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Biomedical subjects

Christopher Jackson

Publications and source records attributed to Christopher Jackson.

9 recordsLinked to original sources
PubMed2006

Improving ecological inference using individual-level data.

In typical small-area studies of health and environment we wish to make inference on the relationship between individual-level quantities using aggregate, or ecological, data. Such ecological inference is often subject to bias and imprecision, due to the lack of individual-level information in the data. Conversely, individual-level survey data often have insufficient power to study small-area variations in health. Such problems can be reduced by supplementing the aggregate-level data with small samples of data from individuals within the areas, which directly link exposures and outcomes. We outline a hierarchical model framework for estimating individual-level associations using a combination of aggregate and individual data. We perform a comprehensive simulation study, under a variety of realistic conditions, to determine when aggregate data are sufficient for accurate inference, and when we also require individual-level information. Finally, we illustrate the methods in a case study investigating the relationship between limiting long-term illness, ethnicity and income in London.

Data Interpretation, Statistical↗
PubMed2005

Plaque rupture after short periods of fat feeding in the apolipoprotein E-knockout mouse: model characterization and effects of pravastatin treatment.

BACKGROUND: These studies examined the early time course of plaque development and destabilization in the brachiocephalic artery of the apolipoprotein E-knockout mouse, the effects of pravastatin thereon, and the effects of pravastatin on established unstable plaques. METHODS AND RESULTS: Male apolipoprotein E-knockout mice were fed a high-fat, cholesterol-enriched diet from the age of 8 weeks. Animals were euthanized at 1-week intervals between 4 and 9 weeks of fat feeding. Acutely ruptured plaques were observed in the brachiocephalic arteries of 3% of animals up to and including 7 weeks of fat feeding but in 62% of animals after 8 weeks, which suggests that there is a sharp increase in the number of plaque ruptures at 8 weeks. These acute plaque ruptures then appear to heal and form buried fibrous caps; after 9 weeks of fat feeding, mice had 1.05+/-0.15 buried fibrous caps at a single site in the brachiocephalic artery. Pravastatin (40 mg/kg of body weight per day for 9 weeks; resultant plasma concentration 16+/-4 nmol/L) had no effect on plasma cholesterol concentration in fat-fed apolipoprotein E-knockout mice but reduced the number of buried fibrous caps by 43% (P<0.0001). In longer-term experiments, the delay of pravastatin treatment until unstable plaques had developed reduced the incidence of acute plaque rupture by 36% (P<0.0001). CONCLUSIONS: Plaque rupture occurs at high frequency in the brachiocephalic arteries of male apolipoprotein E-knockout mice after 8 weeks of fat feeding. Pravastatin treatment inhibits early plaque rupture and is also effective when begun after unstable plaques have developed.

Animals↗
PubMed2005

Comparison of survival by allocation to medical therapy, surgery, or heart transplantation for ischemic advanced heart failure.

BACKGROUND: To ascertain survival of ischemic advanced heart failure patients by treatment allocation, we examined the outcome of transplant assessment patients allocated to medical therapy, high-risk conventional surgery, or transplantation. METHODS: Patients were identified from the Papworth transplant database and excluded if primary etiology was not ischemic. Grouping was undertaken according to treatment allocation at initial assessment, and analysis was performed by intention to treat. Survival was computed from the time of assessment and Cox regression used to stratify patients according risk with the Heart Failure Survival Score. RESULTS: From May 1993 to September 2001, a total of 755 patients were admitted for transplant assessment, with 348 (46.1%) identified as having heart failure of ischemic origin. Variables required for calculation of the Heart Failure Survival Score was available in 273 patients (78.4%), and 20 patients (7.3%) were lost to follow-up. Of the remaining 253 patients, 89 (35.2%) were allocated to medical therapy, 32 (12.6%) to surgery, and 132 (52.2%) to transplantation. The relative risk (95% confidence limit) of death compared with medical therapy was 0.62 (0.28, 1.40) for surgery and 0.38 (0.24, 0.61) for transplantation in medium- to high-risk patients. For low-risk patients, the relative risks for death compared with medical therapy were 1.87 (0.63, 5.60) for surgery and 1.97 (0.79, 4.96) for transplantation. CONCLUSIONS: Transplantation improved survival of medium- and high-risk patients compared with medical therapy. In the low-risk group, this was not evident. However, repeated assessment of risk is required because the hazard for death rises steadily after the third year in these patients.

