A risk profile for identifying community-dwelling elderly with a highrisk of recurrent falling: results of a 3-year prospective study

Introduction: The aim of the prospective study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling. Materials and methods: The study was designed as a 3-year prospective cohort study. A total of 1365 community-dwelling persons, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam participated in the study. During an interview in 1995/1996, physical, cognitive, emotional and social aspects of functioning were assessed. A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly. Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up. Results: The incidence of recurrent falls at the 3-year follow-up point was 24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87 fractures that resulted from a fall, including 20 hip fractures, 21 wrist fractures and seven humerus fractures. Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling: two or more previous falls, dizziness, functional limitations, weak grip strength, low body weight, fear of falling, the presence of dogs/cats in the household, a high educational level, drinking 18 or more alcoholic consumptions per week and two interaction terms (high educationx18 or more alcohol consumptions per week and two or more previous falls x fear of falling) (AUC=0.71). Discussion: At a cut-off point of 5 on the total risk score (range 0-30), the model predicted recurrent falling with a sensitivity of 59% and a specificity of 71%. At a cut-off point of 10, the sensitivity and specificity were 31% and 92%, respectively. A risk profile including nine predictors that can easily be assessed seems to be a useful tool for the identification of community-dwelling elderly with a high risk of recurrent falling. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Hyperglycemia Activates Caspase-1 and TXNIP-Mediated IL-1β Transcription in Human Adipose Tissue

Contains fulltext : 96993.pdf (publisher's version ) (Closed access)OBJECTIVE: Obesity is characterized by elevated levels of proinflammatory cytokines, including interleukin (IL)-1beta, that contribute to the development of insulin resistance. In this study, we set out to investigate whether hyperglycemia drives IL-1beta production and caspase-1 activation in murine and human adipose tissue, thus inducing insulin resistance. RESEARCH DESIGN AND METHODS: ob/ob animals were used as a model to study obesity and hyperglycemia. Human adipose tissue fragments or adipocytes were cultured in medium containing normal or high glucose levels. Additionally, the role of thioredoxin interacting protein (TXNIP) in glucose-induced IL-1beta production was assessed. RESULTS: TXNIP and caspase-1 protein levels were more abundantly expressed in adipose tissue of hyperglycemic ob/ob animals as compared with wild-type mice. In human adipose tissue, high glucose resulted in a 10-fold upregulation of TXNIP gene expression levels (P < 0.01) and a 10% elevation of caspase-1 activity (P < 0.05), together with induction of IL-1beta transcription (twofold, P < 0.01) and a significant increase in IL-1beta secretion. TXNIP suppression in human adipocytes, either by a small interfering RNA approach or a peroxisome proliferator-activated receptor-gamma agonist, counteracted the effects of high glucose on bioactive IL-1 production (P < 0.01) mainly through a decrease in transcription levels paralleled by reduced intracellular pro-IL-1beta levels. CONCLUSIONS: High glucose activates caspase-1 in human and murine adipose tissue. Glucose-induced activation of TXNIP mediates IL-1beta mRNA expression levels and intracellular pro-IL-1beta accumulation in adipose tissue. The concerted actions lead to enhanced secretion of IL-1beta in adipose tissue that may contribute to the development of insulin resistance

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. CONCLUSION: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH

Analysis of queries sent to PubMed at the point of care: Observation of search behaviour in a medical teaching hospital

Contains fulltext : 69801.pdf ( ) (Open Access)BACKGROUND: The use of PubMed to answer daily medical care questions is limited because it is challenging to retrieve a small set of relevant articles and time is restricted. Knowing what aspects of queries are likely to retrieve relevant articles can increase the effectiveness of PubMed searches. The objectives of our study were to identify queries that are likely to retrieve relevant articles by relating PubMed search techniques and tools to the number of articles retrieved and the selection of articles for further reading. METHODS: This was a prospective observational study of queries regarding patient-related problems sent to PubMed by residents and internists in internal medicine working in an Academic Medical Centre. We analyzed queries, search results, query tools (Mesh, Limits, wildcards, operators), selection of abstract and full-text for further reading, using a portal that mimics PubMed. RESULTS: PubMed was used to solve 1121 patient-related problems, resulting in 3205 distinct queries. Abstracts were viewed in 999 (31%) of these queries, and in 126 (39%) of 321 queries using query tools. The average term count per query was 2.5. Abstracts were selected in more than 40% of queries using four or five terms, increasing to 63% if the use of four or five terms yielded 2-161 articles. CONCLUSION: Queries sent to PubMed by physicians at our hospital during daily medical care contain fewer than three terms. Queries using four to five terms, retrieving less than 161 article titles, are most likely to result in abstract viewing. PubMed search tools are used infrequently by our population and are less effective than the use of four or five terms. Methods to facilitate the formulation of precise queries, using more relevant terms, should be the focus of education and research

Circulating Lipoproteins Are a Crucial Component of Host Defense against Invasive Salmonella typhimurium Infection

Contains fulltext : 79883.pdf (Publisher’s version ) (Open Access)BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS), thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/-) mice, with a 7-fold increase in LDL, are resistant against infection with Salmonella typhimurium (survival 100% vs 5%, p<0.001), and 100 to 1000-fold lower bacterial burden in the organs, compared with LDLR+/+ mice. Protection was not due to differences in cytokine production, phagocytosis, and killing of Salmonella organisms. The differences were caused by the excess of lipoproteins, as hyperlipoproteinemic ApoE-/- mice were also highly resistant to Salmonella infection. Lipoproteins protect against infection by interfering with the binding of Salmonella to host cells, and preventing organ invasion. This leads to an altered biodistribution of the microorganisms during the first hours of infection: after intravenous injection of Salmonella into LDLR+/+ mice, the bacteria invaded the liver and spleen within 30 minutes of infection. In contrast, in LDLR-/- mice, Salmonella remained constrained to the circulation from where they were efficiently cleared, with decreased organ invasion. CONCLUSIONS: plasma lipoproteins are a potent host defense mechanism against invasive Salmonella infection, by blocking adhesion of Salmonella to the host cells and subsequent tissue invasion

The Epidemic of Hip Fractures: Are We on the Right Track?

Background: Hip fractures are a public health problem, leading to hospitalization, long-term rehabilitation, reduced quality of life, large healthcare expenses, and a high 1-year mortality. Especially older adults are at greater risk of fractures than the general population, due to the combination of an increased fall risk and osteoporosis. The aim of this study was to determine time trends in numbers and incidence rates of hip fracture-related hospitalizations and admission duration in the older Dutch population. Methods and Findings: Secular trend analysis of all hospitalizations in the older Dutch population (≥65 years) from 1981 throughout 2008, using the National Hospital Discharge Registry. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of hospital admissions and hospital days due to a hip fracture were used as outcome measures in each year of the study. Between 1981 and 2008, the absolute number of hip fractures doubled in the older Dutch population. Incidence rates of hip fracture-related hospital admissions increased with age, and were higher in women than in men. The age-adjusted incidence rate increased from 52.0 to 67.6 per 10,000 older persons. However, since 1994 the incidence rate decreased (percentage annual change -0.5%, 95% CI: -0.7; -0.3), compared with the period 1981-1993 (percentage annual change 2.3%, 95% CI: 2.0; 2.7). The total number of hospital days was reduced by a fifth, due to a reduced admission duration in all age groups. A possible limitation was that data were obtained from a linked administrative database, which did not include information on medication use or co-morbidities. Conclusions: A trend break in the incidence rates of hip fracture-related hospitalizations was observed in the Netherlands around 1994, possibly as a first result of efforts to prevent falls and fractures. However, the true cause of the observation is unknown