Acute coronary events in general practice: the Imminent Myocardial Infarction Rotterdam Study

With the advent of coronary care units in the early sixties, the first concentrated effort was made to reduce mortality from myocardial infarction. Subsequent experience has demonstrated that in-hospital deaths, particularly those from arrhythmias, have decreased from some thirty-five per cent to below ten per cent. However, several studies had indicated that up to 60% of the total mortality from acu· te coronary events, i.e. sudden cardiac death and acute myocardial infarction, took place in pre-hospital phase 1-6 and as early as the late sixties, both clinicians and epidemiologists began to realize that the greatest further gains had to be achieved by decreasing mortality in that particular phase. In 1969, Bondurant7 stated: "the pre-hospital mortality due to ischaemic heart disease is greater than the total mortality due to any other single cause of death" and also: "the pre-hospital phase of acute myocardial infarction poses the greatest single medical problem of our nation in terms of loss of potential salvageable life". This seems to apply to the U.S.A. as well to the entire western world of today. Fulton et al. from Edinburgh, Scotland, concluded also in 1969: "The majority of deaths occur before patients with acute myocardial infarction reach hospital. Most of these are sudden and unattended medically. In many, symptoms of ischaemic heart disease have been present, but often they have passed unnoticed or at least undeclared. It is difficult to conceive of any system which would allow effective treatment of these patients. Therefore, reliable identification of those prone to sudden death and the development of prophylactlcmeasures would do as much or more to combat the problem of acute coronary attacks as any other approach. Thus, the emphasis began to swing away from further intra-hospital efforts at reducing death from coronary atherosclerotic heart disease (C.A.H.D.) to the out-of-hospital pre-coronary phase. For instance, Lown and Wolf stated in 1971: "Coronary care units, while effective in lowering hospital mortality, can not significantly reduce sudden cardiac death, which occurs primarily out-of-hospital and accounts for the majority of deaths from coronary heart disease

Resource allocation and feedback in wireless multiuser networks

This thesis focuses on the design of algorithms for resource allocation and feedback in wireless multiuser and heterogeneous networks. In particular, three key design challenges expected to have a major impact on future wireless networks are considered: cross-layer scheduling; structured quantization codebook design for MU-MIMO networks with limited feedback; and resource allocation to provide physical layer security. The first design challenge is cross-layer scheduling, where policies are proposed for two network architectures: user scheduling in single-cell multiuser networks aided by a relay; and base station (BS) scheduling in CoMP. These scheduling policies are then analyzed to guarantee satisfaction of three performance metrics: SEP; packet delay; and packet loss probability (PLP) due to buffer overflow. The concept of the τ-achievable PLP region is also introduced to explicitly describe the tradeoff in PLP between different users. The second design challenge is structured quantization codebook design in wireless networks with limited feedback, for both MU-MIMO and CoMP. In the MU-MIMO network, two codebook constructions are proposed, which are based on structured transformations of a base codebook. In the CoMP network, a low-complexity construction is proposed to solve the problem of variable codebook dimensions due to changes in the number of coordinated BSs. The proposed construction is shown to have comparable performance with the standard approach based on a random search, while only requiring linear instead of exponential complexity. The final design challenge is resource allocation for physical layer security in MU-MIMO. To guarantee physical layer security, the achievable secrecy sum-rate is explicitly derived for the regularized channel inversion (RCI) precoder. To improve performance, power allocation and precoder design are jointly optimized using a new algorithm based on convex optimization techniques

Structured data entry for narrative data in a broad specialty: patient history and physical examination in pediatrics.

BACKGROUND: Whereas an electronic medical record (EMR) system can partly address the limitations, of paper-based documentation, such as fragmentation of patient data, physical paper records missing and poor legibility, structured data entry (SDE, i.e. data entry based on selection of predefined medical concepts) is essential for uniformity of data, easier reporting, decision support, quality assessment, and patient-oriented clinical research. The aim of this project was to explore whether a previously developed generic (i.e. content independent) SDE application to support the structured documentation of narrative data (called OpenSDE) can be used to model data obtained at history taking and physical examination of a broad specialty. METHODS: OpenSDE was customized for the broad domain of general pediatrics: medical concepts and its descriptors from history taking and physical examination were modeled into a tree structure. RESULTS: An EMR system allowing structured recording (OpenSDE) of pediatric narrative data was developed. Patient history is described by 20 main concepts and physical examination by 11. In total, the thesaurus consists of about 1800 items, used in 8648 nodes in the tree with a maximum depth of 9 levels. Patient history contained 6312 nodes, and physical examination 2336. User-defined entry forms can be composed according to individual needs, without affecting the underlying data representation. The content of the tree can be adjusted easily and sharing records among different disciplines is possible. Data that are relevant in more than one context can be accessed from multiple branches of the tree without duplication or ambiguity of data entry via "shortcuts". CONCLUSION: An expandable EMR system with structured data entry (OpenSDE) for pediatrics was developed, allowing structured documentation of patient history and physical examination. For further evaluation in other environments, the tree structure for general pediatrics is available at the Erasmus MC Web site (in Dutch, translation into English in progress) 1. The generic OpenSDE application is available at the OpenSDE Web site 2

