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Biomedical subjects

S M Cobbe

Publications and source records attributed to S M Cobbe.

At least 19 recordsLinked to original sources

Abnormal haemoglobin levels in acute coronary syndromes.

BACKGROUND: Anaemia is an adverse prognostic marker in acute coronary syndromes (ACS), but the epidemiology of abnormal haemoglobin levels in such patients is uncertain. AIMS: To investigate the prevalence, nature and predictors of abnormal haemoglobin levels in ACS patients at admission. DESIGN: Observational study. METHODS: All emergency admissions from January to April 2005 were assessed within 24-48 h of hospital admission. ACS patients (unstable angina, non-ST-elevation or ST-elevation myocardial infarction) were enrolled (n = 320, 190 men). Clinical information was recorded. RESULTS: Overall, 71% had unstable angina; 18% non-ST-elevation myocardial infarction (MI), and 11% ST-elevation MI. Mean +/- SD haemoglobin was 14.3 +/- 1.7 g/dl in men and 13.2 +/- 1.5 g/dl in women. Abnormal haemoglobin was more common in men (65, 34%) than in women (34, 22%) (p = 0.013). Anaemia (haemoglobin <13 g/dl in men, or <12.0 g/dl in women) was recorded in 35 (18%) men and 24 (18%) women. All had admission haemoglobin >8 g/dl, and anaemia was usually normocytic. Multivariate predictors of anaemia (OR, 95%CI) were age (1.07, 1.04-1.1) and serum albumin (0.90, 0.81-1.00). Elevated haemoglobin (>16 g/dl) was recorded in 30 (16%) men and 4 (3%) women (p < 0.01), and was more common in ST-elevation MI patients (26%) than in unstable angina or non-ST elevation MI patients (9%) (p = 0.005). In patients who underwent invasive management with a post-procedure haemoglobin the following day (n = 85), 15 (18%) new cases of anaemia were detected. Admission duration correlated with haemoglobin (p < 0.01), creatinine (p < 0.01), troponin I (p < 0.01) and C-reactive protein (p < 0.01). Anaemia was more common in those who died in hospital (3, 60%) than in those who survived (56, 18%) (adjusted p = 0.0135). DISCUSSION: Abnormal haemoglobin levels were common in our ACS admissions. Anaemia was generally mild. Increasing age and interventional management were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. Interventions to prevent and detect anaemia in this setting merit prospective testing.

Anemia↗

Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain.

OBJECTIVE: To assess whether antibodies to human heat shock protein 60 (anti-huhsp60) or to mycobacterial heat shock protein 65 (anti-mhsp65) predict an adverse one year prognosis in patients admitted with acute cardiac chest pain. DESIGN: Prospective observational study. SETTING: Teaching hospital. PATIENTS: 588 consecutive emergency admissions of patients with acute chest pain of suspected cardiac origin. MAIN OUTCOME MEASURES: Anti-huhsp60 and anti-mhsp65 titres were assayed on samples drawn on the morning after admission. The end points after discharge were coronary heart disease death, non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, angiogram, or readmission with further cardiac ischaemic chest pain. RESULTS: During follow up after discharge (mean of 304 days, range 1-788 days), 277 patients had at least one of the study outcomes. Patients with increased titres of anti-huhsp60 had an adverse prognosis (hazard ratio 1.56 (95% confidence interval 1.09 to 2.23) comparing highest versus lowest quartiles, p = 0.015). Anti-mhsp65 titres were not predictive. CONCLUSIONS: Patients admitted with acute cardiac chest pain and increased titres of anti-huhsp60 had an adverse one year prognosis.

Acute Disease↗

The electrophysiological and mechanical effects of 2,3-butane-dione monoxime and cytochalasin-D in the Langendorff perfused rabbit heart.

