Implications of estimating road traffic serious injuries from hospital data.

To determine accurately the number of serious injuries at EU level and to compare serious injury rates between different countries it is essential to use a common definition. In January 2013, the High Level Group on Road Safety established the definition of serious injuries as patients with an injury level of MAIS3+(Maximum Abbreviated Injury Scale). Whatever the method used for estimating the number or serious injuries, at some point it is always necessary to use hospital records. The aim of this paper is to understand the implications for (1) in/exclusion criteria applied to case selection and (2) a methodological approach for converting ICD (International Classification of Diseases/Injuries) to MAIS codes, when estimating the number of road traffic serious injuries from hospital data. A descriptive analysis with hospital data from Spain and the Netherlands was carried out to examine the effect of certain choices concerning in- and exclusion criteria based on codes of the ICD9-CM and ICD10. The main parameters explored were: deaths before and after 30 days, readmissions, and external injury causes. Additionally, an analysis was done to explore the impact of using different conversion tools to derive MAIS3 + using data from Austria, Belgium, France, Germany, Netherlands, and Spain. Recommendations are given regarding the in/exclusion criteria and when there is incomplete data to ascertain a road injury, weighting factors could be used to correct data deviations and make more real estimations.

Increased densities of resting and activated microglia in the dentate gyrus follow senile plaque formation in the CA1 subfield of the hippocampus in the triple transgenic model of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease that is characterised by the presence of ß-amyloid (Aß) plaques, neurofibrillary tangles (NFTs) and synaptic loss specifically in brain regions involved in learning and memory such as the neocortex and the hippocampus. Aß depositions in the form of neuritic plaques trigger activation of microglia that is believed to be a common neuropathological feature of AD brains. As an integral part of the hippocampus, the dentate gyrus (DG) plays an important role in cognitive function. Although post-mortem studies suggest later involvement of the DG into the AD progression, changes in microglia have not been studied in this subfield of the hippocampus. In the present study the numerical density (Nv, #/mm(3)) of both resting (identified by tomato lectin staining) and activated (identified by Mac-1 immunoreactivity) microglia was analysed in the molecular layer (ML) of the DG in the triple transgenic (3xTg-AD) mouse model of AD at different ages (9, 12 and 18 months). The 3xTg-AD mouse model of AD showed a significant increase in the Nv of resting (by 75%) and activated (by 67%) at 18 months of age compared to non-Tg controls. These results indicate a complex microglial remodelling during AD progression.

Increased hippocampal CA1 density of serotonergic terminals in a triple transgenic mouse model of Alzheimer's disease: an ultrastructural study.

Alzheimer's disease (AD) is a neurodegenerative pathology that deteriorates mnesic functions and associated brain regions including the hippocampus. Serotonin (5-HT) has an important role in cognition. We recently demonstrated an increase in 5-HT transporter (SERT) fibre density in the hippocampal CA1 in an AD triple transgenic mouse model (3xTg-AD). Here, we analyse the ultrastructural localisation, distribution and numerical density (N(v)) of hippocampal SERT axons (SERT-Ax) and terminals (SERT-Te) and their relationship with SERT fibre sprouting and altered synaptic N(v) in 3xTg-AD compared with non-transgenic control mice. 3xTg-AD animals showed a significant increase in SERT-Te N(v) in CA1 at both, 3 (95%) and 18 months of age (144%), being restricted to the CA1 stratum moleculare (S. Mol; 227% at 3 and 180% at 18 months). 3xTg-AD animals also exhibit reduced N(v) of perforated axospinous synapses (PS) in CA1 S. Mol (56% at 3 and 52% at 18 months). No changes were observed in the N(v) of symmetric and asymmetrical synapses or SERT-Ax. Our results suggest that concomitant SERT-Te N(v) increase and PS reduction in 3xTg-AD mice may act as a compensatory mechanism maintaining synaptic efficacy as a response to the AD cognitive impairment.

Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) affects memory and neurogenesis. Adult neurogenesis plays an important role in memory function and impaired neurogenesis contributes to cognitive deficits associated with AD. Increased physical/ cognitive activity is associated with both reduced risk of dementia and increased neurogenesis. Previous attempts to restore hippocampal neurogenesis in transgenic mice by voluntary running (RUN) and environmental enrichment (ENR) provided controversial results due to lack of non-transgenic (non-Tg) control and inclusion of social isolation as "standard" housing environment. Here, we determine the effect of RUN and ENR upon hippocampal neurogenesis in a triple transgenic (3xTg-AD) mouse model of AD, which mimics AD pathology in humans. We used single and double immunohistochemistry to determine the area density of hippocampal proliferating cells, measured by the presence of phosphorylated Histone H3 (HH3), and their potential neuronal and glial phenotype by co-localizing the proliferating cells with the immature neuronal marker doublecortin (DCX), mature neuronal marker (NeuN) and specific astroglial marker (GFAP). Our results show that 3xTg-AD mice in control environment exhibit impaired hippocampal neurogenesis compared to non-Tg animals at 9 months of age. Exposure to RUN and ENR housing restores hippocampal neurogenesis in 3xTg-AD animals to non-Tg control levels. Differentiation into neurones and glial cells is affected neither by transgenic status nor by housing environment. These results suggest that hippocampus of 3xTg-AD animals maintains the potential for cellular plasticity. Increase in physical activity and/or cognitive experience enhances neurogenesis and provides a potential for stimulation of cognitive function in AD.

