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Exploiting the potential of routine data to better understand the disease burden posed by allergic disorders.

The Department of Health and Scottish Executive are currently undertaking independent reviews of allergy services in England (and Wales) and Scotland. Each review will assess the disease burden posed by allergic problems, involving secondary analyses of routine National Health Service (NHS) datasets. Major suggestions for re-structuring and/or re-focusing the NHS efforts to better deal with allergic disease are anticipated. The UK has some of the best datasets of routine health data in the world, but despite their strengths, they have important limitations. These include gaps in data collection, particularly in relation to monitoring of Accident & Emergency and out-patient consultations, and in-patient prescribing, thereby resulting in considerable under-estimates of hospital workload. The current gaps in service monitoring are likely to under-estimate the burden and workload associated with allergic problems, particularly in secondary care. One major limitation of existing data sources is the general inability to link individual patient level data between different datasets. By unlocking this potential there are very considerable potential gains to be made. Data linkage techniques currently being developed in the UK offer exciting new possibilities of looking across the primary-, secondary- and tertiary-care interfaces and also assessing short-and long-term social and educational outcomes in relation to allergic disorders. The current reviews of allergy services being undertaken need to be cognisant of these inherent limitations of existing data sources and would do well to recommend strategic initiatives that could enhance the availability, accessibility and quality of these datasets. Ideally, this should include investment in central data repositories staffed by teams with the necessary technical and statistical expertise, which would also take responsibility for progressing data linkage capabilities.

Drug Prescriptions↗

Paenibacillus isolates possess diverse dextran-degrading enzymes.

AIMS: To isolate and identify dextran-degrading organisms from sugar mill and compost samples, and to examine the diversity of the dextranolytic enzymes produced. METHODS AND RESULTS: Fifteen dextranolytic prokaryotes were purified at various temperatures from sugar-mill or compost samples, using indicator plates containing blue dextran. A 16S rRNA gene sequence analysis showed that 12 isolates purified at 40, 50 or 70 degrees C were closely aligned to Paenibacillus spp. The three isolates purified at 60 degrees C had identical 16S rDNA sequences, with highest affinity to Bacillus spp. Liquid culture of the 11 isolates purified at 40 or 50 degrees C produced dextranolytic activity in the spent media with maximal activity at 40 or 45 degrees C under the assay conditions used. Hydrolysis of blue dextran in activity gels showed that the 12 Paenibacillus isolates produced from one to five dextranolytic proteins, ranging from 70 to 120 kDa. Based on 16S rDNA sequence, growth habit in liquid culture and dextranolytic enzyme pattern, the 12 Paenibacillus-like isolates could be differentiated into six distinct groups, one of which was capable of growth at 70 degrees C. CONCLUSIONS: The Bacillales, especially the Paenibacillus, are a valuable environmental repository for dextranolytic enzymes of diverse size and potentially diverse activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Dextranolytic enzymes produced by Paenibacillus spp. are an exploitable resource for those interested in modifying the structure of dextrans.

Bacillus↗

The development of research in nursing in the United Kingdom.

The last 30 years have seen considerable development in research in nursing. Nursing is building a repository of research-based knowledge. Formal structures around which research can be developed and organized are being established. Research findings are still not being implemented in practice, but strategies to address this issue are being developed. Nurses are being educated to utilize research findings in practice. The Report of the Task-force on the Strategy for Research in Nursing, Midwifery and Health Visiting was published in May 1993 (DoH, 1993). It advocates that research in nursing should be fully integrated in health-services research and outlines future strategy in four key areas: priorities, education, practice and careers.

Career Mobility↗

Student perceptions of a virtual learning environment for a problem-based learning undergraduate medical curriculum.

