Detection of all four dengue serotypes in Aedes aegypti female mosquitoes collected in a rural area in Colombia

The Aedes aegypti vector for dengue virus (DENV) has been reported in urban and periurban areas. The information about DENV circulation in mosquitoes in Colombian rural areas is limited, so we aimed to evaluate the presence of DENV in Ae. aegypti females caught in rural locations of two Colombian municipalities, Anapoima and La Mesa. Mosquitoes from 497 rural households in 44 different rural settlements were collected. Pools of about 20 Ae. aegypti females were processed for DENV serotype detection. DENV in mosquitoes was detected in 74% of the analysed settlements with a pool positivity rate of 62%. The estimated individual mosquito infection rate was 4.12% and the minimum infection rate was 33.3/1,000 mosquitoes. All four serotypes were detected; the most frequent being DENV-2 (50%) and DENV-1 (35%). Two-three serotypes were detected simultaneously in separate pools. This is the first report on the co-occurrence of natural DENV infection of mosquitoes in Colombian rural areas. The findings are important for understanding dengue transmission and planning control strategies. A potential latent virus reservoir in rural areas could spill over to urban areas during population movements. Detecting DENV in wild-caught adult mosquitoes should be included in the development of dengue epidemic forecasting models.

Swiss Interdisciplinary Management Programme for Heart Failure (SWIM-HF): a randomised controlled trial study of an outpatient inter-professional management programme for heart failure patients in Switzerland.

PRINCIPLES: International guidelines for heart failure (HF) care recommend the implementation of inter-professional disease management programmes. To date, no such programme has been tested in Switzerland. The aim of this randomised controlled trial (RCT) was to test the effect on hospitalisation, mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerland.METHODS: Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF. A total of 42 eligible patients were randomised to an intervention (n = 22) or usual care group (n = 20). Medical treatment was optimised and lifestyle recommendations were given to all patients. Intervention patients additionally received a home visit by a HF-nurse, followed by 17 telephone calls of decreasing frequency over 12 months, focusing on self-care. Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care. Data were collected at baseline, 3, 6, 9 and 12 months. Mixed regression analysis (quality of life) was used. Outcome assessment was conducted by researchers blinded to group assignment.RESULTS: After 12 months, 22 (52%) patients had an all-cause re-admission or died. Only 3 patients were hospitalised with HF decompensation. No significant effect of the intervention was found on HF related to quality of life.CONCLUSIONS: An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies.

IVA in addition to BMD can change the osteoporosis management in 25% of clinical routine patients

Introduction Vertebral fracture is one of the major osteoporoticfractures which are unfortunately very often undetected. In addition,it is well known that prevalent vertebral fracture increases dramaticallythe risk of future additional fracture. Instant Vertebral Assessment(IVA) has been introduced in DXA device a couple of years ago toease the detection of such fracture when routine DXA are performed.To correctly use such tool, ISCD provided clinical recommendationon when and how to use it. The aim of our study was to evaluate theISCD guidelines in clinical routine patients and see how often itmay change of patient management.Methods During two months (March and April 2010), a medicalquestionnaire was systematically given to our clinical routine patientto check the validity of ISCD IVA recommendations in our population.In addition, all women had BMD measurement at AP spine,femur and 1/3 radius using a Discovery A System (Hologic, Waltham,USA). When appropriate, IVA measurement had been performedon the same DXA system and had been centrally evaluated by twotrained doctors for fracture status according to the semi-quantitativemethod of Genant. The reading had been performed when possiblebetween L5 and T4.Results Out of 210 women seen in the consultation, 109 (52 %)of them (mean age 68.2 ± 11.5 years) fulfilled the necessary criteriato have an IVA measurement. Out of these 109 women, 43 (incidence39.4 %) had osteoporosis at one of the three skeletal sitesand 31 (incidence 28.4 %) had at least one vertebral fracture. 14.7 %of women had both osteoporosis and at least one vertebral fractureclassifying them as "severe osteoporosis" while 46.8 % did not haveosteoporosis and no vertebral fracture. 24.8 % of the women hadosteoporosis but no vertebral fracture while 13.8 % of women didhave osteoporosis but vertebral fracture (clinical osteoporosis).Conclusions In 52 % of our patients, IVA was needed accordingto ISCD criteria. In half of them the IVA test influenced of patientmanagement either may changing the type of treatment of simplyby classifying patient as "clinical osteoporosis". IVA appears to bean important tool in clinical routine but unfortunately is not yetvery often use in most of the centers.

