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K R Abrams

Publications and source records attributed to K R Abrams.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems.

BACKGROUND: The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients. METHODS: Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables. RESULTS: Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3. 5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups. CONCLUSIONS: This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.

Adult↗
PubMed2000

Modelling publication bias in meta-analysis: a review.

Meta-analysis is now a widely used technique for summarizing evidence from multiple studies. Publication bias, the bias induced by the fact that research with statistically significant results is potentially more likely to be submitted and published than work with null or non-significant results, poses a threat to the validity of such analyses. The implication of this is that combining only the identified published studies uncritically may lead to an incorrect, usually over optimistic, conclusion. How publication bias should be addressed when carrying out a meta-analysis is currently a hotly debated subject. While statistical methods to test for its presence are starting be used, they do not address the problem of how to proceed if publication bias is suspected. This paper provides a review of methods, which can be employed as a sensitivity analysis to assess the likely impact of publication bias on a meta-analysis. It is hoped that this will raise awareness of such methods, and promote their use and development, as well as provide an agenda for future research.

Bayes Theorem↗
PubMed2000

Bayesian methods in health technology assessment: a review.

BACKGROUND: Bayesian methods may be defined as the explicit quantitative use of external evidence in the design, monitoring, analysis, interpretation and reporting of a health technology assessment. In outline, the methods involve formal combination through the use of Bayes's theorem of: 1. a prior distribution or belief about the value of a quantity of interest (for example, a treatment effect) based on evidence not derived from the study under analysis, with 2. a summary of the information concerning the same quantity available from the data collected in the study (known as the likelihood), to yield 3. an updated or posterior distribution of the quantity of interest. These methods thus directly address the question of how new evidence should change what we currently believe. They extend naturally into making predictions, synthesising evidence from multiple sources, and designing studies: in addition, if we are willing to quantify the value of different consequences as a 'loss function', Bayesian methods extend into a full decision-theoretic approach to study design, monitoring and eventual policy decision-making. Nonetheless, Bayesian methods are a controversial topic in that they may involve the explicit use of subjective judgements in what is conventionally supposed to be a rigorous scientific exercise. OBJECTIVES: This report is intended to provide: 1. a brief review of the essential ideas of Bayesian analysis 2. a full structured review of applications of Bayesian methods to randomised controlled trials, observational studies, and the synthesis of evidence, in a form which should be reasonably straightforward to update 3. a critical commentary on similarities and differences between Bayesian and conventional approaches 4. criteria for assessing the reporting of a Bayesian analysis 5. a comprehensive list of published 'three-star' examples, in which a proper prior distribution has been used for the quantity of primary interest 6. tutorial case studies of a variety of types 7. recommendations on how Bayesian methods and approaches may be assimilated into health technology assessments in a variety of contexts and by a variety of participants in the research process. METHODS: The BIDS ISI database was searched using the terms 'Bayes' or 'Bayesian'. This yielded almost 4000 papers published in the period 1990-98. All resultant abstracts were reviewed for relevance to health technology assessment; about 250 were so identified, and used as the basis for forward and backward searches. In addition EMBASE and MEDLINE databases were searched, along with websites of prominent authors, and available personal collections of references, finally yielding nearly 500 relevant references. A comprehensive review of all references describing use of 'proper' Bayesian methods in health technology assessment (those which update an informative prior distribution through the use of Bayes's theorem) has been attempted, and around 30 such papers are reported in structured form. There has been very limited use of proper Bayesian methods in practice, and relevant studies appear to be relatively easily identified. RESULTS: Bayesian methods in the health technology assessment context 1. Different contexts may demand different statistical approaches. Prior opinions are most valuable when the assessment forms part of a series of similar studies. A decision-theoretic approach may be appropriate where the consequences of a study are reasonably predictable. 2. The prior distribution is important and not unique, and so a range of options should be examined in a sensitivity analysis. Bayesian methods are best seen as a transformation from initial to final opinion, rather than providing a single 'correct' inference. 3. The use of a prior is based on judgement, and hence a degree of subjectivity cannot be avoided. However, subjective priors tend to show predictable biases, and archetypal priors may be useful for identifying a reasonable range of prior opinion.

