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P Stephens

Publications and source records attributed to P Stephens.

At least 19 recordsLinked to original sources
PubMed2005

Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997-2003.

AIMS: To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. METHODS: Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997-2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of "patient treatment days" (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. RESULTS: Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274% in Ireland and by 56% in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). CONCLUSIONS: Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance.

Drug Prescriptions↗
PubMed2004

Comparison of national administrative and commercial databases to monitor expenditure and costs of statins across Europe.

OBJECTIVES: To compare data on statin utilisation and costs across Europe from routine administrative databases with those from a commercial source. METHODS: Observational study in European Union member states and Norway. Comparison of data collected from national administrative databases used to reimburse pharmacists and data from a standard commercial source (Intercontinental Marketing Services Health): detailed data by drug for the year 2000. RESULTS: There were differences among the data from administrative databases and those from the commercial source; these differences were of a consistent pattern in each country. In general, the commercial data recorded greater utilisation (reflecting both public and private use, range from 0 to +55%, median +15%), lower cost per defined daily doses (as commercial data sources used ex-factory price rather than expenditure to the state used in administrative databases, range from -70% to -6%, median -39%) and similar utilisation per 1000 head of population per day (range from -15 to +47%, median -1%). CONCLUSIONS: Administrative databases can give useful utilisation data, which are broadly comparable with those from commercial sources. Cost data differ more, and the figures for each may be useful in different settings. Standards for data collection from the administrative databases are required.

Databases, Factual↗
PubMed2004

Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: lessons learned from other inflammatory diseases?

The new era of pharmacogenetics has identified a potential for individuals to receive customized treatments for a variety of disease states. For such individualized treatments to fulfil their potential, it will be essential for clinicians to be able to monitor disease activity, ideally in a rapid, noninvasive fashion. The accessibility of the skin offers much potential to develop noninvasive tests of metabolic and disease activity for clinical use. Impaired human wound healing in the skin is a chronic inflammatory disorder in which the development of such tests has considerable potential, aiding clinical decision making and monitoring responses to treatment. This review article discusses how studies in other human diseases have highlighted potential biochemical markers (biomarkers) of disease activity in secreted biofluids, as aids to determining disease and metabolic activity within tissues. Using, as examples, lessons learned in the study of disease activity and prognosis of other chronic inflammatory conditions, such as osteoarthritis and periodontal disease, this review highlights the potential of dermal extracellular matrix (ECM) components (collagens, proteoglycans, hyaluronan and glycoproteins) for such uses. The limitations of currently utilized techniques and the concept that analysis of ECM components in wound fluid may represent useful biomarkers of disease activity are also discussed.

Biomarkers↗
PubMed2004

Development of an anti-Salmonella typhi Vi ELISA: assessment of immunocompetence in healthy donors.

We have developed a solid-phase enzyme-linked immunosorbent assay (ELISA) to study the vaccination responses to Vi capsular polysaccharide of Salmonella typhi (S. typhi Vi) vaccine. Purified S. typhi Vi polysaccharide was biotinylated and bound to streptavidin coated microtitre plates. Reproducibility was determined across a range of IgG antibody levels: mean interassay coefficients of variation (CVs) were <11.9% for non-vaccinated sera with low levels and <11.1% for sera with very high levels of anti-S. typhi Vi IgG. Specificity was assessed by inhibition studies using salmonella antigen. We have developed the ELISA based on normal adult serum responses to test immunization with S. typhi Vi vaccine. We also report here anti-S. typhi Vi IgG levels in a group of healthy preschool children. In non-vaccinated adult sera (n = 104), the median value of anti-S. typhi Vi IgG, expressed in S. typhi Vi arbitrary units (AU/ml), was 5.3 AU/ml and in non-vaccinated sera from children (n = 44) the median value was 1.4 AU/ml. The data from immunization of healthy volunteers (n = 23) show that geometric mean levels of anti-S. typhi Vi IgG were significantly higher (P < 0.0001) for post-vaccination subjects (39.2 AU/ml) compared to paired prevaccination (3.9 AU/ml) values. A total of 21/23 vaccine recipients had <8 AU/ml S. typhi Vi IgG in their sera prior to vaccination and of these 20/21 (95%) exhibited threefold increases and 14/21 (67%) fourfold increases in their S. typhi Vi IgG following vaccination. Based on the data in this study, we propose a threefold increase in anti-S. typhi Vi IgG post-vaccination to be considered a positive vaccination response. The ability to demonstrate clearly an antibody rise in response to immunization with S. typhi Vi capsular polysaccharide vaccine suggests that this is likely to be a useful vaccine for the assessment of B cell function in patients with suspected immune deficiency.

Adult↗
PubMed2004

Increased prescribing trends of paediatric psychotropic medications.