UNLABELLED: Procedures that reduce contraction are used to facilitate optical measurements of membrane potential, but it is unclear to what extent they affect the excitability of the heart. This study has examined the electrophysiological consequences of a range of extracellular [Ca2+] (0.7-2.5 mmol l(-1)), 2,3-butane-dione monoxime (BDM; 1-20 mmol l(-1)) and cytochalasin-D (Cyto-D; 1-5 micromol l(-1)). METHODS: Monophasic action potentials (MAPs) were recorded from the basal epicardial surface of the left ventricle of isolated rabbit hearts. Conduction delay (CD) and time to 90% repolarisation of the monophasic action potential (MAPD90) were measured. The effects of BDM and Cyto-D on restitution were studied at a [Ca2+] of 1.9 mmol l(-1). Restitution curves for MAPD90 were generated using a standard S1-S2 protocol. RESULTS: All manoeuvres decreased left ventricular developed pressure (LVDP): 0.7 mmol l(-1) Ca2+ to 74.0 +/- 6.1%, 20 mmol l(-1) BDM to 4.5 +/- 1.0%, and 5 micromol l(-1) Cyto-D to 12.8 +/- 3.5% of control value. CD decreased from a control value (33.3 +/- 1.0 ms, n= 16) to 93.0 +/- 2.2% in 0.7 mmol l(-1) Ca2+, but increased to 133.7 +/- 10.5% in 20 mmol l(-1) BDM and 127.4 +/- 10.6% in 5 micromol l(-1) Cyto-D. At 350 ms pacing cycle length, MAPD90 (control = 119.6 +/- 1.7 ms n= 16) was prolonged by reduced extracellular [Ca2+]. BDM had no effects on MAPD90 at control pacing rates. Cyto-D caused a significant prolongation (to 115.0 +/- 3.0% of control, n= 6) at the highest concentration studied (5 micromol l(-1)). Both BDM (20 mmol l(-1)) and Cyto-D (3 micromol l(-1)) flattened the restitution curves but neither agent altered maximum MAPD90. CONCLUSIONS: Extracellular [Ca2+] of 1.9 mmol l(-1) in conjunction with a moderate dose of Cyto-D (3 micromol l(-1)) reduced contractility with minimal effects on action potential duration and conduction at a fixed pacing cycle length. However, both BDM and Cyto-D had pronounced effects on electrical restitution.

Action Potentials↗

A randomized comparison of the effects of aspirin and clopidogrel on thrombotic risk factors and C-reactive protein following myocardial infarction: the CADET trial.

A randomized, double-blind multicenter trial-the Clopidogrel and Aspirin: Determination of the Effects on Thrombogenicity (CADET) trial-was carried out to compare the effects of clopidogrel vs. aspirin on thrombotic variables and C-reactive protein (CRP), over a 6-month period of treatment, in patients with an acute myocardial infarction within the previous 3-7 days, who were not scheduled for major surgery including coronary artery bypass grafting. Patients (n = 184) were randomly allocated to aspirin (75 mg day(-1)) or clopidogrel (75 mg day(-1)). Blood samples were taken at baseline and then at clinic visits at 1, 3 and 6 months. By 1 month, clottable and immunonephelometric fibrinogen, D-dimer, von Willebrand factor, factor VIII and CRP were significantly (P < 0.05) reduced from baseline values in both treatment groups; as well as tissue plasminogen activator antigen in the aspirin group only. At 6 months, there were no differences between treatment groups (P > 0.05) for any of the variables, whether or not potential confounding variables were adjusted for. Similarly, there were no differences between treatments in the difference between baseline and final values for any of the variables. Aspirin and clopidogrel were thus found to have similar effects on thrombotic variables and CRP in this patient population.

Aged↗

Surviving out of hospital cardiac arrest at home: a postcode lottery?

OBJECTIVE: To find out if the response time, distance travelled to scene, and geographical location affect survival from out of hospital cardiac arrest (OHCA). METHODS: Retrospective cohort study over 10 years, 1 December 1991 to 1 August 2001. Outcome and demographic data were obtained for 1956 OHCAs occurring at home, in the Lothians region, from the Heartstart Scotland database. Survival rates to hospital admission and discharge were examined by postcode district. RESULTS: Certain postcode areas were served by quicker response times and shorter journeys. The survival to admission rate was greater in those areas where the median response time was <10 minutes (13.5% versus 8.1%, p<0.05). There was greater survival to discharge in these areas but not significantly so (4.1% versus 3.2%, p = 0.42). Survival to admission was more likely in areas where the median distance travelled was <four miles (13.3% versus 9.7%, p<0.05) but not survival to discharge (4.0% versus 3.7%, p = 0.72). A close correlation between distance travelled and response time was shown (Pearson = 0.93, p<0.01), likewise between distance travelled and survival to admission (Spearman = -0.87, p<0.01). Certain areas, particularly those at greater geographical distance from ambulance dispatch points, were found to be associated with significantly lower survival to admission rates. CONCLUSIONS: Survival to admission from OHCA is strongly influenced by response time and distance travelled to the scene. The geographical location of an arrest can potentially influence survival to admission. Measures should be taken to strategically position ambulance dispatch points and to task the nearest geographically available vehicle to attend an OHCA.

