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Flu experts fear countries are unprepared for a future pandemic
SCIENCE AND MEDICINE
Stroke contributes to women’s higher mortality after cardiac surgery omen undergoing cardiac surgery are more likely than their male counterparts to experience new stroke, transient ischaemic attack, or coma. Furthermore, women have a higher 30-day mortality than men when these neurological complications occur, US researchers report this week (Circulation 2001; 103: 2133–37). It is well known that women have higher morbidity and mortality after cardiac surgery than men but this difference has usually been attributed to factors such as female patients being older and having smaller coronary arteries. “For the most part, the importance of perioperative complications for surgical outcomes in women have not been closely examined, despite the growing appreciation of their importance for mortality”, the investigators note. “A couple of years back we found that women undergoing cardiac surgery at our institution were at higher risk of suffering perioperative strokes. We wanted to confirm these results and did so by analysing the Society of Thoracic Surgery National Cardiac Surgery Database”, explains lead investigator Victor Dávila-Román (Barnes-Jewish Hospital at Washington University Medical Center, St Louis, MO, USA). The investigators reviewed the clinical information on nearly 420 000
W
(32% female) patients entered into the database during 1996–97. Women had experienced more new neurological events than men (3·8% vs 2·4%, p=0·001) and had a higher mortality at 30 days (5·7% vs 3·5, p=0·001). Adjustment for other risk factors, such as age and other comorbid conditions, by multivariable logistic regression analysis revealed female sex to be independently associated with increased risk of neurological events. “We believe that, since the majority of these women are menopausal, oestrogen may play a role in the occurrence of neurologic events”, says Dávila-Román, adding that animal studies support the notion that oestrogen is neuroprotective. His view is shared by Patricia Hurn (Johns Hopkins School of Medicine, Baltimore, MD, USA): “The clinical value of oestrogen or combined oestrogen/progestin hormone therapy remains controversial for primary or secondary stroke prevention. However, in animals and cultured neurons, oestrogen has been widely demonstrated to reduce brain injury and protect cell viability once an ischaemic insult occurs.” One striking finding is that even short-term oestrogen therapy delivered before or after experimental stroke strongly reduces brain damage in rodents of either sex, says Hurn.
“Oestrogen’s protection involves several mechanisms and includes both improved blood flow to the compromised brain region, as well as direct interruption of neuronal cell ‘death pathways’. Considering the amount and strength of favourable pre-clinical evidence, it is enticing to speculate that oestrogen-based preventative therapy could reduce neurological injury in women undergoing cardiac surgery.” Davila-Roman’s group has already begun a prospective, doubleblind randomised, placebo-controlled study on the use of oestrogen given during cardiac surgery. Not all are convinced, however, that a low circulating oestrogen concentration is the main culprit. Joel Simon (University of California, San Francisco, CA, USA) cautions that: “The observational evidence regarding postmenopausal hormone therapy and stroke is inconsistent and many studies have detected no association.” Simon was lead investigator of the Heart & Estrogen/progestin Replacement Study (HERS; Circulation 2001; 103: 638–42). “While low circulating oestrogen levels cannot be excluded as an aetiological factor”, says Simon “the HERS results would suggest that other explanations might need to be explored.” Sarah Ramsay
Flu experts fear countries are unprepared for a future pandemic
F
ears that countries will not be able to make enough effective drugs available in response to an imminent influenza pandemic were heard at a Royal Society meeting (London, UK, April 25–26). The side effects and the high-level of cross-resistance of amantadine and rimantidine do not make these drugs an ideal choice in a pandemic. By contrast, the neuraminidase inhibitors zanamivir and oseltamivir are proven to be much more effective for treatment and prophylaxis. Furthermore, resistance to zanamivir or oseltamivir has not yet been observed. Fred Hayden (University of Virginia, USA) presented modelling data on the impact of oseltamivir during pandemic influenza and showed his drug could decrease hospital visits and reduce the duration of symptoms. However, mid-way through the meeting delegates were surprised to
THE LANCET • Vol 357 • May 5, 2001
hear that GlaxoSmithKline would no longer be actively promoting zanamivir in the UK. This is an unexpected development since GlaxoSmithKline fought a distribution battle with the National Institute for Clinical Excellence, who initially did not approve the drug in 1999, then gave it the goahead last autumn. A relatively mild influenza season this year meant sales were down. An issue shared by delegates was how will drugs be made available in the advent of a pandemic. Obtaining drugs by prescription only will not suffice. Drugs really need to be made available over the counter. In addition, in the UK, at £24 a course, this treatment is considered expensive and would need to be made available at a subsidised cost. David Fedson (Pasteur-Merieux MSD, Lyon, France) pointed out that providing treatment and supplying vaccines on such a large scale
as required in pandemics is a political, economical and legal issue. “National governments need to nationalise their vaccination and antiviral facilities. It can’t be the governments alone that decide who receives the drug. We need a global programme where everyone takes responsibility.” On the issue of stockpiling, delegates agreed that each country has to have a contract with industry. Governments need to make a decision as to whether there needs to be a drug stockpile. “For this to happen we need to ascertain the stability of the drugs, then work with governments to persuade them to buy an equivalent amount of stockpile. Government and industry need to forge a partnership whereby they keep a supply of bulk chemical that could be mobilised immediately at the start of a pandemic”, concluded David Fedson. Pam Das
1419
