Lancet: `Small Increased Risk’ Of GBS From 2009 Pandemic Jab

Photo Credit PHIL

 

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Guillain-Barré Syndrome (GBS) is a rare, occasionally deadly, neurological disorder that gained notoriety in 1976 after it was linked to an emergency flu vaccine that was rolled out in anticipation of a `swine flu’ pandemic.

 

As it turned out, the feared pandemic never came.

 

But before the campaign was abandoned - among the 40 million people who were vaccinated - around 500 people developed GBS and 25 died.

 

While not all of those cases were likely caused by the vaccine, the incidence of Guillain-Barré Syndrome was  around 1 in every 100,000 vaccinations. Or five times the expected background rate of this disease.

 

I was a young paramedic at the time, and chronicled my small part in that bit of influenza history some time ago in Deja Flu, All Over Again.

 

In the United States, somewhere between 3,000 and 6,000 people develop the disorder each year. While most GBS victims fully recover, some people are left with permanent nerve damage.

 

This from the CDC Guillain-Barré page.

What causes GBS?

Many things can cause GBS; about two-thirds of people who develop GBS symptoms do so several days or weeks after they have been sick with diarrhea or a respiratory illness. Infection with the bacterium Campylobacter jejuni is one of the most common risk factors for GBS. People also can develop GBS after having the flu or other infections (such as cytomegalovirus and Epstein Barr virus). On very rare occasions, they may develop GBS in the days or weeks after getting a vaccination.

 

In 2010 studies showed you are many times more likely to develop GBS in the weeks following an influenza infection, than you are after getting the flu vaccine (see Lancet: The Influenza - Guillain Barré Syndrome Connection).

 

Still, some risk of developing GBS is assumed likely with flu vaccines, although most years it is too small to measure.  

 

Today, The Lancet has published a meta-analysis on the 2009 unadjuvanted monovalent pandemic flu vaccine and its association with GBS, finding a `small increase’ in risk.

 

 

Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis

Dr Daniel A Salmon PhD. Michael Proschan PhD , Richard Forshee PhD , Paul Gargiullo PhD , William Bleser MSPH , Dale R Burwen MD , Francesca Cunningham PharmD , Patrick Garman PhD , Sharon K Greene PhD , Grace M Lee MD , Claudia Vellozzi MD f, W Katherine Yih PhD , Bruce Gellin MD , Nicole Lurie MD , the H1N1 GBS Meta-Analysis Working Group†

Summary

Background

The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome.

Methods

Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barré syndrome per million vaccinations. We used a self-controlled risk-interval design.

Findings

Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barré syndrome (incidence rate ratio 2·35, 95% CI 1·42—4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barré syndrome per million people vaccinated.

Interpretation

The modest risk of Guillain-Barré syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks.

Funding

US Federal Government.

 

Based on these numbers, the U.S. might have seen an additional 100-150 cases of GBS due to the rollout of the monovalent pandemic flu shot. Of those, 80% would be expected to recover completely.

 

There is no such thing as a 100% benign, completely safe drug.

 

Yesterday, in FDA: Drug Safety Communication On Azithromycin & Cardiac Risk, we looked at the small risk of adverse cardiac arrhythmias associated with a very popular – and lifesaving – antibiotic.

Every year, thousands of people die, or experience serious complications, as a result of taking over-the-counter (OTC) medications.

 

Prescription drugs, being generally stronger, are even more problematic. It is always a balancing act - a risk-reward calculation - when deciding to take any drug.

 

Regarding the risks of taking the 2009 H1N1 monovalent shot - balanced against a possible increase of 1.6 cases of GBS per million vaccine recipients - we must compare:

 

The CDC has estimated that the 2009 pandemic flu infected more than 60 million Americans. The virus hospitalized more than 200,000, and killed more than 12,000 (most under the age of 65).

 

Harder to measure, but Influenza infections have been linked to increases in Narcolepsy (cite Narcolepsy Onset is Seasonal and Increased Following the H1N1 Pandemic in China).

 

Influenza infections have also been linked to GBS and developing Parkinson’s Syndrome later in life (Revisiting The Influenza-Parkinson’s Link).

 

While there were other, mostly minor and temporary adverse effects linked to the flu shot - even if we assume a modest 50% effectiveness at preventing infection – when it comes to seeing a good outcome, the flu shot wins by a mile.

 

That is not to say that the flu shot is perfect. Most years it provides `moderate’ protection, and this year we are seeing particularly disappointing Vaccine Effectiveness (VE) numbers (see Helen Branswell CP article Flu shot gave minimal help to seniors).

 

As we’ve discussed often, there is a pressing need for better flu vaccines (see CIDRAP: The Need For `Game Changing’ Flu Vaccines).

 

But until they can be developed - the flu shots available now have an enviable safety record - and the CDC considers it to be the best single preventative action you can take against the flu.

Adding To A Feverish Debate

Photo Credit –CDC PHIL

#6881

 

Long time readers may recall that during the summer of 2011 we looked at a study (see A Feverish Debate) that questioned the conventional wisdom of using antipyretic meds (ibuprofen, acetaminophen or paracetamol, etc) to reduce influenza-related fever.

 

This contrarian view made headlines when researchers from the Wellington based Medical Research Institute of New Zealand, published a paper (Antipyretic therapy for influenza infection—benefit or harm?) in the New Zealand Medical Journal.

 

You can read the entire paper, but their conclusion read:

 

We conclude that there is an insufficient evidence base to support the use of antipyretics in the treatment of fever from influenza infection.

 

The limited evidence that does exist suggests that the administration of antipyretics may have the potential to increase the severity of influenza illness and the risk of mortality.

 

We suggest that randomised controlled trials of the effect of antipyretics in the treatment of influenza are undertaken as an urgent priority.

 

We are still waiting for results from RCTs to support their concerns, but the idea of letting a fever run its course (at least, up to a point) as part of the body’s natural immune system’s defense isn’t new.

 

In a another story - also from 2011 - the American Academy of Pediatrics (AAP) released a report on the use of antipyretics in children, suggesting that we ought not over-treat fevers.

 

Clinical Report—Fever and Antipyretic Use in Children

Janice E. Sullivan, MD, Henry C. Farrar, MD,

ABSTRACT EXCERPTS

Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature.

 

Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications.

(Continue . . . .)

 

 

Today, a study appears in the Journal of Pediatrics on another possible (albeit, rare) adverse effect seen in a small number of young children with fever and dehydration at a hospital in Indiana who received treatment with NSAIDs.

