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Biomedical subjects

S J Bowman

Publications and source records attributed to S J Bowman.

At least 19 recordsLinked to original sources

Direct healthcare costs and predictors of costs in patients with primary Sjogren's syndrome.

OBJECTIVES: To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sjögren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. METHODS: A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. RESULTS: Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. CONCLUSION: This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.

Adult↗

Analysis of the insertion/deletion related polymorphism within T cell antigen receptor beta variable genes in primary Sjögren's syndrome.

OBJECTIVE: To analyse T cell receptor beta variable (TCRBV) gene polymorphisms (insertion/deletion related polymorphism (IDRP) and BV6S7) in primary Sjögren's syndrome (PSS). METHODS: Genomic DNA was extracted from blood samples from patients fulfilling the modified European criteria for PSS (n = 61). Healthy control blood samples were obtained from the Blood Transfusion Service (n = 121). As a disease control group, samples from patients with systemic lupus erythematosus (n = 42) were analysed. BV6S7 was genotyped using an established PCR/RFLP method. The IDRP was determined by comparison of the intensity of PCR product bands from within BV9S2 and an internal control region (BV9S1), to ascertain whether 0, 1, or 2 copies of the insertion were present. RESULTS: There was a decrease (p = 0.018) in the proportion of PSS patients with the deleted/deleted genotype. There was no association with specific BV6S7 alleles or genotypes with either the PSS group or the hypergammaglobulinaemic subgroup. There were no significant differences in haplotype frequencies after Bonferroni correction. CONCLUSIONS: A reduced proportion of patients with PSS have the deleted/deleted genotype. Eighty nine per cent of PSS patients have at least one extra germline copy of BV13S2*1. This may relate to previous observations of increased BV13 specific T cells and mRNA in the salivary glands.

Gene Deletion↗

Review of presentations at the 6th European Lupus Meeting 3-5 March 2005.

The 6th European Lupus Meeting was held at the Royal College of Physicians of London and was attended by 450 delegates. The conference brought together leading speakers from Europe and North America who reviewed current knowledge and exciting new developments in both clinical and basic science aspects of systemic lupus erythematosus. This review summarizes the major points covered in each session.

Animals↗

Measurement of fatigue and discomfort in primary Sjogren's syndrome using a new questionnaire tool.

OBJECTIVE: Fatigue is a prominent symptom in primary Sjögren's syndrome (PSS). We set out to compare existing instruments and a new tool for measuring fatigue and general discomfort in PSS, with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. METHODS: Groups of female Caucasian PSS patients completed a new questionnaire developed from PSS patients' own vocabulary, as well as the SF-36, WHOQOL-BREF and HAD scales. For comparison, the questionnaire was also completed by groups of SLE and RA patients and healthy controls. RESULTS: Each disease group differed significantly from healthy controls on each facet of fatigue and general discomfort in the new tool. Somatic fatigue was worst in RA, while mental fatigue was worst in PSS and SLE. The facets of somatic fatigue and discomfort in the new tool correlated well with comparable domains in existing scales. CONCLUSIONS: Fatigue in PSS can be measured using this new Sjögren's-based psychometric instrument. The new questionnaire tool was more sensitive than the SF-36, WHOQOL-BREF and HAD at distinguishing the three rheumatic disorders from controls.

Adult↗

Estimating the prevalence among Caucasian women of primary Sjögren's syndrome in two general practices in Birmingham, UK.

OBJECTIVE: To establish the prevalence among women of primary Sjögren's syndrome (PSS) in Birmingham, UK. METHODS: Eight hundred and forty-six female Caucasians from two general practitioner lists were invited to complete a questionnaire that included a screening question on dry eyes and mouth. Individuals who responded positively were evaluated further. RESULTS: Overall, 65/% of individuals who were sent a questionnaire responded. Two had possible PSS, but were negative for anti-Ro/La antibodies. Our estimates of the prevalence of PSS ranged from < 0.1% up to 0.4%, depending on the assumptions used. CONCLUSION: Our data support previous studies suggesting a prevalence of PSS in the community of 0.1-0.6% rather than those suggesting a higher figure.

Adult↗

The efficacy of a fluoride varnish in reducing enamel demineralization adjacent to orthodontic brackets: an in vitro study.

