Gaining insight into the Clinical Practice Guideline development processes: qualitative study in a workshop to implement the GRADE proposal in Spain

Background  

The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out.     

Implementing and complying with the Smoke-free Hospitals Project in Catalonia, Spain.

The objective of the study was to describe the implementation of measures for preventing tobacco consumption developed in the Catalan Network of Smoke-free Hospitals. Information from 25 hospitals that are actively involved in the Catalan Network of Smoke-free Hospitals (April 2004) was used. The degree of implementation of the Smoke-free Hospitals Project was analysed by means of the Self-Audit Questionnaire of the European Network for Smoke-free Hospitals; each hospital was analysed globally and according to the duration of its Network membership (<1 year: implementation stage; > or =1 year: consolidation stage). In terms of global indicators, there were high levels of commitment (64.8%), communication (74.7%), tobacco control (77.4%) and implementation of smoke-free environments (81.0%). A lower degree of implementation (<50%) was found in education and training, health promotion and healthy workplaces. According to the duration of Network membership, significant differences were observed for communication, environment, healthy workplaces and follow-up. Deficits were observed in areas such as specialist training and cessation support, and further input is required here. By identifying areas needing attention, providing a guide for policy development and by administering it periodically, one can ensure that progress is kept on track.     

Morphological features in human cortical brain microvessels after head injury: a three-dimensional and immunocytochemical study

We studied the morphology of cortical microvessels in the brains of 10 patients who had died after receiving a traumatic head injury (THI). Scanning electron microscopy (SEM) of vascular corrosion casts, confocal microscopy of histological sections after immunocytochemistry, and detection of apoptosis by terminal dUTP nick end labeling (TUNEL) were used. Microvascular casts showed an angioarchitectonic distribution that was defined as normal according to results obtained in a previous, nontraumatic series of subjects. However, when we compared them with previous works, the cast surface of some of the microvessels showed three types of morphological alterations: longitudinal folds, sunken surfaces with craters, and a significant flattening with reduction of lumen. The vessels that were primarily affected were the arterioles and capillaries of the middle and deep cortical vascular zones. Immunostaining with the monoclonal antibody MAS-336 against endothelial cells also showed the presence of longitudinal folds with a thinning of the vascular lumen, cytoplasmic round bodies, and a thickening of the endothelial cell membrane. The TUNEL technique revealed a positive staining of some endothelial cells. The structural alterations we observed indicate that microvessels undergo endothelial cell damage after THI. We suggest that this kind of lesion and the secondary functional injury to the blood-brain barrier (BBB) could play an important role in the development of the secondary lesions that these patients show in the subacute phase.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions

Senescence accelerated mice P8 (SAMP8) show significant age‐related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age‐associated increase of PAS‐positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4‐8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. β/A4(Aβ) protein‐like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age‐associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood–brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age‐related increase in phosphorylated tau in SAMP8 mice brains, but early age‐related Aβ deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence‐accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders.