What's new in the other general journals
http://www.100md.com
《英国医生杂志》
Until recently, hormone replacement therapy (HRT) was thought to be good for incontinence. The latest analyses from the women's health initiative trials show that it isn't. In these two placebo controlled trials, HRT with or without progestogen increased the risk of incontinence in women who were originally continent and made symptoms worse for women who already had problems. The risks were highest for stress incontinence: hormone replacement doubled the risk of new symptoms compared with placebo (relative risk 1.87 with combined HRT and 2.15 with oestrogen alone). Any kind of hormone therapy made existing symptoms more frequent, more bothersome, and more likely to limit women's activities compared with placebo.
The two women's health initiative trials were set up originally to test the impact of oestrogen with or without progestogen on heart disease and osteoporosis in healthy postmenopausal women. More than 23 000 women were included in the analysis of incontinence after one year of treatment. Women in the active treatment groups took oestrogen plus medroxyprogesterone or oestrogen alone.
Does this spell the end for hormone replacement therapy in the management of incontinence? The authors don't say so, but a linked editorial warns doctors to stop prescribing long term oestrogens as a treatment for any kind of incontinence in postmenopausal women.
JAMA 2005;293: 935-48
JAMA 2005;293: 998-1001
Ciprofloxacin is better than co-amoxiclav for cystitis
Cystitis is common and usually easy to treat. But bacterial resistance to the traditional co-trimoxazole has increased the prescribing of alternatives such asco-amoxiclav and ciprofloxacin. In the first head to head trial, ciprofloxacin was significantly more effective than co-amoxiclav, curing more women of their symptoms, their infection, and their vaginal reservoir of bacteria. A total of 322 women with symptoms of cystitis and a positive urine culture (mostly Escherichia coli) took co-amoxiclav (500 mg amoxicillin, 125 mg clavulanate) or ciprofloxacin (250 mg) twice daily for three days and were followed up for four months.
Co-amoxiclav cured 93/160 (58%) women of their symptoms, ciprofloxacin cured 124/162 (77%)—a significant difference that appeared within two weeks of treatment (figure). This held true even when women with resistant strains were excluded—so co-amoxiclav's poorer performance was not due to a higher incidence of bacterial resistance. Ciprofloxacin was also better at eradicating bacteria from the bladder (153/161 (95%) v 118/156 (76%)) and from the vagina (90% v 55%).
Credit: JAMA
Fears about the impact of fluoroquinolones such as ciprofloxacin on bacterial resistance continue to drive the search for effective but less damaging alternatives. This trial suggests that co-amoxiclav is not one of them.
JAMA 2005;293: 949-55
Most 2 year old children have encountered herpesvirus 6
Human herpesvirus 6 (HHV-6) causes an unpleasant illness in infants and children, but we know little about its epidemiology. To find out more, researchers studied a population based cohort of 277 children from birth to 2 years by repeatedly analysing their saliva for viral DNA. Primary infection was common: 40% of children were infected by 1 year of age, increasing to 77% by the age of 2 (figure). The peak age of acquisition was between 9 and 21 months. Infection made most children ill (93%), and symptoms included fever (57%), irritability (69%), runny nose (65%), rash (31%), roseola (23%), and diarrhoea (26%). The illness lasted for a median of nine days, significantly longer than other childhood illnesses reported during the study. Nearly half the ill children were taken to a doctor, indicating that symptoms of HHV-6 infection are often worrying to parents. None of the infected children had seizures, although studies of children in emergency departments have reported an incidence of up to 13%.
Credit: NEJM
Girls were more likely to acquire the virus than boys (hazard ratio 1.7, 95% CI 1.2 to 2.4), as were children with older brothers or sisters (hazard ratio 2.1, 1.4 to 2.9). In this study, infected children carried on shedding HHV-6 for at least 12 months, giving them plenty of opportunity to infect younger siblings.
