Accuracy of reporting cardiac related events during long term follow up.
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Coronary Artery Bypass↗
Biomedical subjects
B Reeves
Publications and source records attributed to B Reeves.
Successful treatment of empyema thoracis with human recombinant deoxyribonuclease.
Fibrinolytic enzymes, particularly streptokinase, are now widely used to treat empyema thoracis. Recent in vitro evidence suggests that streptokinase has no effect on pus viscosity but that deoxyribonuclease (DNase) reduces the viscosity of pus. We report the first use of human recombinant DNase given intrapleurally to treat an empyema which had not resolved after standard treatment with streptokinase.
Aged↗
The National Liver Transplantation audit: an overview of patients presenting for liver transplantation from 1994 to 1998. On behalf of the Steering Group of the UK Liver Transplantation Audit.
BACKGROUND: The aim of this study was to describe current clinical practice in liver transplantation in the UK and Ireland, to provide overall 1-year graft and patient survival rates, and to study some preoperative risk factors. METHODS: All patients receiving a liver transplant in the UK or Ireland between 1 March 1994 and 30 September 1998 were included. Data were collected on patients at the time of transplantation, 3 months after grafting and annually thereafter until the patient's death. The main outcome measures were graft and patient survival at 1 year. RESULTS: A total of 3102 liver transplants were carried out, of which 87 per cent were first transplants. The mean age at first transplantation was 42 (range 0-76) years. The most common indications for transplantation were primary biliary cirrhosis, alcoholic cirrhosis and posthepatitis C cirrhosis, but variations existed between sexes and centres. Risk factors associated with lower graft and patient survival were the presence of acute disease, being transplanted from hospital, and the need for renal and/or ventilatory support before operation. CONCLUSION: Donor and recipient demographics are consistent with data held by the European Liver Transplant Registry, as are 1-year graft and patient survival rates. Variation across centres in factors such as the primary indication for liver transplantation, population demographics, the clinical status of each patient, incidence of retransplantation and other risk factors contributes to the problem of adjusting for case mix.
Adolescent↗
Development and validation of a questionnaire to evaluate the effectiveness of evidence-based practice teaching.
AIM: The aim of this study was to develop and validate a questionnaire to evaluate the effectiveness of evidence-based practice (EBP) teaching. METHODS: The 152 questionnaires completed by health care professionals with a range of EBP experience were used in this study. Cronbach's alpha for the knowledge and attitude questions indicated a satisfactory level of internal consistency (i.e. >0.60). RESULTS: The discriminative validity was evidenced by a statistically significant difference in the knowledge and attitude scores of 'novices' (i.e. little or no prior EBP education) compared with 'experts' (i.e. health care professionals and academics currently teaching EBP). Moderate to good (> or =0.4) sensitivity index scores were observed for both knowledge and attitude scores as the result of comparing individuals before and after an EBP intervention. CONCLUSIONS: The results of this validation study indicate that the developed questionnaire is a satisfactory tool with which to evaluate the effectiveness of EBP teaching interventions.
Education, Medical↗
Randomised controlled trial of an integrated versus an optometric low vision rehabilitation service for patients with age-related macular degeneration: study design and methodology.
A number of studies have measured the outcomes of low vision care but these have usually been longitudinal case series, thus constituting very low quality of evidence for effectiveness. To date, there have been no randomised controlled trials (RCTs) which have evaluated the effectiveness and cost effectiveness of different models of care in low vision. The size of the low vision population and the paucity of systematic evaluation have created a pressing need for evidence about cost-effectiveness in order to inform service developments for low vision rehabilitation. This paper describes the study design and methodology of a three-arm RCT currently under way in Manchester. The baseline population recruited is also described. A traditional hospital-based optometric service is being compared with an integrated service (comprising the addition of community-based rehabilitation officer input) and with more generic community input (which is non-integrated and is not vision specific). A wide range of outcome measures are being assessed at recruitment and 12 months post-intervention, including low vision specific and generic quality of life measures, patterns of low vision aid use, and task performance. The rationale for the trial is discussed and the main study outcomes are described.
