Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes.

In inflammatory diseases such as rheumatoid arthritis, functions of chondrocytes including synthesis of matrix proteins and proteinases are altered through interactions with cells of the infiltrating pannus. One of the major secreted products of mononuclear inflammatory cells is IL-1. In this study we found that recombinant human IL-1 beta suppressed synthesis of cartilage-specific type II collagen by cultured human costal chondrocytes associated with decreased steady state levels of alpha 1 (II) and alpha 1(IX) procollagen mRNAs. In contrast, IL-1 increased synthesis of types I and III collagens and levels of alpha 1(I), alpha 2(I), and alpha 1(III) procollagen mRNAs, as we described previously using human articular chondrocytes and synovial fibroblasts. This stimulatory effect of IL-1 was observed only when IL-1-stimulated PGE2 synthesis was blocked by the cyclooxygenase inhibitor indomethacin. The suppression of type II collagen mRNA levels by IL-1 alone was not due to IL-1-stimulated PGE2, since addition of indomethacin did not reverse, but actually potentiated, this inhibition. Continuous exposure of freshly isolated chondrocytes from day 2 of culture to approximately half-maximal concentrations of IL-1 (2.5 pM) completely suppressed levels of type II collagen mRNA and increased levels of types I and III collagen mRNAs, thereby reversing the ratio of alpha 1(II)/alpha 1(I) procollagen mRNAs from greater than 6.0 to less than 1.0 by day 7. IL-1, therefore, can modify, at a pretranslational level, the relative amounts of the different types of collagen synthesized in cartilage and thereby could be responsible for the inappropriate repair of cartilage matrix in inflammatory conditions.

Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes.

Immortalized human chondrocytes were established by transfection of primary cultures of juvenile costal chondrocytes with vectors encoding simian virus 40 large T antigen and selection in suspension culture over agarose. Stable cell lines were generated that exhibited chondrocyte morphology, continuous proliferative capacity (> 80 passages) in monolayer culture in serum-containing medium, and expression of mRNAs encoding chondrocyte-specific collagens II, IX, and XI and proteoglycans in an insulin-containing serum substitute. They did not express type X collagen or versican mRNA. These cells synthesized and secreted extracellular matrix molecules that were reactive with monoclonal antibodies against type II collagen, large proteoglycan (PG-H, aggrecan), and chondroitin-4- and chondroitin-6-sulfate. Interleukin-1 beta (IL-1 beta) decreased the levels of type II collagen mRNA and increased the levels of mRNAs for collagenase, stromelysin, and immediate early genes (egr-1, c-fos, c-jun, and jun-B). These cell lines also expressed reporter gene constructs containing regulatory sequences (-577/+3,428 bp) of the type II collagen gene (COL2A1) in transient transfection experiments, and IL-1 beta suppressed this expression by 50-80%. These results show that immortalized human chondrocytes displaying cartilage-specific modulation by IL-1 beta can be used as a model for studying normal and pathological repair mechanisms.

Redefining the coronary care unit: an observational study of patients admitted to hospital in England and Wales in 2003.

BACKGROUND: Coronary care units were developed in the 1960s as specially equipped and staffed areas where patients with acute myocardial infarction could be monitored and offered rapid resuscitation from life-threatening arrhythmias. Awareness of the morbidity and mortality of the wider spectrum of acute coronary ischaemia was unrecognized at that time. AIM: To examine the relative frequencies with which thrombolytic treatment and resuscitation from cardiac arrest are provided for patients with myocardial infarction in cardiac care units (CCUs), emergency departments (EDs) and other medical wards. DESIGN: Observational study. METHODS: We analysed records from the National Audit of Myocardial Infarction Project (MINAP) for 61 688 patients admitted to 230 acute hospitals in England and Wales during 2003, and who received a final diagnosis of myocardial infarction, for locations of initiation of thrombolytic therapy and of first cardiac arrest within hospital. RESULTS: Overall, 84% of 27 881 patients with ST-segment-elevation infarction, but only 42% of 30 382 patients with non-ST-elevation infarction, were admitted to a CCU. Of those receiving thrombolytic treatment for ST-elevation infarction, 68.3% of 21 595 did so in the ED. Within the first 4 h after arrival, the majority of episodes of cardiac arrest occurred in the ED: 709 (57%) vs. 488 (39%) in CCU, and 49 (4%) in medical wards. DISCUSSION: The traditional role of the CCU in providing early resuscitation and thrombolytic treatment for patients with ST elevation infarction has largely been devolved to the ED. The role of the CCU should be re-evaluated, and the service re-designed to provide specialist care for all presentations of acute coronary syndrome.