New England Journal of Medicine 2005;352: 768-76
Breast cancer genes are associated with non-invasive breast cancer
Women with non-invasive breast cancer (ductal carcinoma in situ) are just as likely as women with invasive breast cancer to have a mutation in one or other of the breast cancer genes, a survey has found. Researchers tested 369 American women with ductal carcinoma in situ who had been recruited for a different case-control study. Three (0.8%) of them had disease-associated mutations in the BRCA1 gene and nine (2.4%) in the BRCA2 gene—figures similar to those for women with invasive breast cancer.
In this survey, which had a bias towards younger women, the mutations were associated with a family history of breast cancer (odds ratio 3.7, 95% CI 1.1 to 12.4), diagnosis at a young age (odds ratio 3.4, 1.0 to 11.7), and a personal history of ovarian cancer. These findings suggest that ductal carcinoma in situ is part of the spectrum of cancers associated with mutations in BRCA1 and BRCA2. Women with non-invasive breast cancer and a family or personal history suggestive of a cancer-causing mutation should be offered the same intensive screening and follow up as women with invasive breast cancer, say the authors.
JAMA 2005;293: 964-9
Clotting factor looks promising for patients with haemorrhagic stroke
In a preliminary trial, recombinant activated factor VIIa (rFVIIa) reduced the risk of rebleeding, death, or disability compared with placebo in patients with haemorrhagic stroke. A total of 399 patients who presented within four hours of an intracerebral bleed, confirmed by computed tomography, were given a low, medium, or high dose of the clotting factor or a placebo. Repeat scanning at 24 and 72 hours showed that the haematoma had grown nearly 50% less in patients who had received the clotting factor (mean growth 4.2 ml in the three treatment groups combined v 8.7 ml in the placebo group), and the effect of treatment was greatest with the highest dose. After three months, 29% of the control patients and 18% in the treated groups had died—a significant reduction in mortality of 38% with the clotting factor (figure).
Credit: NEJM
The results look hopeful, but not enough to establish a new treatment. Serious side effects remain a worry. In this trial, seven myocardial infarctions and nine cerebral infarctions (5% of all patients treated with clotting factor) occurred in the treatment groups, and none in the placebo group. The authors say further work on safety is a priority.
New England Journal of Medicine 2005;352: 777-85
Bipolar disorder is often missed in primary care patients
When researchers screened consecutive attenders at a primary care clinic in New York, they found that nearly 1 in 10 (112/1157, 9.8%) had a history of bipolar disorder. Only nine of these patients had ever been diagnosed, and only seven had taken a mood stabilising agent such as lithium in the past month. Most (75/112, 68%) had current symptoms of depression, anxiety, or substance misuse. Primary care doctors at the clinic had recorded a diagnosis of depression in half the patients who screened positive, but they consistently missed the bipolar history, increasing the risk of hypomania and other adverse effects that can be triggered by inappropriate treatment with antidepressants. This study found more patients with bipolar disorder than expected—possibly because it took place in an urban primary care clinic that served a low income population (90% of patients screened reported an annual income below $18 000 a year (￡9400, 13 600). Even so, the researchers say, it's clear that patients with this disabling mental illness are being missed.
JAMA 2005;293: 956-63
New mutation is responsible for drug resistance in patients with lung cancer
Non-small cell lung cancer is a leading cause of death from cancer in the developed world. Standard chemotherapy is not particularly effective, but 10-20% of patients respond well to drugs which target the receptor for epidermal growth factor, thanks to specific mutations in the receptor's gene. Even these patients relapse in the end, however. No one is quite sure why, but a biochemical study of one patient's tumour and some clever structural modelling suggest that a second mutation in the same gene could be responsible. The tumour specimens came from a 71 year old man with an adenocarcinoma containing one of the lucky mutations. Treatment with gefitinib gave him two years free of cancer. When his tumour recurred, researchers compared samples from the recurrence with samples from his original tumour. Both had the first lucky mutation, but the recurrence also had a new and less welcome mutation—a single base pair change that switched off his sensitivity to gefitinib. Something similar can happen to patients with chronic myeloid leukaemia, and second generation drugs have been developed to overcome it. These researchers hope their findings will guide similar developments in patients with non-small cell lung cancer.
