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Random treatment allocation in a clinical trial is unlikely to be harmful
Patients who receive a randomly assigned treatment as part of a randomized controlled trial (RCT) have the same health outcomes as those who receive individualized treatment tailored by their physician, suggests a new study in PLoS Medicine.
The study will be reassuring to those patients and physicians who fear that taking part in an RCT is worse for a patient's health than receiving a treatment based on a physician's personal judgment.
RCTs are considered by physicians as the "gold standard" for telling whether a new treatment works. In an RCT, patients are randomly assigned to receive the new treatment or a "control" (usually the existing standard treatment).
The study's authors, led by Cary Gross at Yale University School of Medicine, examined previous RCTs that included information on the health outcomes of patients who participated in the trials as well as patients who were eligible to participate but who did not in the end take part.
They only considered RCTs where these non-participants had access to exactly the same treatments as those being tested in the RCTs. Unlike the trial participants (who received treatment randomly), these non-participants received individualized treatment recommended by their physician.
The authors found 25 RCTs that met these requirements, involving nearly 18,000 patients. Overall 45% of patients had received a randomly assigned treatment as part of a clinical trial, while 55% of patients did not in the end participate in the trial and received individualized treatment. Most of the RCTs studied new treatments for cancer, problems of the heart and circulation, and obstetric and gynecological problems.
The health outcomes recorded in the trials varied and included, for example, death or recurrence of cancer. In 22 of these trials, the health outcomes were no different (statistically) in patients who received randomly assigned treatment and those who received individualized treatment. In one trial the randomized patients fared better, and in the remaining two trials the patients receiving individualized treatment fared better.
These findings, say the authors, suggest that "randomized treatment allocation as part of an RCT is unlikely to be harmful."
This does not imply, they say, that all research is free of risk, as the risks and benefits of experimental treatment may vary substantially between studies. "However, in the situation in which patients will have access to the treatments that are used in the study setting regardless of whether the patient enrolls, prospective participants and their referring physicians should be reassured: there is no evidence that random treatment assignment leads to worse clinical outcomes."
Citation: Gross CP, Krumholz HM, Van Wye G, Emanuel EJ, Wendler D (2006) Does random treatment assignment cause harm to research participants? PLoS Med 3(6): e188.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030188
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-gross.pdf
CONTACT:
Cary Gross
Yale School of Medicine
Internal Medicine
333 Cear St
PO Box 208025
New Haven, CT 06520-8025 United States of America
+1-203-688-8588
+1-203-688-4092 (fax)
cary.gross@yale.edu
Ensuring death with dignity after disaster
When a major natural disaster strikes, one of the tasks is to manage the dead efficiently but with dignity. Lessons can be learned from what happened after the South Asian tsunami in December 2004. An international group of researchers has studied what took place and has issued recommendations as to what should be done in future catastrophes.
Over a quarter of a million people died in the tsunami. There is very little agreement about the best way to handle and identify so many bodies. Most guidelines are based on experience gained from transport accidents and from terrorist incidents. These guidelines may not be relevant; for example, natural disasters often cause many more deaths than transport accidents or terrorist attacks. It is important for survivors that the bodies of the dead are handled with respect and that the dead are identified so survivors know what has happened to missing relatives. However, at the same time many people are afraid of what the effect of many dead bodies might be on the living; one belief is that dead bodies are a source of disease. Such a belief can lead to the inappropriately rapid burial of bodies before identification has taken place.
Researchers from the UK, USA, Thailand, Indonesia and Sri Lanka set out to study how the bodies were recovered, identified and disposed of, and what, if any, were the health effects of the large number of bodies on survivors. They interviewed key people involved in the handling of the dead in Thailand, Indonesia and Sri Lanka.
There were a huge number of people and agencies involved; for example, in Indonesia 42 different organizations were involved in recovering bodies. None of the countries had sufficient refrigerated storage available to store bodies until they could be identified. Some effective alternatives were used (such as temporary burial in shallow graves) with the intention of exhuming the bodies later for identification. However, many bodies were hurriedly buried in mass graves because they were decomposing; these bodies were almost impossible to identify.
Methods and efficiency of identification varied between and within countries. One hospital in Sri Lanka excelled by systematically photographing all bodies brought in and recording sex, height, and personal effects: 87% of the bodies brought here were identified. But in most areas rates of identification were much lower. Simple methods of identification were the most useful: photographs, dental records, and personal effects found on the bodies. DNA analysis was only useful for a small number of bodies.
Procedures for disposal of the bodies also differed widely, and in some cases were dictated by religious needs--for example, in some Muslim communities all bodies were buried within 24 hours, making counting and identification of the dead very difficult. Mass graves were often used, but these caused problems; haphazard arrangement of the bodies meant that later exhumation and identification would be impossible.
