Archive

Archive for May, 2016

Coronary Artery Bypass Surgery

Alexander and Smith present a review of Coronary Artery Bypass Surgery. This include current indications and mortality and complications.

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Statin Associated Side Effects

Thompson et al published a comprehensive review of statin associated side effects. This is an excellent review. In particular, the discussion of statin associated myotoxicity: diagnosis, a score (note does not include CK) and management. It also reviews: risk of diabetes mellitus, central nervous system side effects (memory, intra-cranial hemorrhage) and liver enzyme abnormalities.

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Reproducibility Crisis

Nature and BMJ have added to the concerns re: reproducibility of scientific findings.
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Health and Well Being in the Older Adult

McClintock et al   present the results of  study of community-dwelling older people (3500 participants: 57 to 85 years) comparing a medical model (disease and organ system based) with a comprehensive model (including measures of mental health, sensory function, mobility and history of bone fractures). The authors argue this comprehensive model is a better measure of health and well being in older adults and closer to the 1946 WHO definition of health: “state of
complete physical, mental and social well-being and not merely the absence of disease or infirmity.” The comprehensive model was independently associated with mortality and morbidity (see definitions in the paper).

 

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Categories: Uncategorized

European Cardiovascular Disease Prevention Guidelines 2016

The “2016 European Guidelines on cardiovascular disease prevention in clinical practice” have been released. These are comprehensive excellent guidelines.

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Categories: Uncategorized

Scientific Reproducibility

Van Bavel et al investigate the correlates of replication success in psychological studies. The authors identified contextual factors. This paper, I believe, has wider implications than psychological domain. At the least it should give us pause for reflection. Supplementary material is available here.

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Categories: Uncategorized

Time Course Analysis of Aspirin in patients with TIA and ischemic stroke

Rothwell et al reviewed 12 secondary prevention trials (15 778 participants) in ischemic stroke and TIAs. Aspirin benefit was early after index event. Dipyridamole conferred benefit when added to aspirin after the 12 week period.

Summary

Background

Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) or ischaemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials. We hypothesised that the short-term benefits of early aspirin have been underestimated.

Methods

Pooling the individual patient data from all randomised trials of aspirin versus control in secondary
prevention after TIA or ischaemic stroke, we studied the effects of aspirin on the risk and severity of recurrent stroke, stratified by the following time periods: less than 6 weeks, 6–12 weeks, and more than 12 weeks after randomisation.
We compared the severity of early recurrent strokes between treatment groups with shift analysis of modified Rankin Scale (mRS) score. To understand possible mechanisms of action, we also studied the time course of the interaction
between effects of aspirin and dipyridamole in secondary prevention of stroke. In a further analysis we pooled data from trials of aspirin versus control in which patients were randomised less than 48 h after major acute stroke,
stratified by severity of baseline neurological deficit, to establish the very early time course of the effect of aspirin on risk of recurrent ischaemic stroke and how this diff ers by severity at baseline.

Findings

We pooled data for 15 778 participants from 12 trials of aspirin versus control in secondary prevention. Aspirin reduced the 6 week risk of recurrent ischaemic stroke by about 60% (84 of 8452 participants in the aspirin group had an ischaemic stroke vs 175 of 7326; hazard ratio [HR] 0·42, 95% CI 0·32–0·55, p<0·0001) and disabling or fatal ischaemic stroke by about 70% (36 of 8452 vs 110 of 7326; 0·29, 0·20–0·42, p<0·0001), with greatest benefi t noted in patients presenting with TIA or minor stroke (at 0–2 weeks, two of 6691 participants in the aspirin group with TIA or minor stroke had a disabling or fatal ischaemic stroke vs 23 of 5726 in the control group, HR 0·07, 95% CI 0·02–0·31, p=0·0004;at 0–6 weeks, 14 vs 60 participants, 0·19, 0·11–0·34, p<0·0001). The eff ect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis odds ratio [OR] 0·42, 0·26–0·70, p=0·0007).These effects were independent of dose, patient characteristics, or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke accrued for aspirin only versus control from 6–12 weeks, but there was no benefit after 12 weeks (stroke risk OR 0·97, 0·84–1·12, p=0·67; severity mRS shift OR 1·00, 0·77–1·29, p=0·97). By contrast, dipyridamole plus aspirin versus aspirin alone had no eff ect on risk or severity of recurrent ischaemic stroke within 12 weeks (OR 0·90, 95% CI 0·65–1·25, p=0·53; mRS shift OR 0·90, 0·37–1·72, p=0·99), but dipyridamole did reduce risk thereafter (0·76,0·63–0·92, p=0·005), particularly of disabling or fatal ischaemic stroke (0·64, 0·49–0·84, p=0·0010). We pooled data for 40 531 participants from three trials of aspirin versus control in major acute stroke. The reduction in risk of recurrent ischaemic stroke at 14 days was most evident in patients with less severe baseline deficits, and was substantial by the second day after starting treatment (2–3 day HR 0·37, 95% CI 0·25–0·57, p<0·0001).

Interpretation

Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identify aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA. The previously unrecognised effect of aspirin on severity of early recurrent stroke, the diminishing benefit with longer-term use,and the contrasting time course of effects of dipyridamole have implications for understanding mechanisms of action.
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