Biomedical subjects

P McEwan

Publications and source records attributed to P McEwan.

At least 19 recordsLinked to original sources

PubMed2006

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↗

PubMed2005

Evaluation of survival and ischaemic and thromboembolic event rates in patients with non-valvar atrial fibrillation in the general population when treated and untreated with warfarin.

OBJECTIVE: To compare survival and adverse outcome of patients with non-valvar atrial fibrillation (NVAF) treated with or without warfarin. DESIGN: Record linkage method to identify patients with a previous hospital diagnosis of atrial fibrillation and to link these patients to international normalised ratio (INR) test results and mortality data. SETTING: Cardiff and the Vale of Glamorgan, Wales. MAIN OUTCOME MEASURES: Mortality, specifically from ischaemic and thromboembolic events. RESULTS: 6108 patients were identified with NVAF, of whom 36.4% received warfarin. Mean survival in the warfarin and non-warfarin groups was 52.0 months and 38.2 months, respectively (p < 0.001), and 14.4 months (p < 0.001) after adjustment for confounding factors. Warfarin treated patients in the upper quartile of INR control had significantly longer survival (57.5 months) than did those in the lowest quartile of control (38.1 months, p < 0.001). The risk of stroke in the warfarin group when treated was lower than that in the non-warfarin group (relative rate (RR) 0.74, p < 0.001). The risk of death from ischaemic stroke was lower in the warfarin group (RR 0.43, p < 0.001). The risk of all ischaemic and embolic events in the warfarin group was lower when they were taking warfarin (RR 0.74, p < 0.001). The risk of bleeding in the warfarin group when treated was greater (RR 1.78, p = 0.001). CONCLUSIONS: Patients with NVAF within the recommended target INR range of 2.0-3.0 survive longer and have reduced morbidity. Probably too few people are anticoagulated with warfarin in NVAF.

Aged↗

PubMed2005

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas.

OBJECTIVE: Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long-term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment-naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal. DESIGN: Retrospective analysis of clinic records of 89 patients (mean age 32.7 +/- 8.4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0.5-3 mg weekly) or bromocriptine (n = 22) (2.5-10 mg daily) for a mean duration of 3.1 years. RESULTS: Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9.6 months (range 1-44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3.6 years, range 1-7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation. CONCLUSIONS: This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long-term remission in 30-40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.

Adolescent↗

PubMed2005

Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population.

OBJECTIVE: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0-3.0 and to explore the relation between achieved INR control and clinical outcomes. DESIGN: Record linkage study of routine activity records and INR measurements. SETTING: Cardiff and the Vale of Glamorgan, South Wales, UK. PARTICIPANTS: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements. MAIN OUTCOME MEASURES: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring. RESULTS: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range. CONCLUSIONS: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.

Aged↗

PubMed2004

Nasal versus oral route for placing feeding tubes in preterm or low birth weight infants.

BACKGROUND: Enteral feeding tubes for preterm or low birth weight infants may be placed via either the nose or mouth. Nasal placement may compromise respiration. However, orally placed tubes may be more prone to displacement, local irritation, and vagal stimulation. OBJECTIVES: To assess the available evidence from randomised controlled trials concerning the effects of nasally placed compared with orally placed feeding tubes on growth and development, and the incidence of adverse consequences in preterm or low birth weight infants. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 - April 2004), EMBASE (1988 - April 2004), and CINAHL (1982- April 2004), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared the use of the nasal versus oral route for placing feeding tubes in preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and analysis of data using relative risk, risk difference and mean difference. MAIN RESULTS: We found only one eligible trial. Forty-two infants participated in the study. This primary aim of the trial was to assess the effect of oral versus nasal placement of feeding tubes on the incidence of apnea and periodic breathing in preterm infants. The trial did not report data on the pre-specified primary outcomes for this review (growth and development). REVIEWERS' CONCLUSIONS: There are insufficient data available to inform practice. A large randomised controlled trial is required to determine if the use of nasally placed feeding tubes compared with orally placed feeding tubes improves growth and development, without increasing adverse consequences in preterm or low birth weight infants.

Enteral Nutrition↗

PubMed2004

Evaluation of the future supply and demand for blood products in the United Kingdom National Health Service.