New England Journal of Medicine 2005;352: 786-92
Routine nutritional supplements don't help after stroke
Three large randomised trials reported last week on the impact of supplementary feeding in inpatients with stroke. The first, which included only patients well enough to eat, found that oral protein supplements had no effect on the risk of death or poor outcome, compared with usual hospital meals (figure). The second failed to find any important benefits from early tube feeding for patients who couldn't swallow, although there was a non-significant reduction in deaths over six months; the third indicated that patients who needed tube feeding did worse if they were fed through a percutaneous endoscopic gastrostomy (PEG) tube rather than a nasogastric tube (absolute increase in risk of death or poor outcome 7.8%, 95% CI 0% to 15.5%). All three trials ended early because the researchers ran out of money, so they were smaller and less robust than intended. Even so, the researchers recruited over 5000 patients, and they say others are unlikely to do any better. For now, they caution against routine oral supplements for patients who can eat, and against routine PEG tube feeding for patients who can't.
Credit: LANCET
Lancet 2005;365: 755-63
Lancet 2005;365: 764-72
Evidence for mass vaccination of young children against influenza is poor
Disease prevention authorities in the United States and Canada are considering extending their influenza vaccination programme to children under 2 years, although a recent systematic review found little evidence to support the move. A close look at data from 24 studies showed that live attenuated vaccines work best in children, reducing the risk of confirmed influenza by 79% (relative risk 0.21, 95% CI 0.08 to 0.52)—but only in children over 2 years. As expected, live attenuated vaccines were less effective against unconfirmed "influenza-like" illnesses, reducing the risk by only 38% in children over 2 years (relative risk 0.62, 0.57 to 0.67). Inactivated vaccines don't seem to work as well as live attenuated vaccines, and in this review at least, did not work at all in children under 2.
Few studies looked at complications such as chest infections, acute otitis media, or hospital admission, and those that did found no difference between children who had been vaccinated and those who had not. The authors found no data at all on mortality. They conclude that much more work needs to be done before mass vaccination of young children against influenza becomes public policy.
The two women's health initiative trials were set up originally to test the impact of oestrogen with or without progestogen on heart disease and osteoporosis in healthy postmenopausal women. More than 23 000 women were included in the analysis of incontinence after one year of treatment. Women in the active treatment groups took oestrogen plus medroxyprogesterone or oestrogen alone.
Does this spell the end for hormone replacement therapy in the management of incontinence? The authors don't say so, but a linked editorial warns doctors to stop prescribing long term oestrogens as a treatment for any kind of incontinence in postmenopausal women.
JAMA 2005;293: 935-48
JAMA 2005;293: 998-1001
Ciprofloxacin is better than co-amoxiclav for cystitis
Cystitis is common and usually easy to treat. But bacterial resistance to the traditional co-trimoxazole has increased the prescribing of alternatives such asco-amoxiclav and ciprofloxacin. In the first head to head trial, ciprofloxacin was significantly more effective than co-amoxiclav, curing more women of their symptoms, their infection, and their vaginal reservoir of bacteria. A total of 322 women with symptoms of cystitis and a positive urine culture (mostly Escherichia coli) took co-amoxiclav (500 mg amoxicillin, 125 mg clavulanate) or ciprofloxacin (250 mg) twice daily for three days and were followed up for four months.
Co-amoxiclav cured 93/160 (58%) women of their symptoms, ciprofloxacin cured 124/162 (77%)—a significant difference that appeared within two weeks of treatment (figure). This held true even when women with resistant strains were excluded—so co-amoxiclav's poorer performance was not due to a higher incidence of bacterial resistance. Ciprofloxacin was also better at eradicating bacteria from the bladder (153/161 (95%) v 118/156 (76%)) and from the vagina (90% v 55%).
