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Biomedical subjects

B White

Publications and source records attributed to B White.

At least 19 recordsLinked to original sources

Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study.

OBJECTIVE: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). PARTICIPANTS AND METHODS: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. RESULTS: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40-0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15-0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9-14.2 (0.86-1.77 effect size) on the mRSS and 0.21-0.55 (0.32-0.83 effect size) on the HAQ-DI score. CONCLUSION: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.

Adult↗

Primary thromboprophylaxis for cancer patients with central venous catheters--a reappraisal of the evidence.

Venous thromboembolism (VTE) is responsible for an estimated 25 000 deaths per annum in UK hospital practice. It is well established that many of these deaths could be prevented through the use of appropriate thromboprophylaxis. This issue is of particular relevance in oncology practice, where the risks of VTE and bleeding are both significantly higher than those observed in general medical patients. Cancer patients with in-dwelling central venous catheters (CVCs) are at particularly high risk of developing thrombotic complications. However, the literature has produced conflicting conclusions regarding the efficacy of using routine primary thromboprophylaxis in these patients. Indeed such is the level of confusion around this topic, that the most recent version of the American College of Chest Physicians (ACCP) guidelines published in 2004 actually reversed their previous recommendation (published in 2001). Nevertheless, minidose warfarin continues to be routinely used in many oncology centres in the UK. In this article, we have performed a systematic review of the published literature regarding the efficacy and the risks, associated with using thromboprophylaxis (either minidose warfarin or low-dose LMWH) in cancer patients with CVC. On the basis of this evidence, we conclude that there is no proven role for using such thromboprophylaxis. However, asymptomatic CVC-related venous thrombosis remains common, and further more highly powered studies of better design are needed in order to define whether specific subgroups of cancer patients might benefit from receiving thromboprophylaxis.

Anticoagulants↗

Prevention and management of venous thromboembolism in people with cancer: a review of the evidence.

Venous thromboembolism (VTE) constitutes an important health problem in developed countries. Owing to their underlying malignancies, people with cancer are at particularly high risk of VTE. The level of this risk is influenced by several factors, including type of cancer and the presence or absence of metastases. However, different types of oncology treatment can also further increase the thrombotic risk. Consequently, primary and secondary thromboprophylaxis in people with cancer should be considered as part of any integrated oncology treatment. Moreover, recent exciting studies have suggested that low molecular weight heparins (LMWH) may also influence overall survival in people with cancer. Clearly, these findings raise the likelihood that the use of LMWH in oncology practice may increase significantly in the near future. However, it is important to appreciate that the use of thromboprophylaxis in people with cancer is complicated by a number of specific problems. In this overview, we have systematically addressed the difficult clinical issues that are involved in the selection of appropriate primary and secondary thromboprophylaxis for people with cancer.

Anticoagulants↗

National Service Framework for long-term conditions--Quo vadis.

There is widespread dismay over the fate of the NSF for Long-term Conditions after all the efforts by so many people in securing its publication only one year ago in March 2005. In order to help to avoid its premature demise, the British Journal of Neurosurgery is pleased to provide a forum for the rapid publication of original papers and reviews that might help to catalyse the NSF's rational implementation. The first two of such papers are published in this Volume.

Delivery of Health Care↗

Evaluation of a modified ACR20 scoring system in patients with rheumatoid arthritis receiving treatment with etanercept.

