Thursday, October 29, 2009

Paracetamol weakens children's response to vacciantion

Paracetamol is sometimes given to infants to reduce their risk of developing fever or a fit caused by fever. In the UK, paracetamol (acetaminophen) is sold over the counter, also present in brands such as Panadol and Calpol. In the US it is more commonly available as Tylenol.

A study published in The Lancet, funded by GlaxoSmithKline Biologicals of Belgium, investigated the effect of giving paracetamol to infants during and immediate after vaccination.

459 healthy infants aged between 9 and 16 weeks were recruited from 10 centres in the Czech Republic and randomised to receive either paracetamol administered every 6 to 8 hrs during the 24 hrs following vaccination or to receive no paracetamol. The parents knew the treatment assigned to their babies.

Researchers found that in both groups, fever above 39.5 degrees C was uncommon, however lower proportion of babies in the paracetamol group had temperature above 38 degrees C. After the primary vaccine doses, more paracetamol doses had to be given to the babies in the control group than the treatment group. They also found that the antibody concentrations following the primary immunisations were significantly lower in the paracetamol group than in the control group and the response varied depending on the vaccination type given.

They concluded that "Although febrile reactions significantly decreased, prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced."

Critics say this is an important study because there was very few published studies on this issue but further study is needed to demonstrate whether the immunity offered by flu vaccination might be reduced by paracetamol. It may be wise not to give paracetamol routinely to babies as a preventive measure.

Source: "Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials" The Lancet 2009; 374: 1339-1350 (press release or f/t via Athens)

Tuesday, October 27, 2009

To screen or not to screen for cancer ?

For decades, people always believe cancer screening saves lives, but a study published in JAMA last week expressed concerns about the harm caused on patients who undergo breast and prostate cancer screening.

Dr Laura Esserman and colleagues who carried out the study found that screening often finds harmless or non-life-threatening tumors that could have gone unnoticed, this has led to huge increase in cancer diagnosis and unnecessary and aggressive treatment for patients while the most lethal, fast-growing cancers are often missed.

They reported 40% increase in breast cancer diagnosis but only 10% decline in late stage cancers. The rate of breast cancer overdiagnosis is as high as 1 in 3 for non-invasive cancers. Similarly, diagnosis in prostate cancer rocketed with the PSA test introduced in the 1980s, but most men with high PSA level turn out not to have cancer. Patients diagnosed with these cancers are often aggressivley and overtreated with radiation and surgery leading to long term harm.

The authors pointed out that the dilemma for breast and prostate cancer is that it is difficult to distingush dangerous cancers from harmless ones and the idea that some cancers are not dangerous and might go away on their own is not always accepted.

Although routine screening has identified more early stage cancers, it has not led to a corresponding reduction in mortality rate in breast and prostate cancer. The study concluded that "screening has value but we need to undertsand what it can and cannot do......., less screening is not necessarily a bad thing" and urged clinicians to rethink the use of breast and prostate cancer screening.

The American Cancer Society (ACS), as a result of the findings of this study, has acknowledged that the benefits of early screening has been overstated.

Source: "Rethinking screening for breast cancer and prostate cancer" JAMA. 2009;302(15): 1685-1692. (f/t via Athens)

Minimally invasive surgery vs open surgery for prostate cancer

Despite limited data on outcome, the use of minimally invasive radical prostatectomy (MIRP) has surged as a result of aggressive marketing of the potential benefits over conventional open surgery even at greater costs.

A study published in JAMA reported mixed results. It was a population-based observational cohort study that identified nearly 2000 men who had MIRP and nearly 7000 had traditional surgery.

The researchers found that use of MIRP increased from 9% in 2003 to 43% in 2006-7. White and Asian living in high income areas are more likely to opt for MIRP. They also found that MIRP was associated with shorter hospital stay and fewer blood transfusion or other postoperative complications. However MIRP was associated with incontinence and erectile dysfunction in the long term.

The authors concluded that their findings reflected "a society and health care system enamored with new technology that increased direct and indirect health care costs but had yet to uniformly realize marketed or potential benefits during early adoption."