Heart rate and QT interval in subjects adapted to beta-blockade: bradycardia and hypotension as uncorrelated adaptations.

Subjects in whom it was found that after a month's treatment with beta-blockers there was a fall of not less than 10 mmHg in systolic blood pressure persisting 54 h after cessation of treatment were considered to have "adapted". Significant falls of blood pressure and heart rate were observed, and were still present after two further weeks of treatment with placebo, but these adaptations were not correlated with each other. Fourteen hypertensive patients and five normotensive subjects received oral propranolol 80 mg, or metoprolol 100 mg, twice daily for 5 days. They were studied before treatment, and 54 h after the last dose. Drug administration was continued for a further 26 days, and the subjects were again examined 54 h after cessation of treatment. Blood was withdrawn at the times of study and contained negligible amounts of drug in the plasma. Records were made of blood pressure and ECG at rest and after exercise, the post-exercise QT being measured at a heart rate of exactly 100 beats per minute, obviating the need for any correction of QT. QT intervals were significantly prolonged, both at rest and on exercise. Responses to intravenous propranolol 10 mg or metoprolol 20 mg were also measured during the study periods, and no hypersensitivity to the drugs was found at rest or after exercise.

Characteristics of patients presenting to a cardiac clinic with palpitation.

BACKGROUND: Palpitation is a very common presenting symptom in primary care and in cardiac clinics, associated with marked disability. Although serious arrhythmias are uncommon causes, treatment of persistent palpitation is difficult. AIM: To describe the cardiological, behavioural and psychological characteristics of consecutive patients presenting to a cardiac clinic with the main complaint of palpitation. DESIGN: Prospective evaluation of consecutive out-patients. METHODS: Participants were 184 consecutive patients with the complaint of palpitation referred to an out-patient cardiac clinic. Three assessments were used. Three to four weeks prior to clinic attendance, measures of symptoms, distress and disability were gathered, and a heart rate perception test was conducted. At the out-patient clinic, a routine clinical assessment was made. Three months later, patients received a questionnaire which included baseline measures of symptoms, distress and disability. RESULTS: Palpitation was associated with arrhythmias in 62 patients (34%), extrasystoles in 75 patients (41%) and awareness of sinus rhythm in 47 patients (26%). Distress and disability were common and persistent. There were significant differences in the characteristics of the three groups. DISCUSSION: Most patients presenting to secondary care with palpitation do not have serious underlying cardiovascular conditions. Concurrent psychological problems are common and persistent. Aetiology may be seen as an interaction of pathology, awareness of normal physiology, and psychological variables. Few patients require specialist cardiological treatment, but simple reassurance is of limited effectiveness. A stepped care approach may improve outcomes and needs rigorous evaluation.

Thrombolytic treatment for myocardial infarction: an examination of practice in 39 United Kingdom hospitals. Myocardial Infarction Audit Group.