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Stroke contributes to women’s higher mortality after cardiac surgery omen undergoing cardiac surgery are more likely than their male counterparts to experience new stroke, transient ischaemic attack, or coma. Furthermore, women have a higher 30-day mortality than men when these neurological complications occur, US researchers report this week (Circulation 2001; 103: 2133–37). It is well known that women have higher morbidity and mortality after cardiac surgery than men but this difference has usually been attributed to factors such as female patients being older and having smaller coronary arteries. “For the most part, the importance of perioperative complications for surgical outcomes in women have not been closely examined, despite the growing appreciation of their importance for mortality”, the investigators note. “A couple of years back we found that women undergoing cardiac surgery at our institution were at higher risk of suffering perioperative strokes. We wanted to confirm these results and did so by analysing the Society of Thoracic Surgery National Cardiac Surgery Database”, explains lead investigator Victor Dávila-Román (Barnes-Jewish Hospital at Washington University Medical Center, St Louis, MO, USA). The investigators reviewed the clinical information on nearly 420 000
W
(32% female) patients entered into the database during 1996–97. Women had experienced more new neurological events than men (3·8% vs 2·4%, p=0·001) and had a higher mortality at 30 days (5·7% vs 3·5, p=0·001). Adjustment for other risk factors, such as age and other comorbid conditions, by multivariable logistic regression analysis revealed female sex to be independently associated with increased risk of neurological events. “We believe that, since the majority of these women are menopausal, oestrogen may play a role in the occurrence of neurologic events”, says Dávila-Román, adding that animal studies support the notion that oestrogen is neuroprotective. His view is shared by Patricia Hurn (Johns Hopkins School of Medicine, Baltimore, MD, USA): “The clinical value of oestrogen or combined oestrogen/progestin hormone therapy remains controversial for primary or secondary stroke prevention. However, in animals and cultured neurons, oestrogen has been widely demonstrated to reduce brain injury and protect cell viability once an ischaemic insult occurs.” One striking finding is that even short-term oestrogen therapy delivered before or after experimental stroke strongly reduces brain damage in rodents of either sex, says Hurn.
“Oestrogen’s protection involves several mechanisms and includes both improved blood flow to the compromised brain region, as well as direct interruption of neuronal cell ‘death pathways’. Considering the amount and strength of favourable pre-clinical evidence, it is enticing to speculate that oestrogen-based preventative therapy could reduce neurological injury in women undergoing cardiac surgery.” Davila-Roman’s group has already begun a prospective, doubleblind randomised, placebo-controlled study on the use of oestrogen given during cardiac surgery. Not all are convinced, however, that a low circulating oestrogen concentration is the main culprit. Joel Simon (University of California, San Francisco, CA, USA) cautions that: “The observational evidence regarding postmenopausal hormone therapy and stroke is inconsistent and many studies have detected no association.” Simon was lead investigator of the Heart & Estrogen/progestin Replacement Study (HERS; Circulation 2001; 103: 638–42). “While low circulating oestrogen levels cannot be excluded as an aetiological factor”, says Simon “the HERS results would suggest that other explanations might need to be explored.” Sarah Ramsay
Flu experts fear countries are unprepared for a future pandemic
F
ears that countries will not be able to make enough effective drugs available in response to an imminent influenza pandemic were heard at a Royal Society meeting (London, UK, April 25–26). The side effects and the high-level of cross-resistance of amantadine and rimantidine do not make these drugs an ideal choice in a pandemic. By contrast, the neuraminidase inhibitors zanamivir and oseltamivir are proven to be much more effective for treatment and prophylaxis. Furthermore, resistance to zanamivir or oseltamivir has not yet been observed. Fred Hayden (University of Virginia, USA) presented modelling data on the impact of oseltamivir during pandemic influenza and showed his drug could decrease hospital visits and reduce the duration of symptoms. However, mid-way through the meeting delegates were surprised to
THE LANCET • Vol 357 • May 5, 2001
hear that GlaxoSmithKline would no longer be actively promoting zanamivir in the UK. This is an unexpected development since GlaxoSmithKline fought a distribution battle with the National Institute for Clinical Excellence, who initially did not approve the drug in 1999, then gave it the goahead last autumn. A relatively mild influenza season this year meant sales were down. An issue shared by delegates was how will drugs be made available in the advent of a pandemic. Obtaining drugs by prescription only will not suffice. Drugs really need to be made available over the counter. In addition, in the UK, at £24 a course, this treatment is considered expensive and would need to be made available at a subsidised cost. David Fedson (Pasteur-Merieux MSD, Lyon, France) pointed out that providing treatment and supplying vaccines on such a large scale
as required in pandemics is a political, economical and legal issue. “National governments need to nationalise their vaccination and antiviral facilities. It can’t be the governments alone that decide who receives the drug. We need a global programme where everyone takes responsibility.” On the issue of stockpiling, delegates agreed that each country has to have a contract with industry. Governments need to make a decision as to whether there needs to be a drug stockpile. “For this to happen we need to ascertain the stability of the drugs, then work with governments to persuade them to buy an equivalent amount of stockpile. Government and industry need to forge a partnership whereby they keep a supply of bulk chemical that could be mobilised immediately at the start of a pandemic”, concluded David Fedson. Pam Das
1419
For personal use. Only reproduce with permission from The Lancet Publishing Group.