Aged↗

Tachycardiomyopathy: a diagnosis not to be missed.

The prognosis of dilated cardiomyopathy is generally poor. In the vast majority of cases the cause of the ventricular dysfunction is irreversible but occasionally potentially curable causes are identified. Tachycardiomyopathy is a rare and potentially treatable cause of heart failure. A patient with a particularly severe case who had an excellent outcome is presented.

Adolescent↗

Myocardial infarction causes increased expression but decreased activity of the myocardial Na+-Ca2+ exchanger in the rabbit.

Na+-Ca2+ exchanger (NCX) protein levels and activity were measured in myocardium from the basal region of the left ventricle of rabbit hearts with significant left ventricular dysfunction (LVD), 8-9 weeks after an apical infarction. NCX protein abundance was higher in the tissue homogenates (121 +/- 11%) and purified membrane fractions (143 +/- 12%) in the LVD compared to the sham-operated (sham) group. NCX mRNA was also higher in the LVD group (126%). Lower NCX protein expression was observed in the membrane fractions from the epicardium compared to the endocardium in both the sham and LVD groups. Transmembrane currents were recorded in isolated cardiomyocytes by single-electrode voltage clamp; [Ca2+]i was measured using Fura-2. Rapid application of 10 mmol l-1 caffeine was used to induce Ca2+ release from the sarcoplasmic reticulum. The subsequent NCX-mediated Ca2+ efflux rate constant was lower (70% of sham) in the LVD group. NCX currents were measured in cardiomyocytes dialysed with 250 nM Ca2+ (50 mmol l-1 EGTA). A lower NCX current (75% of sham) was observed in the LVD group. Lower NCX activity was also observed in cardiomyocytes isolated from the epicardium compared to the endocardium; a transmural difference that was also seen in the LVD group. Reduced activity despite increased protein expression may result from reduced Ca2+ sensitivity of the allosteric regulation of NCX. However, measurements indicated increased Ca2+ sensitivity in the LVD group. Cardiomyocytes from LVD hearts displayed a marked reduction in the transverse tubule area (59% of sham) and the surface area/volume ratio (80% of sham). Disrupted transverse tubule structure may contribute to the decrease in NCX activity despite increased protein expression in LVD.

Algorithms↗

Presentation, management, and outcome of out of hospital cardiopulmonary arrest: comparison by underlying aetiology.

OBJECTIVE: To describe and compare presentation, management, and survival by aetiology of cardiopulmonary arrest. DESIGN, SETTING, AND PATIENTS: A retrospective cohort study was undertaken of all 21 175 first out of hospital cardiopulmonary arrests in Scotland between May 1991 and March 1998. MAIN OUTCOME MEASURE: Discharge alive from hospital. RESULTS: Presumed cardiac disease accounted for 17 451 cases (82%), other internal aetiologies for 1814 (9%), and external aetiologies for 1910 (9%). Arrests caused by presumed cardiac disease had a better risk profile in terms of presence of a witness, bystander cardiopulmonary resuscitation, call-response interval, and use of defibrillation; 1265 (7%) of those who arrested from presumed cardiac disease were discharged alive, compared with only 77 (2%) of those with non-cardiac disorders (p < 0.001). Among those defibrillated, call-response interval was associated with survival following arrests from both presumed cardiac and non-cardiac causes (p < 0.001). CONCLUSIONS: Out of hospital cardiopulmonary arrests from non-cardiac causes were associated with worse crude survival than arrests from cardiac causes. Improvements in call-response interval and basic life support skills in the community would improve survival irrespective of the aetiology and should therefore be encouraged.