OBJECTIVE: To investigate the effects of a virtual learning environment (VLE) on group interaction and consultation of information resources during the preliminary phase, self-study phase and reporting phase of the problem-based learning process in an undergraduate medical curriculum. METHODS: A questionnaire was administered to 355 medical students in Years 1 and 2 to ask them about the perceived usefulness of a virtual learning environment that was created with Blackboard for group interaction and the use of learning resources. RESULTS: The students indicated that the VLE supported face-to-face interaction in the preliminary discussion and in the reporting phase but did not stimulate computer-mediated distance interaction during the self-study phase. They perceived that the use of multimedia in case presentations led to a better quality of group discussion than if case presentations were exclusively text-based. They also indicated that the information resources that were hyperlinked in the VLE stimulated the consultation of these resources during self-study, but not during the reporting phase. CONCLUSIONS: Students indicated that the use of a VLE in the tutorial room and the inclusion of multimedia in case presentations supported processes of active learning in the tutorial groups. However, if we want to exploit the full potential of asynchronous computer-mediated communication to initiate in-depth discussion during the self-study phase, its application will have to be selective and deliberate. Students indicated that the links in the VLE to selected information in library repositories supported their learning.

Attitude of Health Personnel↗

Conservation and divergence of plant microRNA genes.

MicroRNA (miRNA) is one class of newly identified, small, non-coding RNAs that play versatile and important roles in post-transcriptional gene regulation. All miRNAs have similar secondary hairpin structures; many of these are evolutionarily conserved. This suggests a powerful approach to predict the existence of new miRNA orthologs or homologs in other species. We developed a comprehensive strategy to identify new miRNA homologs by mining the repository of available ESTs. A total of 481 miRNAs, belonging to 37 miRNA families in 71 different plant species, were identified from more than 6 million EST sequences in plants. The potential targets of the EST-predicted miRNAs were also elucidated from the EST and protein databases, providing additional evidence for the real existence of these miRNAs in the given plant species. Some plant miRNAs were physically clustered together, suggesting that these miRNAs have similar gene expression patterns and are transcribed together as a polycistron, as observed among animal miRNAs. The uracil nucleotide is dominant in the first position of 5' mature miRNAs. Our results indicate that many miRNA families are evolutionarily conserved across all major lineages of plants, including mosses, gymnosperms, monocots and eudicots. Additionally, the number of miRNAs discovered was directly related to the number of available ESTs and not to evolutionary relatedness to Arabidopsis thaliana, indicating that miRNAs are conserved and little phylogenetic signal exists in the presence or absence of these miRNAs. Regulation of gene expression by miRNAs appears to have existed at the earliest stages of plant evolution and has been tightly constrained (functionally) for more than 425 million years.

Base Sequence↗

UPSC-BASE--Populus transcriptomics online.

The increasing accessibility and use of microarrays in transcriptomics has accentuated the need for purpose-designed storage and analysis tools. Here we present UPSC-BASE, a database for analysis and storage of Populus DNA microarray data. A microarray analysis pipeline has also been established to allow consistent and efficient analysis (from small to large scale) of samples in various experimental designs. A range of optimized experimental protocols is provided for each step in generating the data. Within UPSC-BASE, researchers can perform standard and advanced microarray analysis procedures in a user-friendly environment. Background corrections, normalizations, quality-control tools, visualizations, hypothesis tests and export tools are provided without requirements for expert-level knowledge. Although the database has been developed primarily for handling Populus DNA microarrays, most of the tools are generic and can be used for other types of microarray. UPSC-BASE is also a repository of Populus microarray information, providing data from 21 experiments on a total of 407 microarray hybridizations in the public domain of the database. There are also an additional 10 experiments containing 347 hybridizations, where the automatically analysed data are searchable.

Databases, Genetic↗

The future of microarray technology: networking the genome search.

In recent years microarray technology has been increasingly used in both basic and clinical research, providing substantial information for a better understanding of genome-environment interactions responsible for diseases, as well as for their diagnosis and treatment. However, in genomic research using microarray technology there are several unresolved issues, including scientific, ethical and legal issues. Networks of excellence like GA(2)LEN may represent the best approach for teaching, cost reduction, data repositories, and functional studies implementation.