OBJECTIVE: To examine use of thrombolytic drugs for myocardial infarction and use of contraindications to treatment in the United Kingdom. DESIGN: Observational study, based on a continuing audit. SETTING: 39 hospitals in the United Kingdom. PATIENTS: 30,029 patients admitted between November 1992 and June 1995 with suspected myocardial infarction. RESULTS: Of 13,628 patients with a final diagnosis of definite myocardial infarction 10,316 (75.7%) were considered eligible for thrombolytic treatment on the basis of typical cardiographic changes or new left bundle branch block. Of these, 8139 (59.7%) were diagnosed at admission to hospital and 6991 (85.9%) were administered thrombolytic drugs; 14.1% were considered too late for treatment or had a clinical contraindication. In 2177 patients (16% of 13,628)-thrombolytic treatment was given in the absence of contraindications and after the diagnosis of infarction had been confirmed by further electrocardiographic evidence. A further 591 (4.3%) with a final diagnosis of definite infarction without typical cardiographic changes also received thrombolytic treatment as did 1018 patients without a final diagnosis of definite infarction. In total, 9459 of 13,628 patients (71.6%) received thrombolytic treatment. The range of use of treatment between hospitals for a final diagnosis of infarction was 49.1-85.4%. This variation reflected differences in the frequency with which a diagnosis of definite myocardial infarction was made at admission, and the subsequent use of clinical contraindications to thrombolytic treatment. CONCLUSIONS: 75.7% of patients with a final diagnosis of definite myocardial infarction were eligible for thrombolytic treatment on the basis of cardiographic changes. Differences between hospitals in the frequency with which a diagnosis of infarction was made on admission, and differences in subsequent use of thrombolytic drugs, results in wide variation in treatment rates. Differences in use of thrombolytic treatment mainly reflect different thresholds for the use of clinical contraindications relating to haemorrhagic risk.

Planning for coronary angioplasty: guidelines for training and continuing competence. British Cardiac Society (BCS) and British Cardiovascular Intervention Society (BCIS) working group on interventional cardiology.

The following recommendations are made: 1 Existing centres undertaking angioplasty should increase their activity, and the target figure of 400 PTCA procedures per million of the United Kingdom population should be achieved by the end of 1996-97, or immediately thereafter. 2 Angioplasty centres should be appropriately equipped to undertake PTCA safely and effectively and provide a reliable emergency service. They should have a minimum of two trained PTCA operators jointly undertaking a minimum of 200 procedures per year at that centre, and have regular meetings to share experience. 3 Angioplasty operators should ensure that where the need arises patients undergoing PTCA can receive immediate attention from a trained operator at any time until discharge from hospital. 4 Trained operators should undertake at least 1-2 PTCA procedures per week (> 60 procedures per year) to maintain competence, and those undertaking so few procedures should increase their activity over the next three years to more than 100 a year. 5 Trainers should have performed at least 500 procedures before formally training others and should undertake a minimum of 125 procedures a year to maintain accreditation as a trainer. 6 Surgical cover for PTCA procedures should be mandatory and on site cover remains the strongly preferred option. Where surgical cover is provided off site, this should be at a centre less than 30 minutes away by road. Whether provided on or off-site it should be possible to establish cardiopulmonary bypass within 90 minutes of the decision being made to refer the patient for surgery. 7 All operators and interventional centres should audit their activity and results, review these data locally with colleagues, and provide regular audit returns to the national database run by BCIS. This will allow future recommendations concerning standards to take more account of risk stratification and actual outcomes, and not place such emphasis merely on volumes of activity. 8 These recommendations should be reviewed in three years.

Can successful treatment of cardiac arrest be a performance indicator for hospitals?