Adult↗

Task Force on Sudden Cardiac Death, European Society of Cardiology.

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.

Advisory Committees↗

Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk.

OBJECTIVES: For large scale follow up studies with non-demented patients in which cognition is an endpoint, there is a need for short, inexpensive, sensitive, and reliable neuropsychological tests that are suitable for repeated measurements. The commonly used Mini-Mental-State-Examination fulfils only the first two requirements. METHODS: In the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5804 elderly subjects aged 70 to 82 years were examined using a learning test (memory), a coding test (general speed), and a short version of the Stroop test (attention). Data presented here were collected at dual baseline, before randomisation for active treatment. RESULTS: The tests proved to be reliable (with test/retest reliabilities ranging from acceptable (r=0.63) to high (r=0.88) and sensitive to detect small differences in subjects from different age categories. All tests showed significant practice effects: performance increased from the first measurement to the first follow up after two weeks. CONCLUSION: Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change. Methods for analysing cognitive change are proposed.

Aged↗

Patient recall of medication details in the outpatient clinic. Audit and assessment of the value of printed instructions requesting patients to bring medications to clinic.

OBJECTIVE: There is no ambiguity when a patient presents their medications in the correct packaging during a consultation and declares, "this is what I am taking, doctor, I take this many, at this time". The aim of this study was to establish the prevalence of consultations in which patients attend both "empty handed" and unsure of their treatment. A re-evaluation was made after a simple intervention. DESIGN: Prospective cross sectional study with subsequent intervention and re-evaluation based on patient completed questionnaire. SETTING: University hospital cardiology outpatient department. PATIENTS: Consecutive patients arriving at clinic reception desks. RESULTS: Altogether 774 of 857 patients were receiving treatment; 15% attended with their tablets and 28% provided a note of their medication in some form; 40% attended empty handed but confident they could recall all aspects of their treatment from memory; 17% attended empty handed and unsure of their treatment. INTERVENTION: Clinic appointment cards were stamped with the request PLEASE BRING YOUR MEDICATIONS WITH YOU TO THE CARDIOLOGY CLINIC. A second unrelated cohort of patients was then surveyed in an identical manner, nine months later. Of these, 329 of 376 patients were receiving medication. Those attending with their tablets in hand now accounted for 78% rather than 15% (chi(2)=423, df=2, p<0.001). The group unsure of their treatment, but attending empty handed, fell from 17% to 2%. CONCLUSIONS: Reprinted appointment cards are highly successful in encouraging patients to attend with their tablets. This provides reliable information for decision making.

Cardiology Service, Hospital↗

Effect of reducing ambulance response times on deaths from out of hospital cardiac arrest: cohort study.

OBJECTIVES: To determine the association between ambulance response time and survival from out of hospital cardiopulmonary arrest and to estimate the effect of reducing response times. DESIGN: Cohort study. SETTING: Scottish Ambulance Service. SUBJECTS: All out of hospital cardiopulmonary arrests due to cardiac disease attended by the Scottish Ambulance Service during May 1991 to March 1998. MAIN OUTCOME MEASURES: Survival rate to hospital discharge and potential improvement from reducing response times. RESULTS: Of 13 822 arrests not witnessed by ambulance crews but attended by them within 15 minutes, complete data were available for 10 554 (76%). Of these patients, 653 (6%) survived to hospital discharge. After other significant covariates were adjusted for, shorter response time was significantly associated with increased probability of receiving defibrillation and survival to discharge among those defibrillated. Reducing the 90th centile for response time to 8 minutes increased the predicted survival to 8%, and reducing it to 5 minutes increased survival to 10-11% (depending on the model used). CONCLUSIONS: Reducing ambulance response times to 5 minutes could almost double the survival rate for cardiac arrests not witnessed by ambulance crews.

Ambulances↗

Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study.