Source: "Comparative Effectiveness of Minimally Invasive vs Open Radical Prostatectomy". JAMA 2009;302(14):1557-1564. (f/t via Athens)

Tuesday, October 20, 2009

Does virus cause CFS?

A new study published in Science suggested that the virus XMRV that may play a role in prostate cancer has a strong link with ME, also known as CFS (chronic fatigue syndrome). It was a case control study that looked for the presence of a retrovirus in the white blood cells of people with CFS.

Researchers compared blood samples from 101 patients with CFS with those from 218 people without. They found that the virus was present in the blood of 67% of the CFS patients, compared with 3.7% of the people without CFS. They also found that the virus XMRV could be transmitted to prostate cancer cells in laboratory experiments.

They concluded that XMRV may be a contributing factor in the develoment of CFS and suggested that the virus could be responsible for some of the abnormal immune response in CFS patients. However, larger studies are needed before any conclusions can be drawn.

Critics say this research has identified a link between XMRV virus and CFS but does not prove the virus causes CFS because it is not clear if the infection occured before the disease is developed. Other limitations of the study include small number of patients tested, there is no report on the characteristics of the healthy people whose blood samples were used and contamination of blood samples could not be ruled out completely. However, the findings would be of interests to patients and doctors.

Source:Vincent C. Lombardi 1, Francis W. Ruscetti et al "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome" Published Online October 8, 2009 Science. DOI: 10.1126/science.1179052 (subscription needed)

who are most vulerable to swine flu?

The NEJM published 2 papers last week on hospitalised patients with H1N1 flu. The findings help remind us who are most vulnerable to swine ful.

One group of researchers found that between June and August 2009, 722 patients with H1N1 virus infection were admitted to an ICU during the winter in Australia or New Zealand.

Of the 722 patients, 92.7% were under 65, 9.1% were pregnant women, 28.6% of the adult patients had a body-mass index (BMI) >35, 32.7 % with asthma and chronic pulmonary disease. The highest age-specific incidence of ICU admission was among infants under the age of 1 whereas the highest number of ICU admissions was among patients 25 to 49 years of age.

Source : "Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand". Published at www.nejm.org October 8, 2009 (10.1056/NEJMoa0908481)

Another group of researchers studied 272 patients who were hospitalized with 2009 H1N1 influenza in the US from April 2009 to mid-June 2009.

Of the 272 patients studied, 7% died, the median age of patients who died was 26. 45% of the patients were children under 18, and 5% were 65 or older, 73% of the patients had at least one underlying medical condition, asthma was the most common condition in both children and adults.

Source: "Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009", Published at www.nejm.org October 8, 2009 (10.1056/NEJMoa0906695),

Thursday, October 15, 2009

Dabigatran vs warfarin - RE-LY trial

At the European Society of Cardiology (ESC) congress in August 2009, researchers reported that a potential thrombin inhibitor, dabigatran etexilate, was more effective than warfarin in reducing strokes and embolism events in people with atrial fibrillation (AF) – a form of irregular heartbeat. The NEJM also released a simultaneous online report of this new trial.

The authors said that warfarin treatment needs regular monitoring because it can cause bleeding and other complications and argued that there is a need for a new anticoagulant drugs that are safe, effective and convenient to use. Dabigatran is already licensed for use in people having hip and knee replacement surgery.

The study, known as the RE-LY trial, the Randomized Evaluation of Long-term Anticoagulation Therapy, recruited over 18,000 people with AF, average age of 71, from 44 countries and 951 centres, who had at least one other risk factor for stroke. People with severe heart valve disorder, condition that increased the risk of bleeding, liver disease, poor kidney or pregnant women were excluded.

Participants were randomly assigned to receive either 110 mg or 150 mg of dabigatran twice a day or warfarin treatment. Participants receiving dabigatran were blinded to what they were taking but those received warfarin were not. Participants were followed up for an average of 2 years.

The researchers found that those who took dabigatran reduced their risk of stroke and systemic embolism by 34%, also reduced risk of bleeding than warfarin. They concluded that the lower dose of dabigatran was as effective as warfarin for preventing stroke and embolism events, the higher dose was more effective than warfarin for preventing these events and there was no need for regular monitoring .