Aged↗
Triphenylsilyl as a protecting group in the synthesis of 1, 12-heterodisubstituted p-carboranes
A triphenylsilyl group is used as an auxiliary in the synthesis of heterodisubstituted p-carboranes via triphenylsilyl-p-carborane (1). The preparation of 1 is statistical, but with recovery of the starting p-carborane, the effective conversion to 1 is about 90%. Carborane 1 has been easily converted to its lithium and copper derivatives, which were reacted with a range of electrophiles including alkyl halides: an aryl iodide, an acetylene bromide, and a sulfenyl chloride. The derivatives of 1 are crystalline and UV active, which facilitates their isolation and purification. The Ph(3)Si group is efficiently removed with fluoride to give monosubstituted p-carboranes I, which upon further nucleophilic substitution yield p-carboranes II. The yields of heterodisubstituted products II are higher than for direct, "statistical" syntheses. For example, 12-pentyl-1, 12-dicarba-closo-dodecaborane-1-carboxylic acid was synthesized from p-carborane via 1 in 62% overall yield, a considerable improvement over the 44% yield obtained by direct methods.
Journal Article↗
Linear discriminant analysis of symptoms in patients with chronic constipation: validation of a new scoring system (KESS).
PURPOSE: The aim of this study was to devise a symptom scoring system to assist in diagnosing constipation and in discriminating among pathophysiologic subgroups. METHOD: A structured symptom scoring questionnaire (11 questions) was completed by 71 chronically constipated patients and by 20 asymptomatic controls. The symptom score was correlated with a previously validated constipation score (Cleveland Clinic Score). All patients underwent colonic transit studies, standard anorectal physiology testing, and evacuation proctography. On the basis of these investigations alone, an observer blinded to the questionnaire results allocated patients to one of three pathophysiologic subgroups: slow-transit constipation, rectal evacuatory disorder, or mixed (slow-transit constipation and rectal evacuatory disorder). Linear discriminant analysis was used to assess the ability of different questionnaire symptoms to discriminate among these subgroups. RESULTS: Total symptom score was strongly correlated with the Cleveland Clinic Score (r = 0.9). The median total score in constipated patients was 20 (range, 11-35) compared with a median of 2 in controls (range, 0-6). Discriminant analysis using cross validation estimated that pathophysiology could be predicted correctly for 55 percent (95 percent confidence interval = 43-67 percent) of patients using just five symptoms. The discriminant function rarely misclassified patients with rectal evacuatory disorder as slow-transit constipation and vice versa, but could not effectively discriminate between patients with single and mixed pathologies. CONCLUSION: This new scoring system is a valid technique to assist in the diagnosis of constipation and is the first study using appropriate statistical methodology to demonstrate a discriminatory ability of multiple symptoms in constipation. At present, symptom analysis does not adequately differentiate major pathophysiologic subgroups for use in clinical practice.
Adult↗
The sensitivity and specificity of direct ophthalmoscopic optic disc assessment in screening for glaucoma: a multivariate analysis.
BACKGROUND: Previous studies have shown that the cup:disc (C/D) ratio has limited sensitivity and specificity. Improved sensitivity and specificity has been found with combinations of disc parameters using stereophotography or disc imaging, but the extent to which these studies reflect what can be achieved by direct assessment is unclear. The purpose of this paper is to report the sensitivities and specificities of a range of disc parameters, both in isolation and in combination, as graded during clinical examination with direct ophthalmoscopy. METHODS: Sixty-seven patients with newly diagnosed primary open angle glaucoma and 145 non-glaucomatous subjects were examined by direct ophthalmoscopy. The following features of the optic disc were graded: vertical and horizontal C/D ratios (uncorrected for disc size), narrowest rim width, presence/absence of disc haemorrhage, focal pallor of the neuroretinal rim, parapapillary atrophy, steepness of the cup-edge and presence/absence of baring of the lamina cribrosa. Subjects were validated as glaucomatous/non-glaucomatous on the basis of visual fields, independently of the results of optic disc gradings. Multiple logistic regression modelling was used to evaluate the effectiveness of combinations of disc parameters. RESULTS: Sensitivities and specificities are limited for all features when considered in isolation. The 'cupping' parameters have the highest sensitivities and specificities but no single cut-off criterion for these parameters has both high sensitivity and specificity. Multiple logistic regression modelling indicated that two disc parameters in combination, narrowest rim width and parapapillary atrophy, were independently associated with glaucoma and achieved best prediction. Combining information from these parameters achieved a sensitivity of 81% (95% CI = 69-89%) and a specificity of 90% (95% CI = 84-95%), a level of discrimination that is not significantly better than narrowest rim width alone in terms of area under the receiver operator characteristic (ROC) curve. CONCLUSION: Disc assessment during clinical examination with direct ophthalmoscopy can achieve comparable sensitivities and specificities with those previously reported for stereophotographic assessment or visual fields screening. However, since the diagnostic accuracy of disc assessment in isolation is inadequate for screening, a combined test strategy is necessary.