The authors say there was virtually no health impact of the dead bodies on survivors. There were no epidemics among the surviving population, and that most effects were on those who handled bodies in temporary morgues, where there were a variety of sharp-implement injuries and splashes with body fluids, along with heat stress and dehydration.
The researchers concluded that the variation in how bodies were handled was due to a lack of national or local planning, along with a lack of practical guidelines. There was little coordination of all of the different organizations involved. However, in some places bodies were handled very well. The authors have suggested guidelines for the possible future management of large numbers of bodies. As the large numbers of bodies did not cause health problems, survivors should be encouraged to identify the dead systematically rather than rushing to bury them because of fear of disease.
Note to editors:
The findings from this study has contributed to a field manual for the management of dead bodies after a disaster, produced by the Pan American Health Organization, World Health Organization, International Committee of the Red Cross and International Committee of Red Cross and Red Crescent Societies. A copy of this manual can be found at: http://www.paho.org/english/dd/ped/DeadBodiesFieldManual.htm
Citation: Morgan OW, Sribanditmongkol P, Perera C, Sulasmi Y, Van Alphen D, et al. (2006) Mass fatality management following the South Asian tsunami disaster: Case studies in Thailand, Indonesia, and Sri Lanka. PLoS Med 3(6): e195.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030195
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-morgan.pdf
CONTACT:
Oliver Morgan
London School of Hygiene and Tropical Medicine
Public Health and Policy
Keppel Street
London, WC1E 7HT United Kingdom
+447905 534 181
omorgan@bigfoot.com
Education and computer reminders to doctors can improve treatment of high blood pressure
General practitioners (GPs) are more likely to treat high blood pressure with the most highly recommended medication when they receive education by pharmacists plus computerized reminders than when they only receive a guideline, according to a clinical trial in Norway published in PLoS Medicine.
But the education and computer reminder program was no better than the simple guideline at improving other aspects of caring for patients with high blood pressure and/or cholesterol, such as properly assessing patients' risk of heart disease and strokes.
In many countries, including Norway, health authorities want GPs to use an older blood pressure drug called a "thiazide", because it is just as effective as newer drugs and yet it is much cheaper. Unfortunately, many GPs still prescribe the newer medications. The researchers, led by Atle Fretheim (Norwegian Knowledge Centre for Health Services, Oslo), found that 17% of patients whose GPs received the education and computer reminder program were given thiazides, compared with 11% of those whose GPs only received the guideline (a statistically significant difference).
In an accompanying study by the same authors, they found that using the education and computer reminder program was--in the long run--likely to be a good way to save money, given that it led to doctors using a cheaper blood pressure medicine.
Fretheim and colleagues studied 146 general practices in two areas of Norway. Each practice was randomly assigned to receive either the education and computer reminder program or just the guideline. Such a study is known as a randomized controlled trial (the "control group" was the group of practices that just received the guideline).
In an accompanying commentary, Chris Del Mar (Bond University, Australia), who was not involved in the trial, notes that even with the education and computer program, only 17% of patients received the recommended medicine, which, he says, "seems a very modest achievement with so much effort." Nevertheless, says Del Mar, the program is "perhaps the best shot that could ever be made at increasing the quality of care for a single condition in primary care". More than that, he says, the program "is cost saving. And that being the case, it is almost criminal not to implement the intervention everywhere."
Citation: Fretheim A, Oxman AD, Håvelsrud K, Treweek S, Kristoffersen DT, et al. (2006) Rational Prescribing in Primary Care (RaPP): A cluster randomized trial of a tailored intervention. PLoS Med 3(6): e134.
PLEASE ADD THE LINKS TO THE PUBLISHED ARTICLES IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030134
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-fretheim.pdf
Related PLoS Medicine Research Article:
Citation: Fretheim A, Aaserud M, Oxman AD (2006) Rational Prescribing in Primary Care (RaPP): Economic evaluation of an intervention to improve professional practice. PLoS Med 3(6): e216.
PLEASE ADD THE LINKS TO THE PUBLISHED ARTICLES IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030216
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-fretheim2.pdf
CONTACT:
Atle Fretheim
Norwegian Knowledge Centre for Health Sciences
K5
PO Box 7004, St. Olavs plass
N-0130 Oslo, 0130 Norway
+47 91 64 98 28
atle.fretheim@nokc.no
Related PLoS Medicine Perspectives article:
Citation: Del Mar C (2006) Improving prescribing practices in primary care. PLoS Med 3(6): e229.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030229
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-del_mar.pdf
Snake bite: gene technology will improve treatment
Scientists are using gene technology to find new treatments for an increasingly wide range of health conditions. Now, a research group in Liverpool, UK is applying the technique to a much neglected problem--they hope to find new and better 'antivenoms' to treat the victims of snakebite. Their study is published in the latest issue of PLoS Medicine.
It is hard to estimate how many people are bitten by snakes but the World Health Organization figure is around 2.5 million a year, with about 125,000 deaths. Most snakebites occur in Southeast Asia and Africa. Another article in the latest PLoS Medicine being published on 5 June discusses the global snakebite problem (see press release issued May 30).