Critics noted that the higher dose of dabigatran was associated with higher risk of heart attack and had more gastric symptoms when compared to warfarin. More patients discontinued taking dabigatran than those with warfarin after 1 and 2 years of follow up due to serious adverse events. They also cautioned that the design that patients and physicians knew of the treatment allocation can bias the outcomes and that long term outcomes should be explored before the drug is licensed for people with AF.

In an accompanying editorial, the author said that dabigatran had greater risk of nonhemorrhagic side effects, “patients already taking warfarin with excellent INR control have little to gain by switching to dabigatran”, however other patients who have AF and at least one additional risk factor for stroke could benefit from it.

The study was funded by Boehringer Ingelheim, the manufacture of dabigatran. All outcome events were assessed by 2 independent investigators who were blinded to the treatment assigned to the participants.

Source: Connolly SJ, Ezekowitz MD, Yusuf S et al. "Dabigatran versus Warfarin in Patients with Atrial Fibrillation". NEJM 2009; 361(12):1139-1151

Online editorial - Gage B. "Can We Rely on RE-LY?". NEJM August 30, 2009

Friday, October 09, 2009

telomeres and the 2009 Nobel Prize

3 American scientists, Elizabeth H. Blackburn, Carol W. Greider and Jack W Szostak, won the 2009 Nobel Prize in Medicine for their research into telomeres and telomerase that led to new insights into aging, cancers and some inherited disease and could lead to new treatments for the diseases.

Their work solved one of the mysteries of how cells duplicate without losing pieces of the chromosomes. Chromosomes are strands of DNA that carry genes. Blackburn found that at the end of each of the chromosomes was the repeating DNA sequence – CCCCAA. Szostak had developed mini-chromosomes and found that each time the cells divided, the mini-chromosomes degraded and eventually vanished completely.

Blackburn and Szostak collaborated in 1980 and made mini-chromosomes with the CCCCAA sequences at either end. They found that when these were injected into yeast, the DNA sequence protected the chromosomes when they were copied. They called the caps “telomeres”. In 1984, Greider, Blackburn’s student, discovered the enzyme, “telomerase”, that makes telomeres.

Further studies discovered that healthy telomeres delayed the aging process in cells, prompting research into anti-aging treatments. Related studies found that defective telomeres had affected the division of bone marrow stem cells and overactive telomerase was associated with the development of cancer.

However, a member of the Prize Committee said that large questions remain to be answered about the working of telomeres and telomerase. Merck, a drug company, is currently running a trial of a cancer vaccine designed to train the body to attack tumor cells that produce telomerase.

Hypertension paradox

What is the paradox?

Dr Aram Chobanian, a world-renowned cardiologist and the Dean of the Boston University Medical School, wrote in the NEJM special article that despite the remarkable successes in lowering blood pressure in patients with hypertension, the prevalence of hypertension continues to increase worldwide. The number of people with uncontrolled blood pressure is also increasing.

He reviewed the development of the anti-hypertensive drug therapy and other evolving approaches such as lifestyle modifications. He recommended a new treatment algorithm for the management of stage 1 and 2 hypertension.

He noted that recent data indicated that about 28% of Americans with hypertension are unaware of their condition, 39% are not receiving treatment and 65% do not have their BP controlled. The controlled rates are even worse in patients with chronic kidney disease, diabetes, and other cardiovascular dysfunction in whom target BP levels of 130/80 mm Hg are recommended.

With the prevalence of hypertension continues to increase worldwide, he asked “what can be done to reverse this trend”. He pointed out that “salt intake and body weight are particularly important in the age-related increase in BP” but some countries such as Finland and GB have achieved significant reductions in dietary sodium through aggressive efforts including education and working with the food industry.

He said that “the failure to adopt healthy lifestyles has been a critical factor in this increase” and must be addressed urgently. He urged a national strategy to promote physical activities combined with changes in dietary intake.

This article was presented as the Shattuck lecture of the Massachusetts Medical Society and available as open access at the NEJM website.

Source: “The Hypertension Paradox — More Uncontrolled Disease despite Improved Therapy” NEJM 2009, 361(9):878-887

2 more publishers offer free H1N1 flu resources

NEJM H1N1 Influenza Centre
contains news updates, policy information, articles on past influenza epidemics, and an interactive map of H1N1 influenza cases worldwide . Click on HealthMap for more info.

BMJ has created a pandemic flu website providing doctors with up to the minute swine flu information on prevention, symptoms, testing and treatment.

BMJ Learning also published a new swine flu module. This module is free to everybody who has registered with BMJ Learning. If you have not yet registered you can do so by completing the registration form. It is free, other swine flu modules are also available.

Wednesday, October 07, 2009

More free H1N1 resources - Ebsco Publishing

Due to the global outbreak of Pandemic H1N1 Influenza, EBSCO Publishing (EBSCO) has made the pertinent influenza information available for free to health care providers worldwide. This site includes more than 50 evidence-based topics.

The publisher claims that the information provided “For Clinicians” and “For Nurses” consolidates the best-available evidence from hundreds of medical and nursing journals and systematic evidence review databases.

Each publication is reviewed cover-to-cover, and each article is evaluated for clinical relevance and scientific validity. The new evidence is then integrated with existing content, and overall conclusions are changed as appropriate representing a synthesis of the best available evidence and ensuring that health care providers stay current with recommendations for monitoring, diagnosing, and treating patients with flu-like illnesses.

Preventing medical errors - punish the persistent offenders

American patient safety experts, Robert Wachter and Peter Pronovost wrote in this week’s NEJM that failure to hold clinicians accountable for patient safety is the main reason medical errors continue to happen in hospitals.

They said that the estimated 100,000 yearly deaths from healthcare-associated infections in the US “could be prevented by strict adherence to infection-control practices including hand hygiene”. In most hospitals in the US, hand-hygiene rates are between 30% and 70%, other safety practices such as using a checklist to reduce bloodstream infection, marking the surgical site to prevent wrong-site surgery and performing a preoperative “time-out” are frequently skipped by physicians.

The authors noted that 4000 wrong-site surgeries still occur each year in the US, but hospitals have been reluctant to punish the persistent offenders for financial reasons. They said that the tradition of weak enforcement of safety rules has led too many physicians to ignore them.

In many American hospitals, physicians can lose their staff privileges for failing to sign discharge summaries or operative notes, this is prompted by regulatory and financial requirements rather than patient safety.

The authors called for penalties on doctors and nurses who repeatedly fail to comply with patient safety measures in parallel with the “no blame” approach embraced by many healthcare providers.

They listed some suggested penalties for failure to adhere to safety practice, for example, healthcare workers who persistently fail the hand hygiene, would be required to undergo training and re-education and lose their staff privileges and loss of pay for a week. Repeated failings by surgeons to conduct a “time-out” prior to surgery would result in loss of access to the operating rooms for 2 weeks with loss of pay. Repeated failure to use and sign surgical lists when inserting catheters would be similarly punished.

Pronovost said finding a workable balance between no blame and individual accountability will be challenging but the right balance will save lives.

Source: "Balancing "No Blame" with Accountability in Patient Safety". NEJM 2009, 361(14):1401-1406

Are you planning postgraduate exams?

Endgames is the BMJ's free interactive quiz to help doctors prepare for their postgraduate examinations.

Questions are made up of case reports and picture quizzes, providing you with a practical and quick revision tool for common topics rather than clinical rarities.

Test your knowledge now. No registration needed.

Springer offers free access to swine flu research

Springer Science+Business Media is offering all journal articles that deal with the H1N1 virus, or swine flu, free of charge on the Springerlink website.

At the springerlink website, use the search term "H1N1" to find the free articles - a total of 318 will be available to print out or download until Dec. 31, 2009.

The company says that by making the articles available it hopes "to push forward scientific research on the causes, cures, and other facets of this virus."

In June 2009, the WHO raised the worldwide pandemic alert level to Phase 6 indicating that the global spread of the H1N1 virus is underway. More than 70 countries are now reporting cases of human infection with H1N1 flu.

No registration nor password needed.