Allergy and Immunology↗

Evaluation of the association between the EQ-5D (health-related utility) and body mass index (obesity) in hospital-treated people with Type 1 diabetes, Type 2 diabetes and with no diagnosed diabetes.

AIMS: The purpose of this study was to characterize the impact of body mass index (BMI) on health-related utility for patients with Type 1 and Type 2 diabetes and those without diabetes. METHODS: The study was conducted in Cardiff and the Vale of Glamorgan, Wales, UK. Health-related utility was measured using the EQ-5D(index). Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire either 6 weeks post discharge for in-patients or at out-patient clinics between January 2002 and July 2003. BMI was calculated from self-reported data within the survey. Patients with diabetes were identified by a previous history of an in-patient admission with diabetes or as an out-patient with diabetes recorded as a coexisting diagnosis. RESULTS: Questionnaires were returned from 27 924 patients of whom 2575 had diabetes. Increasing BMI was found to reduce utility in all three groups. BMI was significantly greater for those with Type 2 diabetes compared with those with Type 1, and those without diabetes (P < 0.001). Multiple regression analysis demonstrated that both BMI and diabetes status had a significant effect on utility. However, the rate of change of utility attributable to BMI was not found to be significantly different between the various groups. CONCLUSIONS: Obesity negatively impacts upon health-related utility and thus quality of life for all patient groups. There was no significant difference in the effect of obesity on utility between those with and without diabetes.

Adolescent↗

Characterization and comparison of health-related utility in people with diabetes with various single and multiple vascular complications.

AIMS: To characterize and compare health-related utility in a large cohort of patients treated in hospital with diabetes and with single and multiple comorbidities. METHODS: The study was conducted in Cardiff and the Vale of Glamorgan, UK. Health-related utility was measured using the EQ5D(index), a standardized instrument for measuring health outcome. Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire 6 weeks post discharge for in-patients and during clinics for patients attending as out-patients between January 2002 and July 2005. Patients with diabetes were identified by a previous history of in-patient admission with diabetes or as an out-patient with diabetes recorded as a coexisting diagnosis. RESULTS: We identified 4502 patients with diabetes. Mean ages were 65.4 and 64.2 years for males and females, respectively. Of these, 2003 (45%) had no recorded vascular complication. Overall, the EQ5D(index) was 0.584 (sd 0.325) for males and 0.533 (sd 0.351) for females. For those without any vascular complications the mean EQ5D(index) was 0.735 (sd 0.288). In a general linear model, the presence of single and multiple complications had a detrimental impact on the EQ5D(index). CONCLUSION: The results of this study provide an indication of the true impact of diabetes in terms of health-related utility. There was a decrease in the mean EQ5D(index) for those with vascular complications. Economic models of diabetes that have used additive or multiplicative methods to assess utility in individuals with several complications may be unreliable, and direct measurements, such as this, are recommended.

Aged↗

Purification and lectin-binding properties of s-laminin, a synaptic isoform of the laminin B1 chain.

The extracellular matrix (ECM) at the vertebrate neuromuscular junction is a repository of functionally important molecules, some of which can regulate the formation of synapses during regeneration. One candidate molecule is s-laminin, a 185-kDa homologue of the laminin B1 chain. Whereas several members of the laminin family are present throughout the ECM ensheathing muscle fibers, immunoreactivity for s-laminin is found selectively at synaptic sites in adult and embryonic rats, and is detectable at a time when synaptogenesis is taking place during development. We have reported previously that a rat schwannoma cell line, D6P2T, produces and releases large amounts of s-laminin in culture. We have now purified s-laminin from medium conditioned by these cells by using a simple three-step procedure. Serum-free, conditioned medium is separated by ion-exchange chromatography on DEAE-Sephacel, followed by size-exclusion chromatography on 500 HR-Sephacryl. Finally, s-laminin is dissociated from other ECM components by agarose gel electrophoresis under reducing conditions and recovered in solution by extracting slices of agarose gel. The purified preparation displays one silver-stained band that is recognized by three monoclonal antibodies known to bind to different epitopes on s-laminin. Lectin-binding studies demonstrate that s-laminin is a glycoprotein and bears many of the carbohydrate moieties present on the B1 and B2 chains of laminin. Thus, the three 185-220-kDa members of the laminin family are related in both their protein and carbohydrate domains.