 

We’ve a press release from Indiana University that warns the administration of NSAIDs to reduce fever may result in AKI - Acute kidney Injury – in young children.

 

Common anti-fever medications pose kidney injury risk for children

Sick children, especially those with some dehydration from flu or other illnesses, risk significant kidney injury if given drugs such as ibuprofen and naproxen, Indiana University School of Medicine researchers said Friday.

 

In an article published online Jan. 25 by the Journal of Pediatrics, Jason Misurac, M.D., and colleagues from IU and Butler University reported that nearly 3 percent of cases of pediatric acute kidney injury over a decade could be traced directly to having taken the common nonsteroidal anti-inflammatory drugs, or NSAIDs.

 

Although relatively few in terms of percentage of total kidney damage cases, the children with problems associated with NSAIDs included four young patients who needed dialysis, and at least seven who may have suffered permanent kidney damage, the researchers said.

 

"These cases, including some in which patients' kidney function will need to be monitored for years, as well as the cost of treatment, are quite significant, especially when you consider that alternatives are available and acute kidney injury from NSAIDs is avoidable," Dr. Misurac, a fellow in pediatric nephrology, said.

 

Although such drugs have been linked to kidney damage in small, anecdotal reports, the study reported Thursday is believed to be the first large-scale study of the incidence and impact of acute kidney injury caused by NSAIDs.

 

The research team evaluated medical records at Riley Hospital for Children at IU Health in Indianapolis from January 1999 through June 2010 and found 1,015 cases in which patients had been treated for acute kidney injury from any cause.

 

After excluding cases in which the acute kidney injuries could possibly be explained by other factors, such as diseases affecting kidney function, the researchers found 27 cases, or 2.7 percent, in which the only factors were the administration of NSAIDs. In nearly all cases, the NSAIDs were administered before the children were admitted to the hospital. Because many of the 1,015 cases involved multiple potential causes of acute kidney injury, the researchers said the 27 cases are likely an underestimate of the number of cases in which NSAIDs contributed to the kidney damage.

 

Among the researchers' findings:

• Most of the children had been treated with recommended dosages.
• All of the children under the age of 5 needed to undergo dialysis temporarily, were more likely than the older children to be placed in an intensive care unit and needed longer hospital stays.
• The average cost for hospital and kidney specialist fees in the 27 cases was nearly $13,500, and the costs were much higher for younger children. At least $375,000 was spent on the NSAID-associated kidney injury cases at Riley Hospital over the study period, the researchers said, but billing data for other specialists were not available in the database, suggesting that the actual costs were likely much higher.

NSAIDs affect kidney function by restricting blood flow to the blood-filtering components of the kidneys, which suggests the risks from the drugs are greater among children who are dehydrated due to the effects of their illness, such as vomiting or diarrhea, Dr. Misurac said.

 

Fever is normal during an infection and not in itself dangerous, he noted, so "one alternative to NSAIDs would be acetaminophen, but another alternative would be no medication at all, at least for a while, to let the body fight the infection."

 

 

In a somewhat related story, I’ve written about studies that suggest that the concurrent use of antipyretics may inhibit the immune response when receiving vaccines.

 

In fact, it has even been theorized that one of the reasons that the elderly often develop less-than-robust immunity from the flu vaccine may be due to their frequent consumption of NSAIDs.

 

Several past blogs on this phenomenon include:

 

Anti-Inflammatory Meds And Vaccines

Common Pain Relievers May Dampen Vaccination Benefits

A Few Inflammatory Remarks

 

For now the evidence against the use of antipyretics (particularly NSAIDs) for fevers and influenza-like illness is very limited.

 

But these reports do show that - even after decades of use by hundreds of millions of people – our understanding of the effects of many commonly used over-the-counter medications remains less than complete.

Study: Adverse Events Associated With Oseltamivir Outpatient Treatment

 

Photo Credit – Wikipedia

 

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Oseltamivir (aka Tamiflu ©) is an oral antiviral that was heavily stockpiled by many nations between 2005 and 2088 in anticipation of a  feared `bird flu’ pandemic. 

 

While that particular pathogen remains in the wings (sorry . . . I couldn’t help myself), a pandemic of porcine origin did emerged in 2009 (H1N1), and so these antivirals saw heavy use, particularly in Japan, Great Britain, and in the United States.

 

That said . . . the  stockpiling, and use, of Tamiflu has not been without some controversy.

 

Critics have pointed out a lack of Randomized Controlled Trials (RCTs) to gauge the effectiveness of the drug, and the BMJ has been working along with the Cochrane group to get the manufacturer, Hoffmann-La Roche, to release unpublished trial data.

 

Although falling short of the `gold standard’ RCTs preferred by the Cochrane group for inclusion in their analyses, we’ve seen a number of observational studies that suggest significant benefits from the drug.

 

In 2010 we saw an observational study that appeared in JAMA  (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.

 

And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.

 

And lastly, in Study: Antiviral Therapy For H5N1, we saw the largest study to date on the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment.

 

The research appears in the IDSA’s  Journal of Infectious Diseases. The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%.

 

But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

Efficacy arguments aside, there have also been concerns raised over possible side effects from the drug.

 

It is axiomatic that all drugs have side effects. In fact, in trials with placebos, test subjects have reported adverse reactions (nocebo effect) even though they were taking pills with no active ingredient.

 

Even the most widely used over-the-counter medications can – and sometimes do – cause serious adverse effects.

 

So the mere existence of adverse effects aren’t enough to counsel against a drug’s use. The risks of adverse effects must be weighed against the benefits the drug may provide.

 

Often these AEs are mild, and transitory, and of little concern.

 

 

But in 2006 we began to see reports out of Japan suggesting that a small number of adolescents taking Tamiflu had experienced serious neuropsychiatric symptoms, including delirium, hallucinations, and convulsions.

 

Whether these symptoms were produced by the drug, or by their viral infection, wasn’t known (see Study: Pediatric Neurological Complications With H1N1). But in November of 2006, the FDA posted this safety warning:

 

Tamiflu (oseltamivir phosphate)

Audience: Pediatric and primary care healthcare professionals and patients

[Posted 11/13/2006] Roche and FDA notified healthcare professionals of revisions to the PRECAUTIONS/Neuropsychiatric Events and Patient Information sections of the prescribing information for Tamiflu, indicated for the treatment of uncomplicated acute illness due to influenza infection in patients 1 year and older who have been symptomatic for no more than 2 days and for the prophylaxis of influenza in patients 1 year and older.