BACKGROUND: We examined the development of new diabetes mellitus in men aged 45 to 64 years during the West of Scotland Coronary Prevention Study. METHODS AND RESULTS: Our definition of diabetes mellitus was based on the American Diabetic Association threshold of a blood glucose level of >/=7.0 mmol/L. Subjects who self-reported diabetes at baseline or had a baseline glucose level of >/=7.0 mmol/L were excluded from the analyses. A total of 5974 of the 6595 randomized subjects were included in the analysis, and 139 subjects became diabetic during the study. The baseline predictors of the transition from normal glucose control to diabetes were studied. In the univariate model, body mass index, log triglyceride, log white blood cell count, systolic blood pressure, total and HDL cholesterol, glucose, and randomized treatment assignment to pravastatin were significant predictors. In a multivariate model, body mass index, log triglyceride, glucose, and pravastatin therapy were retained as predictors of diabetes in this cohort. CONCLUSIONS: We concluded that the assignment to pravastatin therapy resulted in a 30% reduction (P:=0.042) in the hazard of becoming diabetic. By lowering plasma triglyceride levels, pravastatin therapy may favorably influence the development of diabetes, but other explanations, such as the anti-inflammatory properties of this drug in combination with its endothelial effects, cannot be excluded with these analyses.

Anticholesteremic Agents↗

Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project.

BACKGROUND: Stroke is a leading cause of death and disability. Although clinical trials of the early lipid-lowering therapies did not demonstrate a reduction in the rates of stroke, data from recently completed statin trials strongly suggest benefit. METHODS AND RESULTS: The effect of pravastatin 40 mg/d on stroke events was investigated in a prospectively defined pooled analysis of 3 large, placebo-controlled, randomized trials that included 19 768 patients with 102 559 person-years of follow-up. In all, 598 participants had a stroke during approximately 5 years of follow-up. The 2 secondary prevention trials (CARE [Cholesterol And Recurrent Events] and LIPID [Long-term Intervention with Pravastatin in Ischemic Disease]) individually demonstrated reductions in nonfatal and total stroke rates. When the 13 173 patients from CARE and LIPID were combined, there was a 22% reduction in total strokes (95% CI 7% to 35%, P:=0.01) and a 25% reduction in nonfatal stroke (95% CI 10% to 38%). The beneficial effect of pravastatin on total stroke was observed across a wide range of patient characteristics. WOSCOPS (West of Scotland Coronary Prevention Study, a primary prevention trial in hypercholesterolemic men) exhibited a similar, although smaller, trend for a reduction in total stroke. Among the CARE/LIPID participants, pravastatin was associated with a 23% reduction in nonhemorrhagic strokes (95% CI 6% to 37%), but there was no statistical treatment group difference in hemorrhagic or unknown type. CONCLUSIONS: Pravastatin reduced the risk of stroke over a wide range of lipid values among patients with documented coronary disease. This effect was due to a reduction in nonfatal nonhemorrhagic strokes.

Anticholesteremic Agents↗

The role of myocardial perfusion scanning, heart rate variability and D-dimers in predicting the risk of perioperative cardiac complications after peripheral vascular surgery.

OBJECTIVES: To study the value of a number of proposed prognostic factors in prediction of the risk of perioperative cardiac events after vascular surgery. DESIGN AND METHODS: Two hundred and ninety-seven patients undergoing peripheral vascular surgery were prospectively studied. Patients underwent preoperative 24 h ambulatory electrocardiography, measurement of haemostatic variables, myocardial assessment of perfusion by dipyridamole-thallium scintigraphy and radionuclide ventriculography. The primary endpoint was cardiac death or nonfatal myocardial infarction within 30 days of surgery. A combined endpoint included the primary endpoint plus occurrence of cardiac failure, unstable angina or serious arrhythmias. RESULTS: The primary endpoint occurred in 21 (7%), and the combined endpoint in 41 (14%) of patients. On multivariate analysis, increased age, previous myocardial infarction, aortic surgery, impaired heart rate variability and a positive thallium scan were independent predictors of primary end-points. Preoperative atrial fibrillation and increased fibrin D-dimer were additional predictors of the combined endpoint. Construction of receiver-operator characteristic curves to examine the incremental value of predictive models showed that sensitivity and specificity of clinical data alone for primary endpoints was 71% and 72% respectively, while for the full model (incorporating heart rate variability and thallium data) this rose to 84% and 80% (p=0.0001). CONCLUSIONS: Preliminary screening using clinical data has limited value in risk assessment prior to vascular surgery but preoperative heart rate variability, D-dimers and thallium scanning provide modest incremental predictive value.

Aged↗