Credit: JAMA
Fears about the impact of fluoroquinolones such as ciprofloxacin on bacterial resistance continue to drive the search for effective but less damaging alternatives. This trial suggests that co-amoxiclav is not one of them.
JAMA 2005;293: 949-55
Most 2 year old children have encountered herpesvirus 6
Human herpesvirus 6 (HHV-6) causes an unpleasant illness in infants and children, but we know little about its epidemiology. To find out more, researchers studied a population based cohort of 277 children from birth to 2 years by repeatedly analysing their saliva for viral DNA. Primary infection was common: 40% of children were infected by 1 year of age, increasing to 77% by the age of 2 (figure). The peak age of acquisition was between 9 and 21 months. Infection made most children ill (93%), and symptoms included fever (57%), irritability (69%), runny nose (65%), rash (31%), roseola (23%), and diarrhoea (26%). The illness lasted for a median of nine days, significantly longer than other childhood illnesses reported during the study. Nearly half the ill children were taken to a doctor, indicating that symptoms of HHV-6 infection are often worrying to parents. None of the infected children had seizures, although studies of children in emergency departments have reported an incidence of up to 13%.
Credit: NEJM
Girls were more likely to acquire the virus than boys (hazard ratio 1.7, 95% CI 1.2 to 2.4), as were children with older brothers or sisters (hazard ratio 2.1, 1.4 to 2.9). In this study, infected children carried on shedding HHV-6 for at least 12 months, giving them plenty of opportunity to infect younger siblings.
New England Journal of Medicine 2005;352: 768-76
Breast cancer genes are associated with non-invasive breast cancer
Women with non-invasive breast cancer (ductal carcinoma in situ) are just as likely as women with invasive breast cancer to have a mutation in one or other of the breast cancer genes, a survey has found. Researchers tested 369 American women with ductal carcinoma in situ who had been recruited for a different case-control study. Three (0.8%) of them had disease-associated mutations in the BRCA1 gene and nine (2.4%) in the BRCA2 gene—figures similar to those for women with invasive breast cancer.
In this survey, which had a bias towards younger women, the mutations were associated with a family history of breast cancer (odds ratio 3.7, 95% CI 1.1 to 12.4), diagnosis at a young age (odds ratio 3.4, 1.0 to 11.7), and a personal history of ovarian cancer. These findings suggest that ductal carcinoma in situ is part of the spectrum of cancers associated with mutations in BRCA1 and BRCA2. Women with non-invasive breast cancer and a family or personal history suggestive of a cancer-causing mutation should be offered the same intensive screening and follow up as women with invasive breast cancer, say the authors.
JAMA 2005;293: 964-9
Clotting factor looks promising for patients with haemorrhagic stroke
In a preliminary trial, recombinant activated factor VIIa (rFVIIa) reduced the risk of rebleeding, death, or disability compared with placebo in patients with haemorrhagic stroke. A total of 399 patients who presented within four hours of an intracerebral bleed, confirmed by computed tomography, were given a low, medium, or high dose of the clotting factor or a placebo. Repeat scanning at 24 and 72 hours showed that the haematoma had grown nearly 50% less in patients who had received the clotting factor (mean growth 4.2 ml in the three treatment groups combined v 8.7 ml in the placebo group), and the effect of treatment was greatest with the highest dose. After three months, 29% of the control patients and 18% in the treated groups had died—a significant reduction in mortality of 38% with the clotting factor (figure).
Credit: NEJM
The results look hopeful, but not enough to establish a new treatment. Serious side effects remain a worry. In this trial, seven myocardial infarctions and nine cerebral infarctions (5% of all patients treated with clotting factor) occurred in the treatment groups, and none in the placebo group. The authors say further work on safety is a priority.