There have been postmarketing reports (mostly from Japan) of self-injury and delirium with the use of Tamiflu in patients with influenza. People with the flu, particularly children, may be at an increased risk of self-injury and confusion shortly after taking Tamiflu and should be closely monitored for signs of unusual behavior. A healthcare professional should be contacted immediately if the patient taking Tamiflu shows any signs of unusual behavior.

 

During the 2009 pandemic millions of doses of Tamiflu were prescribed, often to children. While we heard reports of some adverse effects (primarily vomiting & nausea), serious reactions were rare. 

 

In 2010 we saw a review in the journal Eurosurveillance: Adverse Effects of Oseltamivir in Children, that looked at the antiviral treatment of a number of students at a primary school in Sheffield, UK during the 2009 pandemic. 

 

While none of the side effects reported were life-threatening, the nausea, vomiting, abdominal pain and other symptoms were bothersome enough that a minority of those who started the Tamiflu (< 10% ) stopped taking the drug.

 

Today we’ve a new, much larger study, that appears in the journal Pharmacoepidemiology and Drug Safety. It examines the risk of AEs (primarily psychiatric in nature) among more than 27,000 matched pairs (by sex, age, week of illness, and location - where half took the drug & half did not).

 

Encouragingly, they research concludes that `no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment.’

Original Report

Risk of adverse events following oseltamivir treatment in influenza outpatients, Vaccine Safety Datalink Project, 2007–2010†

Sharon K. Greene^,, Lingling Li, David K. Shay, Alicia M. Fry, Grace M. Lee, Steven J. Jacobsen, Roger Baxter, Stephanie A. Irving, Michael L. Jackson, Allison L. Naleway, James D. Nordin, Komal J. Narwaney, Tracy A. Lieu

Article first published online: 5 NOV 2012

 

While comforting, this study doesn’t mean that oseltamivir is completely without side effects. Only that their research didn’t turn up an statistically significant increases in the AEs they were tracking among those taking the drug.

 

There are other concerns when it comes to use of oseltamivir, including the possibility that overuse will help generate resistant strains of the influenza virus.

 

But for now, oseltamivir remains one of the few pharmacological options we have available to treat severe influenza.

FDA Statement On Azithromycin & Cardiovascular Risks

 

 

 

# 6334

 

 

Yesterday in NEJM: Cardiovascular Risks Of Taking Azithromycin I wrote about a study that found a `small absolute increase in cardiovascular deaths’ among patients taking the macrolide antibiotic Azithromycin when compared to a control group taking no antibiotics or with taking amoxicillin.

In response to that study, the FDA has released the following statement:

 

FDA Statement regarding azithromycin (Zithromax) and the risk of cardiovascular death

[05-17-2012] The U.S. Food and Drug Administration (FDA) is aware of the study published in the New England Journal of Medicine, on May 17, 2012, that compared the risks of cardiovascular death in patients treated with azithromycin (Zithromax), amoxicillin, ciprofloxacin (Cipro), levofloxacin (Levaquin), and no antibacterial drug.  The study reported a small increase in cardiovascular deaths, and in the risk of death from any cause, in persons treated with a 5-day course of azithromycin (Zithromax) compared to persons treated with amoxicillin, ciprofloxacin, or no drug. The risks of cardiovascular death associated with levofloxacin treatment were similar to those associated with azithromycin treatment.  FDA is reviewing the results from this study and will communicate any new information that results from the FDA review.

 

Patients taking azithromycin should not stop taking their medicine without talking to their healthcare professional.

 

Healthcare professionals should be aware of the potential for QT interval prolongation and heart arrhythmias when prescribing or administering antibacterial drugs. (See additional information below.)

 

Azithromycin belongs to a class of antibacterial drugs called macrolides, which have been associated with cardiovascular effects; specifically, prolongation of the QT interval. Prolongation of the QT interval can lead to torsades de pointes (TdP), an abnormal heart rhythm, which can be fatal.  Azithromycin was the only macrolide examined in the published study; the study did not address other macrolide antibacterial drugs, such as clarithromycin (Biaxin) and erythromycin, regarding the potential for cardiovascular death.

 

In 2011, FDA reviewed macrolide drug labeling information related to QT interval prolongation and TdP. The WARNINGS AND PRECAUTIONS section of the Zmax drug label (azithromycin extended release for oral suspension) was revised in March 2012 to include new information regarding risk for QT interval prolongation, which appears to be low. The drug labels for clarithromycin and erythromycin also contain information about QT interval prolongation in the WARNINGS section. FDA is in the process of updating risk information in the drug labels for additional macrolide antibacterial drugs.

 

FDA-approved indications for azithromycin include:

• Acute bacterial exacerbations of chronic pulmonary disease
• Acute bacterial sinusitis
• Community-acquired pneumonia
• Pharyngitis/tonsillitis
• Uncomplicated skin and skin structure infections
• Urethritis and cervicitis
• Genital ulcer disease

FDA will communicate any new information on azithromycin and this study or the potential risk of QT interval prolongation after the agency has completed its review.

NEJM: Cardiovascular Risks Of Taking Azithromycin

 

 

# 6331

 

 

Although it isn’t always fully appreciated, one of the `truths’ about medicine is that all drugs carry with them some risk of side effects. There is simply no such thing as a 100% safe and totally benign drug.

 

Often, adverse effects are so rare as to not show up during a drug’s clinical trials, and only become apparent after the drug has been in wide use for years.

 

It is axiomatic that anytime you take a drug, you must weigh its likely benefits against any potential health risks it may introduce. 

 

Today the NEJM has an article about the potential cardiovascular risks of taking one of the world’s most popular antibiotics; azithromycin. 

 

`Zith’ is a macrolide antibiotic chemically similar to erythromycin that is effective against a wide variety of bacteria. It is commonly used for middle ear infections, bronchitis, pneumonia, sinusitis and several sexually transmitted infections.

 

While generally well tolerated (and effective), known side effects include gastrointestinal difficulties (nausea, vomiting, diarrhea)  among less than 5% of those taking the drug, and more rarely, abnormal liver tests, allergic reactions, and nervousness.

 

Although some antibiotics are known to cause potentially dangerous cardiac arrhythmias, up until now `Zith’  has not been counted among them. 

 

Today’s study in the NEJM finds a small absolute increase in cardiovascular deaths during a 5-day treatment course with azithromycin compared to taking no antibiotics or with taking amoxicillin, particularly among those with cardiac risk factors.

 

Azithromycin and the Risk of Cardiovascular Death

Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Kathi Hall, B.S., Patrick G. Arbogast, Ph.D., and C. Michael Stein, M.B., Ch.B.