In addition to the clinical management of blood supplies, the UK National Blood Service (NBS) examines short-term supply and demand to predict any potential shortages in blood supplies. However, very little data are available on the medium- and long-term trends. This paper describes blood product use in a United Kingdom Hospital Trust in 1999 and combines it with donor information to project the effect of demographic changes on demand and supply over the next 25 years. Overall, 2801 (4%) inpatients received transfusions of blood products. The proportion of inpatients receiving blood products increased with age. Patients aged >70 years used 46% of the total blood product supply, whereas patients aged <30 years used 10%. The estimated total cost associated with blood product use was pound 2 million during 1999 (2001-2002 prices). The results show that within 20 years, demand for blood products is expected to increase by 20% relative to the supply. The estimates in this study are a valuable aid to better long-term planning of supplies. As there is a paucity of data concerning blood product use in UK hospitals and blood use varies greatly between hospitals, further studies are required to guide blood product use policy.

Adult↗

PubMed2004

Evaluating the performance of the Framingham risk equations in a population with diabetes.

AIMS: The Framingham risk equations are widely used to estimate risk of coronary heart disease (CHD). The purpose of this study was to evaluate the reliability of these equations in predicting CHD risk in people with diabetes and the reliability of using imputed mean HDL-cholesterol values. METHODS: Data describing the baseline characteristics of recognized CHD risk factors for 938 people aged 30-74 years were extracted from the Cardiff Diabetes Database. Data describing CHD events were available for up to 4 years following the baseline year (1996). Several mathematical techniques were used to assess the reliability of predictions provided by the Framingham equations in this population. RESULTS: Thirty-four percent of males and 25% of females who experienced CHD events had a predicted 10-year CHD risk >/= 30%. Seventy-five percent of males and 58% of females had a predicted 10-year CHD risk >/= 20%. Using imputed HDL-cholesterol values, 26% of males and 6% of females who later developed CHD events had a 10-year CHD risk >/= 30%. Using imputed HDL-cholesterol values, the CHD risk predicted by the Framingham equations consistently underestimated the actual risk of CHD events. However, refitting the Framingham risk equations to the Cardiff data resulted in only marginal improvements in discriminatory capabilities. CONCLUSIONS: The Framingham risk equations can be unreliable when applied to the diabetic population, tending to underestimate an individual's probability of progressing to CHD; the equations perform marginally better in women than in men. The use of imputed mean HDL-cholesterol values improved the reliability of the estimates of risk.

Adult↗

PubMed2004

Systematic review of transpyloric versus gastric tube feeding for preterm infants.

AIM: To determine if enteral tube feeding by the transpyloric versus the gastric route improves feeding tolerance, and growth and development, without increasing adverse events, in preterm infants. METHODS: Systematic review of randomised controlled trials. A search was made of the Cochrane Controlled Trials Register (CCTR; 2003, issue 1), Medline (1966 to April 2003), and Embase (1980 to April 2003), and references in previous reviews. The data were extracted, analysed, and synthesised using the standard methods of the Cochrane Neonatal Collaborative Review Group. RESULTS: Data were found from eight trials. No evidence of an effect on growth or development was found, but transpyloric feeding was associated with a greater incidence of gastrointestinal disturbance: relative risk (RR) 1.45, 95% confidence interval (CI) 1.05 to 2.09. Transpyloric feeding was also associated with increased mortality: RR 2.46, 95% CI 1.36 to 4.46. However, the trial that contributed most to this finding may have been affected by allocation bias. No significant differences were detected in the incidence of other adverse events, including necrotising enterocolitis, intestinal perforation, and aspiration pneumonia. CONCLUSIONS: No evidence of benefit was found, but evidence of harm was found. Feeding by the transpyloric route cannot be recommended for preterm infants.

Enteral Nutrition↗

PubMed2002

Transpyloric versus gastric tube feeding for preterm infants.