BACKGROUND: Although resuscitation from cardiac arrest prevents more deaths from acute myocardial infarction (MI) than any other treatment, results have not been audited widely nor performance standards proposed. METHODS: The Myocardial Infarction National Audit Project (MINAP) uses electronic transmission of a 53-item dataset to a central cardiac audit database (CCAD). From October 2000 to August 2002, transmission by 218 hospitals of data from 55,906 cases of MI with 4934 attempted resuscitations from a first arrest, allowed for examination of factors determining survival, and for possible future measurement of success in resuscitation as a performance indicator. We investigated two possible indicators: (i) numbers of survivors from arrest in ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) per 1000 cases of MI; and (ii) observed/expected (O/E) ratios for survival taking all VF/VT arrests rather than MI as the denominator, and adjusting for differing age structures and admission delays among individual hospitals. FINDINGS: Of the 4934 reported patients suffering a first arrest, 1778 (36%) survived to be discharged from hospital. The presenting rhythm was VF/VT in 2321 (47%) patients of whom 1461 (63%) survived. Survival for all 218 hospitals together had the relatively small 95% confidence limits of 26 (25-27) survivors from VF/VT per 1000 MI. However, the small numbers from individual hospitals made it impossible in most cases, whichever of the two indicators was used, to separate quality of performance and completeness of reporting from the factor of chance. INTERPRETATION: Audit of success in resuscitation is essential if performance in the treatment of MI is to be assessed. However, the relatively small numbers of arrests occurring in individual hospitals means that if year on year improvements are to be documented, audit must be carried out among groups of hospitals or on a national scale.

British Cardiac Society Working Group on the definition of myocardial infarction.

The British Cardiac Society commissioned this report to help address inconsistencies in the terminology for acute coronary syndromes and wide variations in the threshold for the diagnosis of myocardial infarction (MI) depending on the assay performed, the precision, and the sensitivity. In addition, several publications have highlighted potential problems with the application of the European Society of Cardiology (ESC)/ American College of Cardiology (ACC) consensus document published in 2000. A revision process has been initiated under the guidance of the ESC, the ACC, and the American Heart Association (AHA). The purpose of this report is to help inform the next revision of the ESC/ACC/AHA guidelines for the diagnosis of MI.

Time delays in provision of thrombolytic treatment in six district hospitals. Joint Audit Committee of the British Cardiac Society and a Cardiology Committee of Royal College of Physicians of London.

OBJECTIVE: To measure the delays between onset of symptoms and admission to hospital and provision of thrombolysis in patients with possible acute myocardial infarction. DESIGN: Observational study of patients admitted with suspected myocardial infarction during six months. SETTING: Six district general hospitals in Britain. SUBJECTS: 1934 patients admitted with suspected myocardial infarction. MAIN OUTCOME MEASURES: Route of admission to hospital and time to admission and thrombolysis. RESULTS: Patients who made emergency calls did so sooner after onset of symptoms than those who called their doctor (median time 40 (95% confidence interval 30 to 52) minutes v 70 (60 to 90) minutes). General practitioners took a median of 20 (20 to 25) minutes to visit patients, rising to 30 (20 to 30) minutes during 0800-1200. The median time from call to arrival in hospital was 41 (38 to 47) minutes for patients who called an ambulance from home and 90 (90 to 94) minutes for those who contacted their doctor. The median time from arrival at hospital to thrombolysis was 80 (75 to 85) minutes for patients who were treated in the cardiac care unit and 31 (25 to 35) minutes for those treated in the accident and emergency department. CONCLUSION: The time from onset of symptoms to thrombolysis could be reduced substantially by more effective use of emergency services and faster provision of thrombolysis in accident and emergency departments.

Determinants and outcomes of coronary angiography after non-ST-segment elevation myocardial infarction. A cohort study of the Myocardial Ischaemia National Audit Project (MINAP).