N Engl J Med 2012; 366:1881-1890 May 17, 2012

 

Conclusions

During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease.

Before anyone starts pitching their Z-packs down the loo, the actual number of cardiovascular incidents was relatively small. And this study was a retrospective analysis of Tennessee Medicaid records between 1992 and 2006 – not a randomized control trial (RCT) - and therefore subject to a number of limitations.

 

Since the full study is behind a pay wall, for more on all of this we turn to coverage from MedPage Today:

 

Azithromycin May Up Risk of Cardiac Death

By Nancy Walsh, Staff Writer, MedPage Today

Published: May 16, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Action Points

• Explain that a Medicaid database study found an increased risk for cardiovascular death, sudden death, and overall all-cause mortality associated with a 5-day course of azithromycin.
• Note that the same findings were not true for amoxicillin or ciprofloxacin compared with controls taking no antibiotics, but there were excess deaths associated with levofloxacin.

Use of a common antibiotic, azithromycin, appears to significantly increase the risk of sudden cardiac death when compared with no antibiotic treatment, according to analysis of data from Medicaid patients.

(Continue . . . )

 

None of this makes azithromycin a `bad medicine’, but it does highlight the need to recognize and balance the risks of taking this (or any other) drug with its likely benefits. 

 

And for some patients with elevated cardiac risk factors, it may be prudent for their doctors to now consider other antibiotic treatments.

 

Although antibiotics can often be lifesaving, evidence continues to mount that their use is less benign that previously thought.

 

The CDC reports that 50% of antibiotic use in hospitals is ` unnecessary or inappropriate’, and better antibiotic stewardship is needed if we are to combat the growing threat of antibiotic resistance.

 

You’ll find the CDC maintains an excellent GET SMART ABOUT ANTIBIOTICS webpage, which provides information on the prudent use of antibiotics.

 

And for more on the potential dangers of antibiotic use (and misuse) you may wish to revisit:

 

The Other Reason Not To Abuse Antibiotics

Get Smart About Antibiotics Week

ECDC/EMEA: Joint Report On Resistant Bacteria

Study: PPIs & Increased Pneumonia Risk

 

 

 

#  5561

 

 

PPIs  are Proton Pump Inhibitors – a group of drugs that greatly reduce gastric acid production and are used for the treatment of Dyspepsia, Peptic ulcer, GERD, Barretts esophagus, and other gastric conditions.

 

These drugs are available as prescription (Nexium, Dexilant, Prilosec, Zegerid, Prevacid, Protonix, Aciphex, Vimovo) medications and over-the-counter (Prilosec OTC (omeprazole), Zegerid OTC (omeprazole), Prevacid 24HR (lansoprazole)) remedies.

 

Like all medicines, the use of PPIs carry with it some risks, and those must be weighed against the (sometimes considerable) health benefits of taking them.

 

Last year the FDA warned consumers to:

 

• Be aware that an increased risk of fractures of the hip, wrist, and spine have been reported in some studies of people who use PPIs. The greatest increased risk for these fractures was seen in those who receive high doses of these medications or use them for a year or longer.
• Read and follow the directions on the “Drug Facts” label when considering the use of an over-the-counter PPI.
• Be aware that the over-the-counter PPIs should only be used as directed for 14 days for the treatment of frequent heartburn. If your heartburn continues, talk to your health care professional. No more than three 14-day treatment courses should be used in one year.

 

Prolonged use of PPIs has also been associated with low magnesium levels, increased incidence of Clostridium difficile,  and a number of studies – going back several years – have suggested a link between their use and increased risks of hospital and community acquired pneumonia.

A couple of examples include:

 

In 2009, Herzig et al. wrote in a JAMA article (doi: 10.1001/jama.2009.722) that : In this large, hospital-based pharmacoepidemiologic cohort, acid-suppressive medication use was associated with 30% increased odds of hospital-acquired pneumonia. In subset analyses, statistically significant risk was demonstrated only for proton-pump inhibitor use.

 

Earlier this year, the CMAJ published a systematic review and meta-analysis of the literature on PPIs (CMAJ. 2011 Feb 22;183(3):310-9) that found: Use of a proton pump inhibitor or histamine(2) receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.

 

Which brings us to today’s study, which adds some more weight to the concerns expressed by these earlier studies.  

 

This time, the study appears in the European Respiratory Journal, and it suggests that recent initiation (< 30 days) of PPI treatment was associated with a three-fold increased risk of CAP (community acquired pneumonia).

 

Microbial evaluation of proton pump inhibitors and the risk of pneumonia

S.C.A. Meijvis, M.C.A. Cornips, G. Paul Voorn, P.C. Souverein, H. Endeman, D.H. Biesma, H.G.M. Leufkens, E.M.W. van de Garde

 

The authors compared the characteristics of 430 hospitalized adults admitted with community-acquired pneumonia against 1,720 patients from a population control group.  The authors write:

 

'After adjusting for co-morbidities, age, sex and pneumonia severity score, recent PPI initiation was independently associated with intensive care unit admission, although this was a small patient group.'

 

 

None of this should be viewed as a condemnation of PPIs, of course.  For many patients, their use can improve the quality, and even duration, of their lives.

 

While a number of studies have indicated an increase in the relative risk of developing complications such as pneumonia and bone fractures, in terms of absolute risk, the dangers appear relatively small.

 

Of course, if you are taking PPIs – or any medication for that matter – that you don’t really need to be taking, you are incurring a health risk without enjoying an offsetting therapeutic benefit.

 

Which means that even though they are available O-T-C, you should discuss using PPIs with your health care provider, especially if you intend to use them longer than the FDA recommended maximum of three 14-day treatment courses in one year.

NSAIDs and Prior Heart Attacks

 

 

 

# 5550

 

 

Between over-the-counter sales and prescriptions, NSAIDs (non-steroidal anti-inflammatory drugs) are likely the most commonly consumed class of medication in the world.  Look in just about any medicine cabinet, and you’ll probably find a bottle of aspirin, naproxen, or ibuprofen.

 

While these drugs have long been associated with increased risks of gastrointestinal bleeding, it has only been in recent years that cardiovascular concerns have emerged. 

 

In 2004 Vioxx, a COX-2 inhibitor which had been marketed by Merck as being less likely to cause stomach bleeding, was abruptly pulled from the market after a study showed that prolonged use increased one’s chances of having a heart attack or stroke.

 

Bextra, another COX-2 inhibitor, was also recalled after it was linked to increased cardiovascular accidents and to several rare, but potentially deadly, skin disorders.

