine up‐titration, the COMFORT‐B score slowly decreases with increasing morphine concentrations at morphine concentrations >20 ng/mL. In nonresponding children, no decrease in COMFORT‐B score is expected. In general, lower baseline COMFORT‐B scores (2.1 points on average) in younger children (postnatal age 10 days. These findings support a dosing regimen previously suggested by Krekels et al, which would put >95% of patients within this morphine target concentration range at steady state. Our modeling approach provides a promising platform for pharmacodynamic research of analgesics and sedatives in children

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE-/- mice

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes. Methods ApoE−/− mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells. Results Surgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged. Conclusions Major orthopedic surgery in ApoE−/− mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated. © 2016 Elsevier Ireland Lt

Energy Expenditure and Metabolic Changes of Free-Flying Migrating Northern Bald Ibis

Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly-labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in-flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well

Endpoints in pediatric pain studies

Assessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the effects of analgesic drugs. Here, we review current and promising new endpoints used in pediatric pain assessment studies

Curso para especialistas en seguridad y salud ocupacional de Latinoamérica

Every year millions of workers die due to health and safety hazards at work. This occurs especially in developing countries, where challenges related to the work conditions are oftensimilar. To improve this situation, the Centre of International Health offers an international. Objective: Training course for specialists in Occupational Health and Safety, where they can interact, develop new ideas and generate improvement of the working conditions in their countries. Methodology: The teaching methods of the first three courses included interactive lectures, project-based learning, presentations, group discussions and the setting-up of a protocol-based epidemiological study. Participants from different professions worked together during two weeks, which has contributed to the exchange of new ideas and the enrichment of the multicultural level and diversity of the courses. Results: All of the 80 participants successfully completed the two-week course. They each designed a protocol-based epidemiological research project, the majority of which have already been implemented or are in their implementation phase. In the evaluation survey all of the participants agreed that the mixture of different professional backgrounds was enriching and they also pointed the excellent quality of the tutors out. Consequently a network in Occupational Health and Safety has been created amongst the participants. Conclusions: The three international and interdisciplinary courses “Occupational Health Crossing Borders” were considered to be a very positive experience for the participants, as well as the tutors. Since 2012, these courses are part of the International Master’s in Occupational Health and Safety of the Ludwig-Maximilian-Universität from Munich, Germany.Anualmente fallecen millones de trabajadores debido a accidentes de trabajo y enfermedades profesionales. Esto afecta especialmente a países en vía de desarrollo donde los desafíos muchas veces se parecen. Para mejorar esta situación, el Centro Internacional de la Salud Objetivo: Ofrece cursos internacionales para profesionales de Seguridad y Salud Ocupacional en los cuales los participantes pueden interactuar y desarrollar nuevas ideas generando cambios a nivel local en sus países. Metodología: El método de enseñanza de los primeros tres cursos incluyó clases interactivas, aprendizaje basado en problemas, presentación de pósteres, discusiones grupales y la formulación de un protocolo de estudio de base epidemiológica. Participantes de diferentes profesiones trabajaron conjuntamente durante dos semanas consecutivas, lo cual favoreció el intercambio de ideas y el nivel de multiculturalidad de los cursos. Resultados: Todos los 80 participantes finalizaron exitosamente el curso de dos semanas de duración. Cada uno de ellos redactó un protocolo de investigación de base epidemiológica, los cuales en su mayoría ya han sido implementados o se encuentran en la fase de implementación. En la evaluación, todos los participantes opinaron que la mezcla de profesionales participantes fue enriquecedora destacando también la excelente calidad de los docentes. Consecuentemente, se estableció una red de contactos de SSO entre los participantes. Conclusiones: Los tres cursos internacionales e interdisciplinarios de “Salud Ocupacional Cruzando Fronteras” fueron positivos tanto para participantes como para docentes. Desde el 2012, estos cursos forman parte de la Maestría Internacional en Seguridad y Salud Ocupacional de la Ludwig-Maximilian-Universität de Múnich, Alemania

Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis

The histological differential diagnosis between melanotic schwannoma, primary leptomeningeal melanocytic lesions and cellular blue nevus can be challenging. Correct diagnosis of melanotic schwannoma is important to select patients who need clinical evaluation for possible association with Carney complex. Recently, we described the presence of activating codon 209 mutations in the GNAQ gene in primary leptomeningeal melanocytic lesions. Identical codon 209 mutations have been described in blue nevi. The aims of the present study were to (1) perform a histological review of a series of lesions (initially) diagnosed as melanotic schwannoma and analyze them for GNAQ mutations, and (2) test the diagnostic value of GNAQ mutational analysis in the differential diagnosis with leptomeningeal melanocytic lesions. We retrieved 25 cases that were initially diagnosed as melanotic schwannoma. All cases were reviewed using established criteria and analyzed for GNAQ codon 209 mutations. After review, nine cases were classified as melanotic schwannoma. GNAQ mutations were absent in these nine cases. The remaining cases were reclassified as conventional schwannoma (n = 9), melanocytoma (n = 4), blue nevus (n = 1) and lesions that could not be classified with certainty as melanotic schwannoma or melanocytoma (n = 2). GNAQ codon 209 mutations were present in 3/4 melanocytomas and the blue nevus. Including results from our previous study in leptomeningeal melanocytic lesions, GNAQ mutations were highly specific (100%) for leptomeningeal melanocytic lesions compared to melanotic schwannoma (sensitivity 43%). We conclude that a detailed analysis of morphology combined with GNAQ mutational analysis can aid in the differential diagnosis of melanotic schwannoma with leptomeningeal melanocytic lesions

Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (BRAF, NRAS, and HRAS genes) and uvea (GNAQ gene). Somatic mutations in the GNAQ gene at codon 209, resulting in constitutive activation of GNAQ, were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These GNAQ-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a BRAF point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No HRAS or NRAS mutations were detected. We conclude that somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that GNAQ-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of GNAQ mutations in primary melanocytic lesions of the CNS needs to be determined in future studies

Як уникнути підйому рівня води?

East Africa’s Lake Victoria provides resources and services to millions of people on the lake’s shores and abroad. In particular, the lake’s fisheries are an important source of protein, employment, and international economic connections for the whole region. Nonetheless, stock dynamics are poorly understood and currently unpredictable. Furthermore, fishery dynamics are intricately connected to other supporting services of the lake as well as to lakeshore societies and economies. Much research has been carried out piecemeal on different aspects of Lake Victoria’s system; e.g., societies, biodiversity, fisheries, and eutrophication. However, to disentangle drivers and dynamics of change in this complex system, we need to put these pieces together and analyze the system as a whole. We did so by first building a qualitative model of the lake’s social-ecological system. We then investigated the model system through a qualitative loop analysis, and finally examined effects of changes on the system state and structure. The model and its contextual analysis allowed us to investigate system-wide chain reactions resulting from disturbances. Importantly, we built a tool that can be used to analyze the cascading effects of management options and establish the requirements for their success. We found that high connectedness of the system at the exploitation level, through fisheries having multiple target stocks, can increase the stocks’ vulnerability to exploitation but reduce society’s vulnerability to variability in individual stocks. We describe how there are multiple pathways to any change in the system, which makes it difficult to identify the root cause of changes but also broadens the management toolkit. Also, we illustrate how nutrient enrichment is not a self-regulating process, and that explicit management is necessary to halt or reverse eutrophication. This model is simple and usable to assess system-wide effects of management policies, and can serve as a paving stone for future quantitative analyses of system dynamics at local scales

Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

<p>Abstract</p> <p>Background</p> <p>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.</p> <p>Methods</p> <p>Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.</p> <p>Results</p> <p>In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).</p> <p>Conclusions</p> <p>The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.</p