Animals↗

Psychometric properties of the Consumer Assessment of Health Plans Study (CAHPS) 2.0 adult core survey.

OBJECTIVE: To estimate the reliability and validity of survey measures used to evaluate health plans and providers from the consumer's perspective. DATA SOURCES: Members (166,074) of 306 U.S. health plans obtained from the National CAHPS Benchmarking Database 2.0, a voluntary effort in which sponsors of CAHPS surveys contribute data to a common repository. STUDY DESIGN: Members of privately insured health plans serving public and private employers across the United States were surveyed by mail and telephone. Interitem correlations and correlations of items with the composite scores were estimated. Plan-level and internal consistency reliability are estimated. Multivariate associations of composite measures with global ratings are also examined to assess construct validity. Confirmatory factor analysis is used to examine the factor structure of the measure. FINDINGS: Plan-level reliability of all CAHPS 2.0 reporting composites is high with the given sample sizes. Fewer than 170 responses per plan would achieve plan-level reliability of .70 for the five composites. Two of the composites display high internal consistency (Cronbach's alpha > or = .75), while responses to items in the other three composites were not as internally consistent (Cronbach's alpha from .58 to .62). A five-factor model representing the CAHPS 2.0 composites fits the data better than alternative two- and three-factor models. CONCLUSION: Two of the five CAHPS 2.0 reporting composites have high internal consistency and plan-level reliability. The other three summary measures were reliable at the plan level and approach acceptable levels of internal consistency. Some of the items that form the CAHPS 2.0 adult core survey, such as the measure of waiting times in the doctor's office, could be improved. The five-dimension model of consumer assessments best fits the data among the privately insured; therefore, consumer reports using CAHPS surveys should provide feedback using five composites.

Benchmarking↗

Stage of change for making an informed decision about Medicare health plans.

OBJECTIVE: To assess the applicability of the transtheoretical model of change (TTM) to informed choice in the Medicare population. DATA SOURCES/STUDY SETTING: Two hundred and thirty-nine new Medicare enrollees randomly selected from the Center for Medicare and Medicaid Services' October 2001 Initial Enrollee File, a repository of data for persons who are going to turn 65 and become entitled to enroll in Medicare in the next 3 months. STUDY DESIGN: Study participants completed TTM measures of stage of change, decisional balance, and self-efficacy for informed choice, as well as measures of Medicare knowledge, perceived knowledge, and information seeking. Model testing was conducted to determine whether well-established relationships between stage of change, decisional balance, and self-efficacy replicate for informed choice in the Medicare population, and whether Medicare knowledge and information-seeking increase across the stages. DATA COLLECTION/EXTRACTION METHODS: Survey data were collected using mail surveys with telephone follow-up for nonresponders. PRINCIPAL FINDINGS: Predicted relationships were established between stage of change for informed choice and decisional balance, self-efficacy, Medicare knowledge, and information seeking. The amount of variance accounted for by stage of change for informed choice was larger than that found for smoking cessation, where the TTM has had its greatest successes. CONCLUSIONS: The methods and findings lay the groundwork for development of TTM-based interventions for Medicare beneficiaries, and provide a prototype for the application of the TTM to informed decision making among other types of consumers who are being asked to take more responsibility for their health care.

Female↗

Barriers to the treatment of hepatitis C. Patient, provider, and system factors.

