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David Turner

Publications and source records attributed to David Turner.

At least 19 recordsLinked to original sources
PubMed2025

Evaluating the Antigen and Eplet Accuracy of DQA1 Imputations With the HaploSFHI Two-Field HLA Typing Inference Tool.

Donor/recipient mismatched HLA antigens can lead to the production of Donor-Specific Antibodies by the recipient, which are deleterious to organ transplants. The HLA-DQ locus is the most frequent target, with both the DQ beta and alpha chains involved. For deceased donors in particular, while HLA-DQB1 has been typed in emergencies for a long time, HLA-DQA1 has only recently been included. No imputation algorithmic tool was available to impute HLA-DQA1 until the development of HaploSFHI, trained on 61,393 two-field typings by NGS methods. We evaluated the accuracy of two-field HLA-DQA1 imputation from serological and two-field level HLA-A, B, DRB1, and DQB1 typings. We report a highly accurate two-field HLA-DQA1 prediction using a French test cohort of 7696 individuals, respectively reaching 92.30% and 96.45% accuracy. The average 'False Positive eplet load' stood at 0.19 and 0.07, respectively, and the average 'False Negative eplet load' at 0.18 and 0.08, respectively. A similar performance was obtained on three independent test cohorts of European ancestry (from the USA, the UK, and Portugal). Interestingly, performance was only slightly inferior on five independent test cohorts of other ethnicities (from Hong Kong and the USA) whereas it was significantly lower for two-field DRB1 imputation from its serological level. These results suggest that DQA1 can reliably be imputed even when information is totally missing, with low error risk at both antigen and eplet levels, even if the reference population is not matched. Similar additional initiatives would be welcome to confirm these findings.

Humans↗
PubMed2006

Clinical relevance of cytogenetic abnormalities at diagnosis of acquired aplastic anaemia in adults.

The outcome of 81 adult aplastic anaemia patients who had successful cytogenetics at diagnosis and received immunosuppressive therapy was evaluated. Ten patients had an abnormal karyotype, six of which had a trisomy. Four of five evaluable patients with a trisomy responded. One patient with monosomy 7 achieved a complete response and later developed haemolytic paroxysmal nocturnal haemoglobinuria but no recurrence of monosomy 7. None of the patients with a non-numerical karyotypic abnormality responded. No significant differences in survival or later clonal disorders were observed between patients with a normal karyotype and those with an abnormal karyotype.

Adolescent↗
PubMed2006

Paediatric home care: a systematic review of randomized trials on costs and effectiveness.

OBJECTIVE: To review systematically randomized trials (RCTs) on the effectiveness and costs of paediatric home care. METHODS: National Health Service (NHS) Centre for Reviews and Dissemination guidelines were followed. In all, 20 electronic and other sources were searched, using specially designed strategies. Economic studies and other selected designs were included, but only RCT findings--on service use, clinical outcomes, costs, and impact on the family--are reported here. Analysis is descriptive, with pooled standard mean differences used where meta-analysis was possible. RESULTS: About 1730 identified records up to August 2001 were potentially relevant. In all, 10 RCTs (24 papers) were finally included, covering five types of paediatric home care--for very low birth weight or medically 'fragile' infants, for asthma or diabetes, for technology-dependent children, for mental health, and generic home care. Paediatric home care may enhance physical and mental development for very low birth weight infants and may be cheaper but the evidence is not strong. Home care for diabetes or asthma may reduce parents' costs with some clinical but no social differences noticeable. No randomized trials for technologically dependent children were found. Home care for mental health may increase parental satisfaction with services and reduce some health service and residential care costs. Generic home care showed no clinical effects at early follow-up. Partial follow-up after five years suggested improved psychological adjustment. No cost data were available for this care model. CONCLUSIONS: Despite recent expansion, research evidence from randomized trials for paediatric home care is slight, and methods used are weak in places. Paediatric home care poses practical and ethical questions that cannot be addressed by RCTs.

Costs and Cost Analysis↗
PubMed2006

Randomised controlled trial of near-patient testing for glycated haemoglobin in people with type 2 diabetes mellitus.

