Stroke prevention in Europe: how are 11 European countries progressing toward the European Society of Cardiology (ESC) recommendations?

PURPOSE: Stroke is a leading cause of death and disability, although studies show that 90% of strokes can be prevented. The evidence base for stroke prevention is well established, and this study aimed to investigate how well European countries are adopting the European Society of Cardiology (ESC) guidelines, particularly toward implementation of the recommended best practice in stroke prevention. MATERIALS AND METHODS: We developed a stroke prevention scorecard - populated with World Health Organization (WHO) data, secondary research, time-series data, and a survey of 550 physicians - to benchmark 11 European countries in the context of the ESC guidelines. RESULTS: All countries were found to have policies in place to manage general behavioral risk factors of noncommunicable disease (NCD), but we found that more needs to be done to address cardiovascular disease - specifically, stroke risk factors. Although ten of the countries in this study endorse the ESC cardiovascular clinical guidelines, implementation is lacking. Eight out of the 11 countries received the lowest score in regard to raising awareness around stroke, and 7 countries were found not to have a stroke registry. Among physicians surveyed in primary care it was reported that less than 30% of patients over 40 years old were screened for blood pressure, whereas even fewer were screened for atrial fibrillation; in 10 out of the 11 countries, less than 20% of patients over 65 years old were screened for atrial fibrillation. CONCLUSION: Although progress is being made in managing the burden of NCDs, our findings reveal opportunities for improvement in the primary prevention of stroke. Further developments in strategic planning, raising awareness, and monitoring disease are required, as is research on barriers to the implementation of best practice screening of blood pressure and atrial fibrillation in primary care.

What do clinicians want from us? An evaluation of Brighton and Sussex University Hospitals NHS Trust clinical librarian service and its implications for developing future working patterns.

BACKGROUND: The Clinical Librarian (CL) Service at Brighton was established in 2003 with the aim of providing high-quality evidence to designated teams and fostering an evidence-based culture. OBJECTIVE: To evaluate the CL service at Brighton and discuss the implication of the findings. METHODS: A combination of internally collected data (n = 167), and an external evaluation of the service by questionnaires (n = 86) of users and non-users and interviews (n = 9) of users. RESULTS: Internal data suggest that the service is valued by its users and that patient care and continuing professional development are the most common uses for searches (confirmed by the external study); that searches generally result in some change in knowledge; and that this knowledge is disseminated. The external study found that visibility of the CL was crucial to the effectiveness of the role and that clinicians used the service mostly to get access to a wider range of resources and/or to save time. Users wanted the CL to include evaluative annotation with the results, and for the CL role to become more embedded in the team. Interview results expanded on the issues of integration of the CL and the need for annotation of results. CONCLUSIONS: To be most effective, CLs would be dedicated to one team, but financial constraints make this unlikely. Alternative working patterns are suggested as a possible compromise.

Anatomy of a founder effect: myotonic dystrophy in Northeastern Quebec.

Founder effects are largely responsible for changes in frequency profiles of genetic variants in local populations or isolates. They are often recognized by elevated incidence of certain hereditary disorders as observed in regions of Charlevoix and Saguenay-Lac-Saint-Jean (SLSJ) in Northeastern Quebec. Dominantly transmitted myotonic dystrophy (DM1) is highly prevalent in SLSJ where its carrier rate reaches 1/550, compared with 1/5,000 to 1/50,000 elsewhere. To shed light on the origin of DM1 in this region, we have screened 50 nuclear DM1 families from SLSJ and studied the genetic variation in a 2.05 Mb (2.9 cM) segment spanning the site of the expansion mutation. The markers analyzed included 22 biallelic SNPs and two microsatellites. Among 50 independent DM1 chromosomes, we distinguished ten DM1-associated haplotypes and grouped them into three haplotype families, A, B and C, based on the relevant extent of allele sharing between them. To test whether the data were consistent with a single entry of the mutation into SLSJ, we evaluated the age of the founder effect from the proportion of recombinant haplotypes. Taking the prevalent haplotype A1_21 (58%) as ancestral to all the disease-associated haplotypes in this study, the estimated age of the founder effect was 19 generations, long predating the colonization of Nouvelle-France. In contrast, considering A1_21 as ancestral to the haplotype family A only, yielded the estimated founder age of nine generations, consistent with the settlement of Charlevoix at the turn of 17th century and subsequent colonization of SLSJ. We conclude that it was the carrier of haplotype A (present day carrier rate of 1/730) that was a "driver" of the founder effect, while minor haplotypes B and C, with corresponding carrier rates of 1/3,000 and 1/10,000, respectively, contribute DM1 to the incidence level known in other populations. Other studies confirm that this might be a general scenario in which a major "driver" mutation/haplotype issued from a founder effect is found accompanied by distinct minor mutations/haplotypes occurring at background population frequencies.

Polymorphisms within a polymorphism: SNPs in and around a polymorphic Alu insertion in intron 44 of the human dystrophin gene.

A polymorphic Yb-type Alu insertion on Xp21.3 shows a genotypic gradient across worldwide populations. We used single strand conformational polymorphism (SSCP), denaturing high-pressure liquid chromatography (DHPLC), and sequencing to characterize the level of polymorphism within this region. Two novel polymorphic sites were found within the Alu insertion itself, and a further seven novel polymorphic sites in the 2-kb flanking region. Our results showed that while DHPLC was more sensitive than SSCP, the limitations of DHPLC included the lack of ability to distinguish between multiple alleles or safely identify mutations on a polymorphic background. We believe that this is the first report of polymorphic single nucleotide polymorphisms (SNPs) within a polymorphic Alu distribution and that together they promise to provide a useful marker for human population and evolutionary genetics.

Human X-chromosomal lineages in Europe reveal Middle Eastern and Asiatic contacts.

Within Europe, classical genetic markers, nuclear autosomal and Y-chromosome DNA polymorphisms display an east-west frequency gradient. This has been taken as evidence for the westward migration of Neolithic farmers from the Middle East. In contrast, most studies of mtDNA variation in Europe and the Middle East have not revealed clinal distributions. Here we report an analysis of dys44 haplotypes, consisting of 35 polymorphisms on an 8 kb segment of the dystrophin gene on Xp21, in a sample of 1203 Eurasian chromosomes. Our results do not show a significant genetic structure in Europe, though when Middle Eastern samples are included a very low but significant genetic structure, rooted in Middle Eastern heterogeneity, is observed. This structure was not correlated to either geography or language, indicating that neither of these factors are a barrier to gene flow within Europe and/or the Middle East. Spatial autocorrelation analysis did not show clinal variation from the Middle East to Europe, though an underlying and ancient east-west cline across the Eurasian continent was detected. Clines provide a strong signal of ancient major population migration(s), and we suggest that the observed cline likely resulted from an ancient, bifurcating migration out of Africa that influenced the colonizing of Europe, Asia and the Americas. Our study reveals that, in addition to settlements from the Near East, Europe has been influenced by other major population movements, such as expansion(s) from Asia, as well as by recent gene flow from within Europe and the Middle East.