Conclusion:
Plasma glucose concentrations above 145 mg/dL (8 mmol/L) independently predicted a poor prognosis.

STUDY

1. Cohort study entered 750 patients (median age 70) with acute stroke (86% ischemic; 14% hemorrhagic). None had diabetes.
2. The upper limit of normal for a fasting plasma glucose concentration is 120 mg/dL (6.5 mmol/L).
3. Because not all glucose measurements in the study were taken tasting, 145 mg/dL ( 8 mmol/L) was used as the cutpoint.
4. Mean follow-up = 1.7 years.

RESULTS

1. Mean times to measurement of glucose = 3.5 h after admission and 14 h after stroke onset.
2. Relative risk (RR) of mortality in patients with hyperglycemia was 1.9.
3. The effect of elevated glucose concentration on survival was greatest in the first month.
4. Even after adjusting for other prognostic variables, hyperglycemia led to higher mortality.

DISCUSSION

1. "Our results show that hyperglycemia predicts higher mortality and morbidity after acute stroke independently of other adverse prognostic factors. "
2. The effect of hyperglycemia on mortality was large. The estimated relative hazard of 1.9 was greater than that for hemorrhagic versus ischemic stroke.
3. Hyperglycemia is not solely a stress response, it predicts outcome.
4. The mechanisms by which hyperglycemia might influence stroke outcome is uncertain. The following have been suggested: increased edema and infarct size; reduced cerebral blood flow; increased local production of lactic acid.
5. "Our results suggest a randomized trial of glucose control is warranted." Randomization should be soon enough after stroke onset to allow treatment during the window of opportunity for pharmacological intervention. Recent studies suggest that this time window lasts for up to three to 12 hours after stroke onset.

CONCLUSION
Plasma glucose concentrations above 145 mg/dL (8 mmol/L) after acute stroke predicted a poor prognosis. The raised concentrations are unlikely to be solely a stress response, and should arguably be treated actively.
BMJ May 3, 1997;314: 1303-06 Original study first author from Western Infirmary, Glasgow, UK 5-18 EFFECT OF LONG TERM TREATMENT WITH SALMETEROL ON ASTHMA CONTROL
Salmeterol [Serevent] is a long acting beta agonist. When inhaled twice daily it causes bronchodilation that is maintained over 24 hours.
Long term salmeterol causes sustained bronchodilation with improvement in symptom control. It does not reduce inflammation in asthmatic airways.
The objective of this study was to determine the effect of adding salmeterol twice daily for 6 months to current treatment of asthma in patients who controlled their inhaled corticosteroid dose according to a management plan.
Conclusion: Adding salmeterol was associated with a reduction in inhaled steroid dose and improved lung function and symptom control.

STUDY

1. Double blind, randomized, cross over study entered 100 subjects with stable mild to moderate asthma.
2. All were taking at least 200 ug of beclomethasone [Vanceril; Beclovent] or budesonide twice daily.
3. All were given salmeterol 50 ug or placebo twice daily in addition to baseline medication, and then crossed-over with a 1 month washout.
4. All were taking a short acting beta agonist as needed.
5. If patients had no symptoms and their morning peak expiratory flow (PEF) was greater than their target PEF, the inhaled steroid was reduced by one puff twice daily. (Target PEF = that at which patient and doctor considered to be reasonably good control.)

RESULTS

1. When compared with placebo, salmeterol treatment was associated with a 17% reduction in inhaled corticosteroid use.
2. Salmeterol was associated with higher morning and evening PEF and FEV1, a reduction in symptoms, and reduced bronchodilator use.
3. There was no significant difference between groups in exacerbations of asthma.

DISCUSSION

1. In this study patients were asked to adjust their inhaled steroid within certain limits according to their PEF and symptoms. This design was chosen to ensure that subjects were not undertreated or overtreated with steroids for a long period and to mimic what is likely to happen in practice when salmeterol is introduced.
2. The relatively low incidence of exacerbations suggested that the regimen was effective.
3. The addition of salmeterol for 6 months was associated with a reduction in inhaled steroids use, and a reduction in PEF and FEV1.
4. The mean inhaled steroid dose was 17% lower with salmeterol than with placebo. The effect of salmeterol was maintained over 6 months with no evidence of tolerance.
5. There was no difference in adverse effects between groups.

CONCLUSION
In subjects who adjusted their inhaled steroid treatment according to guidelines, the addition of salmeterol 50 ug twice daily was associated with reduction in inhaled steroid use and improved lung function and symptom control.
BMJ May 17, 1997; 314: 1441-46 Original investigation first author from City Hospital, Nottingham, UK

Comment:
My understanding is that, except for the mildest forms of asthma (requiring only occasional beta-agonist inhalations), steroid inhalations are the drugs of first choice. Beta-agonists, short and long-acting are often added as needed. Which to give? — short, or long-acting? This decision should be individualized. Long-acting may be preferred by many patients as a matter of convenience.
The decision is not either steroids or beta-agonist, but to judiciously balance the two. RTJ