Microdisplacement printing.

We describe a new patterning technique that employs microcontact printing to replace preformed labile self-assembled monolayers (SAMs) selectively; we call this "microdisplacement printing". We demonstrate that this technique results in ordered molecular regions of both the patterning ("displacing") molecule as well as the remnant labile film, here 1-adamantanethiolate. The existence of the 1-adamantanethiolate SAM before patterning hinders lateral surface diffusion of the patterning molecules, and therefore permits the use of molecules that are otherwise too mobile to pattern by other methods.

Thermally enhanced neutralization in hyperthermal energy ion scattering.

Neutralization probabilities are presented for hyperthermal energy Na+ ions scattered from a Cu(001) crystal as a function of surface temperature and scattered velocity. A large enhancement in neutralization is observed as the temperature is increased. Velocity-dependent charge transfer regimes are probed by varying the incident energy, with the most prominent surface temperature effects occurring at the lowest energies. The data agree well with results obtained from a model based on the Newns-Anderson Hamiltonian, where the effects of both temperature and velocity are incorporated.

Size isn't everything.

Clinical trials now often involve thousands of patients, and statisticians emphasize the importance of trial size in ensuring that 'correct' answers are obtained. However, when a good treatment appears for a disease that was hitherto untreatable - for example, oranges for scurvy or streptomycin for tuberculosis - only a small trial is needed. Large trials are only needed to demonstrate small effects. The meta-analysis of small trials is often misleading, and may hide undesirable effects of individual drugs. The concept of equivalence between treatments is important, and while a statistically adequate equivalence trial may have to be very large, many clinicians will question the need for extreme statistical propriety. Clinical trials often do not reflect 'real world' practice, and the clinical relevance of a trial is more important than its size.

Pathological features of witnessed out-of-hospital cardiac arrest presenting with ventricular fibrillation.

OBJECTIVES: To determine which characteristic pathological features are predictive of the presenting rhythm and survival in victims of community cardiac arrest. DESIGN: Case-controlled retrospective autopsy study. SETTING: County of Nottinghamshire with a total population of 993 914 and an area of 2183 square kilometers. SUBJECTS: Between January 1, 1991 and December 31, 1994, 1535 witnessed cardiac arrests attended by the Nottinghamshire Ambulance Service, of which 1083 had an autopsy performed. RESULTS: Ischaemic heart disease accounted for 72.3% of cases with a further 3.6% of deaths from other cardiac causes and the remainder from non-cardiac causes. Old healed myocardial infarction was present in 39.4%, and visible fresh occlusive thrombus was found in 23.8% of cases overall. Logistic regression analysis of deaths from cardiac causes revealed that younger age (odds ratio of 0.98 (95% CI 0.97-0.99)), two vessel coronary artery disease (odds ratio of 1.65 (95% CI 1.08-2.52)) and heart weight greater than 500 grams (odds ratio of 1.56 (95% CI 1.12-2.17)) were found to be independent predictors of developing ventricular fibrillation compared to other rhythms of arrest. Being male, visible occlusive thrombus and having survived a previous myocardial infarction were found not to be independent variables. There were no outstanding pathological features in the 31 patients who survived to hospital admission and subsequently died, compared with non-survivors who were considered to have died from a cardiac cause. CONCLUSIONS: Among those who had a witnessed out-of-hospital cardiac arrest from a cardiac cause, increasing heart weight (the most likely cause of which is left ventricular hypertrophy), younger age and two vessel coronary artery disease appear to be much more important pathological features in the development of ventricular fibrillation than a previous myocardial infarction and fresh visible occlusive thrombus.

Geographical distribution of cardiac arrest in Nottinghamshire.