OBJECTIVES: To test the hypothesis that fluoride varnish is effective in reducing demineralization (white spot) lesions adjacent to bonded orthodontic brackets. DESIGN: Two similar samples of extracted bovine incisors, with bonded orthodontic brackets, were separated into an experimental group (fluoride varnish was applied) and control group (no fluoride varnish) to examine the preventive effects of fluoride varnish. SETTING AND SAMPLE POPULATION: The dental clinic of the State University of Maringá--UEM (Maringá, Paraná, Brazil). Thirty-eight extracted bovine incisors with bonded orthodontic brackets. EXPERIMENTAL VARIABLE: Fluoride varnish was applied topically to half of the sample of extracted bovine teeth. No varnish was applied to the other half. OUTCOME MEASURE: The depths of enamel demineralization (white spot) lesions were measured from polarized light microscopy images using image analysis software. RESULTS: The teeth in both the experimental and control groups had been exposed to a cariogenic environment twice a day for 35 days. Those teeth that had been treated with two applications of fluoride varnish (one at the outset and another 15 days later) demonstrated about 38% less mean lesion depth than teeth where no varnish had been applied. CONCLUSION: Orthodontists may wish to consider the application of fluoride varnish during fixed orthodontic therapy to help reduce the development of enamel white spot lesions.

Animals↗

Collaborative research into outcome measures in Sjögren's syndrome. Update on disease assessment.

Sjögren's syndrome (SS) is a multisystem immune-mediated disorder characterized by inflammation of exocrine glands leading to clinical symptoms of dryness, particularly of the eyes and mouth which can be severe and disabling. It can occur in association with other rheumatic disorders or as a primary entity (PSS), often associated with B-cell hyperreactivity manifested by hypergammaglobulinaemia and anti-Ro and/or anti-La autoantibodies. These patients are more likely to have systemic involvement, for example of the pulmonary, neurological or haematological systems, and have a 44 times increased risk of non-Hodgkins lymphoma, this being the major adverse outcome in this disorder. Clinical trials of new therapies in disorders such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been advanced by the development of internationally agreed assessment and outcome measures such as the American College of Rheumatology/EULAR core datasets of disease activity in RA and measures of activity and damage in SLE such as BILAG, SLEDAI, SLICC etc. No such equivalent consensus exists for SS and as a result clinical trials have all used different, unvalidated, ad hoc measures of disease assessment and outcome. One attempt to bring a coherent approach to this issue is the "Copenhagen model" or disease assessment wheel that places each disease manifestation within specific categories depending on their presumed pathogenesis. Attempts have also been made to develop this into a severity tool by grading specific manifestations according to severity. In March 2000, interested specialists from around Europe met to develop a consensus on the broad principles underpinning disease assessment in SS (particularly PSS). It was agreed to adopt the international approach of dividing assessment into: exocrine and-nonexocrine disease activity (potentially reversible and including sicca symptoms and objective measures and systemic symptoms (particularly fatigue) and clinical features), damage (present for over 6 months), health-related and generic quality of life, and standard approaches to adverse events/toxicity and health economic aspects. The workshop also began the process of developing specific measures of sicca symptoms and systemic activity and damage. In order to convert this approach into detailed, experimentally validated assessment tools, a UK-based collaboration has focused on the development of systemic and sicca symptom questionnaires and a prospective evaluation in Europe of systemic activity and damage measures is planned.

Cooperative Behavior↗

Hematological manifestations of rheumatoid arthritis.

OBJECTIVE: To inform clinical rheumatologists about the common and rarer hematological manifestations of rheumatoid arthritis with an emphasis on diagnosis and therapy and a particular reference to Felty's syndrome. METHODS: Literature review. RESULTS: The hematological manifestations can be conveniently categorized into the broad areas of; anemia, particularly NSAID induced iron deficiency anemia and the anemia of chronic disease, neutropenia, particularly Felty's syndrome and the large granular lymphocyte syndrome and drug induced neutropenia; thrombocytopenia, particularly autoimmune and drug induced thrombocytopenia; and hematological malignancy. Rarer conditions, their diagnosis and therapy are also described in this review. CONCLUSION: Hematological manifestations of rheumatoid arthritis are very common. A logical approach using easily available tests should allow straightforward decisions about diagnosis and therapy to be made, even in patients with some of the rarer manifestations.

Anemia↗

Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

OBJECTIVE: To identify HLA class II associations with anti beta(2)-glycoprotein I (beta2GPI) antibodies in a cohort of Caucasian patients with systemic lupus erythematosus (SLE) and to determine whether these HLA genotypes act as restriction elements for lymphocyte proliferation to native human beta2GPI in vitro. METHODS: Anti-beta2GPI antibodies were detected in patient sera using enzyme-linked immunosorbent assays (ELISAs). HLA class II alleles (DRB1, DQB1) were determined by polymerase chain reaction-based DNA genotyping. In vitro peripheral blood mononuclear cell (PBMC) responses to native human beta2GPI were measured in a 7-day proliferation assay. RESULTS: We identified three groups of Caucasian SLE patients using these ELISAs. In group 1, 16 out of 18 SLE patients (89%) with anti-beta2GPI antibodies were positive for HLA-DRB1*0401/4/8, DR11 or DRB1*1302 (P=0.001 vs controls) compared with 23 out of 53 patients (43%) in group 2 with anti-cardiolipin antibodies only, 57 out of 151 patients (38%) in group 3 (SLE patients without anticardiolipin antibodies) and 109 out of 225 controls (48%). Fourteen patients with anti-beta2GPI antibodies had greater median stimulation indices to beta2GPI in vitro compared with the 15 controls studied (P=0.04). CONCLUSION: The HLA class II and PBMC proliferation data suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.

