All you need to read in the other general journals
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39562.643426.80 (Published 01 May 2008) Cite this as: BMJ 2008;336:984
Heparin contaminant linked to clusters of anaphylaxis worldwide
Earlier this year, clusters of serious hypersensitivity reactions to heparin alerted regulatory authorities in the US and Germany to a possible contaminant in the supply. An unusual oversulphated form of chondroitin sulphate has since been found in heparin used in over a dozen countries, and recent experiments confirm that the contaminant can cause the kind of symptoms reported by patients worldwide⇑.
Scientists used contaminated and clean preparations of heparin from the US Food and Drug Administration to test the biological activity of oversulphated chondroitin sulphate in human plasma and in pigs. The contaminant activated the kinin-kallikrein pathway in human plasma and induced potent anaphylotoxins derived from complement (C3a and C5a). Both could explain the hypotension and other allergic symptoms common to many cases. Intravenous infusions of contaminated heparin or synthetic oversulphated chondroitin sulphate caused hypotension in pigs. The cardiovascular changes were accompanied by an increase in kallikrein activity.
The US authorities first encountered the problem in patients having dialysis, but other cases soon came to light, including 81 potentially related deaths. One manufacturer recalled all their heparin products at the end of February. Deaths in the US associated with heparin returned to expected numbers in March.
Current treatments for intestinal worms are inadequate
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Intestinal nematodes infest hundreds of millions of children and adults worldwide, and experts estimate that they cause a global burden of disease comparable to malaria. The World Health Organization wants three quarters of those at risk treated regularly by the year 2010. Four drug treatments are currently available so researchers carefully reviewed the evidence to find out which drugs were likely to be most effective against the most common soil transmitted nematodes Ascaris lumbricoides, Trichuris trichiura, and the hookworms Ancylostoma duodenale and Necator americanus.
It was hard going. Many of the 20 trials they found were old, small, badly done, and hard to interpret. No trials tested modern doses of levamisole, and publication bias hampered evaluation of the rest (albendazole, mebendazole, and pyrantel pamoate).
Despite these limitations, the researchers are fairly sure that single doses of albendazole, mebendazole, and pyrantel pamoate are an effective treatment for A lumbricoides; albendazole is probably the best treatment for hookworm; and nothing works particularly well against T trichiura.
The world’s poor need new drugs to protect them from the serious morbidity caused by these neglected parasites, say the researchers. They also need proper trials to guide better use of the drugs we already have.
PCI and CABG associated with comparable survival in patients with diseased left coronary arteries
Coronary artery bypass grafting (CABG) is the standard revascularisation treatment for most people with ischaemic heart disease affecting the left main coronary artery. Percutaneous coronary intervention (PCI) with stenting is also possible, and randomised trials comparing the two are still ongoing. In the meantime, doctors must rely on observational data from registries to get an idea of their relative effectiveness and safety.
An analysis of data from the main registry in Korea suggests that overall survival after PCI is similar to survival after CABG in carefully matched patients suitable for either procedure (hazard ratio for the stenting group 1.18, 95% CI 0.77 to 1.80). Follow-up in both groups lasted about three years. The authors found no difference in the risk of death, heart attack, or stroke (1.10, 0.75 to 1.62). But, as expected, patients who had PCI were more likely to need further revascularisation (4.76, 2.80 to 8.11).
The authors then did separate comparisons for those who had bare metal or drug eluting stents. They found a hint that drug eluting stents might be associated with worse outcome than CABG (hazard ratio for composite outcome 1.4, 0.88 to 2.22). The difference wasn’t statistically significant, but this analysis was too weak to rule out the possibility of harm.
Clinical monitoring of HIV can work
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In developed countries, people with HIV can monitor their viral load and switch drugs when it increases beyond a certain threshold (virological treatment failure). In developing countries, the switch from first line to second line drugs is usually triggered by HIV related symptoms, or at most a falling CD4 count. Does it matter⇑?
Not much, say researchers from the UK and Denmark. They modelled what would happen to people with HIV treated according to their viral load, their clinical symptoms, or their CD4 count and found that survival over five years was roughly the same for all three strategies (83%, 82%, and 82% of potential life years lived). After 20 years, the model suggested a slight advantage for viral load monitoring, mainly because of a reduction in drug resistance.