 

In 2005, the FDA required the inclusion of a `black box warning’ for prescription NSAIDs and a couple of  years later stiffened the labeling requirements on O-T-C NSAIDs as well.

 

The controversy over their safety has continued, and earlier this year the BMJ published an open access meta-analysis on the safety of NSAIDs.

 

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

Abstract

Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.

Design Network meta-analysis.

 

Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.

 

Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.

 

Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.

 

Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo.

 

Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.

Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

 

 

It should be noted that while the risk of developing cardiovascular complications for those on NSAIDs was 2 to 4 times higher than placebo, in absolute terms the number of adverse events detected was fairly low.

 

Of the seven drugs examined, naproxen appeared to pose the least cardiovascular risk.

 

Jump ahead to today, and we’ve another study – this time appearing in the American Heart Association  Journal Circulation – that looks at the risks of NSAID use among those who have previously had a heart attack.

 

Researchers found that even short duration treatment (1 week) with NSAIDs resulted in a 45% increased risk of death or recurrent M.I. in those who had previously had a heart attack.

 

I’ve some excerpts from the abstract below, but follow the link to read it in its entirety.

 

Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction

A Nationwide Cohort Study

Anne-Marie Schjerning Olsen, MB; Emil L. Fosbøl, MD, PhD; Jesper Lindhardsen, MD; Fredrik Folke, MD, PhD; Mette Charlot, MD; Christian Selmer, MD; Morten Lamberts, MD; Jonas Bjerring Olesen, MD; Lars Køber, MD, DMSc; Peter R. Hansen, MD, PhD, DMSc; Christian Torp-Pedersen, MD, DMSc Gunnar H. Gislason, MD, PhD

Background — Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI).

<SNIP>

Conclusions— Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

 

The authors write that there were some limitations to this study, most notably:

 

The main limitation of the study is inherent to the observational design. There is a lack of information about important clinical parameters such as blood pressure, body mass index, smoking habits, lipid levels, and left ventricular ejection fraction. Therefore, the effect of unmeasured confounders cannot be excluded.

 

While this study looked at the safety of NSAID use among those who have already had a heart attack, more study is needed to determine the overall cardiovascular safety of this class of medications.

 

The authors conclude by saying:

 

Further studies, preferably randomized clinical studies, are warranted to establish the cardiovascular safety of NSAIDs, but given the additional evidence from randomized trials and other observational studies of selective COX-2 inhibitors and nonselective NSAIDs, the accumulating evidence suggests that we must limit NSAID use to the absolute minimum in patients with established cardiovascular disease.

 

The bottom line is, if you have a history of heart problems and wish to take NSAIDs (even those available over-the-counter), you need to talk to your doctor about the risks.

 

For everyone else, it is important to remember that no drug is 100% safe or benign – even those available O-T-C .

 

That doesn’t mean we shouldn’t use them, but it does mean we should weigh their risks against their benefits, before we take them.

Japan: Investigating Pediatric Vaccines

 

 

UPDATED:  0850hrs EST  03/08/11

Reuters is reporting that while the Japanese suspension on the use of both vaccines remains in effect, a government panel has been unable to find any apparent link between the use of these two vaccines and the four deaths.  

 

Japan panel finds no link to vaccines, deaths: report

 

They state, however, that further investigation is warranted.

 

 

# 5361

 

 

Over the past couple of days concerns have been raised in Japan – and around the world - over the safety of two widely used pediatric vaccines (Pfizer’s Prevnar & Sanofi’s ActHIB) after the sudden deaths of four recently vaccinated children.

 

Prevnar is a pneumococcal conjugate vaccine, while ActHib is a Haemophilus influenzae type b vaccine.

 

Both are viewed as highly successful in the prevention of serious childhood infections.

 

The four children – aged 6 months to 2 years – all died within a day or two of receiving one or both vaccines, although no direct link between their deaths and the vaccines has been established. 

 

Both vaccines have been given to millions of children over the past decade, and both have an excellent safety profile. 

 

But when you give tens of millions of vaccinations each year, a small number of unexpected – and most probably unrelated – serious medical events are apt to occur within a few days among those receiving a shot.

 

And it should be noted that at least two of these children reportedly had serious underlying medical conditions.

 

Nevertheless, Japan has suspended the use of both vaccines pending an investigation. A step that has not been followed by other countries.

 

First, a brief report from Vaccine Daily News on the suspension of these vaccines.

 

 Japan suspends use of two vaccines

by Jeffrey Bigongiari on March 7, 2011

 

Next we get a piece by Matthew Herper in Forbes on this vaccine scare, which includes reassuring comments from Dr. William Schaffner (Chairman of the department of medicine at Vanderbilt University School of Medicine) and Dr. Paul Offit, a vaccine researcher at Children’s Hospital in Philadelphia.

 

Don’t Be Frightened By Japan’s Vaccine Scare

Mar. 7 2011 - 5:35 pm |

 

 

While it is within the realm of possibility that one or both of these vaccines contributed to these child deaths (hence the investigation), the track record of both of these vaccines is very good – making that unlikely.

 

And even if causation is found, the spectacular success of the HiB vaccine in preventing childhood illness and deaths in this country cannot be overstated. 

 

 

There is no such thing, of course, as a completely benign – 100% safe – vaccine.   Side effects – even serious ones – while rare, can occur.

 

All drugs have a risk/reward benefit that must be taken into consideration before taking.  But the evidence is that the Hib and Prevnar vaccines are overwhelmingly safe, and save thousands of lives each year.

 

We’ll obviously await word on the investigation into these deaths with considerable interest, but for now, we’ve no compelling evidence to implicate these vaccines in these fatalities.

JAMA: Cell Phone Use Stimulates Brain Activity

 

 

 

# 5334

 

 

Concerns over the potential health ramifications of long-term & frequent cell phone use continues despite a number of studies that have yielded inconsistent results.

 

In May of 2010, the International Agency for Research on Cancer (IARC) released their long-delayed INTERPHONE report, which was unable to establish a link between cell phone use and brain tumors  (see The IARC Cell Phone Report)

 

Of course, it can sometimes take years – or even decades – of research before the full effect of a new technology like cellular communications can be adequately established.

 

Today we’ve a new study that looks at how cell phone radiation affects brain activity, which is published in the February 23rd issue of JAMA.

 

The short version is: Prolonged exposure to cell phone radiation has now been shown to increase brain activity, but the clinical significance (if any) of such increases are unknown.

 

First a link and some excerpts from the abstract, followed by links to a video, press release, after which I will return.