Antivenoms to treat snakebite are conventionally made by injecting horses or sheep with snake venom. The animals' immune systems respond to the venom by producing the antivenoms. However, when given to a snakebite patient, antivenoms can trigger unpleasant side-effects, as well as acting against the venom.
Recent scientific discoveries have led to new ways of finding which parts of an animal's genetic sequence are active in any one particular part of the body, and also whether the proteins produced from these genes are likely to cause illness. A snake's venom gland, where the venom is made, can be analysed this way. The Liverpool researchers wanted to use this information to develop a more rational way of designing antivenoms.
The research team studied the venom glands of the carpet viper, the snake responsible for most snake bites in West Africa. They isolated expressed sequence tags (ESTs) produced by the venom glands. Each EST is a small part of the active part of a gene. They then focused on one group of genes that make proteins called snake venom metalloproteinases (SVMPs), which destroy other proteins, and which cause many of the severe symptoms, such as bleeding, seen after snakebite. They identified seven parts of these SVMPs that were likely to be clinically important, and engineered them into a single string of DNA. This product is known as an immunogen--that is, it can produce an immune response in an animal.
When this immunogen was tested, the researchers found that the serum (the part of the blood that contains antibodies) recognised many of the SVMP toxins in snake venom. It also had an inhibitory effect against bleeding caused by small doses of snake venom.
These results suggest that it is possible to use some of the newest genetic techniques to design immunogens that would be an improvement over conventional antivenoms, which act against whole venom. This approach could mean that lower doses of antivenoms would be needed than for conventional antivenoms. In addition, it may also be possible to design antivenoms that work against different species of snake venom. Results such as this may persuade a company that it is worth investing further in such antivenoms.
Citation: Wagstaff SC, Laing GD, Theakston RDG, Papaspyridis C, Harrison RA (2006) Bioinformatics and multiepitope DNA immunization to design rational snake antivenom. PLoS Med 3(6): e184.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030184
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-wagstaff.pdf
CONTACT:
Simon Wagstaff
Liverpool University School of Medicine
Venom Research Unit
Pembroke Place
Liverpool, L3 5QA
United Kingdom
+441517053164
+441517053371 (fax)
simonw@liv.ac.uk
THE FOLLOWING RESEARCH ARTICLES WILL ALSO BE PUBLISHED ONLINE:
Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications
Da-Wei Gong and colleagues from the University of Maryland show that higher levels in obese individuals of acute-phase serum amyloid A, which is secreted by adipose tissue, may contribute to the chronic low-level inflammatory state that puts such individuals at higher risk for cardiovascular complications.
Citation: Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, et al. (2006) Acute-phase serum amyloid A: An inflammatory adipokine and potential link between obesity and its metabolic complications. PLoS Med 3(6): e441.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pbio.0030441
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-gong.pdf
CONTACT:
Da-Wei Gong
University of Maryland
660 W. Redwood St
HH426
Baltimore, MD 21201 United States of America
+1-410-706-1672
+1-410-706-1622 (fax)
dgong@medicine.umaryland.edu
Improving Imperfect Data from Health Management Information Systems in Africa Using Space-Time Geostatistics
Peter Gething and colleagues from the University of Southampton combine incomplete data on malaria in Kenyan outpatients from a health management information system with a geostatistical modelling framework to predict values for the missing data and thus allow evidence-based decision making and allocation of resources.
Citation: Gething PW, Noor AM, Gikandi PW, Ogara EAA, Hay SI, et al. (2006) Improving imperfect data from health management information systems in Africa using space–time geostatistics. PLoS Med 3(6): e271.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030271
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-gething.pdf
CONTACT:
Peter Gething
University of Southampton
School of Geography
University of Southampton
Highfield Campus
Southampton, Hants SO17 1BJ United Kingdom
+447815425885
pgething@soton.ac.uk
Training village volunteers to diagnose and treat malaria reduces illness and deaths
In a new study in Thailand, François Nosten (Mahidol University, Thailand) and colleagues found that in the remote malarious north western border area, early detection of malaria by trained village volunteers using rapid diagnostic tests and treatment with a combination of malaria drugs (mefloquine-artesunate) reduced illness and deaths from multidrug-resistant falciparum malaria.
Citation: Carrara VI, Sirilak S, Thonglairuam J, Rojanawatsirivet C, Proux S, et al.(2006) Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: The Tak Malaria Initiative. PLoS Med 3(6): e183.
PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030183
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-06-nosten.pdf
CONTACT:
François Nosten
Mahidol University
Faculty of Tropical Medicine
Shoklo Malaria Research Unit
POBOX 46
SMRU
Mae Sot, TAK 63110 Thailand
+66 55 545 021
+66 55 545 020 (fax)
SMRU@tropmedres.ac
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