BACKGROUND: to analyse the incidence of out-of-hospital cardiac arrest in Nottinghamshire; to ascertain its geographical distribution; and to determine whether the geography of coronary heart disease mortality and out-of-hospital cardiac arrest are the same. METHODS AND RESULTS: population based, retrospective study in the County of Nottinghamshire with a total population of 993,914 in an area of 2183 km2 divided into 191 electoral areas. In the 4 years from 1 January, 1991 to 31 December, 1994, 1634 patients sustained a cardiac arrest attributed to a cardiac cause (International Classification of Diseases codes 390-414 and 420-429) and were attended by the Nottinghamshire Ambulance Service. The overall crude mean incidence rate of community cardiac arrest per electoral area was 40.2 per 100,000 population (range 0-121.2). Thirteen electoral areas, relatively deprived according to the Townsend score, had a significantly greater than expected incidence rate of cardiac arrest (median of 75.6/100,000 per electoral area; interquartile range (IQR) 65.3, 83.8). Twelve relatively affluent electoral areas had a significantly lower than expected incidence rate (median of 18.5/100,000 per area (IQR 13.0, 28.7). After adjusting for deprivation index, there were no differences in coronary heart disease (CHD) mortality and community cardiac arrest in urban and rural electoral areas. Apart from response times by ambulance crews, the events that follow the cardiac arrest such as bystander resuscitation, ventricular fibrillation found as the presenting rhythm and survival were similar in all electoral areas. CONCLUSIONS: increasing level of deprivation is associated with areas of increased incidence of out-of-hospital cardiac arrest in Nottinghamshire, and the effect is apparently different from that on CHD mortality. There is scope for reducing incidence rates of community cardiac arrest and to introduce strategies to improve survival in areas identified as having high rates of community cardiac arrest.

The defibrillator in acute myocardial infarction trial (DINAMIT): study protocol.

BACKGROUND: The implantable cardioverter/defibrillator (ICD) has been shown to be superior to antiarrhythmic drug therapy for the secondary prevention of sudden cardiac death. Its role in the primary prevention of sudden death after myocardial infarction is unknown. Methods and Results The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) is a randomized, open-label, parallel-group comparison of ICD therapy versus no ICD therapy in selected survivors of acute myocardial infarction. It will test the hypothesis that reduction of sudden arrhythmogenic death by means of the ICD will result in reduction of overall mortality rates in patients at high risk after acute myocardial infarction. Accordingly, this international multicenter study aims to enroll patients shortly after their infarction (day 6 to day 40) who have reduced left ventricular function (left ventricular ejection fraction

Combined treatment with losartan and an ACE inhibitor in mild to moderate heart failure: results of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Although the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in patients with heart failure are well recognized, there are theoretical advantages in combining ACE inhibition with angiotensin (AT)1 receptor antagonism. METHODS: Twenty patients with mild to moderate heart failure and maximally treated with an ACE inhibitor were randomly assigned to losartan or placebo. Patients underwent repeated assessment of exercise tolerance, quality of life, central and regional hemodynamics, and neurohumoral and biochemical parameters over a period of 12 weeks. RESULTS: Losartan treatment was well tolerated in terms of adverse events, heart rate, and blood pressure response, and there were no significant changes in serum creatinine or potassium. After 12 weeks of treatment, no significant differences were observed between the losartan and placebo groups in exercise tolerance, quality of life, central and regional hemodynamics, or neurohumoral parameters. CONCLUSIONS: In patients with mild to moderate heart failure already maximally treated with an ACE inhibitor, additional treatment with losartan is well tolerated, but we have not observed any significant improvement in exercise capacity, quality of life, central and regional hemodynamics, or neurohormones. Our data suggest that the combination of losartan with an ACE inhibitor does not offer any substantial advantages over treatment with an ACE inhibitor alone in these patients.

Circadian variation in witnessed out of hospital cardiac arrest.