The researchers assumed adults would begin first line treatment with stavudine, lamivudine, and nevirapine when they developed stage 4 HIV disease. They modelled various strategies of clinical monitoring. In all of them adults were switched to second line drugs if they developed new and serious HIV related events after at least six months of first line treatment.
These findings suggest that laboratory monitoring isn’t essential for effective use of antiretrovirals in resource poor settings, say the researchers. Lack of sophisticated tests must not be allowed to hold up the desperately needed expansion of access to antiretroviral drugs.
Indian registry reveals gaps in the treatment of acute coronary syndrome
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A new registry holding data on patients with acute coronary syndrome from 50 cities across India shows that many are poor, take too long to get to hospital, and miss out on relatively cheap but life saving treatments. Three quarters of more than 20 000 patients registered over four years paid for their own treatment. Poor patients were less likely than others to receive all types of drug treatment except aspirin and, as a result, were more likely to die within a month of admission (8.2% (poorest) v 5.5% (richest)). Few patients of any social class had a percutaneous coronary intervention (7.5%).
Only one in 20 of the whole cohort went to hospital in an ambulance, despite the urgency of their symptoms. The rest went in private cars or public transport. About two thirds made it within 12 hours, but only 38.1% got to hospital within four hours.
Patients in this registry were a decade younger than patients in similar registries from developed countries (mean age 57) and a greater proportion had myocardial infarction with ST segment elevation on their admitting electrocardiogram. Thrombolysis was given to 58.5% of patients with ST segment elevation—in 50 minutes on average.
A linked comment describes the registry as a milestone that gives a comprehensive overview of care for the first time (p 1394). Interventions to improve access to treatments and reduce delays should follow.
New stent inches ahead of paclitaxel eluting stent for selected patients
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The treatment of coronary artery disease has come a long way since Gruentzig performed the first balloon angioplasty in 1977. The latest innovation is a new drug eluting stent that the manufacturers hope will overcome some of the limitations dogging existing stents. The new one elutes everolimus, an immunosuppressant that inhibits smooth muscle proliferation. It has just completed its first serious road test in a head to head trial against the popular paclitaxel eluting stent⇑.
In men and women with one or two uncomplicated coronary artery lesions, the new stent worked as well as the old one, with comparable rates of target vessel failure at nine months (7.2% v 9.0%; difference −1.9%, 95% CI −5.6% to 1.8%). The everolimus eluting stent was associated with fewer major cardiovascular events (4.6% v 8.1%; relative risk 0.56, 0.34 to 0.94) and a slower loss of coronary artery lumen in the three quarters of participants who had follow-up angiograms at eight months.
These results are a promising start that should help satisfy the regulatory authorities, says an editorial (p 1952) But cardiologists and patients will need more reassurance on safety, including the risk of potentially catastrophic late stent thrombosis. The four events in this trial (two in each group) weren’t enough to make meaningful comparisons between the stents.
Prescriptions for ezetimibe soar in the US, but not in Canada
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After a new lipid lowering drug ezetimibe was licensed in the US in 2002, the number of prescriptions dispensed rose by 27 200 a month, according to analysis of national prescribing data. By the end of 2006, the number of prescriptions each month had reached 1 360 000. After the same drug was licensed seven months later in neighbouring Canada, use increased by a more modest 1954 prescriptions a month. By 2006, prescriptions for ezetimibe accounted for more than 15% of all prescriptions for lipid lowering drugs in the US. In Canada, this proportion was only 3.4%.
These pronounced differences in penetration and market share could have something to do with direct to consumer advertising, say researchers. The drug has been heavily promoted to doctors in both countries but has been promoted to patients only in the US. Direct to consumer advertising is banned in Canada.
Ezetimibe inhibits intestinal absorption of cholesterol and reduces serum concentrations of mainly low density lipoprotein cholesterol. There is no evidence that is prevents cardiovascular events or slows the progression of atherosclerosis, so it is not recommended as first line treatment for either primary or secondary prevention.