Adult↗
Impulsiveness, serotonin genes and repetition of deliberate self-harm (DSH).
BACKGROUND: Few studies have investigated independent associations of psychological, biological and social variables with repeated deliberate self-harm (DSH). Serotonin function has been linked to impulsive and suicidal behaviour and genetic polymorphisms have been identified within the serotonin system that could account for this link. This study tested hypotheses linking impulsiveness, genetic polymorphisms of tryptophan hydroxylase (TPH) and the 5-HT2c receptor and repeated DSH. METHODS: Individuals presenting after DSH were interviewed, completed personality questionnaires and gave venous blood samples. Genotypes were determined for TPH intron7 and 5-HT2c (cys-ser) polymorphisms. Follow-up to identify repetition of DSH was for 1 year. RESULTS: Males with the 5-HT2c serine variant were more impulsive than those with the cysteine variant (039 standardized units, P = 0.041, 95% CI 0.017 to 0.076). There was no association between impulsiveness and the TPH intron7 polymorphism overall but a weak association with the L allele in men (0.41 standardized units, P = 0.05, 95 % CI 0.001 to 0.82). Impulsiveness, although high in the group as a whole, did not distinguish those who repeated DSH. CONCLUSIONS: The personality trait of impulsiveness may in part be related to genotypes of the 5-HT2c receptor and TPH gene in men. Impulsiveness does not differ between those who do and do not repeat DSH.
Adult↗
A systematic review of the effectiveness of critical appraisal skills training for clinicians.
The aim of this paper is to undertake a descriptive systematic review of the effectiveness of critical appraisal skills training for clinicians. Of the 10 controlled studies which examined this issue and were found to meet the eligibility criteria of this review, all used a study population of either medical students or doctors in training. The studies used a variety of different intervention 'dosages' and reported a range of outcomes. These included participants' knowledge of epidemiology/biostatistics, their attitudes towards medical literature, their ability to appraise medical literature, and medical literature reading behaviour. An overall improvement in assessed outcomes of 68% was reported after critical appraisal skills training, particularly in knowledge relating to epidemiology and biostatistics. This review appears to provide some evidence of the benefit of teaching critical appraisal skills to clinicians, in terms of both knowledge of methodological/statistical issues in clinical research and attitudes to medical literature. However, these findings should be considered with caution as the methodological quality of studies was generally poor, with only one study employing a randomized controlled design. There is a need for educators within the field of evidence-based health to consider the implications of this review.
Clinical Competence↗
The value of short and simple measures to assess outcomes for patients of total hip replacement surgery.