New England Journal of Medicine 2005;352: 777-85
Bipolar disorder is often missed in primary care patients
When researchers screened consecutive attenders at a primary care clinic in New York, they found that nearly 1 in 10 (112/1157, 9.8%) had a history of bipolar disorder. Only nine of these patients had ever been diagnosed, and only seven had taken a mood stabilising agent such as lithium in the past month. Most (75/112, 68%) had current symptoms of depression, anxiety, or substance misuse. Primary care doctors at the clinic had recorded a diagnosis of depression in half the patients who screened positive, but they consistently missed the bipolar history, increasing the risk of hypomania and other adverse effects that can be triggered by inappropriate treatment with antidepressants. This study found more patients with bipolar disorder than expected—possibly because it took place in an urban primary care clinic that served a low income population (90% of patients screened reported an annual income below $18 000 a year (￡9400, 13 600). Even so, the researchers say, it's clear that patients with this disabling mental illness are being missed.
JAMA 2005;293: 956-63
New mutation is responsible for drug resistance in patients with lung cancer
Non-small cell lung cancer is a leading cause of death from cancer in the developed world. Standard chemotherapy is not particularly effective, but 10-20% of patients respond well to drugs which target the receptor for epidermal growth factor, thanks to specific mutations in the receptor's gene. Even these patients relapse in the end, however. No one is quite sure why, but a biochemical study of one patient's tumour and some clever structural modelling suggest that a second mutation in the same gene could be responsible. The tumour specimens came from a 71 year old man with an adenocarcinoma containing one of the lucky mutations. Treatment with gefitinib gave him two years free of cancer. When his tumour recurred, researchers compared samples from the recurrence with samples from his original tumour. Both had the first lucky mutation, but the recurrence also had a new and less welcome mutation—a single base pair change that switched off his sensitivity to gefitinib. Something similar can happen to patients with chronic myeloid leukaemia, and second generation drugs have been developed to overcome it. These researchers hope their findings will guide similar developments in patients with non-small cell lung cancer.
New England Journal of Medicine 2005;352: 786-92
Routine nutritional supplements don't help after stroke
Three large randomised trials reported last week on the impact of supplementary feeding in inpatients with stroke. The first, which included only patients well enough to eat, found that oral protein supplements had no effect on the risk of death or poor outcome, compared with usual hospital meals (figure). The second failed to find any important benefits from early tube feeding for patients who couldn't swallow, although there was a non-significant reduction in deaths over six months; the third indicated that patients who needed tube feeding did worse if they were fed through a percutaneous endoscopic gastrostomy (PEG) tube rather than a nasogastric tube (absolute increase in risk of death or poor outcome 7.8%, 95% CI 0% to 15.5%). All three trials ended early because the researchers ran out of money, so they were smaller and less robust than intended. Even so, the researchers recruited over 5000 patients, and they say others are unlikely to do any better. For now, they caution against routine oral supplements for patients who can eat, and against routine PEG tube feeding for patients who can't.
Credit: LANCET
Lancet 2005;365: 755-63
Lancet 2005;365: 764-72
Evidence for mass vaccination of young children against influenza is poor
Disease prevention authorities in the United States and Canada are considering extending their influenza vaccination programme to children under 2 years, although a recent systematic review found little evidence to support the move. A close look at data from 24 studies showed that live attenuated vaccines work best in children, reducing the risk of confirmed influenza by 79% (relative risk 0.21, 95% CI 0.08 to 0.52)—but only in children over 2 years. As expected, live attenuated vaccines were less effective against unconfirmed "influenza-like" illnesses, reducing the risk by only 38% in children over 2 years (relative risk 0.62, 0.57 to 0.67). Inactivated vaccines don't seem to work as well as live attenuated vaccines, and in this review at least, did not work at all in children under 2.
Few studies looked at complications such as chest infections, acute otitis media, or hospital admission, and those that did found no difference between children who had been vaccinated and those who had not. The authors found no data at all on mortality. They conclude that much more work needs to be done before mass vaccination of young children against influenza becomes public policy.