OBJECTIVE: To evaluate a modified American College of Rheumatology 20 (mACR20) scoring system for patients with rheumatoid arthritis. METHODS: The data were evaluated from one study on patients with methotrexate (MTX)-naive early rheumatoid arthritis (ERA) and another study on patients with DMARD-refractory late rheumatoid arthritis (LRA). For mACR20 scoring, acute-phase reactant measurements were excluded, and 20% improvement from baseline was determined by 2 or 3 of the 4 remaining ACR components. RESULTS: For full joint counts with data from patients with ERA, marked differences favoured 25 mg etanercept (ETN) over 10 mg ETN by using the unmodified ACR20 (69% v 55%), the mACR20(3 of 4) (63% v 49%) and the mACR20(2 of 4) (72% v 58%). An assessment of 28 joints showed similar findings. In the trial on patients with LRA, considerably more patients in both ETN groups achieved a clinical response compared with placebo by using the ACR20, the mACR20(3 of 4) and the mACR20(2 of 4), whether using full or 28 joint counts. The mACR20(3 of 4) and full joint counts with data on patients with ERA showed a marked difference between the MTX and 10 mg ETN groups (63% v 49%), which was not observed with the ACR20. CONCLUSION: Patterns of improvement indicated by mACR20 scores were consistent with standard ACR20 scores.

Antirheumatic Agents↗

Standards for head injury management in acute hospitals: evidence from the six million population of the Eastern region.

OBJECTIVES: To develop standards of care for head injury and thereby identify and prioritize areas of the service needing development; to report the findings from a survey of compliance with such standards in the Eastern region of UK. METHODS: The standards were collaboratively developed through an inclusive and iterative process of regional surveys, multidisciplinary conferences, and working groups, following a method similar to that used by the Society of British Neurological Surgeons. The standards cover seven topics relating to all aspects of service delivery, with standards within each objective. Each standard has been designated a priority level (A, B, or C). The standards were piloted using a self-assessment questionnaire, completed by all 20 hospitals of the Eastern region. RESULTS: Full compliance was 36% and a further 30% of standards were partially met across the region, with some areas of service delivery better than others. Seventy eight per cent of level A standards were either fully or partially met. Results were better in the north of the region compared with the south. CONCLUSION: A survey of compliance with the head injury standards indicate that, with their whole systems approach and subject to further refinement, they are a useful method for identifying deficiencies in service provision and monitoring for quality of care both within organisations and regionally.

Craniocerebral Trauma↗

Measuring autonomy in disabled people: Validation of a new scale in a UK population.

OBJECTIVE: To evaluate the validity and reliability of an English version of the Impact on Participation and Autonomy Questionnaire (IPA). The original Dutch IPA has been shown to load onto five factors. DESIGN: A validation study. SETTING: Outpatients clinics and people's homes. SUBJECTS: Two hundred and thirteen people with multiple sclerosis, rheumatoid arthritis, spinal cord injury, and general practice attendees, stratified by level of disability (median age 54, 42% male, 58% female). INCLUSION CRITERIA: English as first language, aged 18-75, Mental Status Questionnaire score >6. INTERVENTIONS: Self- and interviewer-administered outcome measures. MAIN MEASURES: IPA, including one new item (66 participants completed the IPA on a second occasion). OTHER MEASURES: Short Form-36 Health Survey (SF-36), London Handicap Scale, three domains of the Functional Limitations Profile (FLP): household management, social integration, emotion. RESULTS: Confirmatory factor analysis confirmed the construct validity of the IPA (Normal Fit Index = 0.98, Comparative Fit Index = 0.99), indicating a good fit to the model. Convergent and discriminant validity were confirmed by the predicted associations, or lack of, with the exception of a poor association between the 'social life/relationships' IPA subscale and FLP-emotion. Internal reliability of the IPA was confirmed (Cronbach alphas >0.8; item-total correlations for all subscales >0.5). Test-retest reliability was confirmed for all items (weighted kappas >0.6) and subscales (intraclass correlation coefficients >0.90). CONCLUSIONS: The English IPA is a valid, reliable and acceptable measure of participation and autonomy in people with a range of conditions and can make a unique and fundamental contribution to outcome assessment. Further research is required to examine the responsiveness of the IPA to change over time, its clinical utility and suitability for use with people from ethnic minorities and with older people.

Persons with Disabilities↗

Circulating levels of beta2-glycoprotein I in thrombotic disorders and in inflammation.