Psychotropic medication use by children in the USA has increased. We used the IMS MIDAS Prescribing Insights to examine prescribing trends in nine countries between the years 2000 and 2002. Trends in seven countries rose significantly from year 2000 to 2002; the UK had the highest increase (68%).

Adolescent↗
PubMed2003

The effect of two nonresorbable suture types on the mechanical performance over a metal suture anchor eyelet.

An understanding of the mechanical properties of different suture materials is valuable when selecting the most appropriate suture and repair technique. Sutures should be strong, easy to handle and have high knot security. The introduction of suture anchors adds an additional variable regarding the effect of stress risers over the eyelet. Improving the mechanical properties of a suture may be a possible method to help avoid failure over stress risers such as the eyelet of suture anchor. This study examined the static and viscoelastic properties of a new polyethylene based non-resorbable suture (Fibrewire) over the eyelet of a standard anchor compared to braid polyester non-resorbable suture (Ethibond). Fibrewire had superior ultimate load properties compared to Ethibond (360.2 N+/-23.8 vs 191.9 N+/-17.3) as well as greater stiffness (61.3 N/mm+/-9.7 vs 8.1 N/mm+/-0.4) when tested in uniaxial tension through a metal anchor eyelet (Mitek) ( p<0.001). Fibrewire demonstrated greater stress relaxation than Ethibond ( p<0.05). Differences in the static and viscoelastic properties of suture may have implications in the post-operative period or during rehabilitation.

Equipment Failure Analysis↗
PubMed2003

Effects of beta-adrenergic antagonists on the QT measurements from exercise stress tests in pediatric patients with long QT syndrome.

It has been proposed that beta-adrenergic antagonist protection against cardiac events in patients with long QT syndrome (LQTS) may be related to a decrease in baseline QTc dispersion. To determine the effects of beta-blocker therapy on QT measurements, we evaluated the exercise tests of 25 pediatric patients with LQTS. Measurements were made of the maximum QTc interval and QTc dispersion during the various segments of the exercise test. There was no statistically significant difference between the pre-beta-blocker and post-beta-blocker maximum QTc interval during the supine (0.473 +/- 0.039 vs 0.470 +/- 0.038 sec), exercise (0.488 +/- 0.044 vs 0.500 +/- 0.026 sec), or recovery (0.490 +/- 0.031 vs 0.493 +/- 0.029 sec) phases of the exercise stress test. There was also no statistically significant difference between the pre-beta-blocker and post-beta-blocker QTc dispersion during the supine (0.047 +/- 0.021 vs 0.058 +/- 0.033 exercise vs 0.063 +/- 0.028 sec), or recovery (0.045 +/- 0.023 vs 0.052 +/- 0.026 sec) phases of the exercise stress test. Therefore, the protection that beta-blockers offer appears not to be related to a reduction of the baseline QTc interval or a decrease of QTc dispersion.

Adolescent↗
PubMed2003

Anaerobic cocci populating the deep tissues of chronic wounds impair cellular wound healing responses in vitro.

BACKGROUND: Anaerobic cocci are estimated to be present in the deep tissues of over 50% of chronic skin wounds. While the part they play in the chronicity of these wounds is uninvestigated, anaerobic cocci have previously been shown to be involved in other chronic inflammatory human conditions. METHODS: In this study the anaerobic microflora of the deep tissues of 18 patients with refractory chronic venous leg ulcers (mean age 80.3 years; mean duration > 24 months) was characterized using strict anaerobic culture conditions. The effect of the anaerobic organisms isolated from these tissues on extracellular matrix (ECM) proteolysis and cellular wound healing responses was studied using in vitro models. RESULTS: Anaerobic organisms were present in the deep tissues of 14 of 18 wounds and were principally Peptostreptococcus spp. The effects of three Peptostreptococcus spp. isolated from these wounds (P. magnus, P. vaginalis and P. asaccharolyticus) on cellular wound healing responses were compared with those of two pathogenic organisms also isolated from these wounds (Pseudomonas aeruginosa and Citrobacter diversus). While the direct ECM proteolytic activity exhibited by the Peptostreptococcus spp. was limited, they did significantly inhibit both fibroblast and keratinocyte proliferation, but only at high concentrations. However, at lower concentrations peptostreptococcal supernatants profoundly inhibited keratinocyte wound repopulation and endothelial tubule formation. The magnitude of these effects varied between strains and they were distinct from those demonstrated by Pseudomonas aeruginosa and Citrobacter diversus. CONCLUSIONS: These studies confirm the importance of anaerobic organisms in chronic wounds and demonstrate an indirect, strain-specific mechanism by which these microorganisms may play a part in mediating the chronicity of these wounds.

Aged↗
PubMed2003

Molecular analysis of the microflora in chronic venous leg ulceration.