BACKGROUND: Enteral feeding tubes for preterm infants may be placed in the stomach (gastric tube feeding) or in the upper small bowel (transpyloric tube feeding). There are potential advantages and disadvantages to both routes. OBJECTIVES: In preterm infants who require enteral tube feeding, does feeding via the transpyloric route versus the gastric route improve feeding tolerance, and growth and development, without increasing adverse consequences? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included electronic searches of MEDLINE and EMBASE (up to December 2001) and of The Cochrane Controlled Trials Register in The Cochrane Library (Issue 3, 2001), and searches of the references in previous reviews including cross references. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing transpyloric with gastric tube feeding in preterm infants. DATA COLLECTION AND ANALYSIS: Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. MAIN RESULTS: Data from eight trials were available. We did not find any evidence of an effect on growth rates: short term weight gain, weighted mean difference -0.7 g/week (95% confidence interval -25.2, 23.8); short term increase in crown heel length, weighted mean difference -0.7 mm/week (95% confidence interval -2.4, 1.0); short term increase in head circumference, weighted mean difference 0.6 mm/wk (95% confidence interval -0.9, 2.1). Longer term growth was reported in one study. There were not any statistically significant differences between the groups in the mean body weight or occipitofrontal head circumference at three months or at six months corrected age. None of the included studies provided data on neurodevelopmental outcomes during infancy or beyond. Transpyloric feeding was associated with a greater incidence of gastro-intestinal disturbance, RR 1.45, 95% CI 1.05, 2.09. There was some evidence that feeding via the transpyloric route increased mortality, RR 2.46, 95% CI 1.36, 4.46; however, the outcomes of the study that contributed most to this finding were likely to have been affected by selective allocation of the less mature and sicker infants to transpyloric feeding. We did not detect any statistically significant differences in the incidence of other adverse events, including necrotising enterocolitis, intestinal perforation, and aspiration pneumonia. REVIEWER'S CONCLUSIONS: We did not find any evidence of benefit, but did find evidence of adverse effects, of transpyloric feeding in preterm infants. Feeding via the transpyloric route cannot be recommended for preterm infants.

Enteral Nutrition↗

PubMed2001

In vivo analysis of porcine endogenous retrovirus expression in transgenic pigs.

Xenotransplantation offers a potential solution to the shortage of donor organs for allotransplantation. In vitro studies that demonstrate the transmission of porcine endogenous retroviruses (PERV) from porcine cells to human cells and cell lines have raised concerns regarding the potential transmission of PERV to both xenograft recipients and their contacts (1-4). While no evidence of infection has been detected in any patients who have been treated with a variety of different porcine tissues (5-8), two studies have shown that severe combined immunodeficient (SCID) mice can be infected by PERV after the transplantation of porcine islets (9-10). To further address the concerns of PERV, expression of this virus in tissues and serum from transgenic pigs that express human decay accelerating factor was investigated. Although viral mRNA expression was detected in a variety of tissues, no evidence of viral release was observed in any of the porcine tissues analyzed by transmission electron microscopy. Analysis of porcine serum using the product-based reverse transcriptase assay suggested that virions may be present in porcine serum from large white pigs. However, using methods based on those previously described by Wilson et al. (4), infectious virus was not detected when activated peripheral blood mononuclear cells from these pigs were cocultivated with human cells known to be permissive for PERV.

Animals↗

PubMed2001

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Animals↗

PubMed2001

Short report: Hyperammonaemia in critically ill septic infants.

Three infants with subphrenic abscess, pyonephrosis, and obstructive ureterocoele respectively had grossly increased concentrations of plasma ammonia. This was considered to be a result of infections with urea splitting organisms. All died in spite of intensive care support, including specific measures to reduce plasma ammonia.

Ammonia↗

PubMed2000

Eight hundred-base sequencing in a microfabricated electrophoretic device.

The human genome will be sequenced using capillary array electrophoresis technology. Although currently achieving only 550 base reads per run, capillary arrays have increased the efficiency and lowered the cost of sequencing by eliminating gel plate preparation, reducing sample volumes, and offering automation and speed. However, much higher throughput and greater cost reductions are needed. The next major advancement in sequencing technology is expected from the development of arrays of microfabricated channels in a plate or "chip" format. For de novo sequencing, the practical utility of the microdevice approach has been limited by device length to a read of 500-600 bases per run. We demonstrate a significant milestone for a microfabricated device by obtaining an average read length of 800 bases in 80 min (98% accuracy) for either M13 standards or DNA sequencing samples from the Whitehead Institute Center for Genomic Research (WICGR) production line. This result is achieved in 40-cm-long channels using a new class of large-scale microfabricated devices. Both microfabrication of extended structures and achievement of long reads are essential steps toward a 384-lane very-large-scale microfluidic (VLSMF) system for ultrahigh-throughput DNA sequencing analysis, currently under construction in our laboratory.

Base Sequence↗

PubMed1999

Ejection fraction by radionuclide ventriculography and contrast left ventriculogram. A tale of two techniques. SAVE Investigators. Survival and Ventricular Enlargement.