Beta2-glycoprotein I (beta2GPI) is a plasma protein suspected to have a role in inhibition of thrombosis. This suspicion is reinforced by the observation that beta2GPI is the major target for autoantibodies in the antiphospholipid syndrome. However, little is known about its circulating levels in common thrombotic diseases or inflammation. We measured beta2GPI levels in 344 healthy controls, 58 normal pregnancies, 102 patients with non-haemorrhagic stroke, 121 patients with acute coronary syndrome and 200 patients with elevated C-reactive protein (CRP). In healthy individuals, we found a strong positive correlation between age and beta2GPI concentration (r = 0.274, P < 0.001) and that beta2GPI levels fall significantly after the eighth week of pregnancy (P = 0.002). We also found significantly reduced levels of beta2GPI in patients with stroke and in elderly patients with myocardial syndrome (P = 0.013 and 0.043). However, in neither group did beta2GPI levels change in the following six months, suggesting that the reduced levels were not a transient post-event phenomenon. In patients with inflammation, beta2GPI levels showed a significant negative correlation with CRP (r = -0.284, P < 0.001) and positively correlated with albumin and transferrin (r = 0.372 and 0.453, respectively with P < 0.001 for both). Furthermore, the largest reduction in beta2GPI levels occurred in patients with the highest CRP values (P < 0.001).

Adult↗

Bone allograft non-union is related to excessive osteoclastic bone resorption: a sheep model study.

Using a sheep femoral allograft model we have investigated the cellular and molecular mechanisms associated with non-union of bone allografts. Histomorphometric analysis revealed that allograft non-unions featured both marked increases in osteoclast (OC) numbers and total eroded bone surface as compared to allografts which had undergone direct union. Three distinct cellular layers lying adjacent to the allograft bone surface were identified in all non-union cases. The outer or fibroblastic layer contained an abundance of fibroblasts and connective tissue. Circumscribing this layer was a band of synovial-like cells consisting mainly of large spindle-shaped mononuclear cells mixed with scattered round-shaped mononuclear cells. The third layer, which was directly juxtaposed to the allograft bone surface, consisted predominantly of multinuclear OCs which were positively identified by calcitonin receptor immunohistochemistry. Interestingly, in-situ hybridisation revealed that surrounding synovial-like cells in non-union allografts, expressed abundant gene transcripts for receptor activator NF-kappaB ligand (RANKL), a membrane bound factor critical for both the induction of OC activity and osteoclastogenesis. We propose that excessive bone resorption by host OCs contributes, at least partially, to the failure of bone allografts. The production of RANKL by synovial-like fibroblasts may be the driving force responsible for the elevated generation and activation of OCs. Based on such evidence novel therapeutic strategies for the treatment of non-union bone allografts using anti-bone resorbing agents may be devised.

Animals↗

A model for decision making at the end-of-life: Queensland and beyond.

This paper addresses when it is legal to withdraw or withhold medical treatment that is needed to keep a patient alive. It draws on cases and legislation from the common law world (including Australia, England and New Zealand) and considers the various legal tests applied in the different jurisdictions. Two of the most common tests employed in this situation are the "best interests of the patient" test and the "substituted judgment" test. Some jurisdictions also include other criteria as well, such as a requirement that withdrawing or withholding of medical treatment is "not inconsistent with good medical practice". This paper analyses these different legal tests, and after identifying the factors that are judged to be legally relevant to consider when deciding to withdraw or withhold treatment, outlines a preferred model. This model addresses who the relevant decision maker should be, and the criteria that should govern their decision. It suggests that family members are better equipped and more appropriate to act as decision makers than health professionals, and also questions the appropriateness of responsible medical opinion as the decisive factor in such cases, preferring instead an approach more consistent with the principles of self determination. The model also proposes a method for resolving any disputes that arise.

Decision Making↗

Long term safety of etanercept in elderly subjects with rheumatic diseases.