BACKGROUND: Hepatitis C virus (HCV) infection is both prevalent and undertreated. OBJECTIVE: To identify barriers to HCV treatment in primary care practice. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A cohort of 208 HCV-infected patients under the care of a primary care physician (PCP) between December 2001 and April 2004 at a single academically affiliated community health center. MEASUREMENTS: Data were collected from the electronic medical record (EMR), the hospital clinical data repository, and interviews with PCPs. MAIN RESULTS: Our cohort consisted of 208 viremic patients with HCV infection. The mean age was 47.6 (+/-9.7) years, 56% were male, and 79% were white. Fifty-seven patients (27.4% of the cohort) had undergone HCV treatment. Independent predictors of not being treated included: unmarried status (adjusted odds ratio [aOR] for treatment 0.36, P=.02), female gender (aOR 0.31, P=.01), current alcohol abuse (aOR 0.08, P=.0008), and a higher ratio of no-shows to total visits (aOR 0.005 per change of 1.0 in the ratio of no-shows to total visits, P=.002). The major PCP-identified reasons not to treat included: substance abuse (22.5%), patient preference (16%), psychiatric comorbidity (15%), and a delay in specialist input (12%). For 13% of the untreated patients, no reason was identified. CONCLUSIONS: HCV treatment was infrequent in our cohort of outpatients. Barriers to treatment included patient factors (patient preference, alcohol use, missed appointments), provider factors (reluctance to treat past substance abusers), and system factors (referral-associated delays). Multimodal interventions may be required to increase HCV treatment rates.

Adult↗

Methicillin-resistant Staphylococcus aureus colonization in a long-term-care facility.

OBJECTIVE: To study the prevalence and risk factors for colonization with MRSA at a long-term-care facility. DESIGN: Cross-sectional surveillance culture survey. SETTING: A 233-bed university-affiliated long-term-care facility. MEASUREMENTS: Surveillance cultures for MRSA were performed on patients of two adjacent nursing units and on new admissions to the entire facility over a 4-month period. RESULTS: On the chronic medical unit, where patients known to be colonized had been cohorted, 20 of 38 (52.6%) were colonized vs 3 of 67 (4.5%) on the skilled/intermediate unit (P less than 0.001), suggesting that little intra-facility spread of MRSA occurs. Twenty-four of 55 (43.6%) chronic medical admissions were colonized vs 6 of 63 (9.5%) admitted to the other units (P less than 0.001). Thirteen of 30 (43.3%) admissions were not previously known to be colonized. By univariate analysis, colonized admissions were younger and more often male; had more listed diagnoses, including pressure sores, a previous positive MRSA culture, and urinary incontinence; were more often fed by feeding tube; and had longer durations of hospital stay prior to admission. Logistic regression analysis showed that the most powerful independent predictors of colonization at admission were: a prior positive culture for MRSA (OR 8.8, 95% CI 2.4, 32.4), male sex (OR 8.2, 95% CI 2.3, 29.7), urinary incontinence (OR 3.8, 95% CI 1.4, 10.4), and presence of pressure sores (OR 2.9, 95% CI 0.9, 9.2). CONCLUSIONS: Unrecognized colonization of nursing home residents with MRSA is common, and nursing homes are unwittingly repositories for patients colonized with MRSA following acute hospitalization. Gloving and careful attention to handwashing may limit spread of MRSA within nursing homes, and identification of colonized patients may be facilitated by targeted surveillance cultures of the most debilitated patients at admission.

Aged↗

Medtronic Freestyle aortic root bioprosthesis: Implant techniques.