OBJECTIVES: We assessed the abilities of two methods to measure ejection fraction (EF)-radionuclide ventriculography (RVG) and contrast left ventriculography (Cath-EFa) to predict cardiovascular events. BACKGROUND: Both RVG and Cath-EFa are commonly used methods to measure left ventricular performance and assess prognosis. Their comparative abilities to predict clinical events have not been reported. METHODS: Both RVG EF and Cath-EFa were measured within 16 days of myocardial infarction (MI) in 688 patients. The results were divided into terciles. Prognosis by terciles was assessed for each technique. A multivariate analysis was performed to determine which EF measurement was a better predictor of prognosis. RESULTS: Average RVG-EF was 32%+/-7, while Cath-EFa was 42%+/-10. Both RVG and Cath-EFa were poorly correlated (R=0.42). Event rate declined across terciles with increasing EF for both techniques (events in lowest to highest tercile of Cath-EFa 40.7%, 25.9%, 11.6%, p < 0.001; and RVG-EF 39.9%, 26.1%, 15.6%, p < 0.001). There was concordance of terciles in 303 of 688 patients (44%). When patients in the highest RVG terciles were in the highest Cath-EFa tercile, the event rate was 7%. However, when patients in the highest RVG terciles were in the lowest Cath-EFa tercile, the event rate was 19%. Both Cath-EFa (p < 0.001) and RVG-EF (p < 0.001) were independent predictors of cardiovascular events. CONCLUSIONS: Ejection fraction measured by RVG or during catheterization is a valuable tool in the risk stratification of postinfarct patients. When disagreement is present between clinical impression and measurement by either method, the use of an alternative measurement is warranted and complementary.

Adult↗

PubMed1999

Toward real-world sequencing by microdevice electrophoresis.

We report results using a microdevice for DNA sequencing using samples from chromosome 17, obtained from the Whitehead Institute Center for Genome Research (WICGR) production line. The device had an effective separation distance of 11.5 cm and a lithographically defined injection width of 150 microm. The four-color raw data were processed, base-called by the sequencing software Trout, and compared to the corresponding ABI 377 sequence from WICGR. With a criteria of 99% accuracy, we achieved average continuous reads of 505 bases in 27 min with 3% linear polyacrylamide (LPA) at 150 V/cm, and 460 bases in 22 min with 4% LPA at 200 V/cm at a temperature of 45 degrees C. In the best case, up to 565 bases could be base-called with the same accuracy in <25 min. In some instances, Trout allowed for accurate base-calling down to a resolution R as low as R = 0.35. This may be due in part to the high signal-to-noise ratio of the microdevice. Unlike many results reported on capillary machines, no additional sample cleanup other than ethanol precipitation was required. In addition, DNA fragment biasing (i.e., discrimination against larger fragments) was reduced significantly through the unique sample injection mechanism of the microfabricated device. This led to increased signal strength for long fragments, which is of great importance for the high performance of the microdevice.

Base Sequence↗

PubMed1997

Sotalol-induced torsades de pointes in patients with renal failure.

The risk of torsades de pointes in patients on sotalol is increased in the setting of renal failure. QT dispersion and prolonged QT intervals have been described as markers for pro-arrhythmia. Four cases of torsades de pointes caused by low dose sotalol in patients with renal failure are reported. All four cases demonstrated that the 12-lead electrocardiogram, with markedly prolonged QT intervals and increased QT dispersion, could have been used to predict pro-arrhythmia.

Adrenergic beta-Antagonists↗

PubMed1996

Proximal narrowing of anomalous right coronary artery from the left coronary sinus: delineation by omniplane transesophageal echocardiogram.

Anomalous origin of the right coronary artery from the left sinus of Valsalva is a serious and potentially fatal, albeit rare, congenital abnormality. It can be associated with marked functional impairment and even sudden death. Transesophageal echocardiography can identify and confirm the course of aberrant coronary arteries and their relationship to the great vessels, as is demonstrated in this report of a 51-year-old female presenting with anomalous right coronary artery with narrowing of its proximal portion.

Cineangiography↗

PubMed1995

Vascular structure, smooth muscle cell phenotype and growth in hypertension.

The media of most blood vessels is occupied by vascular smooth muscle cells. In areas they may be replaced by glomus cells, pericytes or renin-secreting myoepithelioid cells. These cells may be regarded as phenotypic variants of vascular smooth muscle cells. In disease, ordinary vascular smooth muscle cells may also assume a spectrum of phenotypes ranging from contractile to largely secretory types. Therefore, the phenotype of smooth muscle cells that is involved in a disease process such as hypertension or one of its complications is likely to affect the structural outcome in blood vessels.

Aging↗