Adolescent↗

Development and assessment of a World Wide Web site for systemic lupus erythematosus patient information.

Patient education is an important component of the management of chronic diseases such as SLE. We have investigated the value of the World Wide Web as a medium for delivery of SLE patient information. Volunteers recruited from the clinic and from the website completed interviews and questionnaires aimed at defining their information needs. A new website was then established and its impact on users tested using knowledge questionnaires. The new website was used extensively (20-30 users each day) over the 24 month period of study until April 2001. A total of 510 participants completed an online questionnaire that showed that for some users it was their first use of the internet to gather lupus information, but the majority (58.9%) accessed it at least monthly for this purpose. We also found that, while most users (56.9%) found current disease information was at an appropriate level, 37.5% thought it was too basic. Knowledge questionnaires from 42 participants before and after using the site showed a significant rise in users' knowledge of the areas covered by the site. As far as we are aware this study is the first to show that a patient-oriented website can have a positive effect on disease knowledge. The relative ease with which good quality information can be disseminated via the web suggests that this medium is likely to be less costly and perhaps more educationally effective than printed information, and so is likely to become a primary vehicle for patient education. The website tested can be found at: www.rheumatology.bham.ac.uk/lupus/intro.html.

Humans↗

Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren's syndrome.

OBJECTIVE: To test the hypothesis that the formation of ectopic germinal center (GC)-like structures in Sjögren's syndrome (SS) is associated with the ectopic expression of the constitutive lymphoid tissue-homing chemokines B cell-attracting chemokine 1 (BCA-1; or, CXCL13) and stromal cell-derived factor 1 (SDF-1; or, CXCL12). METHODS: Immunohistochemical and immunofluorescence analysis was used to determine the expression of the constitutive chemokines BCA-1 (CXCL13) and SDF-1 (CXCL12) in salivary glands from 5 SS patients and 3 non-SS patients. In addition, the expression of their respective receptors (CXCR5 and CXCR4) was examined on infiltrating lymphocytes. Human tonsil was used as a positive control for secondary lymphoid tissue. RESULTS: BCA-1 (CXCL13) was expressed within lymphoid aggregates in SS, which shared many structural features with GCs in tonsil. BCA-1 (CXCL13) was completely absent in control biopsy samples from patients who did not have SS. High levels of BCA-1 (CXCL13) were also found on endothelial cells in salivary glands from SS patients. Diseased SS tissue was infiltrated by CXCR5-expressing B cells which organized into GC-like clusters. In complete contrast, SDF-1 (CXCL12), a constitutive chemokine involved in leukocyte retention within lymphoid tissue, was expressed by epithelial cells in both diseased and control samples. The chemokine receptor for SDF-1, CXCR4, was expressed on T cells that accumulated in a periductal distribution in diseased tissue. CONCLUSION: The ectopic expression of BCA-1 (CXCL13) on endothelial cells and within GC-like structures, together with the strong expression of SDF-1 (CXCL12) on ductal epithelial cells, is a unique feature of inflamed glands in SS. By creating a local microenvironment supportive of focal B cell aggregation and differentiation, with structural features that are remarkably similar to GCs, BCA-1 (CXCL13) and SDF-1 (CXCL12) may contribute to the excessive production of high-affinity, class-switched autoantibodies and to the high incidence of B cell lymphomas classically associated with SS.

B-Lymphocytes↗

Posttreatment evaluation of the distal jet appliance.

This study analyzed molar distalization with the distal jet appliance, its effect on the anchor teeth, and the outcome at the completion of orthodontic treatment. Pretreatment, after distalization, and posttreatment lateral cephalometric radiographs were evaluated for 21 adolescent girls and 12 adolescent boys. The mean age of the subjects at the time of the pretreatment radiograph was 12.8 +/- 2.2 years. The mean time for the correction of the Class II molar relationship was 6.7 +/- 1.7 months, and the mean total treatment time was 25.7 +/- 3.9 months. The results of this study showed that the distal jet appliance distalized the maxillary molars, but there was significant loss of anchorage. The distal jet also showed less tipping of the maxillary molars and better bodily movement of molars because the force was applied closer to the center of resistance. The observations of treatment outcome indicate that the 1.8-mm mean net anterior movement of the maxillary first molar was more than offset by the 4.8-mm mesial movement of the mandibular first molar. There was no significant increase in lower face height. Consequently the effect on the facial balance was negligible.

Adolescent↗