Bayes Theorem↗
PubMed1999

Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis.

BACKGROUND: Few studies have described the perinatal risks associated with infertility, other than for infertility treated by in-vitro fertilisation or gamete intrafallopian transfer. The aim of this analysis was to estimate the risks of perinatal death associated with treated and untreated infertility. METHODS: A population-based case-control study of perinatal deaths was carried out in Leicestershire Health District over the period 1990-94, during which 60,922 babies were delivered. Of these, 567 perinatal deaths were associated with 542 women. 972 mothers were randomly selected as controls. Medical, obstetric, and social data were collected for cases and controls from the medical notes and interviews with the women. The relative risks of perinatal death associated with treated and untreated infertility before the index pregnancy were estimated as odds ratios by means of unconditional logistic regression analysis. FINDINGS: 65 (10%) of cases and 34 (3.5%) of the controls had infertility before the index pregnancy. History of infertility in the index pregnancy, irrespective of treatment, increased the risk of perinatal death (odds ratio 2.9 [95% CI 1.8-4.5]). The population attributable risk fraction for perinatal death related to infertility was 6.2% (3.4-9.0). 45 (54%) of the deaths, even in the untreated group, were associated with immaturity. Compared with women without infertility, women with untreated infertility were at increased risk of perinatal death (3.3 [1.6-6.8]). The risk of perinatal death associated with multiple births did not explain this finding. Similarly, treated infertility also increased the risk of perinatal death (2.7 [1.5-4.7]); the risks associated with multiple births explained some, but not all, of this excess. In Leicestershire, the overall underlying risk of a mother experiencing at least one perinatal death over the study was 9.0 per 1000 women. For women who experience infertility, this risk increases by about 18 per 1000 (6-30). INTERPRETATION: Counselling for women before any form of infertility treatment should include discussion of the risks of perinatal death. Our results would benefit from confirmation. However, we advocate that at antenatal booking a history of infertility, irrespective of treatment, should be sought, because these women have a significantly increased risk of perinatal death, particularly associated with prematurity.

Adult↗
PubMed1999

Systematic reviews and meta-analysis: a structured review of the methodological literature.

OBJECTIVE: To systematically review methods for systematic review/meta-analysis in order to identify the different methodological and statistical methods that have been proposed. A summary of the main findings is presented here, with emphasis given to health services research topics. METHODS: A thorough systematic search for methodological papers was carried out using a variety of methods, including the use of electronic databases. Approximately 1000 potentially relevant references were identified, a number of them from education, psychology and sociology. RESULTS: After briefly reviewing the procedural methods required to carry out a review, and the basic statistical methods used to combine study estimates, less established methods are discussed. These include methods for dealing with publication bias, meta-regression, meta-analysis of individual patient data, the synthesis of non-randomized evidence alone and in combination with randomized studies. Bayesian modelling and economic evaluation through meta-analysis. Recommendations for meta-analytical practice are given; these are either distilled from previous guidelines, or constructed where there appears to be a broad consensus across the literature. CONCLUSIONS: It is hoped that this review will provide a consistent and comprehensive, but concise, description of the methods available for synthesizing evidence, that it will promote better quality reviews of the results of health services research and identify specific areas which require methodological development.

Bayes Theorem↗
PubMed1998

Rate of decline in renal function in Indo-Asians and Whites with diabetic nephropathy.

The incidence of end-stage renal failure (ESRF) is higher in the Indo-Asian ethnic group as compared to the White. To investigate whether this might be associated with faster rates of progression to ESRF in Indo-Asian diabetic patients, we studied a total of 39 Type 2 diabetic patients, using the Department of Nephrology database showing serial serum creatinine measurements from the time of first referral to the clinic until they reached a level of >500 micromol l(-1) or ESRF requiring renal replacement therapy (RRT), either dialysis or renal transplantation. They were grouped into Indo-Asian (n = 24) and White (n = 15). The rate of progression of those who developed ESRF, calculated as the slope of log serum creatinine against time, was not significantly different between the Indo-Asian and White patients, p = 0.73. We conclude that the higher incidence of ESRF in the Indo-Asian Type 2 diabetic patient with nephropathy is therefore not due to a faster rate of deterioration in renal function.