 

 

Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism

Nora D. Volkow, MD; Dardo Tomasi, PhD; Gene-Jack Wang, MD; Paul Vaska, PhD; Joanna S. Fowler, PhD; Frank Telang, MD; Dave Alexoff, BSE; Jean Logan, PhD; Christopher Wong, MS

(EXCERPTS)

Objective To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity

Conclusions In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.

The link to the press release, embargoed until yesterday afternoon, follows:

 

Cell Phone Use May Have Effect on Brain Activity, But Health Consequences Unknown

FOR RELEASE: 3 P.M. (CT) TUESDAY, FEBRUARY 22, 2011

Media Advisory: To contact Nora D. Volkow, M.D., call the NIH press office at 301-496-5787 or email

nmb@od.nih.gov.

To contact editorial co-author Lennart Hardell, M.D., Ph.D., email lennart.hardell@orebroll.se.

Cell Phone Use May Have Effect on Brain Activity, But Health Consequences Unknown

CHICAGO – In a preliminary study, researchers found that 50-minute cell phone use was associated with increased brain glucose metabolism (a marker of brain activity) in the region closest to the phone antenna, but the finding is of unknown clinical significance, according to a study in the February 23 issue of JAMA.

 

“The dramatic worldwide increase in use of cellular telephones has prompted concerns regarding potential harmful effects of exposure to radiofrequency-modulated electromagnetic fields (RF-EMFs). Of particular concern has been the potential carcinogenic effects from the RF-EMF emissions of cell phones. However, epidemiologic studies of the association between cell phone use and prevalence of brain tumors have been inconsistent (some, but not all, studies showed increased risk), and the issue remains unresolved,” according to background information in the article. The authors add that studies performed in humans to investigate the effects of RF-EMF exposures from cell phones have yielded variable results, highlighting the need for studies to document whether RF-EMFs from cell phone use affects brain function in humans.

(Continue . . . )

 

 

This study basically used PET scans (Positron emission tomography) to chart the brain’s activity via it’s uptake of F-FDG, a radioactive pharmaceutical used for imaging the heart, lungs, and brain.

 

Participants underwent PET Scans with cell phones placed on their left and right ears; once with the right cell phone `on’ (with sound muted) for 50 minutes and once with both cell phones `off’.

 

Areas of the brain in close proximity to the antennas of the activated cell phones demonstrated increased glucose uptake, indicating increased localized brain activity in response to the RF (radio frequency) emissions.

 

This study indicates that the prolonged use of a cell phone does affect brain activity. What all this might mean in regards to human health is unknown for now.

 

In an accompanying editorial, Cell Phone Radiofrequency Radiation Exposure and Brain Glucose Metabolism, Henry Lai, PhD & Lennart Hardell, MD, PhD write:

 

“Although the biological significance, if any, of increased glucose metabolism from acute cell phone exposure is unknown, the results warrant further investigation. An important question is whether glucose metabolism in the brain would be chronically increased from regular use of a wireless phone with higher radiofrequency energy than those used in the current study. Potential acute and chronic health effects need to be clarified. Much has to be done to further investigate and understand these effects.”

 

These authors also question whether the changes to brain function detected in this study could adversely affect other physiological functions of the body.

 

Admittedly, not many answers from this study. 

But it raises a lot of questions.

Australia: Panvax Investigated For Febrile Convulsions

 

 

 

# 4941

 

Late last week Australia’s Therapeutic Goods Administration (TGA) issued an advisory on recent reports of a higher-than-expected number of pediatric febrile convulsions following administration of CSL’s monovalent Panvax  (pandemic) H1N1 flu vaccine

 

CSL’s trivalent seasonal flu shot came under scrutiny last April with similar adverse reactions.

 

The total number of reports were small (several hundred) out of tens of thousands of shots given, but significantly higher than normal.

 

Most of the side effects were related to fever, with some children experiencing febrile convulsions. Others experienced nausea and vomiting, or injection site inflammation (see Australia Investigating Adverse Vaccine Reactions).

 

This latest announcement regarding the Panvax vaccine suggests that the incidence of side effects for this monovalent shot -  while higher than usual – was a fraction of that seen with CSL’s seasonal vaccine.

 

Thus far, we’ve not seen excessive reports like these from other countries or from other manufacturer’s vaccines.

 

Two reports. 

 

First, excerpts from the TGA’s advisory, then a news report from The Sydney Morning Herald that suggests that these side effects may not prove as common as originally stated.

 

 

Suspected adverse reactions to Panvax® reported to the TGA 30 September 2009 to 17 September 2010

22 September 2010

 

The national immunisation program with Panvax® began on 30 September 2009. The TGA has been closely monitoring any side effects from the use of the vaccine.

 

As at 17 September 2010 a total of 1960 suspected side effects had been reported to the TGA following vaccination with Panvax® in Australia. The great majority of reported side effects have been mild and common problems such as headache, gastrointestinal upset, and soreness, swelling, or redness at the injection site. Most of the side effects that have been reported are well recognised and listed in the Panvax® Product Information. Of the suspected side effects reported, only 190 related to Panvax Junior®, and the majority of these reports were of fever (151) and/or vomiting (98).

The TGA's assessment remains that Panvax® is a safe, effective vaccine for prevention of the H1N1 influenza.

As at 17 September 2010 the TGA had received 48 reports of febrile convulsions in children following Panvax/Panvax Jr administration. Nine of these had occurred in children who had also been given other vaccines at the same time as they received Panvax.

 

(Continue . . .)

 

 

 

 

Swine flu jab for children may not be so harmful

Mark Metherell

September 28, 2010

The Commonwealth chief medical officer, Jim Bishop, has sought to play down concerns following the revelation that a second influenza vaccine, Panvax, has been linked to febrile convulsions in infant recipients of the vaccine.

(Continue . . . )

 

 

While often dramatic, febrile convulsions in young children are not uncommon with a fever, and only rarely prove serious.

 

Febrile Seizures Fact Sheet

EMA To Review Pandemrix Vaccine

 

 

# 4840

 

 

The EMA (European Medicines Agency) is a London based EU regulatory agency that is responsible for the scientific evaluation of drugs developed by pharmaceutical companies for use in the European Union. 

 

It is roughly the EU equivalent to the United State’s FDA.

 

Today the EMA announced that they will review GSK’s Pandemrix vaccine to see if they can ascertain any causal link between it - and reports of unusual occurrences of narcolepsy – mostly in children, reported in Sweden and Finland  (see Finland Suspends Use of Pandemrix Vaccine) in recent days.

 

For now, no causal link has been established and the number of reported cases of narcolepsy (which afflicts several thousand  Europeans each year) remains small. 