OBJECTIVES: To evaluate the performance of a patient assessed outcome measure, the Oxford Hip Score, in a national study of primary hip replacement surgery. DESIGN: A survey of patients' health status before undergoing primary hip replacement surgery and three months and one year after surgery. SETTING: 143 hospitals in three NHS English regions. PATIENTS: 7151 patients admitted for primary total hip replacement surgery over a period of 13 months from September 1996. MAIN MEASURES: For patients, Oxford Hip Score and satisfaction with hip replacement and, for surgeons, American Anesthesiologists' Society (ASA) classification of physical status. RESULTS: The response rates to the postal questionnaire at three and 12 months follow up were 85.2% and 80.7%, respectively. Including all three administrations of the questionnaire, all except two items of the Oxford Hip Score were completed by 97% or more respondents and only one item at one administration appeared marginally to reduce the reliability of the score. The effect sizes for changes in the score from baseline to three months was 2.50 and to 12 months was 3.05. Patients rated by surgeons as being healthy preoperatively by the ASA classification were somewhat more likely to return a completed questionnaire at three months (79.4% versus 75.3%) and 12 months (72.4% versus 70.3%) than those rated as having poorer health. CONCLUSIONS: Overall there was little evidence of difficulties for patients in completing the Oxford Hip Score or of unreliable data, except in relation to one questionnaire item. The instrument was very responsive to change over time and score changes for the Oxford Hip Score related well to patients' satisfaction with their surgery. The instrument is an appropriate measure in terms of validity, responsiveness, and feasibility for evaluating total hip replacement from the
Aged↗
Observer variability in optic disc assessment: implications for glaucoma shared care.
Demonstrating that optometrists can make valid and reliable assessments of optic disc features is an important prerequisite for establishing schemes for shared care/co-management. Previous studies have estimated observer variability among experts in the assessment of optic disc cupping, but there has been a paucity of information on observer variability amongst optometrists. This paper describes a study to investigate intra- and inter-observer variability for a range of disc features, as graded by both ophthalmologists and optometrists. Five observers (three optometrists and two ophthalmologists) graded 48 stereo-pairs of optic disc photographs from 48 patients on two separate occasions. Each observer graded the following features: vertical and horizontal C/D ratios, narrowest rim width, the presence/absence of a disc haemorrhage, focal pallor of the neuroretinal rim, peri-papillary atrophy, the steepness of the cup-edge and the presence/absence of the cribriform sign. The average intra- and inter-observer standard deviation (SD) of differences are, respectively, 0.11 and 0.19 for the vertical C/D ratios and 0.10 and 0.18 for the horizontal C/D ratios. For the vertical C/D ratio the average weighted kappa (kappa w) is 0.79 within observers and 0.46 between observers. Percentage agreements for the presence/absence of a disc haemorrhage range from 96 to 100% (average kappa = 0.92) within observers and from 90 to 98% (average kappa = 0.77) between observers. For other disc features, average kappa w values range from 0.67 to 0.71 within observers and from 0.23 to 0.46 between observers. Intra- and inter-observer comparisons (within and between different professionals) across all disc features are comparable for the optometrists and ophthalmologists, thus demonstrating that optometrists can make valid assessments of disc features. The implications for shared care are discussed.
Glaucoma, Open-Angle↗
Loss of heterozygosity and microsatellite instability at the MLL locus are common in childhood acute leukemia, but not in infant acute leukemia.
Rearrangements involving the MLL gene at chromosome 11q23 are associated with leukemia and are present in up to 70% of infant leukemias. Loss of heterozygosity (LOH) has been shown for anonymous polymorphic markers at 11q23 in adult leukemias. To study LOH at the MLL locus, we have identified two new polymorphic microsatellite markers: a GAA repeat (mllGAAn) in intron 6 of the MLL gene and a GA (mllGAn) repeat in the 5' flanking region of the gene, approximately 2 kb upstream of the translation initiation codon. The heterozygosity index of mllGAAn is 0.54, which renders it useful for analyzing LOH. We screened two groups of leukemia patients to study LOH at the mllGAAn marker. Group A (n = 18) was selected on the basis of presentation before 18 months. Cytogenetic and reverse transcription-polymerase chain reaction analysis showed that 9 of these 18 children had translocations involving MLL. No LOH was observed. Group B (n = 36) were randomly selected children who had presented with leukemia between 1993 and 1994. Cytogenetic analysis of this group showed a variety of different chromosomal abnormalities. LOH was shown in 9 of 20 individuals (45%) who were informative. Microsatellite instability (MSI) was demonstrated in 1 of 18 individuals in group A and 5 of 36 individuals (13.9%) in group B. MSI and LOH were observed simultaneously in three individuals. Loss of an allele was confirmed in one individual by fluorescence in situ hybridization. Individuals with MSI or LOH at mllGAAn were selected for analysis at anonymous polymorphic markers D11S1364 and D11S1356, which flank the MLL gene. No LOH or MSI was observed at these markers in those individuals who were informative. These results show that LOH at the MLL gene locus is a common event during leukemogenesis. Furthermore, the presence of MSI at this locus suggests that the region is a hotspot for genetic instability.