Cardiac Surgical Procedures↗
PubMed2005

A validated simple model to predict coexistent coronary disease in patients undergoing mitral valve surgery.

OBJECTIVE: The primary limitation of the American Heart Association/American College of Cardiology guidelines is specificity. To improve the selection process, we proposed a simple additive model including age (1 point for every 5 years above 50), male sex (2 points), hypercholesterolemia (2 points), angina (3 points), and electrocardiographic evidence of ischemia (3 points). We recommend screening angiography at 3 or more points. This model was previously derived from 359 patients at Papworth Hospital. METHODS: The validation cohort was a consecutive series of patients who underwent mitral valve surgery at the Royal Brompton Hospital. Preoperative coronary angiography reports were obtained, and coronary disease was defined as luminal narrowing of 50% in 2 or more views. Sensitivities and specificities were calculated for the American Heart Association/American College of Cardiology criteria, the simple additive model, and a logistic regression model. Receiver operating characteristic curves were used to validate accuracy and compare discrimination with logistic regression. RESULTS: From 1998 through 2003, angiographic details were available for 342 (86%) of 396 patients who underwent mitral valve surgery. The sensitivity and specificity of the American Heart Association/American College of Cardiology guidelines were 100% and 5%, respectively; those of the simple additive model were 91% and 44%, respectively; and those of logistic regression were 93% and 41%, respectively. The receiver operating characteristic areas for the simple additive and logistic regression model were 0.78 (95% confidence interval, 0.73-0.84) and 0.80 (95% confidence interval, 0.74-0.85), respectively. CONCLUSIONS: This is the third independent cohort to highlight the poor specificity of the American Heart Association/American College of Cardiology guidelines. Although high sensitivity is achieved, the cost is the majority of patients requiring screening angiography. Our validated simple model improved the specificity and selection; however, this was achieved at the expense of decreased sensitivity.

Aged↗
PubMed2004

Elevation of activated protein C in synovial joints in rheumatoid arthritis and its correlation with matrix metalloproteinase 2.

OBJECTIVE: To investigate the involvement of the anticoagulant serine protease activated protein C (APC) in tissue remodeling in rheumatoid arthritis (RA). METHODS: PC/APC, matrix metalloproteinase 2 (MMP-2), and MMP-9 were detected in synovial fluid by Western blotting, and their antigen levels were quantified by enzyme-linked immunosorbent assay in patients with osteoarthritis (OA) or RA. Enzymatic activity of MMP-2 was assayed using a specific fluorogenic substrate. We developed an improved assay to measure APC activity in synovial fluid utilizing a chromogenic substrate following immunoprecipitation with a specific PC/APC antibody. PC/APC and MMP-2 were localized by immunohistochemistry in RA, OA, and normal synovial tissues. RESULTS: Synovial fluid analysis demonstrated that APC is present in both RA and OA synovial fluid, with APC activity being markedly higher in RA (mean +/- SEM 462 +/- 112 ng/ml versus 136 +/- 42 ng/ml; P < 0.02). A correlation (r(2) = 0.61) was found between APC and MMP-2 activity levels in RA patients, but not in OA patients. Immunohistochemical studies of synovial sections showed colocalization of APC and MMP-2 in endothelial and synovial lining cells. Additionally, APC and MMP-2 coimmunoprecipitated with an anti-PC/APC antibody. CONCLUSION: Our results show, for the first time, that APC and MMP-2 are coordinately up-regulated and tightly bound in RA synovial fluid and colocalized in synovia. Their association suggests that APC may modulate MMP-2 activity in RA.

Arthritis, Rheumatoid↗
PubMed2004

The perennial problem with potassium.