There is growing evidence to suggest that the resident microflora of chronic venous leg ulcers impairs cellular wound-healing responses, thereby playing an important role in maintaining the non-healing phenotype of many of these wounds. The significance of individual species of bacteria will remain unclear until it is possible to characterize fully the microflora of such lesions. The limitations and biases of culture-based microbiology are being realized and the subsequent application of molecular methods is revealing greater diversity within mixed bacterial populations than that demonstrated by culture alone. To date, this approach has been limited to a small number of systems, including the oral microflora. Here, for the first time, the comprehensive characterization of the microflora present in the tissue of a chronic venous leg ulcer is described by the comparison of 16S rDNA sequences amplified directly from the wound tissue with sequences obtained from bacteria that were isolated by culture. The molecular approach demonstrated significantly greater bacterial diversity than that revealed by culture. Furthermore, sequences were retrieved that may possibly represent novel species of bacteria. It is only by the comprehensive analysis of the wound microflora by both molecular and cultural methods that it will be possible to further our understanding of the role of bacteria in this important condition.

Acinetobacter↗
PubMed2002

Noninvasive imaging of isolated persistent fifth aortic arch.

Persistent fifth aortic arch was suspected by echocardiography and confirmed by magnetic resonance imaging (MRI) in an infant with a heart murmur. Selected images including three dimensional reconstruction from MRI demonstrating this very rare congenital anomaly are presented.

Aorta, Thoracic↗
PubMed2002

Heterogeneity within the gram-positive anaerobic cocci demonstrated by analysis of 16S-23S intergenic ribosomal RNA polymorphisms.

Peptostreptococci are gram-positive, strictly anaerobic bacteria which, although regarded as members of the commensal human microflora, are also frequently isolated from sites of clinical infection. The study of this diverse group of opportunist pathogens has been hindered by an inadequate taxonomy and the lack of a valid identification scheme. Recent re-classification of the Peptostreptococcus family into five distinct genus groups has helped to clarify the situation. However, this has been on the basis of 16S rRNA sequence determinations, which are both time-consuming and expensive. The aim of the present study was to evaluate the use of PCR-amplified ribosomal DNA spacer polymorphisms for the rapid differentiation of the currently recognised taxa within the group of anaerobic gram-positive cocci. A collection comprising 19 reference strains with representatives of each of the 15 species, two close relatives and two of the well-characterised groups, together with 38 test strains was studied. All strains were identified to species group level by phenotypic means. Amplification of the 16S-23S intergenic spacer region (ISR) with universal primers produced distinct banding patterns for all the 19 reference strains and the patterns could be differentiated easily visually. However, of the 38 test strains, less than half could be speciated from ISR analysis alone. Only five groups produced correlating banding patterns for all members tested (Peptoniphilus lacrimalis, P. ivorii, Anaerococcus octavius, Peptostreptococcus anaerobius and Micromonas micros). For other species, either the type strain differed significantly from other species members (e.g., A. hydrogenalis) or there appeared to be considerable intra-species variation (e.g., A. vaginalis). Partial 16S rRNA gene sequences for the 'trisimilis' and 'betaGAL' groups showed that both are most closely related to the Anaerococcus group. This work highlights the heterogeneous nature of a number of Peptostreptococcus species and hence the need for still further revision of the taxonomy of this important group of pathogens.

Anaerobiosis↗
PubMed2001

Persistence of sulphonamide resistance in Escherichia coli in the UK despite national prescribing restriction.

BACKGROUND: There is a clear association between heavy antimicrobial consumption within a population and the frequent recovery of resistant bacteria, but whether a reduction in antimicrobial use can reverse this process is less clear. We investigated the effect of a national restriction of sulphonamide prescribing in the UK on the prevalence of sulphonamide resistance in Escherichia coli. METHODS: Consecutive clinical isolates of E coli were collected at the Royal London Hospital in 1991 and 1999. These collections, each of more than 350 isolates, were compared. Minimum inhibitory concentrations of sulphamethoxazole and eight other antimicrobials were determined. The presence and locations of sulphonamide-resistance genes were examined by PCR, plasmid extraction, Southern hybridisation, and transconjugation. FINDINGS: Despite a huge decrease in sulphonamide prescriptions (from 3,208,000 [corrected] prescriptions per year in 1991 to 77,000 [corrected] in 1999), the frequency of resistance remained high in 1999 (165/359 [46.0%] vs 143/360 [39.7%] in 1991; difference 6.2% [95% CI 20.9 to 13.3]). Integron-borne sulI was present in 16.4% of isolates in 1991 and 17.5% in 1999. The prevalence of sulII increased from 26.7% in 1991 to 36.5% in 1999 (difference 9.8% [3.1 to 16.5] p=0.0046). SulII was located on large plasmids, at least some of which were conjugative multiresistance determinants. INTERPRETATION: These results show that a huge decrease in antibiotic prescribing does not necessarily reduce resistance within a useful time. The main reason seems to be the genetic linkage of the index resistance to other resistance determinants.