OBJECTIVES: To determine the long term safety profile of the tumour necrosis factor (TNF) antagonist etanercept in subjects with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) aged > or =65 years in comparison with subjects aged <65 years. METHODS: Safety data from an integrated database of 4322 subjects enrolled in 18 RA trials, 2 PsA trials, and 2 AS trials were analysed. Safety end points included subject incidence of all adverse events (AE), serious adverse events (SAE), infectious events (IE), medically important infections (MII), and deaths. Events of particular interest in subjects treated with TNF modulating biological treatments, including demyelinating diseases, tuberculosis, lymphomas, and cardiovascular diseases, were also evaluated. RESULTS: The incidence of AE, SAE, IE, MII, and malignancies was not significantly raised in elderly subjects in comparison with subjects aged <65 years. No cases of tuberculosis were reported in the trials. Demyelinating diseases were seen only in subjects aged <65 years. The incidence and types of death in the elderly subjects were consistent with the expected rates for subjects of comparable age. CONCLUSIONS: Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly, and the risk of AE in these studies was no greater in subjects aged > or =65 years than in younger subjects.

Adult↗

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗

Sclerosing mesenteritis.

Sclerosing mesenteritis is a rare benign process involving mesenteric fat that has non-specific histology and imaging characteristics, which are critical to the diagnosis. It has two different pathological variants: mesenteric panniculitis (acute or subacute) and retractile mesenteritis (chronic). This case study illustrates the radiological findings of sclerosing mesenteritis, describes certain signs that suggest the diagnosis and reviews recent published literature.

Biopsy↗

Response to desmopressin of factors XI, X and V in patients with factor VIII deficiency and von Willebrand disease.

Desmopressin [1-deamino-8-d-arginine vasopressin (DDAVP)] has been successfully used in the treatment of type 1 von Willebrand disease (VWD) and mild haemophilia A (MHA). Data suggest that DDAVP can increase factor XI (FXI) plasma levels and may represent an effective treatment for mild FXI deficiency. We assessed the DDAVP response of FXI coagulant activity (FXI:C), FXI antigen (FXI:Ag), factor V coagulant activity (FV:C), and factor X coagulant activity (FX:C) in 33 individuals with VWD or MHA. DDAVP did not produce a clinically significant increase in FXI:C, FXI:Ag, FX:C or FV:C in any patient. The mean +/- SD FXI:C pre-DDAVP (time 0) and at 1 h post-DDAVP was 90.7 (+/-22.9) U/dl and 92.1 (+/-20.9) U/dl, respectively. The mean (+/-SD) FXI:Ag at time 0 and 1 h was 92.2 (+/-20.1) U/dl and 89.9 (+/-21.3) U/dl, respectively. There was a small reduction at 1 h post-DDAVP in both FV:C, from 101.8 (+/-20.9) U/dl to 97.2 (+/-21.4) U/dl (P < 0.001), and FX:C from 103 (+/-19.5) U/dl to 98.8 (+/-18.7) U/dl (P < 0.001). No significant increase in FXI:C, FXI:Ag, FV:C or FX:C levels was seen at 4 h post-DDAVP. This study failed to demonstrate a clinically significant increase in the levels of FXI, FX or FV following administration of DDAVP.

Adolescent↗

The diagnosis and management of common inherited bleeding disorders.

Inherited bleeding disorders can be associated with significant morbidity and mortality. Bleeding episodes can be safely and effectively managed in the majority of patients provided the coagulation defect is identified and corrected with the appropriate replacement therapy. It is imperative that these patients are treated in centres that can provide full coagulation support, and a comprehensive care plan is formulated for each individual.

Blood Coagulation Disorders, Inherited↗

Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?

Patients with meningococcal disease have increased plasma levels of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha, with higher levels associated with fatal outcome. This study investigated whether polymorphisms in genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and IL-1Ra, are associated with the outcome in patients with meningococcal disease. Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389 controls. The IL-6 -174 G/G and IL-10 -1082 A/A genotypes were more frequent in nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL-10). An association was also found between meningococcal disease and the IL-1RN VNTR polymorphism, but no association was observed with the LTA +252, TNF -308, IL-10 -592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in meningococcal disease.

Adult↗