BACKGROUND: The problem of spurious hyperkalaemia in blood samples delivered to hospitals from local general practitioners' (GP) surgeries remains a source of diagnostic confusion and potential danger to patients. We have carried out retrospective and prospective audits of serum potassium measurements to assess the influences of blood sample delivery time and temperature during transit from GP surgeries to a centralized laboratory on the risk of spurious serum potassium measurements. METHOD: The retrospective audit included serum potassium measurements made by the pathology laboratory at Addenbrooke's Hospital on 51 843 patients attending either the hospital itself or one of 62 local GP surgeries during the months August 2001 to February 2002 (i.e. summer through to winter). The probability of spurious potassium measurements on GP patients relative to blood sample delivery time and temperature was modelled by least-squares multiple linear regression. The prospective audit included serum potassium measurements made on 40 patients presenting early in the day at the Sutton GP surgery near Ely, Cambridgeshire, during the months February to May 2002. RESULTS: Low blood sample delivery temperature had a greater impact on the probability of spurious potassium measurements than long delivery time. Low delivery temperature also had a greater impact on the probability of spurious hyperkalaemia than it had on the probability of spurious normokalaemia. At temperatures below 20.3 degrees C, the probabilities of both spurious hyper- and normokalaemia for samples delivered from the most distant and closest GP surgeries to Addenbrooke's increased significantly. CONCLUSIONS: Maintaining blood sample delivery temperatures a few degrees above 20 degrees C will minimize the risk of spurious serum potassium measurements on samples from GP patients.

Blood Preservation↗
PubMed2003

An audit of the use of epidural injections for back pain and sciatica.

An audit was conducted to determine if epidural injections for back pain and sciatica were practised in accordance with guidelines prescribed by the National Health and Medical Research Council (NHMRC). More than 80% of injections were used for conditions for which they were not indicated, and which the NHMRC considers experimental. Most commonly, epidural injections afforded no benefit to the patients, yet were often repeated. In no instance was informed consent recorded as recommended by the NHMRC. The practice of epidural injections is dissonant both with the evidence-based literature and with recommended guidelines, and squanders both financial and professional resources.

Adrenal Cortex Hormones↗
PubMed2003

Porcine or human stentless valves for aortic valve replacement? Results of a 10-year comparative study.

BACKGROUND AND AIM OF THE STUDY: Stentless porcine valves in the aortic position exhibit similar excellent hemodynamic performance to homografts, but have the advantage of availability. Their performance was compared over a 10-year period in a single-surgeon and single-institution series. METHODS: Demographic, operative and mortality data were obtained retrospectively. Survivors were interviewed by telephone according to a defined protocol. Definitions and analyses were in accordance with joint STS/AATS guidelines. RESULTS: A total of 408 stentless porcine and homograft aortic valve replacements (AVR) was performed between 1991 and 2001. Five patients were excluded due to incomplete data, in addition to 82 patients who underwent AVR with a free-standing root replacement technique. Hence, 321 patients (217 males, 104 females; mean age 67 +/- 12 years) had a subcoronary implant. The median time to follow up was 4.9 years (range: 2.9-6.6 years). No differences were noted between homograft and stentless porcine valves in one- and five-year freedom from structural valve deterioration (99.1 versus 97.2% and 95.7 versus 93.1%; p = 0.10), reoperation (99.2 versus 99.4% and 97.8 versus 96.7%; p = 0.45) and endocarditis (98.3 versus 99.4% and 97.4 versus 99.4%; p = 0.14). Overall one- and five-year survival comparing homograft to stentless porcine valve was 90.4 versus 92.3% and 80.8 versus 73.7%, respectively; p = 0.23. Independent predictors of mortality on multivariate analysis were: ventricular function (p < 0.0001), increasing age (p < 0.001), increasing serum creatinine (p < 0.001) and concomitant coronary surgery (p = 0.05). Treated hypercholesterolemia was independently protective against mortality, with an odds ratio of 0.26 (CI 0.10 to 0.66; p = 0.005). CONCLUSION: The porcine stentless valve, when implanted in the subcoronary position, is an excellent alternative to the homograft and shows excellent clinical performance and durability at mid term.

Age Factors↗