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《英国医生杂志》
Abciximab reduces mortality in patients having a primary angioplasty for heart attack
The latest meta-analysis of abciximab for patients with heart attack shows that it can reduce the risk of reinfarction across the board (2.1% v 3.3%, P < 0.001; figure) but reduces mortality only when combined with primary angioplasty, not fibrinolysis. Among patients who had primary angioplasty, mortality six to 12 months after treatment was 4.4% in the abciximab groups compared with 6.2% among controls (odds ratio 0.69, 95% CI 0.52 to 0.92, P = 0.01). That translates to a number needed to treat of 55.6 to prevent one death.
Credit: JAMA
The authors analysed 11 randomised trials including more than 27 000 patients with heart attack and ST segment elevation. Most of them (85.3%) were given fibrinolytic drugs. Abciximab made no difference to short or long term mortality in these patients, but it did increase the risk of serious bleeding (5.2% v 3.1%, P < 0.001).
Abciximab reduces platelet aggregation by inhibiting glycoprotein IIb/IIIa. It's known to cause bleeding so patients having abciximab are usually given only half the recommended dose of fibrinolytic agent. All three fibrinolysis trials in this review adopted this strategy, but it wasn't enough to prevent a clear increase in the risk of serious bleeding. These findings combined with a neutral effect on mortality probably mean doctors should stop using abciximab in patients having fibrinolysis, say the authors.
JAMA 2005;293: 1759-65
Combined vaccine less effective than single meningitis C vaccine
A new combined vaccine against Streptococcus pneumoniae and group C Neisseria meningitidis has disappointed researchers in a randomised trial done in the United Kingdom. The vaccine, which was developed in response to overcrowded immunisation schedules, did not protect children as well as the single meningitis C vaccine. Worse, the combined vaccine reduced infants' immunological responses to other vaccines including diphtheria and Haemophilus influenzae type B (mean concentrations of antibodies against Hib 2.11 μg/ml in the combined vaccine group v 3.36 μg/ml in the control group; for diphtheria 0.74 μg/ml v 1.47 μg/ml; P < 0.05 for both comparisons). The trial included 240 infants who received the combined vaccine or a single meningitis C vaccine as part of their usual schedule at 2, 3, and 4 months. One month after the last dose, children who had the combined vaccine had lower antibody titres against meningitis C than children who had the regular single vaccine. The combined vaccine was also associated with more minor symptoms such as irritability (65.2% v 48.7%, P = 0.02), but only after the final dose. All the children who were given the combined vaccine launched a satisfactory immune response against Streptococcus pneumoniae.
The researchers say their results were unexpected and could signal the end for this particular combination of vaccines. Of course it's possible that a separate pneumococcal vaccine would also reduce the effectiveness of co-administered meningitis C vaccine (and maybe others). Further trials need to be done to find out.
JAMA 2005;293: 1751-8
New kind of anti-obesity drug shows promise
Rimonabant is the first in a new class of anti-obesity drug, which targets cannabinoid receptors in a complex neuroregulatory system known to control food intake and energy balance in laboratory animals. In the first clinical trial in 1507 obese humans, rimonabant and a reduced calorie diet induced a modest weight loss of 3.4-6.6 kg over one year, more than the weight loss achieved by controls taking a placebo (1.8 kg). A higher dose of the new drug (20 mg) worked better than the lower dose (5 mg) in this trial but was also associated with more side effects, most notably psychiatric symptoms including mood disturbance (1.5% v 0.3% in both placebo and lower dose groups).
The higher dose of rimonabant had a notable and beneficial impact on waist circumference, high density lipoprotein cholesterol, triglycerides, insulin resistance, and prevalence of the metabolic syndrome. Some of these improvements were independent of weight loss, and the authors hypothesise that the drug has direct effects on metabolism as well as food intake. It's more than likely. The endocannabinoid system has peripheral outposts in adipose tissue, gut, and skeletal muscle as well as acting centrally to regulate energy balance.