OBJECTIVE: To investigate determinants of, and outcomes from, coronary angiography and intervention in patients with non-ST-segment elevation myocardial infarction (NSTEMI). DESIGN: Observational study. SETTING: 44 British hospitals with interventional facilities. PATIENTS: 13,489 admissions with NSTEMI; July 2005 to December 2006. MAIN OUTCOME MEASURES: Rate of angiography during index admission; death and readmission to hospital within 180 days. RESULTS: Significantly lower rates of angiography were seen for women, the elderly, the most deprived and those having cardiac, and most non-cardiac, comorbidities. Performance of angiography, compared with no angiography, was not associated with lower rate of readmission (multiple adjusted hazard ratio (HR) = 0.96, 95% CI 0.74 to 1.24) unless accompanied by coronary intervention (HR = 0.73, 95% CI 0.56 to 0.95). Angiography was associated with reduction in 180-day mortality for survivors of hospitalisation (HR = 0.59, 95% CI 0.49 to 0.72); with greater reduction when followed by an intervention (HR = 0.34, 95% CI 0.28 to 0.42). This mortality benefit after intervention was seen both in women (HR = 0.42, 95% CI 0.29 to 0.60) and men (HR = 0.31, 95% CI 0.24 to 0.41), and across age groups: <65 years (HR = 0.25, 95% CI 0.14 to 0.44), 65-79 years (HR = 0.29, 95% CI 0.22 to 0.39) and > or =80 years (HR = 0.52, 95% CI 0.37 to 0.74). Mortality benefit was not significantly attenuated by the presence of comorbidities. CONCLUSION: Performance of angiography and coronary intervention after NSTEMI was associated with mortality benefit that persisted in the presence of both cardiac and non-cardiac comorbidities. Mortality benefit was seen across age groups and was similar for both sexes.

The impact of pre-hospital thrombolytic treatment on re-infarction rates: analysis of the Myocardial Infarction National Audit Project (MINAP).

OBJECTIVE: To examine the frequency and determinants of re-infarction after thrombolytic treatment of ST-elevation myocardial infarction (STEMI). DESIGN: Observational study of national registry. SETTING: Emergency ambulance services and admitting hospitals in England and Wales. PATIENTS: 35 356 patients with STEMI given thrombolytic treatment in 2005-6. MAIN OUTCOME MEASURES: Re-infarction during hospital admission. RESULTS: For 22 391 patients (63.3%) the presence or absence of re-infarction was recorded, and 1460 (6.5%) had re-infarction. Re-infarction rates with in-hospital treatment were similar for reteplase (6.5%) and tenecteplase (6.4%). When the interval from pre-hospital treatment to hospital arrival was greater than 30 minutes re-infarction rates were 12.5% for reteplase, and 11.4% for tenecteplase. Overall, re-infarction rates were higher after pre-hospital treatment with tenecteplase than reteplase (9.6% vs 6.6%, p = 0.005). After multivariate analysis independent predictors of re-infarction for tenecteplase were pre-hospital treatment, OR 1.44 (95% CI 1.21 to 1.71, p<0.001) and weight in the highest quartile compared to the lowest, OR 1.66 (95% CI 1.19 to 2.31, p = 0.003). For reteplase neither factor predicted re-infarction. Bleeding was less common with pre-hospital treatment-overall 1.8% against 3.1%; intracerebral bleeding 0.4% against 0.7%. CONCLUSION: Pre-hospital treatment with tenecteplase was associated with higher re-infarction rates. Longer intervals from pre-hospital treatment to arrival in hospital were associated with high re-infarction rates for both tenecteplase and reteplase. Differences in the use of adjunctive anti-thrombotic therapy in the two treatment environments may underlie the differences in re-infarction rates and bleeding complications observed between pre-hospital and in-hospital thrombolytic treatment.

Evaluation of risk scores for risk stratification of acute coronary syndromes in the Myocardial Infarction National Audit Project (MINAP) database.

OBJECTIVE: To compare the discriminative performance of the PURSUIT, GUSTO-1, GRACE, SRI and EMMACE risk models, assess their performance among risk supergroups and evaluate the EMMACE risk model over the wider spectrum of acute coronary syndrome (ACS). DESIGN: Observational study of a national registry. SETTING: All acute hospitals in England and Wales. PATIENTS: 100 686 cases of ACS between 2003 and 2005. MAIN OUTCOME MEASURES: Model performance (C-index) in predicting the likelihood of death over the time period for which they were designed. The C-index, or area under the receiver-operating curve, range 0-1, is a measure of the discriminative performance of a model. RESULTS: The C-indexes were: PURSUIT C-index 0.79 (95% confidence interval 0.78 to 0.80); GUSTO-1 0.80 (0.79 to 0.81); GRACE in-hospital 0.80 (0.80 to 0.81); GRACE 6-month 0.80 (0.79 to 0.80); SRI 0.79 (0.78 to 0.80); and EMMACE 0.78 (0.77 to 0.78). EMMACE maintained its ability to discriminate 30-day mortality throughout different ACS diagnoses. Recalibration of the model offered no notable improvement in performance over the original risk equation. For all models the discriminative performance was reduced in patients with diabetes, chronic renal failure or angina. CONCLUSION: The five ACS risk models maintained their discriminative performance in a large unselected English and Welsh ACS population, but performed less well in higher-risk supergroups. Simpler risk models had comparable performance to more complex risk models. The EMMACE risk score performed well across the wider spectrum of ACS diagnoses.