Prediction and discrimination of osteoporotic hip fracture in postmenopausal women.

Osteoporotic hip fractures increase dramatically with age and are responsible for considerable morbidity and mortality. Several treatments to prevent the occurrence of hip fracture have been validated in large randomized trials and the current challenge is to improve the identification of individuals at high risk of fracture who would benefit from therapeutic or preventive intervention. We have performed an exhaustive literature review on hip fracture predictors, focusing primarily on clinical risk factors, dual X-ray absorptiometry (DXA), quantitative ultrasound, and bone markers. This review is based on original articles and meta-analyses. We have selected studies that aim both to predict the risk of hip fracture and to discriminate individuals with or without fracture. We have included only postmenopausal women in our review. For studies involving both men and women, only results concerning women have been considered. Regarding clinical factors, only prospective studies have been taken into account. Predictive factors have been used as stand-alone tools to predict hip fracture or sequentially through successive selection processes or by combination into risk scores. There is still much debate as to whether or not the combination of these various parameters, as risk scores or as sequential or concurrent combinations, could help to better predict hip fracture. There are conflicting results on whether or not such combinations provide improvement over each method alone. Sequential combination of bone mineral density and ultrasound parameters might be cost-effective compared with DXA alone, because of fewer bone mineral density measurements. However, use of multiple techniques may increase costs. One problem that precludes comparison of most published studies is that they use either relative risk, or absolute risk, or sensitivity and specificity. The absolute risk of individuals given their risk factors and bone assessment results would be a more appropriate model for decision-making than relative risk. Currently, a group appointed by the World Health Organization and lead by Professor John Kanis is working on such a model. It will therefore be possible to further assess the best choice of threshold to optimize the number of women needed to screen for each country and each treatment.

Interpretation and use of FRAX in clinical practice.

The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review INTRODUCTION: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. METHODS: This study reviews the resource documents and joint position statements of ISCD and IOF. RESULTS: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. CONCLUSIONS: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

Comparing Bone Microarchitecture by Trabecular Bone Score (TBS) in Caucasian American Women with and Without Osteoporotic Fractures.

Several cross-sectional studies have shown the ability of the TBS to discriminate between those with and without fractures in European populations. The aim of this study was to assess the ability of TBS to discriminate between those with and without fractures in a large female Caucasian population in the USA. This was a case-control study of 2,165 Caucasian American women aged 40 and older. Patients with illness or taking medications known to affect bone metabolism were excluded. Those in the fracture group (n = 289) had at least one low-energy fracture. BMD was measured at L1-L4, TBS calculated directly from the same DXA image. Descriptive statistics and inferential tests for difference were used. Univariate and multivariate logistic regression models were created to investigate possible association between independent variables and the status of fracture. Odds ratios per standard deviation decrease (OR) and areas under the ROC curve were calculated for discriminating parameters. Weak correlations were observed between TBS and BMD and between TBS and BMI (r = 0.33 and -0.17, respectively, p < 0.01). Mean age, weight, BMD and TBS were significantly different between control and fracture groups (all p ≤ 0.05), whereas no difference was noted for BMI or height. After adjusting for age, weight, BMD, smoking, and maternal and family history of fracture, TBS (but not BMD) remained a significant predictor of fracture: OR 1.28[1.13-1.46] even after adjustment. In a US female population, TBS again was able to discriminate between those with and those without fractures, even after adjusting for other clinical risk factors.

Fracture Discrimination by Combined Bone Mineral Density (BMD) and Microarchitectural Texture Analysis.

The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient Mice

The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PAC1) is a G-protein-coupled receptor binding the strongly conserved neuropeptide PACAP with 1000-fold higher affinity than the related peptide vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in neuronal differentiation and synaptic plasticity. To gain further insight into the biological significance of PAC1-mediated signaling in vivo, we generated two different mutant mouse strains, harboring either a complete or a forebrain-specific inactivation of PAC1. Mutants from both strains show a deficit in contextual fear conditioning, a hippocampus-dependent associative learning paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling declarative learning such as the Morris water maze or the social transmission of food preference are observed. At the cellular level, the deficit in hippocampus-dependent associative learning is accompanied by an impairment of mossy fiber long-term potentiation (LTP). Because the hippocampal expression of PAC1 is restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated signaling at the mossy fiber synapse is involved in both LTP and hippocampus-dependent associative learning.