BACKGROUND: The Medtronic Freestyle aortic root bioprosthesis is a complete porcine aortic root to allow implantation (1) as a subcoronary valve replacement by removing graft sinus aorta, (2) as a cylinder with the sinotubular junction intact within the aorta (root inclusion), or (3) as a complete aortic root replacement. The choice among the three implant techniques depends on surgeon preference or upon the pathology encountered. The advantages and differences among the three implant techniques are examined. METHODS: The Medtronic Freestyle bioprosthesis was implanted in 1163 patients in a Food and Drug administration (FDA) clinical trial between August 1992 and October 1997. There were 21 centers in the international trial using a single data repository. Clinical data was collected prior to and at operation, at 3 to 6 months and annually. The data were compiled and statistical analysis performed at the data center. RESULTS: Patients having subcoronary valve implants were older (80% > 65 years) and aortic occlusion time was about 20 minutes less than the other methods. Patients having aortic root replacement presented with more aortic valve insufficiency (20%). Pathology of the aortic root and ascending aorta requiring repair was 26%, and larger (27 mm) valves were used in 40% of patients. Risk of operation was lowest (5.0%) with subcoronary valve implants and highest (11.7%) with root replacement technique. Thromboembolism was higher, early and late, with root inclusion (3.0, 3.9%/patient per year) and root replacement (3.2, 3.0%/patient per year) than for subcoronary implants (1.8, 1.6%/patient per year). There were more patients taking warfarin at the 4-year point with root inclusion (20%) or root replacement techniques (24%) than among patients having subcoronary implants (14%). Explants of the valve occurred in 2% of patients, none of whom had aortic root replacement. CONCLUSIONS: The Medtronic Freestyle bioprosthesis is an effective and versatile device for replacement of the aortic valve. It offers implant techniques that can treat the aortic root pathology encountered at surgery and allows the operation to proceed according to surgeon preference.

Aged↗

Integrating self and system: an empty intersection?

Synthesizing individual and family therapies can founder if the underlying epistemological assumptions concerning "what is self" are not taken into account. Most individual therapies assume self "really" exists as a relatively stable internal entity, the repository of residues of experience where traits, memories, et cetera are organized via internal schemas. Such a view tends to treat self as a thing, and implies that psychological problems are the result of internal deficits or conflicts; this can lead to difficulties in therapy. In contrast, ecosystemic views employ constructivist and contextualist approaches that are more fluid. However, by basing autopoetic self-organization in language, ecosystemic epistemology still separates subject from object. Adopting a perspective in which self has no fixed, distinguishing characteristics can resolve many difficulties and create a dimensionless point where self and system, individual and family, therapist and client can meet without hindrance.

Family Therapy↗

Phylogeny of adeleid blood parasites with a partial systematic revision of the haemogregarine complex.

The phylogenetic relationships of taxa representative of blood parasitic adeleids were investigated in a cladistic analysis. Two phylogenetic analyses were performed. Monophyly of species of Haemogregarina (sensu lato) of some marine fishes with species of Haemogregarina (sensu stricto) was not supported in either analysis. A new genus, Desseria n.g., was created to accommodate these species. The historical burden placed on the genus Haemogregarina Danilewsky, 1885 as a repository for poorly known and inadequately described species is partially relieved through taxonomic revisions involving the genera Haemogregarina, and Desseria n.g.

Animals↗

Development of an in vitro clonal culture and characterization of the rRNA gene cluster of Perkinsus atlanticus, a protistan parasite of the clam Tapes decussatus.

Perkinsus atlanticus cultures were established either with trophozoites isolated from fresh gills, with hypnospores isolated from tissues incubated in fluid thioglycollate medium, or directly from infected hemocytes of carpet shell clams Tapes decussatus from Algarve (Southern Portugal), using a culture medium and conditions optimized for Perkinsus marinus. Perkinsus atlanticus isolates were cloned by limiting dilution, and their identity unequivocally established by PCR-based species-specific diagnostic assays, and by sequencing the complete rRNA gene cluster. The rRNA gene cluster is 7.5-kb in length including 5S, IGS, SSU, ITS1, 5.8S, ITS2, LSU, and an inter-cluster spacer. rDNA sequences of the P. atlanticus clone were between 98.3-100% identical to P. atlanticus sequences previously obtained from clam tissue (non-clonal) isolates. Based on the IGS sequences available from Perkinsus species, a set of primers was designed to amplify P. atlanticus and the two clonally cultured Perkinsus species (P. marinus and P. andrewsi) currently available from a recognized repository. This Perkinsus "genus-specific" PCR-based assay complements the species-specific assays developed earlier and strengthen the detection of Perkinsus species for which specific detection assays are not yet available.

Animals↗