 

Still, the number of cases among recently vaccinated children has been sufficient to raise concerns, and an investigation will be conducted.

 

 

The EMA press release (h/t Ironorehopper on FluTrackers) provides additional details.

 

 

European Medicines Agency starts review of Pandemrix

The European Medicines Agency has launched a review of Pandemrix on the request of the European Commission to investigate whether there is a link between cases of narcolepsy and vaccination with Pandemrix. A limited number of cases was reported, all collected through spontaneous reporting systems, mainly in Sweden and Finland. Pandemrix, an influenza vaccine, has been used since September 2009 for vaccination against H1N1 influenza in at least 30.8 million Europeans.

 

Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. Its precise cause is unknown, but it is generally considered to be triggered by a combination of genetic and environmental factors, including infections.

 

Although the cases of narcolepsy have been reported in temporal association with the use of Pandemrix, it is at present not known if the vaccine caused the disorder. The Agency’s Committee for Medicinal Products for Human Use (CHMP) will look carefully at all of the available data to determine whether there is evidence for a causal association. As part of this evaluation the Committee will also consider the so-called background rate for narcolepsy, i.e. the number of cases that would normally be expected to be diagnosed.

 

The Committee will be working with experts from across the EU to assess this possible safety concern and any impact on the benefit risk balance of Pandemrix. The Committee will consider at its September 2010 meeting the need for any provisional measures pending completion of the evaluation.

 

The Agency is also liaising with the European Centre for Disease Prevention and Control (ECDC), international regulatory partners and the World Health Organization (WHO).

 

The European Medicines Agency will provide updates as new information becomes available.

Notes:

1. On 24 August 2010, Finland’s National Institute for Health and Welfare recommended that vaccination with Pandemrix be discontinued until the suspected link with narcolepsy is thoroughly evaluated.
2. Pandemrix has been authorised in the European Union since September 2009. The vaccine was extensively used during the 2009 (H1N1) pandemic, with at least 30.8 million Europeans vaccinated.

 

 

 

The Pandemrix vaccine was an adjuvanted monovalent pandemic H1N1 shot, and as such, was not licensed for use in the United States.

Finland Suspends Use of Pandemrix Vaccine

 

 

 

# 4832

 

 

 

Over the past several days European media sources have been reporting on concerns surfacing – first in Sweden, and now in Finland – over what appears to be an increase in reported cases of narcolepsy among children who received GSK’s Pandemrix vaccine.

 

While any connection between the vaccine and the increases in Narcolepsy remains unproven, as a precaution, Finland has suspended the use of the Pandemrix monovalent H1N1 vaccine.

 

It may take months, or perhaps even years, to establish a causal relationship . . .  assuming, of course, that one even exists.

 

Finland’s National Institute for Health and Welfare has released a lengthy press release on the matter, excerpts of which you can find below.  

 

I’ll return with a few comments.

 

 

 

National Institute for Health and Welfare recommends discontinuation of Pandemrix vaccinations

25 Aug 2010

The Finnish National Institute for Health and Welfare (THL) recommends that vaccination with Pandemrix vaccine is discontinued until an explanation is found for the observed rise in cases of narcolepsy among children and adolescents. THL’s recommendation is based on a proposal from the Finnish National Advisory Committee on Vaccines. The Committee convened on Tuesday 24 August 2010 to consider the matter.

 

The discontinuation of vaccinations is a safety measure put in place until the matter can be fully investigated. At present there is no swine flu epidemic, so there is no immediate need for swine flu vaccinations in Finland. Moreover, a large part of the Finnish population already has some protection from swine flu as a result of vaccination or from having had swine flu. The vaccine may still be used upon consideration in individual cases, for instance for people travelling to areas where an epidemic is in progress.

 

A number of different reasons may be behind the observed rise in the incidence of narcolepsy: A(H1N1) infection, vaccination, a compound effect of infection and vaccination, or some other factor entirely. Infections in general are known to cause narcolepsy.

 

So far, the THL register for adverse events following immunization (AEFI) has received reports of six cases where narcolepsy has followed vaccination. The number is consistent with the annual incidence of narcolepsy under normal circumstances. However, in addition to the above, AEFI reports have not yet been submitted for a further nine possible cases. The symptoms of all the children with narcolepsy started at the end of 2009 and beginning of 2010.

 

(Continue . . . )

 

 

Worldwide, somewhere in the order of 90 million people have received GSK’s adjuvanted Pandemrix vaccine, including millions of children. Thus far, only Sweden and Finland have reported any concerns over narcolepsy, and those numbers are small.

 

Narcolepsy is probably more common than most people realize, with its prevalence estimated at being between 25 and 50 per 100,000 people.  

 

According to the NHLBI (NIH) webpages on Narcolepsy:

 

Narcolepsy affects between 50,000 and 2.4 million people in the United States. Symptoms usually begin during the teen or young adult years. The disorder also can develop later in life or in children, but it's rare before age 5. Narcolepsy affects both men and women.

<snip>

 

It can take as long as 10 to 15 years after the first symptoms appear before narcolepsy is recognized and diagnosed. This is because narcolepsy is fairly rare. Also, many of the symptoms of narcolepsy are liked symptoms of other illnesses.

 

Narcolepsy, by all accounts, is under-diagnosed by the medical community. Which means that the true incidence is probably far higher than statistics might indicate.

 

While Health Authorities in Finland have suggested that the increase in narcolepsy could be due to the H1N1 virus itself (neurological manifestations are not uncommon following viral infections), or the vaccine, or some compound effect of infection and vaccination, another possibility needs to be considered as well.

 

Given the concerns over seeing a repeat of the 1976 swine flu fiasco, where a few hundred cases of GBS (Guillain Barre Syndrome) were linked to the vaccine, elaborate surveillance and reporting systems were put in place to look for any unusual spike in adverse affects.

 

Greater scrutiny, better reporting systems, and the public’s concern over the vaccine’s safety might well account for a greater number of diagnoses of narcolepsy in children over the past 6 months.

 

Essentially, the harder we look for diseases, the more we are likely to find.

 

Of course, it is possible the vaccine is the culprit here.   Time, and further study, will tell.

 

In the meantime, the halting of the Pandemrix vaccine should have little impact, since the seasonal vaccine that will be offered in Finland this fall contains the H1N1 strain, along with H3N2 and Influenza B.

 

For Americans that might be concerned, Pandemrix is an adjuvanted vaccine, and was not offered in this country.

Australia: CSL Recalls Pediatric Flu Vax

# 4613

 

 

About six weeks ago we began seeing reports of an unexpected number of adverse side effects among children under the age of 5 who had received CSL Ltd. Fluvax seasonal flu vaccine. 