BACKGROUND: Tight glycaemic control in people with type 2 diabetes can lead to a reduction in microvascular and possibly macrovascular complications. The use of near-patient (rapid) testing offers a potential method to improve glycaemic control. AIM: To assess the effect and costs of rapid testing for glycated haemoglobin (HbA1c) in people with type 2 diabetes. DESIGN OF STUDY: Pragmatic open randomised controlled trial. SETTING: Eight practices in Leicestershire, UK. METHOD: Patients were randomised to receive instant results for HbA1c or to routine care. The principal outcome measure was the proportion of patients with an HbA1c <7% at 12 months. We also assessed costs for the two groups. RESULTS: Of the 681 patients recruited to the study 638 (94%) were included in the analysis. The mean age at baseline was 65.7 years (SD = 10.8 years) with a median (interquartile range) duration of diabetes of 4(1-8) years. The proportion of patients with HbA1c < 7% did not differ significantly between the intervention and control groups (37 versus 38%, odds ratio 0.95 [95% confidence interval = 0.69 to 1.31]) at 12 months follow up. The total cost for diabetes-related care was 390 UK pounds per patient for the control group and 370 UK pounds for the intervention group. This difference was not statistically significant. CONCLUSION: Near-patient testing for HbA1c alone does not lead to outcome or cost benefits in managing people with type 2 diabetes in primary care. Further research is required into the use of rapid testing as part of an optimised patient management model including arrangements for patient review and testing.

Aged↗
PubMed2005

Practice costs of implementing guidelines for asthma and angina: findings from a randomised controlled trial.

We collected information about the costs of three interventions (dissemination of full guidelines or prioritised review criteria or criteria plus feedback) to improve care of adults with stable angina or asthma within the context of a randomised controlled trial. The cost of criteria with feedback was pound180 per practice compared to pound9.60-31.45 for the other interventions. Total mean costs borne by practices varied between pound838 and pound2127 per practice depending upon disease and intervention type.

Adult↗
PubMed2004

The costs of stress urinary incontinence.

SUI affects individuals' quality of life. It also has resource implications for individuals, health services and society in general. Quantification of these costs can aid decision making by illustrating the size of the problem and identifying conditions and groups for whom large costs are incurred. However, comparatively little is known about these costs as few costing studies have been carried out in the UK and no studies have identified costs by types of urinary incontinence.

Cost of Illness↗
PubMed2004

Comprehensive decision analytical modelling in economic evaluation: a Bayesian approach.

Decision analytical models are widely used in economic evaluation of health care interventions with the objective of generating valuable information to assist health policy decision-makers to allocate scarce health care resources efficiently. The whole decision modelling process can be summarised in four stages: (i) a systematic review of the relevant data (including meta-analyses), (ii) estimation of all inputs into the model (including effectiveness, transition probabilities and costs), (iii) sensitivity analysis for data and model specifications, and (iv) evaluation of the model. The aim of this paper is to demonstrate how the individual components of decision modelling, outlined above, may be addressed simultaneously in one coherent Bayesian model (sometimes known as a comprehensive decision analytical model) and evaluated using Markov Chain Monte Carlo simulation implemented in the specialist software WinBUGS. To illustrate the method described, it is applied to two illustrative examples: (1) The prophylactic use of neurominidase inhibitors for the prevention of influenza. (2) The use of taxanes for the second-line treatment of advanced breast cancer. The advantages of integrating the four stages outlined into one comprehensive decision analytical model, compared to the conventional 'two-stage' approach, are discussed.

Adolescent↗
PubMed2004

Transition programs in cystic fibrosis centers: perceptions of team members.

We previously surveyed cystic fibrosis (CF) center directors and adult patients with CF to assess their perceptions regarding transition from a pediatric to an adult setting. An important finding in those studies was a lack of standard programs for transfer of young adults with CF from pediatric to adult care settings. Patients with CF typically receive care from clinics utilizing a multidisciplinary approach, suggesting that every member of the CF team can impact the transition process. Our purpose in this study was to gain an appreciation for various team members' perspectives on transition. An Internet survey was offered to all CF centers across the country to be completed by team members, excluding physicians. We received 291 completed surveys, nearly half completed by nurses, but our respondents included social workers, nutritionists, respiratory therapists, and a few team members with other training. Nearly half of the respondents work for both pediatric and adult teams. The majority of respondents (71.8%) reported that their adult patients receive care from an internist in a separate adult program, but nearly 20% reported that a pediatrician follows their adult patients. A minority thought that age (37.4% of respondents), marriage (16.2%), and pregnancy (27.1%) were criteria for transfer, though most (86.2%) suggested that patients should be transferred by age 21 years. Criteria precluding transfer included patient/family resistance (45%), disease severity (34%), and developmental delay (31.3%). It was uncommon (11.4%) for an introduction to the concept of transition at the time of diagnosis. Over one-half of patients did not meet the adult team until time of transfer. Team members' perceptions of patients' concerns were similar to what we had previously measured in physicians, again far greater than what we have measured in patients themselves. In many ways, what we have measured here in team members reflects what we have reported by physicians, demonstrating slow development of standard transition programs and an overestimate of patients' concerns regarding transition. These differences may impede the successful transition of patients into an adult program. It is clear from this study that team members have an interest in and opinions on transition, and are likely play a vital role in the transition process. Standard programs of transition should be developed, and team members should be engaged in that process.

Adolescent↗
PubMed2004

D-LogP: an alignment-free 3D description of local lipophilicity for QSAR studies.

The major hurdle to overcome in the development of 3D-QSAR models using steric, electrostatic, or lipophilic "fields" is related to both conformation selection and subsequent suitable overlay (alignment) of compounds. Therefore, it is of some interest to provide a conformationally sensitive lipophilicity descriptor that is alignment-independent. In this chapter we describe the derivation and parametrization of a new descriptor called 3D-LogP and demonstrate both its conformational sensitivity and its effectiveness in QSAR analysis. The 3D-LogP descriptor provides such a representation in the form of a rapidly computable description of the local lipophilicity at points on a user-defined molecular surface.

Computers↗
PubMed2004

844ins68 in the cystathionine beta-synthase gene in Israel and review of its distribution in the world.

The 844ins68 allele in the cystathionine beta-synthase gene is always found in cis with the T833C mutation further indicating that its origin is monophyletic and that it might be a useful anthropogenetic marker. Its frequency was examined in 1087 randomly chosen subjects from Israel (twelve Jewish communities and Palestinians), and found to range from 0.034 to 0.125. The heterogeneity among the Jewish communities spans most of the range encountered among Caucasoid populations and is in accordance both with other genetic markers examined in the Jewish communities and with genetic distance and discriminant analyses. 844ins68 cannot distinguish between various European regions, because of the marked heterogeneity of the allele frequency distribution in Europe. This distribution of the insertion does not follow a recognised pattern of any known colonisation process. Its use as a reliable anthropogenetic marker discriminating between the major human groups may also be problematic until more populations are sampled.

Arabs↗
PubMed2003

Irradiation reduces interstitial fluid transport and increases the collagen content in tumors.

PURPOSE: We have shown that the interstitial diffusion of large molecules is significantly hindered in tumors with high collagen levels. Because large therapeutic agents (e.g., monoclonal antibodies and viral vectors) will be combined with radiation or chemotherapy, it is significant to determine how cytotoxic therapies modify the transport and composition of the interstitial space in tumors. To test the hypothesis that radiation alters tumor interstitial transport, we measured tumor hydraulic conductivity (K) and hyaluronan and collagen type I levels after irradiation. EXPERIMENTAL DESIGN: K and the quantification of interstitial matrix components were determined in sections of s.c. implants of the human colon adenocarcinoma LS174T. K was measured on days 1 and 5 after 10 Gy of irradiation or on day 5 after 30 Gy of irradiation. RESULTS: Compared with control tumors, K decreased by approximately 12-fold after 10 or 30 Gy of irradiation on day 5. At 24 h after irradiation with 10 Gy, the decrease in K was not significant. Five days after 10 and 30 Gy of irradiation, the decrease in K was associated with significantly higher levels of collagen type I. The collagen type I content was not changed 24 h after irradiation with 10 Gy. Irradiation did not significantly increase hyaluronan levels in LS174T tumors. CONCLUSIONS: After irradiation, the decrease in K and increase in collagen type I levels could significantly hinder the convective movement and diffusion of large therapeutic agents in tumors.