Lancet 2005;365: 1389-97
New test clarifies the link between kidney function and heart failure
People with chronic kidney disease have a higher risk for ischaemic heart disease than people with healthy kidneys. Renal function could be a useful predictor for heart failure too, according to a recent cohort study of 4383 older American men and women. Instead of using traditional measures of renal function, the researchers measured participants' serum concentrations of cystatin C, a new more sensitive marker that unlike creatinine is not influenced by age, sex, or muscle bulk. During a median follow-up of 8.3 years, 763 participants developed heart failure. The researchers found a clear, significant, and direct relation between risk of heart failure and serum concentration of cystatin C at baseline (figure) The hazard ratios for heart failure for each quintile of cystatin C from lowest to highest were 1.30 (95% CI 0.96 to 1.75), 1.44 (1.07 to 1.94), 1.58 (1.18 to 2.12), and 2.16 (1.61 to 2.91). The relation was independent of other risk factors for heart failure.
Credit: ANNALS OF INTERNAL MEDICINE
Serum concentration of creatinine and estimated glomerular filtration rate were not independently associated with risk of heart failure in this cohort, probably because they are blunter instruments for measuring renal function than cystatin C. We won't know for certain until more work is done in other cohorts, but the authors say their results are a promising start for cystatin C as a new improved test of renal function and an indicator of heart failure risk. Unfortunately, only one company in the United States can measure it.
Annals of Internal Medicine 2005;142: 497-505
Pacing prolongs survival for some patients with heart failure
Between a third and a quarter of patients with severe heart failure have intraventricular conduction defects that upset the timing of ventricular contraction (cardiac dyssynchrony). The heart becomes less efficient, and heart failure gets worse. Biventricular pacing is technically tricky but reduces overall mortality in these patients by about a third (figure). In a large randomised trial, 813 patients with severe heart failure and cardiac dyssynchrony were treated with the best medical treatments with or without biventricular pacing. Over the next 30 months, 20% of patients in the pacing group died compared with 30% of patients in the control group (hazard ratio 0.64, 95% confidence interval 0.48 to 0.85, P < 0.002), a clear result that, the authors say, establishes biventricular pacing as an effective treatment for patients with heart failure and cardiac dyssynchrony. They estimate that one death and three hospitalisations are prevented for every nine devices implanted, which is similar to the benefit such patients get from blockers.
Credit: NEW ENGLAND JOURNAL OF MEDICINE
Various US national guidelines already endorse ventricular pacing for selected patients, but questions remain about how best to select them. Intraventricular conduction defects prolong the QRS complex, which is relatively easy to see on an electrocardiogram. Echocardiography is more expensive but probably more accurate.
New England Journal of Medicine 2005;352: 1539-49
Big serving bowls encourage overeating
When 40 American graduate students were asked to help themselves to snacks before a super bowl game, those who were offered the snacks out of large bowls ate 56% more (142 calories per person) than students who were offered the same snacks out of smaller bowls. Researchers had put the same weight of peanuts, crisps, and pretzels on two different tables—one set with two large bowls and one set with four smaller bowls. They led the students to one or other alternately, told them to help themselves, then weighed the students' plates. The plates were weighed again an hour later after the super bowl game, and the researchers assumed the difference had been eaten, not thrown at the screen or at each other.
Students who were offered the big bowls took more and ate more than the others, and in a logistic regression analysis, bowl size was independently associated with snack consumption for men (P = 0.02) but not women. The authors think that big serving bowls at home, just like big crisp packets in the supermarket or supersized buckets of popcorn at the cinema, encourage overeating because they imply that eating more is acceptable, or even desirable. The authors suggest further trials to find out if the same "portion distortion" could be harnessed to better effect by serving large bowls of fruit and vegetables instead.
JAMA 2005;293: 1727-8
Prisoners may be awake and in pain during execution by lethal injection
An American attorney has called for an immediate halt to executions by lethal injection after the publication of a study proposing that at least some condemned prisoners are awake, paralysed, and in pain as they die. He and others canvassed six American states for information about their execution protocols, all of which use sequential injections of thiopental, a muscle relaxant (pancuronium), and potassium chloride to kill condemned prisoners. Adequate anaesthesia is essential. Without it the prisoners would feel asphyxiation and severe pain from the potassium chloride. But toxicology reports on postmortem blood samples from 49 prisoners executed in Arizona, Georgia, and North and South Carolina recorded a wide range of serum concentrations of thiopental, most of them too low to be effective: 43/49 prisoners had too little thiopental on board to stop them responding to pain and 21/49 (43%) prisoners had serum concentrations of thiopental consistent with being drowsy but responsive to voice commands. Officials in Texas and Virginia reported to researchers that untrained executioners administered the lethal sequence of drugs remotely from behind a wall or curtain and without monitoring the prisoner's level of consciousness, or anything else.