OBJECTIVES: To examine the effect on circadian variation of out of hospital cardiac arrest according to the underlying aetiology and presenting rhythm of arrest, and to explore strategies that might help to improve survival outcome using circadian variation. DESIGN: Population based retrospective study. SETTING: County of Nottinghamshire with a total population of 993 914 and an area of 2183 km(2). SUBJECTS: Between 1 January 1991 and 3 December 1994, all witnessed cardiac arrests attended by the Nottinghamshire Ambulance Service, of which 1196 patients had a cardiac cause for their arrest (ICD, 9th revision, codes 390-414 and 420-429) and 339 had a non-cardiac cause. RESULTS: The circadian variation of the cardiac cases was not significantly different from that of non-cardiac cases (p = 0.587), even when adjusted for age, sex, or presenting rhythm of arrest. For cardiac cases, the circadian variation of those who presented with ventricular fibrillation was significantly different from those presenting with a rhythm other than ventricular fibrillation (p = 0.005), but was similar to the circadian variation of bystander cardiopulmonary resuscitation (p = 0.306) and survivors (p = 0.542). Ambulance response time was also found to have a circadian variation. CONCLUSIONS: There is a common circadian variation of out of hospital cardiac arrest, irrespective of underlying aetiology, where the presenting rhythm is other than ventricular fibrillation. This is different from the circadian variation of cases of cardiac aetiology presenting with ventricular fibrillation. The circadian variation of ventricular fibrillation, and consequently survival, may be affected by the availability of bystander cardiopulmonary resuscitation and the speed of ambulance response.

Renal function, neurohormonal activation, and survival in patients with chronic heart failure.

BACKGROUND: Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation. METHODS AND RESULTS: The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001). CONCLUSIONS: Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.

Comparison of the SF-36 health survey questionnaire with the Nottingham Health Profile in long-term survivors of a myocardial infarction.

BACKGROUND: Health-related quality of life, an important outcome measure in health interventions, can readily be assessed by questionnaire. Two widely evaluated examples are the Short Form 36 (SF-36) and Nottingham Health Profile (NHP) questionnaires, but as yet the discriminatory power of these tools has not been compared in a large population of patients with coronary heart disease. METHODS: All 4-year survivors of a myocardial infarction, identified from the Nottingham heart attack register, were sent the SF-36, NHP and additionally the Rose angina and dyspnoea questionnaires. Mean scores on the SF-36 and NHP were compared with age- and sex-adjusted norms in patients under and over 65 years. Sensitivity of the respective tools was assessed in distinguishing patients with differing degrees of cardiovascular symptomatology. RESULTS: In patients under 65 years the SF-36 and NHP differed to the same extent from normative data--scores were lower in the comparable domains physical functioning/mobility, bodily pain/pain and energy/vitality, but not in mental health/emotional reaction scores. In social functioning/social isolation results were disparate--SF-36 scores were lower and the NHP similar to normative data. In patients over 65 years mean scores in all five domains were not significantly different from normative data for either tool. The SF-36 was more sensitive than the NHP at detecting the impact of breathlessness, particularly in patients with mild symptoms. Similarly, the SF-36, but not the NHP, could distinguish the effect of differing degrees of angina severity and frequency on social functioning. CONCLUSION: At least in myocardial infarction survivors, the SF-36 appears a more sensitive tool and may have benefits for assessing health-related quality of life in this patient group.

Five men with chest pain.

The above ECGs represent typical findings in patients with chest pain. I hope that most GPs will have scored 100 per cent--but never forget that it is the patient's history and physical examination that really matters, not the ECG. All the information needed to interpret theses traces is included in 'The ECG Made Easy', 5th edition, written by the author and published by Churchill Livingstone. If you want some more practice at ECG interpretation, try '100 ECG Problems', also by the author and published by Churchill Livingstone.

Different causes of heart failure need different treatment strategies.

No one would now believe that all infections will respond to a single antibiotic, nor that all known antibiotics should be given to all patients with infection. It is obvious that some patients with specific causes of heart failure need specific treatment, but whether heart failure of ischaemic or nonischaemic origin need different treatments is not certain. Only when parallel clinical trials have been conducted with individual drugs in separate groups of patients with ischaemic or nonischaemic heart failure will the need for different treatment strategies be known. Until then, there will be a dependency on second-rank evidence (that which can be derived from trials with 'surrogate' end-points, from meta-analysis of small trials and from subset analysis of different patient groups within single trials). The best evidence at present comes from subset analysis of two studies, with bisoprolol (Cardiac Insufficiency Bisoprolol Study; CIBIS) and amlodipine (Prospective Randomised Amlodipine Survival Evaluation; PRAISE). These suggest that patients with different causes of heart failure respond to treatment in different ways.