Adenocarcinoma↗
PubMed2003

The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity.

Cytotoxicity of methylating agents is caused mostly by methylation of the O6 position of guanine in DNA to form O6-methylguanine (O6-meG). O6-meG can direct misincorporation of thymine during replication, generating O6-meG:T mismatches. Recognition of these mispairs by the mismatch repair (MMR) system leads to cell cycle arrest and apoptosis. MMR also modulates sensitivity to other antitumor drugs. The base excision repair (BER) enzyme MED1 (also known as MBD4) interacts with the MMR protein MLH1. MED1 was found to exhibit thymine glycosylase activity on O6-meG:T mismatches. To examine the biological significance of this activity, we generated mice with targeted inactivation of the Med1 gene and prepared mouse embryonic fibroblasts (MEF) with different Med1 genotype. Unlike wild-type and heterozygous cultures, Med1-/- MEF failed to undergo G2-M cell cycle arrest and apoptosis upon treatment with the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Similar results were obtained with platinum compounds' 5-fluorouracil and irinotecan. As is the case with MMR-defective cells, resistance of Med1-/- MEF to MNNG was due to a tolerance mechanism because DNA damage accumulated but did not elicit checkpoint activation. Interestingly, steady state amounts of several MMR proteins are reduced in Med1-/- MEF, in comparison with Med1+/+ and Med1+/- MEF. We conclude that MED1 has an additional role in DNA damage response to antitumor agents and is associated with integrity of the MMR system. MED1 defects (much like MMR defects) may impair cell cycle arrest and apoptosis induced by DNA damage.

Animals↗
PubMed2003

Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials.

OBJECTIVE: To review the clinical effectiveness of oseltamivir and zanamivir for the treatment and prevention of influenza A and B. DESIGN: Systematic review and meta-analyses of randomised controlled trials. DATA SOURCES: Published studies were retrieved from electronic bibliographic databases; supplementary data were obtained from the manufacturers. SELECTION OF STUDIES: Randomised controlled, double blind trials that were published in English, had data available before 31 December 2001, evaluated treatment or prevention of naturally occurring influenza with zanamivir or oseltamivir (if given using the formulation and dosage licensed for clinical use), and reported at least one end point of relevance. REVIEW METHODS: The main outcome measures were the median time to the alleviation of symptoms (for treatment trials) and number of flu episodes avoided (for prevention trials). Three population groups were defined: children aged 12 years and under; otherwise healthy individuals aged 12 to 65 years; and "high risk" individuals (those with certain chronic medical conditions or aged 65 years and older). RESULTS: Seventeen treatment trials and seven prevention trials identified met the inclusion criteria. All trials included compared one of the drugs against placebo or standard care. Treatment of children, otherwise healthy individuals, and high risk populations with zanamivir reduced the median duration of symptoms in days respectively by 1.0 (95% confidence interval 0.5 to 1.5), 0.8 (0.3 to 1.3), and 0.9 (-0.1 to 1.9) for the intention to treat population. The corresponding results, in days, for oseltamivir were 0.9 (0.3 to 1.5), 0.9 (0.3 to 1.4), and 0.4 (-0.7 to 1.4). The effect of giving zanamivir and oseltamivir prophylactically resulted in a relative reduction of 70-90% in the odds of developing flu, depending on the strategy adopted and the population studied. CONCLUSIONS: Evidence from randomised controlled trials consistently supports the view that both oseltamivir and zanamivir are clinically effective for treating and preventing flu. However, evidence is limited for the treatment of certain populations and for all prevention strategies.

Acetamides↗
PubMed2003

Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course.