Whether or not postmortem blood samples give an accurate picture of premortem anaesthesia, the authors say their findings are serious enough to stop capital punishment by lethal injection pending a public review. They add that standards of care during human executions fall well below those enforced by the American Veterinary Medical Association for animals.
Lancet 2005;365: 1412-4
Hyponatraemia is common among Boston marathon competitors
Nearly 15 000 people ran the Boston marathon in 2002. An estimated 1900 competitors were hyponatraemic by the time they crossed the finish line, 90 of them critically hyponatraemic with serum concentrations of sodium below 130 mmol/l. In a sample of 488 runners recruited just before the start, hyponatraemia was associated with weight gain during the race (odds ratio 4.2, 95% CI 2.2 to 8.2) (figure), longer racing time (odds ratio for > 4 hours compared with < 3.5 hours, 7.4, 2.9 to 23.1), and a body mass index of less than 20. Women were more at risk than men in this study, but only because of their smaller body size and longer racing times. Drinking only water during the race and the use of non-steroidal anti-inflammatory drugs (NSAIDs) were not associated with hyponatraemia.
Credit: NEW ENGLAND JOURNAL OF MEDICINE
The researchers weighed competitors before and after the race and used weight gain as a proxy for fluid intake. Their findings confirm what many athletes already know—that drinking too much of anything during competitions can dangerously upset your electrolyte balance. Sports drinks containing electrolytes do not seem to help, probably because most of them are hypotonic. A typical drink contains only 18 mmol of sodium per litre. So what should marathon runners do? The authors suggest a weigh-in before and after lengthy training runs to help them titrate their hydration more precisely.
The latest meta-analysis of abciximab for patients with heart attack shows that it can reduce the risk of reinfarction across the board (2.1% v 3.3%, P < 0.001; figure) but reduces mortality only when combined with primary angioplasty, not fibrinolysis. Among patients who had primary angioplasty, mortality six to 12 months after treatment was 4.4% in the abciximab groups compared with 6.2% among controls (odds ratio 0.69, 95% CI 0.52 to 0.92, P = 0.01). That translates to a number needed to treat of 55.6 to prevent one death.
Credit: JAMA
The authors analysed 11 randomised trials including more than 27 000 patients with heart attack and ST segment elevation. Most of them (85.3%) were given fibrinolytic drugs. Abciximab made no difference to short or long term mortality in these patients, but it did increase the risk of serious bleeding (5.2% v 3.1%, P < 0.001).
Abciximab reduces platelet aggregation by inhibiting glycoprotein IIb/IIIa. It's known to cause bleeding so patients having abciximab are usually given only half the recommended dose of fibrinolytic agent. All three fibrinolysis trials in this review adopted this strategy, but it wasn't enough to prevent a clear increase in the risk of serious bleeding. These findings combined with a neutral effect on mortality probably mean doctors should stop using abciximab in patients having fibrinolysis, say the authors.
JAMA 2005;293: 1759-65
Combined vaccine less effective than single meningitis C vaccine
A new combined vaccine against Streptococcus pneumoniae and group C Neisseria meningitidis has disappointed researchers in a randomised trial done in the United Kingdom. The vaccine, which was developed in response to overcrowded immunisation schedules, did not protect children as well as the single meningitis C vaccine. Worse, the combined vaccine reduced infants' immunological responses to other vaccines including diphtheria and Haemophilus influenzae type B (mean concentrations of antibodies against Hib 2.11 μg/ml in the combined vaccine group v 3.36 μg/ml in the control group; for diphtheria 0.74 μg/ml v 1.47 μg/ml; P < 0.05 for both comparisons). The trial included 240 infants who received the combined vaccine or a single meningitis C vaccine as part of their usual schedule at 2, 3, and 4 months. One month after the last dose, children who had the combined vaccine had lower antibody titres against meningitis C than children who had the regular single vaccine. The combined vaccine was also associated with more minor symptoms such as irritability (65.2% v 48.7%, P = 0.02), but only after the final dose. All the children who were given the combined vaccine launched a satisfactory immune response against Streptococcus pneumoniae.