Adult↗
PubMed1998

Identification of a human VPF/VEGF 3' untranslated region mediating hypoxia-induced mRNA stability.

Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia stability region RNA. Thus, increased VPF/VEGF mRNA stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

Base Sequence↗
PubMed1996

Quantitative methods in nursing research.

This paper considers some of the general principles that are common to much of quantitative research in nursing. In particular, the role of hypothesis testing is considered, and the use of estimation is emphasized. Confidence intervals are advocated as a means of assessing both statistical and clinical significance. These principles and methods are illustrated using examples taken from the nursing literature. Finally, more complicated situations and the role of design are discussed.

Bias↗
PubMed1994

Biopsy of inoperable pancreatic tumors does not adversely influence patient survival time.

PURPOSE: To determine the influence of pancreatic biopsy on the survival times of patients with inoperable tumors of the pancreas. MATERIALS AND METHODS: One hundred seventy patients were examined; results of histologic analysis confirmed pancreatic malignancy in 119. The biopsy and nonbiopsy groups were comparable for age, sex, the presence of liver metastases, and nodal status. RESULTS: No statistically significant difference was demonstrated between the survival time for the biopsy group (median, 23 weeks) and that for the nonbiopsy group (median, 22 weeks). The estimated relative risk for death (biopsy group compared with nonbiopsy group) was 0.85 (95% confidence limits = 0.61, 1.18). CONCLUSION: Pancreatic biopsy does not appear to adversely influence survival time for patients with inoperable pancreatic tumors. Because histologic examination aids clinical management, biopsy should be part of the diagnostic work-up for patients with suspected inoperable pancreatic carcinoma.

Aged↗
PubMed1994

Modelling the pattern of cell distribution around implanted materials.

The analysis of the cellular soft tissue response has traditionally focused on using highly skilled human assessment to determine the severity or presence of a particular type of response. This has taken the form of many different assessment criteria, some even attempting some form of 'quantitative' grading index. With the complexity of this response and the availability of high performance computer systems it is not sufficient and no longer necessary to describe a tissue response subjectively. The soft tissue response to a number of implanted materials has been analysed using a combination of immunohistochemistry and image analysis to reproducibly stain and count the cells involved in a soft tissue response to implanted materials, as well as measure their position relative to the implanted material. The combination of cell count and pattern of cell distribution revealed that although the magnitude of the cellular responses changes with respect to time the position of cells with respect to an implanted material does not change significantly over time. The position of cells is controlled more by the type of implant material and the change in subject the material is implanted in.

Animals↗
PubMed1991

High energy neutron treatment for pelvic cancers: study stopped because of increased mortality.

OBJECTIVE: To compare high energy fast neutron treatment with conventional megavoltage x ray treatment in the management of locally advanced pelvic carcinomas (of the cervix, bladder, prostate, and rectum). DESIGN: Randomised study from February 1986; randomisation to neutron treatment or photon treatment was unstratified and in the ratio of 3 to 1 until January 1988, when randomisation was in the ratio 1 to 1 and stratified by site of tumour. SETTING: Mersey regional radiotherapy centre at Clatterbridge Hospital, Wirral. PATIENTS: 151 patients with locally advanced, non-metastatic pelvic cancer (27 cervical, 69 of the bladder, seven prostatic, and 48 of the rectum). INTERVENTION: Randomisation to neutron treatment was stopped in February 1990. MAIN OUTCOME MEASURES: Patient survival and causes of death in relation to the development of metastatic disease and treatment related morbidity. RESULTS: In the first phase of the trial 42 patients were randomised to neutron treatment and 14 to photon treatment, and in the second phase 48 to neutron treatment and 47 to photon treatment. The relative risk of mortality for photons compared with neutrons was 0.66 (95% confidence interval 0.40 to 1.10) after adjustment for site of tumour and other important prognostic factors. Short term and long term complications were similar in both groups. CONCLUSIONS: The trial was stopped because of the increased mortality in patients with cancer of the cervix, bladder, or rectum treated with neutrons.

Fast Neutrons↗