Huntington disease is caused by a dominantly transmitted CAG repeat expansion mutation that is believed to confer a toxic gain of function on the mutant protein. Huntington disease patients with two mutant alleles are very rare. In other poly(CAG) diseases such as the dominant ataxias, inheritance of two mutant alleles causes a phenotype more severe than in heterozygotes. In this multicentre study, we sought differences in the disease features between eight homozygotes and 75 heterozygotes for the Huntington disease mutation. We identified subjects homozygous for the Huntington disease mutation by DNA testing and compared their clinical features (age at onset, symptom presentation, disease severity and disease progression) with those of a group of heterozygotes, who were assessed longitudinally. The age at onset of symptoms in the homozygote cases was within the range expected for heterozygotes with the same CAG repeat lengths, whereas homozygotes had a more severe clinical course. The observation of a more rapid decline in motor, cognitive and behavioural symptoms in homozygotes was consistent with the extent of neurodegeneration as available at imaging in three patients, and at the post-mortem neuropathological report in one case. Our analysis suggests that although homozygosity for the Huntington disease mutation does not lower the age at onset of symptoms, it affects the phenotype and the rate of disease progression. These data, once confirmed in a larger series of patients, point to the possibility that the mechanisms underlying age at onset and disease progression in Huntington disease may differ.

Adolescent↗
PubMed2002

Typing of multiple single nucleotide polymorphisms in cytokine and receptor genes using SNaPshot.

Associations have been described between polymorphisms in cytokine genes and severity of autoimmune diseases, outcome of infectious disease, and outcome following transplantation. Many methods now exist for typing single nucleotide polymorphisms (SNPs) and these can be applied to typing cytokine gene and cytokine receptor gene variation. A system for typing multiple cytokine and receptor gene polymorphisms using a primer extension method, SNaPshot (Applied Biosystems, Foster City, CA, USA), has been assessed. The development of this methodology may enable other laboratories to type for cytokine SNPs in different populations and facilitate research into the effect of genetic polymorphism in the cytokine network in transplantation and disease.

Adult↗
PubMedDate not supplied

A vision for older adults and health promotion.

Our rapidly aging population is expected to place heavy demands on all segments of society, particularly the health care resources needed to attend to health concerns associated with aging. Is this a looming crisis, as some predict, or a challenge to use resources more wisely and to help older adults and their caregivers share in the responsibility for health promotion and chronic disease self-management activities? Community-based organizations serving older adults are uniquely positioned to augment health care providers' health promotion counseling activities and to bridge the gap between the research and practice of health promotion in older adults. They already play a crucial role by providing appropriate health promotion education, screening and referral, service planning, and reinforcement to facilitate self-care activities and behavior changes that promote healthy aging. By increasing teamwork across the network of services for the aging, the health sector, public and private organizations, and academe, there is a great opportunity to enhance the health and well-being of all older Americans.

Aged↗
PubMedDate not supplied

Actual time required for dynamic fluoroscopic intraoperative cholangiography.

OBJECTIVES: This study was undertaken to determine the actual amount of time a dynamic fluoroscopic intraoperative cholangiogram adds to a laparoscopic cholecystectomy. A secondary objective was to define the information gained from this procedure. METHODS: A consecutive case study of 52 patients undergoing laparoscopic cholecystectomy was used. Time was recorded from placement of a laparoscopic hemoclip across the cystic duct at its junction with the gallbladder until successful completion of the intraoperative cholangiogram. The mean, median, and range of times for these cases, as well as the results and false-negative rates, were determined. RESULTS: Cholangiography was successfully completed in 96% of patients. The mean time added to laparoscopic cholecystectomy by the addition of dynamic fluoroscopic intraoperative cholangiography was 4.3 minutes. The median time was 3.0 minutes. The times ranged from 2.0 minutes to 16.0 minutes. Choledocholithiasis was present in 15.4% of these patients. The false-positive rate was zero in this study. CONCLUSIONS: Dynamic fluoroscopic intraoperative cholangiogram was fast and efficient. The information gained was significant in that 15% of patients proceeded on to laparoscopic common bile duct exploration. We conclude that intraoperative cholangiography should be a routine addition to laparoscopic cholecystectomy.

Cholangiography↗