Serotonin fibre sprouting and increase in serotonin transporter immunoreactivity in the CA1 area of hippocampus in a triple transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease that deteriorates cognitive functions and associated brain regions such as the hippocampus, being the primary cause of dementia. Serotonin (5-HT) is widely present in the hippocampus, being an important neurotransmitter involved in learning and memory. Although recent evidence suggests alterations in 5-HT neurotransmission in AD, it is not clear how hippocampal 5-HT innervation is modified. Here, we studied hippocampal 5-HT innervation by analysing: (i) the expression, density and distribution of 5-HT transporter (SERT)-immunoreactive fibres; (ii) the specific morphological characteristics of serotonergic fibres and their relation to amyloid plaques; and (iii) the total number of 5-HT neurons within the raphe nuclei in triple transgenic mouse model of AD. We used quantitative light microscopy immunohistochemistry comparing transgenic and non-transgenic animals of different ages (3, 6, 9, 12 and 18 months). The transgenic animals showed a significant increase in SERT fibres in the hippocampus in a subfield-, strata- and age-specific manner. The increase in SERT fibres was specific to the CA1 stratum lacunosum-moleculare. An increase in SERT fibres in transgenic animals was observed at 3 months (by 61%) and at 18 months (by 74%). No changes, however, were found in the total number of raphe 5-HT neurons at any age. Our results indicate that triple transgenic mice display changes in the expression of SERT and increased SERT fibres sprouting, which may account for imbalanced serotonergic neurotransmission associated with (or linked to) AD cognitive impairment.

Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease.

The formation of cerebral senile plaques composed of amyloid ß peptide (Aß) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of Aß. In a triple transgenic model of AD (3 × Tg-AD), we found a significant increase in activated microglia at 12 (by 111%) and 18 (by 88%) months of age when compared with non-transgenic (non-Tg) controls. This microglial activation correlated with Aß plaque formation, and the activation in microglia was closely associated with Aß plaques and smaller Aß deposits. We also found a significant increase in the area density of resting microglia in 3 × Tg-AD animals both at plaque-free stage (at 9 months by 105%) and after the development of A plaques (at 12 months by 54% and at 18 months by 131%). Our results show for the first time that the increase in the density of resting microglia precedes both plaque formation and activation of microglia by extracellular Aß accumulation. We suggest that AD pathology triggers a complex microglial reaction: at the initial stages of the disease the number of resting microglia increases, as if in preparation for the ensuing activation in an attempt to fight the extracellular Aß load that is characteristic of the terminal stages of the disease.

Astroglia in dementia and Alzheimer's disease.

Astrocytes, the most numerous cells in the brain, weave the canvas of the grey matter and act as the main element of the homoeostatic system of the brain. They shape the microarchitecture of the brain, form neuronal-glial-vascular units, regulate the blood-brain barrier, control microenvironment of the central nervous system and defend nervous system against multitude of insults. Here, we overview the pathological potential of astroglia in various forms of dementias, and hypothesise that both atrophy of astroglia and reactive hypertrophic astrogliosis may develop in parallel during neurodegenerative processes resulting in dementia. We also show that in the transgenic model of Alzheimer's disease, reactive hypertrophic astrocytes surround the neuritic plaques, whereas throughout the brain parenchyma astroglial cells undergo atrophy. Astroglial atrophy may account for early changes in synaptic plasticity and cognitive impairments, which develop before gross neurodegenerative alterations.

[Induced prescription in primary health care in area Bilbao]. / Prescripción inducida en atención primaria de la Comarca Bilbao.