The researchers say their results were unexpected and could signal the end for this particular combination of vaccines. Of course it's possible that a separate pneumococcal vaccine would also reduce the effectiveness of co-administered meningitis C vaccine (and maybe others). Further trials need to be done to find out.
JAMA 2005;293: 1751-8
New kind of anti-obesity drug shows promise
Rimonabant is the first in a new class of anti-obesity drug, which targets cannabinoid receptors in a complex neuroregulatory system known to control food intake and energy balance in laboratory animals. In the first clinical trial in 1507 obese humans, rimonabant and a reduced calorie diet induced a modest weight loss of 3.4-6.6 kg over one year, more than the weight loss achieved by controls taking a placebo (1.8 kg). A higher dose of the new drug (20 mg) worked better than the lower dose (5 mg) in this trial but was also associated with more side effects, most notably psychiatric symptoms including mood disturbance (1.5% v 0.3% in both placebo and lower dose groups).
The higher dose of rimonabant had a notable and beneficial impact on waist circumference, high density lipoprotein cholesterol, triglycerides, insulin resistance, and prevalence of the metabolic syndrome. Some of these improvements were independent of weight loss, and the authors hypothesise that the drug has direct effects on metabolism as well as food intake. It's more than likely. The endocannabinoid system has peripheral outposts in adipose tissue, gut, and skeletal muscle as well as acting centrally to regulate energy balance.
Lancet 2005;365: 1389-97
New test clarifies the link between kidney function and heart failure
People with chronic kidney disease have a higher risk for ischaemic heart disease than people with healthy kidneys. Renal function could be a useful predictor for heart failure too, according to a recent cohort study of 4383 older American men and women. Instead of using traditional measures of renal function, the researchers measured participants' serum concentrations of cystatin C, a new more sensitive marker that unlike creatinine is not influenced by age, sex, or muscle bulk. During a median follow-up of 8.3 years, 763 participants developed heart failure. The researchers found a clear, significant, and direct relation between risk of heart failure and serum concentration of cystatin C at baseline (figure) The hazard ratios for heart failure for each quintile of cystatin C from lowest to highest were 1.30 (95% CI 0.96 to 1.75), 1.44 (1.07 to 1.94), 1.58 (1.18 to 2.12), and 2.16 (1.61 to 2.91). The relation was independent of other risk factors for heart failure.
Credit: ANNALS OF INTERNAL MEDICINE
Serum concentration of creatinine and estimated glomerular filtration rate were not independently associated with risk of heart failure in this cohort, probably because they are blunter instruments for measuring renal function than cystatin C. We won't know for certain until more work is done in other cohorts, but the authors say their results are a promising start for cystatin C as a new improved test of renal function and an indicator of heart failure risk. Unfortunately, only one company in the United States can measure it.
Annals of Internal Medicine 2005;142: 497-505
Pacing prolongs survival for some patients with heart failure
Between a third and a quarter of patients with severe heart failure have intraventricular conduction defects that upset the timing of ventricular contraction (cardiac dyssynchrony). The heart becomes less efficient, and heart failure gets worse. Biventricular pacing is technically tricky but reduces overall mortality in these patients by about a third (figure). In a large randomised trial, 813 patients with severe heart failure and cardiac dyssynchrony were treated with the best medical treatments with or without biventricular pacing. Over the next 30 months, 20% of patients in the pacing group died compared with 30% of patients in the control group (hazard ratio 0.64, 95% confidence interval 0.48 to 0.85, P < 0.002), a clear result that, the authors say, establishes biventricular pacing as an effective treatment for patients with heart failure and cardiac dyssynchrony. They estimate that one death and three hospitalisations are prevented for every nine devices implanted, which is similar to the benefit such patients get from blockers.