Predictors of in-hospital mortality for patients admitted with ST-elevation myocardial infarction: a real-world study using the Myocardial Infarction National Audit Project (MINAP) database.

OBJECTIVE: Although early thrombolysis reduces the risk of death in STEMI patients, mortality remains high. We evaluated factors predicting inpatient mortality for patients with STEMI in a "real-world" population. DESIGN: Analysis of the Myocardial Infarction National Audit Project (MINAP) database using multivariate logistic regression and area under the receiver operating curve analysis. SETTING: All acute hospitals in England and Wales. PATIENTS: 34 722 patients with STEMI from 1 January 2003 to 31 March 2005. RESULTS: Inpatient mortality was 10.6%. The highest odds ratios for inpatient survival were aspirin therapy given acutely and out-of-hospital thrombolysis, independently associated with a mortality risk reduction of over half. A 10-year increase in age doubled inpatient mortality risk, whereas cerebrovascular disease increased it by 1.7. The risk model comprised 14 predictors of mortality, C index = 0.82 (95% CI 0.82 to 0.83, p<0.001). A simple model comprising age, systolic blood pressure (SBP) and heart rate (HR) offered a C index of 0.80 (0.79 to 0.80, p<0.001). CONCLUSION: The strongest predictors of in-hospital survival for STEMI were aspirin therapy given acutely and out-of-hospital thrombolysis, Previous STEMI models have focused on age, SBP and HR We have confirmed the importance of these predictors in the discrimination of death after STEMI, but also demonstrated that other potentially modifiable variables impact upon the prediction of short-term mortality.

Early impact of insulin treatment on mortality for hyperglycaemic patients without known diabetes who present with an acute coronary syndrome.

OBJECTIVE: To determine the effect of insulin for the management of hyperglycaemia in non-diabetic patients presenting with acute coronary syndrome. METHODS: An observational study from the MINAP (National Audit of Myocardial Infarction Project) database during 2003-5 in 201 hospitals in England and Wales. Patients were those with a final diagnosis of troponin-positive acute coronary syndrome who were not previously known to have diabetes mellitus and whose blood glucose on admission was > or = 11 mmol/l. The main outcome measure was death at 7 and 30 days. RESULTS: Of 38,864 patients who were not previously known to be diabetic, 3835 (9.9%) had an admission glucose > or = 11 mmol/l. Of patients having a clear treatment strategy, 36% received diabetic treatment (31% with insulin). Mortality at 7 and 30 days was 11.6% and 15.8%, respectively, for those receiving insulin, and 16.5% and 22.1%, respectively, for those who did not. Compared with those who received insulin, after adjustment for age, gender, co-morbidities and admission blood glucose concentration, patients who were not treated with insulin had a relative increased risk of death of 56% at 7 days and 51% at 30 days (HR 1.56, 95% CI 1.22 to 2.0, p<0.001 at 7 days; HR 1.51, 95% CI 1.22 to 1.86, p<0.001 at 30 days). CONCLUSION: In non-diabetic patients with acute coronary syndrome and hyperglycaemia, treatment with insulin was associated with a reduction in the relative risk of death, evident within 7 days of admission, which persists at 30 days.

Where are we today? Early results from MINAP, the National Audit of Myocardial Infarction Project.