Blotting, Southern↗
PubMed2001

Social support, negative life events and pupil misbehaviour among young Norwegian adolescents.

Relationships between negative life events, perceived social support and pupil misbehaviour were assessed in a national representative sample of 1057 Norwegian young adolescents aged 14 and 15. Negative life events were significantly associated with pupil misbehaviour among both male and female adolescents. Support from parents, friends and teachers was negatively associated with pupil misbehaviour.

Adolescent↗
PubMed2001

Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity.

BACKGROUND: Oral mucosal wounds are characterized by rapid re-epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts. OBJECTIVES: To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) -2 and tissue inhibitors of metalloproteinases (TIMPs) could play an important part in mediating these in vitro differences. METHODS: Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA expression and protein production were studied in three-dimensional collagen lattices using quantitative competitive reverse transcriptase-polymerase chain reaction (QCRT-PCR), enzyme-linked immunosorbent assay (ELISA), zymography and reverse zymography. RESULTS: Oral mucosal fibroblasts exhibited increased levels of the 62-kDa active form of MMP-2 and lattice contraction when compared with skin fibroblasts. Oral mucosal and skin fibroblast MMP-2 gene expression and synthesis of the 72-kDa pro-MMP-2 was similar as assessed by QCRT-PCR, zymography and ELISA. Differential MMP-2 activation was, however, related to phenotypic differences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography. CONCLUSIONS: These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.

Adolescent↗
PubMed2000

An integrated map of human 6q22.3-q24 including a 3-Mb high-resolution BAC/PAC contig encompassing a QTL for fetal hemoglobin.

Genetic studies have previously assigned a quantitative trait locus (QTL) for hemoglobin F and F cells to a region of approximately 4 Mb between the markers D6S408 and D6S292 on chromosome 6q23. An initial yeast artificial chromosome contig of 13 clones spanning this region was generated. Further linkage analysis of an extended kindred refined the candidate interval to 1-2 cM, and key recombination events now place the QTL within a region of <800 kb. We describe a high-resolution bacterial clone contig spanning 3 Mb covering this critical region. The map consists of 223 bacterial artificial chromosome (BAC) and 100 P1 artificial chromosome (PAC) clones ordered by sequence-tagged site (STS) content and restriction fragment fingerprinting with a minimum tiling path of 22 BACs and 1 PAC. A total of 194 STSs map to this interval of 3 Mb, giving an average marker resolution of approximately one per 15 kb. About half of the markers were novel and were isolated in the present study, including three CA repeats and 13 single nucleotide polymorphisms. Altogether 24 expressed sequence tags, 6 of which are unique genes, have been mapped to the contig.

Base Sequence↗
PubMed2000

Regional variation in ampicillin and trimethoprim resistance in Escherichia coli in England from 1990 to 1997, in relation to antibacterial prescribing.

Over 200 hospitals in England report resistance data for bacteraemia and meningitis isolates to the Public Health Laboratory Service. We reviewed ampicillin and trimethoprim resistance rates from 1990 to 1997 for Escherichia coli, which is the species reported most frequently from these bacteraemias. Ampicillin resistance was relatively stable over time, but varied between Health Regions. The proportion of ampicillin-resistant E. coli in the East Anglia region remained </=42% in all years except one and that in the South Western region always remained <50%. At the other extreme, the proportions of ampicillin-resistant isolates in the Northern and Trent regions never fell below 59%. The prevalence of resistance to trimethoprim rose over time in most regions; again, however, the prevalence of resistant isolates was lowest in the East Anglia and South Western regions, whereas the highest resistance rates were reported from Mersey, NW Thames, NE Thames and North Western regions. These observations were related to data for community prescribing, which accounts for most ampicillin and trimethoprim use. Prescribing data for ampicillin and trimethoprim from 1987 to 1997 were obtained from the IMS-HEALTH Medical Data Index, and data for all antibacterial drugs between 1995 and 1997 from the Prescription Pricing Authority. Correlations between resistance rates and prescribing of specific antibiotics were weak, although there was some trend for regions with high total prescribing to have higher rates of ampicillin resistance. The South Western region was conspicuous both for low rates of resistance and low prescribing. Several factors may determine the lack of wider and more obvious relationships between resistance and prescribing. In particular, regions may be inappropriately large areas to test the relationship, isolates from bacteraemias may not be representative of those experiencing selection pressure in the community and the resistance data may have been distorted by nosocomial strains, although this seems unlikely with E. coli.

Ampicillin↗