Acute Disease↗
Reporting of precision of estimates for diagnostic accuracy: a review.
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Confidence Intervals↗
Patient-prosthesis mismatch is negligible with modern small-size aortic valve prostheses.
BACKGROUND: Concern has been raised about residual significant gradients when small aortic prostheses are used, particularly in patients with large body surface areas. We studied the performance of six types of small aortic prostheses using dobutamine stress echocardiography. METHODS: Sixty-three patients (mean age, 67 +/- 7 years) who had undergone aortic valve replacement 17 +/- 6 months previously were studied. Two bileaflet mechanical prostheses (St. Jude Medical and CarboMedics: sizes, 19 mm and 21 mm) and two biological prostheses (Medtronic Intact and St. Jude BioImplant: size, 21 mm) were evaluated. A graded infusion of dobutamine was given and Doppler studies of valve performance were carried out. RESULTS: All prostheses except one biological valve had acceptable hemodynamic performance under stress. Using regression modeling, gradient at rest was the only variable found to predict gradient under stress (p < 0.001). Moreover, the most important predictor of gradient at rest was valve design, which accounted for 72% of the variance (p < 0.001). This relationship was independent of valve size (19 mm or 21 mm) or material (ie, mechanical or biological). Body surface area accounted for 4% of the variance in gradient only. CONCLUSIONS: The main predictor of transprosthetic gradient is the inherent characteristics of each particular prosthesis, with relatively insignificant contribution from variations in body surface area. Patient-prosthesis mismatch is not a problem of clinical significance when certain modern valve prostheses are used.
Aged↗
Health-technology assessment in surgery.
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Attitude of Health Personnel↗
Infections in adults undergoing unrelated donor bone marrow transplantation.
This study retrospectively reviews infections over a 7-year period in 60 consecutive adults (median age 25 years) undergoing their first unrelated donor bone marrow transplant (UD-BMT). T-cell depletion was employed in 93%. More than half the patients had one or more severe, potentially life-threatening, infections. There was a high incidence of invasive fungal infections (Aspergillus 17, Candida four), despite the use of itraconazole or amphotericin prophylaxis. Ten Aspergillus infections occurred beyond 100 d. Two patients (11%) with invasive aspergillosis survived. Clustering of infections was noted, with invasive fungal infections significantly associated with bacteraemias (OR 3.73, P=0.06) and multiple viral infections (OR 4.25, P=0.05). There were 21 severe viral infections in 16 patients, with CMV disease occurring in four patients only; viral pneumonitis was predominantly due to 'community respiratory' viruses. Most early bacteraemias (68%) were due to Gram-positive organisms. The majority of episodes of Gram-negative sepsis were caused by non-fastidious non-fermentative bacteria, such as Pseudomonas spp. and Acinetobacter spp., historically regarded as organisms of low pathogenicity. In patients with successful engraftment and minimal graft-versus-host disease, late infections suggestive of continued immune dysfunction (shingles, recurrent lower respiratory infections, Salmonella enteritis and extensive warts) were common.
Adolescent↗
An investigation of the t(12;21) rearrangement in children with B-precursor acute lymphoblastic leukaemia using cytogenetic and molecular methods.
The t(12;21) is the commonest recurrent translocation in childhood acute lymphoblastic leukaemia (ALL), the presence of which has been suggested to be a good prognostic feature. We have studied 22 childhood cases of B-precursor ALL with this rearrangement, and have found no significant differences in event-free survival between these and a control group of patients with similar phenotypes. Using a variety of cytogenetic and molecular techniques, we have confirmed a strong association with co-expression of myeloid markers, frequent deletions of the short-arm of the untranslocated chromosome 12 homologue and duplication of the derivative chromosome 21. Intragenic deletion of the untranslocated ETV6 gene in 3/12 informative patients points to the likelihood of this gene being a target for deletion.
Child↗