The Myocardial Infarction National Audit Project (MINAP) was developed primarily as a response by the profession to the audit requirements of the National Service Framework for coronary heart disease. MINAP began to collect data in October 2000 and by October 2002, 223 hospitals in England and Wales had returned data on patients with acute myocardial infarction. MINAP provides contemporary analyses of hospital performance, with the ability to compare local performance against the national aggregate. In the third quarter of 2002, 67% of patients received thrombolytic treatment within 30 minutes of hospital arrival. At the same time only 37% of patients received treatment within 60 minutes of calling for help, and only about 20% reached hospital within 30 minutes of calling for help. In order to improve speed of access to thrombolytic treatment there is a need for increased use of pre-hospital treatment.

Trends in the provision of thrombolytic treatment between 1993 and 1997. Myocardial Infarction Audit Group.

OBJECTIVE: To evaluate trends in provision of thrombolytic treatment between 1993 and 1997. DESIGN: Observational study. SUBJECTS: 3714 patients in 15 UK hospitals who had an admission diagnosis of myocardial infarction. MAIN OUTCOME MEASURES: Changes in prehospital and hospital delay before thrombolytic treatment; use of emergency services. RESULTS: Between 1993 and 1997 the proportion of patients who called for help within 30 minutes of the onset of symptoms fell from 42.6% to 36.0%; difference 6.6% (95% confidence intervals (CI) 3.3% to 10%). The direct use of the emergency service by patients and by doctors sending an ambulance without seeing the patient increased by 18.9%. Patients given thrombolytic treatment within 90 minutes of calling for help increased from 28.2% to 39.1%; difference 10.9% (95% CI 7.2% to 14.7%). Over the same period the proportion of patients treated in emergency departments increased from 4.4% to 17.3%, and the median delay from arrival to treatment in emergency departments fell from 53 to 36 minutes. Median delays for patients treated in cardiac care units after assessment in the emergency department fell from 63 to 54 minutes. CONCLUSION: Between 1993 and 1997 there was an increase in the proportion of patients with definite infarction having thrombolytic treatment within 90 minutes of a call for help. This was mainly the result of greater use of the emergency service and more rapid treatment of a larger proportion of eligible patients in emergency departments. Longer delays by patients have cancelled out some of this improvement.

A randomized controlled trial of a brief educational and psychological intervention for patients presenting to a cardiac clinic with palpitation.

BACKGROUND: We sought to determine whether a brief psycho-educational intervention reduced disability in patients with benign palpitation. METHOD: In a pragmatic randomized controlled trial within a cardiology clinic at a district general hospital, 80 consecutive patients diagnosed as having benign palpitation--either palpitation due to awareness of extrasystoles or sinus rhythm--with associated distress or disability were randomized to an intervention group (usual care plus nurse-delivered intervention based on cognitive-behavioural principles) or to a control group (usual care). Principal outcome was difference in proportion of participants with good or excellent researcher-rated activity levels at 3 months. Subsidiary outcomes were self-rated symptoms, distress and disability, researcher-rated unmet treatment needs. RESULTS: The principal outcome showed a statistically and clinically significant benefit for the intervention group, with a number needed to treat of 3 (95% CIs 2 to 7). All but one subsidiary outcomes also showed a difference in favour of the intervention group, and several differences reached statistical significance. Significantly more of the control group had unmet treatment needs at 3 months. CONCLUSIONS: A brief, nurse-delivered, psycho-educational intervention, was an effective treatment for benign palpitation. Further evaluation, including assessment of cost-effectiveness, is needed. The findings have application to the care of patients presenting with other types of 'unexplained' medical symptoms.

Dual effect of disopyramide on atrial and atrioventricular conduction and refractory periods.

Disopyramide has been shown in conditions of cholinergic blockade to have a depressant effect upon sinus node automaticity and the atrial refractoriness. It also prolongs atrioventricular conduction and increases atrioventricular refractoriness. These effects may often be masked in vivo by the anticholinergic effects of the drug.