MAIN OBJECTIVES: to know the proportion of induced prescription (IP) in Area Bilbao and its source, the proportion of cost IP accounts for, the proportion of IP in the main therapeutic groups, the attitude of GP when requested for prescription and its influence on cost, the proportion of disagreement with requested prescription, the reasons for disagreement, and the proportion with letter from specialist. SECONDARY OBJECTIVES: to know the proportion of IP in the remaining therapeutic groups, in drugs of low clinical value, in generic drugs and in new drugs with low or no therapeutic improvement. DESIGN: A descriptive cross-sectional study.Setting. Primary health care. PARTICIPANTS: Drugs prescribable under National Health Service prescribed by and/or requested to GPs. Main results. 7.922 drugs were analysed. Type of prescription: IP, 48.3% (95% CI, 47.2-49.4); GP prescription (GPP), 50.6% (95% CI, 49.5-51.7); unknown source, 1,1% (95% CI, 0.9-1.3). Main source, public specialist (72.2%), private specialist (16.6%). IP accounted for 62.5% of cost. In the most prescribed therapeutic group, central nervous system (24.2%), IP, 39.8%; GPP, 58.9%; in cardiovascular system (19.1%), IP, 56.2%; GPP, 43.1%. 98.4% of requested prescription was actually prescribed, 1.2% was changed and 0.4%, suppressed. Proportion of disagreement, 11%; reasons for disagreement, no need for medical treatment (23.9%), therapeutic group (34.4%), active ingredient (13.2%), brand name (28.5%). There was a 62.4% with letter from specialist. CONCLUSIONS: Primary care is not accountable for a substantial proportion of prescription. GP prescribes a considerable proportion of drugs without agreement. It would be necessary a system that allows to separate the cost by care levels and also improve their communication.

Prescripción inducida en atención primaria de la Comarca Bilbao / Induced prescription in primary care in the Country of Bilbao

Objetivos. Principales: conocer la proporción de prescripción inducida (PI) en Comarca Bilbao y su procedencia, la proporción de gasto correspondiente a la PI, la proporción de PI en los principales grupos terapéuticos, la actitud del médico de atención primaria ante la prescripción solicitada y su influencia en el gasto, la proporción de desacuerdo con dicha prescripción y los motivos de desacuerdo, y la proporción con informe del especialista. Secundarios: conocer la proporción de PI en los demás grupos terapéuticos, en fármacos VINE, EFG y en los de nula o baja mejora terapéutica. Diseño. Estudio transversal, descriptivo. Emplazamiento. Atención primaria. Participantes. Fármacos financiables prescritos por y/o solicitados a los médicos de familia de EAP. Resultados principales. Se estudiaron 7.922 fármacos. Tipo de prescripción: PI, 48,3 por ciento (IC del 95 por ciento, 47,2-49,4); del médico de atención primaria (PRO), 50,6 por ciento (IC del 95 por ciento, 49,5-51,7); desconocida, 1,1 por ciento (IC del 95 por ciento, 0,9-1,3). Procedencia principal: especialista público (72,2 por ciento), especialista privado (16,6 por ciento). Un 62,5 por ciento del gasto correspondió a la PI. En el grupo terapéutico más prescrito, sistema nervioso central (24,2 por ciento), PI, 39,8 por ciento; PRO, 58,9 por ciento; en aparato cardiovascular (19,1 por ciento), PI, 56,2 por ciento, PRO, 43,1 por ciento. Se prescribió el fármaco solicitado en un 98,4 por ciento de los casos, se cambio en el 1,2 por ciento y se suprimió en un 0,4 por ciento. Proporción de desacuerdo, 11 por ciento; motivos de desacuerdo, no hay necesidad de tratar (23,9 por ciento), grupo terapéutico (34,4 por ciento), principio activo (13,2 por ciento), marca comercial (28,5 por ciento). Hubo informe de especialista en un 62,4 por ciento de los casos. Conclusiones. Se detecta una proporción considerable de prescripción no atribuible a atención primaria y una proporción importante de fármacos que el médico de primaria prescribe sin estar de acuerdo. Sería necesario un sistema que permitiera separar el gasto por niveles, así como mejorar la comunicación entre éstos (AU)

[Evaluation of the type II diabetic population attended by a primary care team]. / Evaluación de la población diabética tipo II atendida en un equipo de atención primaria.

OBJECTIVES: To find the degree of control, the prevalence of complications and cardiovascular risk factors (CVRF), and the drugs treatment used for type II diabetics. DESIGN: A descriptive crossover study. SETTING: Rekaldeberri Health Centre, Bilbao. PATIENTS: 202 diabetes II patients selected at random. INTERVENTIONS: Data were gathered by interviews, physical examinations and further tests. MAIN RESULTS: 52.2% of the sample were women. Average age was 66.6 50% of the diabetics had been diagnosed for 8 years or more. Microalbuminuria was detected in 21.9% of the patients, Microangiopathy in 24.8%, Neuropathy in 11.4% and diabetic foot in 10.4%. The years of evolution and appearance of complications had a significant connection. 64.4% of patients had a good or acceptable metabolic control. Worse metabolic control of diabetes was connected with the appearance of retinopathy and neuropathy. 47.5% were hypertensive. 21.3% smoked, 35.6% had cholesterol figures over 250 mgr/dl. Their mean Body mass index was 28.1. 40.6% were treated exclusively by diet, 9.9% with insulin and 35.6% with medicines taken orally. CONCLUSIONS: A high percentage of diabetics had a good or acceptable control of their disease. Prevalence of complications was less than in other studies, whereas CVRFs were similar. We do not discount the presence of bias in the comparison because of different diagnostic methods.