Safety of nifedipine GITS in stable angina: The ACTION trial

Aim: We describe the safety profile of nifedipine GITS as assessed from adverse events reported in the ACTION trial in which 7,665 patients with stable, symptomatic coronary artery disease were randomly assigned nifedipine GITS or placebo and followed for a mean of 4.9 years. Methods: All adverse events were coded using the COSTART coding dictionary. The incidence rate for each event was calculated as the number of patients with the event concerned divided by the total time 'at risk'. Hazard ratios comparing nifedipine with placebo and their 95% confidence intervals were obtained by Cox proportional-hazards analysis. Results: As reported previously, nifedipine significantly reduced the incidence of cardiovascular events and procedures [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.83-0.95]. Apart from the known side effects of nifedipine, which include peripheral oedema, vasodilatation, hypotension, asthenia, constipation, leg cramps, non-specific respiratory complaints, impotence and polyuria, and which were reported more frequently in patients assigned nifedipine, the incidence rates of most other adverse events were similar. There were no differences in the occurrence of gastrointestinal haemorrhage, myocardial infarction and suicide. The rate of occurrence of death or new cancer excluding non-melanoma skin cancer for patients with no history of cancer at baseline was 2.53/100 patient years for patients assigned nifedipine and 2.37/100 patient years for patients assigned placebo (HR 1.06, 95% CI 0.93-1.22). Conclusion: Overall nifedipine GITS was well tolerated by patients with stable symptomatic angina

Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial

BACKGROUND: Beta blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. METHODS: In a multicentre, double-blind, and randomised parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat. FINDINGS: The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p=0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. The composite endpoint of mortality or all-cause admission occurred in 1116 (74%) of 1511 on carvedilol and in 1160 (76%) of 1518 on metoprolol (0.94 [0.86-1.02], p=0.122). Incidence of side-effects and drug withdrawals did not differ by much between the two study groups. INTERPRETATION: Our results suggest that carvedilol extends survival compared with metoprolo

Preferential benefits of nifedipine GITS in systolic hypertension and in combination with RAS blockade: further analysis of the ‘ACTION' database in patients with angina

A retrospective analysis of the database from A Coronary Disease Trial Investigating Outcome with Nifedipine (ACTION) evaluated the effectiveness of nifedipine gastrointestinal therapeutic system (GITS) (i) in combination with renin angiotensin system (RAS) blockers and (ii) in patients with isolated systolic hypertension (ISH). Analysed on an intention-to-treat basis, treatment groups were compared by the log-rank test without adjustment for covariates and hazard ratios with 95% CIs were obtained using Cox proportional hazards models. Of 7665 randomized patients, 1732 patients were receiving RAS blockade at baseline, the addition of nifedipine GITS significantly reduced any cardiovascular (CV) event (−20% P<0.05), the composite of death, any CV event and revascularization (−16% P<0.05) and coronary angiography (−22% P<0.01). These benefits were achieved with relatively small differences in systolic (3.2 mm Hg) and diastolic blood pressure (BP) (2.3 mm Hg). In 2303 patients (30.0%) who had ISH at baseline (1145 nifedipine GITS and 1158 placebo), nifedipine significantly reduced the primary efficacy end point (−18% P<0.03), any CV event (−22% P<0.01) and new heart failure (−40% P<0.01). The benefits were associated with between-group differences in achieved BP of 4.7 and 3.3 mm Hg for systolic and diastolic BP, respectively. In summary, the lowest CV event rates were seen in those receiving (i) the combination of RAS blockade and nifedipine GITS and (ii) in those specifically treated for ISH

Effects of early intracoronary streptokinase on infarct size estimated from cumulative enzyme release and on enzyme release rate: A randomized trial of 533 patients with acute myocardial infarction

The effects of early intracoronary streptokinase (SK) on enzymatic infarct size and rate of enzyme release were studied in a randomized multicenter trial. A total of 533 patients with acute myocardial infarction (AMI) were allocated to either the SK treatment group (n = 269) or the conventional (control) treatment group (n = 264). Enzymatic infarct size was represented by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase (HBDH) released by the heart per liter of plasma in the first 72 hours. Rate of enzyme release was represented by the ratio of HBDH quantities released in 24 hours and 72 hours. On an "intention to treat" basis, the SK group had a smaller (by 30%; p = 0.0001) median enzymatic infarct size and a higher (by 35%; p = 0.0001) median rate of enzyme release than the control group. Limitation of infarct size was less apparent in patients tre

Neurocognitive function in children with compensated hypothyroidism: lack of short term effects on or off thyroxin

BACKGROUND: Although thyroxin therapy clearly is beneficial to children with frank hypothyroidism there is little data on the effects of thyroxin in children with compensated or subclinical hypothyroidism. The objective of this study was to determine the effect of thyroxin therapy on cognitive function in children with compensated hypothyroidism. The hypothesis was that thyroxin therapy would change neuropsychological function. METHODS: Eleven patients with a history of sub clinical hypothyroidism entered the study. At the start of the study, six out of the 11 were on thyroxin therapy, while 5 were off therapy. All patients underwent a battery of neuropsychological testing and thyroid function tests at the start of study. Based on the results of thyroid function tests, two of the 5 patients who were off thyroxin were started back on thyroxin. All of the 6 patients who were on thyroxin were taken off thyroxin. All patients then underwent repeat neuropsychological testing and thyroid functions after an average of 91 days. RESULTS: Thyroxin therapy could not be shown to have an effect on neuropsychological function in this short term study. Our patients had attention problems as compared to the normal population. No significant differences were found between our subjects and normal population standards in verbal processing, visual processing, motor speed/coordination and achievement. CONCLUSION: In this small, short term study, thyroxin therapy could not be shown to affect neuropsychological function in children with compensated hypothyroidism. These children may have attention problems but appear to have normal verbal and visual processing, motor speed/coordination and achievement

Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarc