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N Engl J Med 2007;357:2277-84 [PubMed]
Computed tomography (CT) generates ionising radiation, so each scan carries a small but detectable increase in the lifetime risk of cancer. For most people, the diagnostic benefit of a scan outweighs the risk, but at least two experts are getting worried about the effects on the US population of a sharp rise in the use of computed tomography for diagnosis and screening. They estimate that 1-2% of all cancers in the US are attributable to radiation from CT scansscans.
Children are particularly vulnerable. They are more radiosensitive than adults and have more remaining years of life in which to develop cancer. In the US, 6-11% of scans are performed in children, often to diagnose or rule out appendicitis. Ultrasound might be a better option, say the experts. Other questionable uses of CT, particularly multiple scans, include the investigation of seizures, chronic headaches, or blunt trauma. Using CT defensively is even harder to justify, but not uncommon.
Anecdotal evidence indicates that up to a third of CT scans could be replaced by other diagnostic tests, or not done at all, say the experts. If that is true, about 20 million adults and more than a million children in the US are irradiated unnecessarily each year.
JAMA 2007;298:2381-8 [PubMed]
If an older woman broke her wrist falling from a standing height or less she would be investigated for osteoporosis. If the same woman broke her wrist in a car crash she wouldn’t because the received wisdom is that “high trauma” fractures are not linked to bone mineral density. Researchers from the US recently put this wisdom to the test and found it to be wrong. Analysis of data from two large cohorts showed a clear, independent, and statistically significant association between low bone mineral density and high trauma fractures in men and women over 65. A drop of one standard deviation in bone mineral density at the hip was associated with a 47% (95% CI 28% to 69%) increase in risk of fracture for women and a 58% (27% to 97%) increase for men. In women, one high trauma fracture predicted another, just like conventional osteoporotic fractures.
If both high and low trauma fractures are associated with osteoporosis, the conventional classification of fractures is unhelpful and should be scrapped, say the authors. Older men and women who break bones skiing or falling from trees should be assessed for osteoporosis in the same way as those who simply trip over a curb.
JAMA 2007;298:2399-405 [PubMed]
Manipulating glucose metabolism with infusions of glucose, insulin, and potassium does not prolong survival in patients with heart attack, according to analyses of data from nearly 23000 patientspatients.
In two key trials, 9.7% (1108/11462) of treated patients and 9.3% (1068/11481) of controls died within 30 days of randomisation (hazard ratio 1.04, 95% CI 0.96 to 1.13). Just under 17% of both groups developed heart failure (0.99, 0.93 to 1.06). Just over a fifth had one or other outcome.
The combined analysis also suggests that the infusions, started soon after admission and continued for 24 hours, increased patients’ risk of death (6.2% v 5.5%; 1.13, 1.02 to 1.26) or heart failure in the first three days. Extra fluid was probably to blame, say the researchers. Men and women treated with glucose, potassium, and insulin had a net gain of almost 600 ml compared with controls. They also had higher serum concentrations of potassium and glucose at the end of treatment. All three independently predicted death at three days.
Patients in both trials had identical infusions of 25% glucose containing 50 U/l of regular insulin and 80 mEq/l of potassium. The researchers failed to find any subgroup likely to benefit, including patients treated within four hours of the onset of symptoms.
JAMA 2007;298:2409-11 [PubMed]
People with dementia are usually diagnosed only when they develop obvious symptoms, usually memory loss. Wouldn’t it be better to screen everyone over a certain age and pick up cases earlier?
Not yet, say three commentators. Firstly, no tests are reliable enough to diagnose (or predict) dementia in asymptomatic people. No biomarkers are available, imaging is impractical and expensive, and cognitive tests would misclassify a substantial proportion of people screened. Secondly, doubts remain over the clinical effectiveness of all available treatments including drugs. No treatment can prevent dementia or halt it at an early enough stage to justify screening. Thirdly, evidence suggests that older people who are well don’t want to be screened. A diagnosis of dementia—even at an early stage—could stop them from driving, curb their independence, and have an adverse effect on their health and life insurance. Finally, no good evidence shows that screening and early treatment—in a comprehensive dementia care programme, for example—improve the outcomes that matter to patients. Screening and treatment are expensive, logistically difficult, and could have a negative effect on other primary care services.
For now, primary care doctors should stick to case finding based on clinical suspicion, say the commentators, in line with current government recommendations in both the US and the UK.
Lancet 2007;370:1840-6 [PubMed]
On 21 June 2007, an Indian man from Kerala arrived in the Italian village of Castiglione di Cervia to visit relatives. He developed a high fever two days later, which triggered an epidemic of similar fevers in the residents of this village and a neighbouring one. A swift investigation led public health officials to the chikungunya virus, a tropical infection spread by some species of mosquito. One of them, Aedes albopictus was already resident in Italy when the index case arrived (having got there on a shipment of old tyres from the US in 1990), and the dense population of mosquitoes around Castiglione di Cervia quickly picked up the virus and passed it on to a total of 205 people in the region. Men, women, and children of all ages were affected, although the attack rate was highest in older residents. High fever, joint pains, and rashes were the most common symptoms, according to an account of the outbreak. One 83 year old man died.
This is the first report of chikungunya virus in Europe, says a linked comment (p 1805). But other vector borne diseases such as blue tongue are already here thanks to the convergence of climate change, rapid international travel, and poor vector control. Public health authorities in rich temperate countries should prepare for more such outbreaks.
Mild cognitive impairment is a loose term used in a heterogeneous group of older people who have memory loss but no other signs of dementia. No standard definition exists, and we don’t know how many people with mild cognitive impairment eventually develop dementia. Clinical trials of cholinesterase inhibitors donepezil, rivastigmine, and galantamine went ahead despite these uncertainties, but a systematic review recently concluded that they don’t workwork.
The authors reviewed eight placebo controlled trials. None of the cholinesterase inhibitors helped delay the onset of dementia or improve scores in the dozens of tests and tasks used as outcome measures by the various trials. Adverse events were common, and people taking cholinesterase inhibitors were consistently more likely to drop out of treatment than those taking a placebo. Data on deaths were too badly reported to be useful.
Seven of the eight trials were totally or partially funded by drug companies. Five of them remain unpublished and the review’s authors were unable to retrieve the results of two trials, despite asking the investigators and their institutions. Many had important weaknesses.
The effects of cholinesterase inhibitors are questionable even for people with established dementia, say the authors. There is no evidence that they help anyone with mild cognitive impairment.
N Engl J Med 2007;357:2237-47 [PubMed]
N Engl J Med 2007;357:2227-36 [PubMed]
Idiopathic thrombocytopenic purpura is an autoimmune disease caused by IgG antibodies attacking circulating platelets. Treatments to suppress, circumvent, or otherwise disable the autoimmune process, such as glucocorticoids or splenectomy, don’t always work, so researchers are currently developing new agents to try and stimulate platelet production instead. The latest is a small molecule that mimics thrombopoietin, the growth factor that regulates platelet production in bone marrowmarrow.
Preliminary results look encouraging. When the manufacturers tested eltrombopag in 118 adults with hard to treat and enduring idiopathic thrombocytopenia, six weeks’ treatment with 50 mg or 75 mg of the drug increased platelet counts significantly more than placebo. The drug also increased platelet counts in a second small trial in patients with thrombocytopenia, hepatitis C, and cirrhosis.
A new pill for thrombocytopenia would be welcome, says an editorial (p 2299). But we still have a lot learn about eltrombopag and it is too early to say what effect, if any, the drug will have on clinical practice. Long term effects and side effects are unknown. Previous attempts to manipulate platelet production—with recombinant thrombopoietin—ended in bone marrow fibrosis and the development of antibodies against the natural as well as the synthetic growth factor.