Influence of ambulance crew's length of experience on the outcome of out-of-hospital cardiac arrest.

AIMS: To investigate whether an ambulance crew's length of experience affected the outcome of out-of-hospital cardiac arrest. METHODS AND RESULTS: This was a population-based, retrospective observational study of attempted resuscitations in 1547 consecutive arrests of cardiac aetiology by Nottinghamshire Emergency Ambulance Service crew. One thousand and seventy-one patients were managed by either a paramedic or a technician crew without assistance from other trained individuals at the scene of arrest. Overall, the chances of a patient surviving to be discharged from hospital alive did not appear to be affected by the paramedic's length of experience (among survivors, 18 months experience vs non-survivors 16 months experience, P = 0.347) but there appears to be a trend in the effect of a technician's length of experience on survival (among survivors, 60 months experience vs non-survivors 28 months experience, P = 0.075). However, when a technician had 4 years of experience or more and a paramedic 1 year's experience, survival rates did improve. Logistic regression analysis, adjusted for factors known to influence outcome, revealed that chances of survival increased once technicians had over 4 years of experience after qualification (odds ratio 2.71, 95% CI 1.17 to 6.32, P = 0.02) and paramedics after just 1 year of experience (odds ratio 2.68, 95% CI 1.05 to 6.82, P = 0.04). CONCLUSIONS: Survival from out-of-hospital cardiac arrest varies with the type of ambulance crew and length of experience after qualification. Experience in the field seems important as paramedics achieve better survival rates after just 1 year's experience, while technicians need to have more than 4 years' experience to improve survival.

Relevance of clinical trial results in myocardial infarction to medical practice: comparison of four year outcome in participants of a thrombolytic trial, patients receiving routine thrombolysis, and those deemed ineligible for thrombolysis.

OBJECTIVE: To assess the medium to long term outcome of patients ineligible for thrombolysis compared to those enrolled in a clinical trial of thrombolysis and patients receiving non-trial thrombolysis. DESIGN: Cohort study based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban/rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1992 categorised as either participants of a thrombolytic trial (group A, n = 140), receiving non-trial thrombolysis (group B, n = 329), or deemed ineligible for lytic treatment (group C, n = 431). MAIN OUTCOME MEASURES: Background characteristics, inhospital treatment, patterns of follow up, referrals to cardiologists, revascularisation rates, and short and long term survival. RESULTS: Clinical trial recruits were younger by almost 10 years, were less likely to have a previous history of myocardial infarction, and more likely to be in Killip class 1 on admission than those ineligible for thrombolysis. Cardiology follow up was mandatory for all surviving trial participants but 22% of patients in group B and 31% of patients in group C received no follow up, and during four years less than 50% ever saw a cardiologist. Revascularisation was performed in 17.2% of patients in group A, 13.6% of patients in group B, and 7.5% of patients in group C. Cumulative mortality at a median of four years was 24.3% in group A, 36.8% in B, and 59.6% in group C. Adjusting for age, sex, previous myocardial infarction, type of infarction, and Killip class in a logistic regression model the odds ratios (OR) of death at four years for groups B and C were 1.60 (95% confidence intervals (CI) 0.97 to 2.63, p = 0.065) and 2.64 (95% CI 1.61 to 4. 32, p < 0.001), respectively, when compared to group A (OR 1). CONCLUSIONS: Patients enrolled into thrombolytic trials are at low risk. Patients deemed ineligible for thrombolysis are high risk, receive less surveillance, are less likely to be revascularised or receive trial proven treatments, have a poor long term outcome not entirely explained by increased age or severity of infarction, and deserve further evaluation.