Credit: NEW ENGLAND JOURNAL OF MEDICINE
Various US national guidelines already endorse ventricular pacing for selected patients, but questions remain about how best to select them. Intraventricular conduction defects prolong the QRS complex, which is relatively easy to see on an electrocardiogram. Echocardiography is more expensive but probably more accurate.
New England Journal of Medicine 2005;352: 1539-49
Big serving bowls encourage overeating
When 40 American graduate students were asked to help themselves to snacks before a super bowl game, those who were offered the snacks out of large bowls ate 56% more (142 calories per person) than students who were offered the same snacks out of smaller bowls. Researchers had put the same weight of peanuts, crisps, and pretzels on two different tables—one set with two large bowls and one set with four smaller bowls. They led the students to one or other alternately, told them to help themselves, then weighed the students' plates. The plates were weighed again an hour later after the super bowl game, and the researchers assumed the difference had been eaten, not thrown at the screen or at each other.
Students who were offered the big bowls took more and ate more than the others, and in a logistic regression analysis, bowl size was independently associated with snack consumption for men (P = 0.02) but not women. The authors think that big serving bowls at home, just like big crisp packets in the supermarket or supersized buckets of popcorn at the cinema, encourage overeating because they imply that eating more is acceptable, or even desirable. The authors suggest further trials to find out if the same "portion distortion" could be harnessed to better effect by serving large bowls of fruit and vegetables instead.
JAMA 2005;293: 1727-8
Prisoners may be awake and in pain during execution by lethal injection
An American attorney has called for an immediate halt to executions by lethal injection after the publication of a study proposing that at least some condemned prisoners are awake, paralysed, and in pain as they die. He and others canvassed six American states for information about their execution protocols, all of which use sequential injections of thiopental, a muscle relaxant (pancuronium), and potassium chloride to kill condemned prisoners. Adequate anaesthesia is essential. Without it the prisoners would feel asphyxiation and severe pain from the potassium chloride. But toxicology reports on postmortem blood samples from 49 prisoners executed in Arizona, Georgia, and North and South Carolina recorded a wide range of serum concentrations of thiopental, most of them too low to be effective: 43/49 prisoners had too little thiopental on board to stop them responding to pain and 21/49 (43%) prisoners had serum concentrations of thiopental consistent with being drowsy but responsive to voice commands. Officials in Texas and Virginia reported to researchers that untrained executioners administered the lethal sequence of drugs remotely from behind a wall or curtain and without monitoring the prisoner's level of consciousness, or anything else.
Whether or not postmortem blood samples give an accurate picture of premortem anaesthesia, the authors say their findings are serious enough to stop capital punishment by lethal injection pending a public review. They add that standards of care during human executions fall well below those enforced by the American Veterinary Medical Association for animals.
Lancet 2005;365: 1412-4
Hyponatraemia is common among Boston marathon competitors
Nearly 15 000 people ran the Boston marathon in 2002. An estimated 1900 competitors were hyponatraemic by the time they crossed the finish line, 90 of them critically hyponatraemic with serum concentrations of sodium below 130 mmol/l. In a sample of 488 runners recruited just before the start, hyponatraemia was associated with weight gain during the race (odds ratio 4.2, 95% CI 2.2 to 8.2) (figure), longer racing time (odds ratio for > 4 hours compared with < 3.5 hours, 7.4, 2.9 to 23.1), and a body mass index of less than 20. Women were more at risk than men in this study, but only because of their smaller body size and longer racing times. Drinking only water during the race and the use of non-steroidal anti-inflammatory drugs (NSAIDs) were not associated with hyponatraemia.
Credit: NEW ENGLAND JOURNAL OF MEDICINE
The researchers weighed competitors before and after the race and used weight gain as a proxy for fluid intake. Their findings confirm what many athletes already know—that drinking too much of anything during competitions can dangerously upset your electrolyte balance. Sports drinks containing electrolytes do not seem to help, probably because most of them are hypotonic. A typical drink contains only 18 mmol of sodium per litre. So what should marathon runners do? The authors suggest a weigh-in before and after lengthy training runs to help them titrate their hydration more precisely.