 

The total number or reports were small (several hundred) out of thousands of shots given, but significantly higher than normal.

 

Most of the side effects were related to fever, with some children experiencing febrile convulsions. Others experienced nausea and vomiting, or injection site inflammation (see Australia Investigating Adverse Vaccine Reactions).  

 

Within days, doctors were advised to suspend giving the shots pending an investigation. No causative agent has been identified, but the company has decided to `retrieve’ all unused doses of the vaccine.

 

CSL’s Fluvax is the first seasonal vaccine to contain the novel (pandemic) H1N1 antigen along with the new H3N2 antigen and a `B’ influenza component.  

 

The monovalent (single antigen) panvax shot for novel H1N1 did not produce these sorts of reactions, and is being recommended for children in Australia instead.

 

Flu vaccines have historically been very safe, and so why this particular formulation should have produced this level of febrile reactions in young children is a bit of a mystery. 

 

One that scientists, no doubt, will continue to be looking at over the summer.

 

This from Bloomberg Businessweek.  A hat tip to RoRo on FluTrackers for this link.

 

CSL Recalls Flu Shot as Side Effects Rise Nine-Fold (Update1)

June 01, 2010, 6:22 AM EDT

 

By Simeon Bennett

June 1 (Bloomberg) -- CSL Ltd., the Southern Hemisphere’s only flu vaccine maker, recalled its seasonal shot for children in Australia after investigations failed to explain a nine-fold increase in fever and convulsions.

CSL is voluntarily withdrawing unused doses of its Fluvax Junior shot from clinics and distributors, the Melbourne-based company said in a statement today. Jim Bishop, Australia’s chief medical officer, said vaccinations should continue to be suspended for children under 5 years, a recommendation initially made on April 23.

 

Fluvax was linked to febrile convulsions in about 9 children in every 1,000 who got the shot, higher than the expected rate of 1 per 1,000, Bishop said in a separate statement. It’s unclear whether Sanofi-Aventis SA’s Vaxigrip and Solvay SA’s Influvac caused similar side effects because insufficient doses have been used in Australia, he said.

(Continue . . . )

Eurosurveillance: Adverse Effects of Oseltamivir in Children

 

 

# 4566

 

 

One of the most commonly cited truisms you’ll find on this blog is that all drugs have side effects, and no medicine is 100% safe.

 

There is always a risk-reward calculation one must make before deciding to ingest any drug, whether it be a doctor’s prescription, a `street’ drug, or an over-the-counter medication.

 

Even medicines we think of as relatively benign – nasal sprays, headache powders, and even so-called `natural’ supplements – can cause adverse or unwanted side effects in some people.

 

OTC Acetaminophen is, after all, the leading cause of acute liver failure in the United States.

 

So it isn’t terribly surprising to be hearing about side effects to Tamiflu (Oseltamivir) among children and staff at a Sheffield school who received it last year during the swine flu outbreak as either a prophylactic or for treatment of the virus.

 

What is a bit remarkable, however, is the percentage of those receiving Tamiflu who reported side effects.  

 

Nearly half of those taking the medication reported at least one symptoms that could be associated with the drug.

 

The word `could’ is used because it is impossible to establish with absolute certainty that the ingestion of Tamiflu was the causative agent for all of these reported symptoms.

 

 

Eurosurveillance, Volume 15, Issue 19 (May 13, 2010) has a research article that examine the incidence of these side effects. 

 

First the (slightly  reparagraphed) abstract and links to the entire study, then a few comments.

 

Adverse drug effects following oseltamivir mass treatment and prophylaxis in a school outbreak of 2009 pandemic influenza A(H1N1) in June 2009, Sheffield, United Kingdom

M Strong ()¹, J Burrows¹, E Stedman², P Redgrave³

1. School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom
2. Medical School, University of Sheffield, Sheffield, United Kingdom
3. NHS Sheffield, Sheffield, United Kingdom

During the containment phase of the 2009 influenza A(H1N1) pandemic, mass treatment and prophylaxis with oseltamivir was used to control an outbreak of pandemic influenza in a primary school in Sheffield, United Kingdom, where ten cases of pandemic influenza had been laboratory confirmed over a three day period in June 2009.

 

A subsequent cross-sectional survey showed that 51 of 297 (17%) pupils and 10 of 58 (17%) reported an influenza-like illness. The most common symptoms were headache, cough, fever, tiredness, sore throat and nausea.

 

Fifty-three staff and 273 pupils took oseltamivir for treatment or prophylaxis. Of this group, 41% (113/273) of pupils and 47% (25/53) of staff reported adverse effects. Overall, 14% (37/273) of pupils and 20% (11/53) of staff did not complete the course of oseltamivir, primarily due to adverse effects.

 

Nausea, vomiting and rash were statistically significantly associated with failing to complete the course of oseltamivir. Given the potential for side effects from oseltamivir, particularly among those without influenza who receive the drug for prophylaxis, our findings have two important implications.

 

Firstly, the benefits of mass treatment in an outbreak setting must clearly be greater than the benefits of targeted treatment. Secondly, any large scale regional or state level system for distribution of antiviral drugs for treatment should ideally include a robust quantification of an individual’s probability of infection with influenza virus in order to avoid unnecessary treatment.

 

 

 

None of the side effects reported were life-threatening, although the nausea, vomiting, abdominal pain and other symptoms were bothersome enough that a number of those who started the Tamiflu elected to stop the drug.

 

Not all of those who failed to finish the regimen did so because of side effects, however.  17% stated they stopped because they `didn’t think it would help’, while 15% said they simply `forgot’.  

 

Only about half of those who stopped taking the drug did so because it made them ill; less than 10% of the total who received the drug. Overall, compliance among the staff and children in this study was high, with 85% of the pupils in this group completing the 10-day regimen.  

 

Understanding the frequency and severity of side effects to antivirals like Tamiflu is vital so that we can make that all important risk-reward calculation between taking the drug or not.

 

We have to balance our odds of catching the virus, its overall virulence, our own health status and likelihood of experiencing complications, our personal contacts (immunocompromised, elderly, or infants), the expected effectiveness of the drug, and any other protective steps we could take instead (vaccination, PPEs, etc) against the possible down sides to taking the drug.

 

It is the same risk-reward calculation we should be making every time we take a powder for a headache, an antibiotic for a sore throat, agree to chemotherapy for cancer, or order `one more for the road’ at our local tavern.

 

None of these decisions should be taken without some regard to their potential consequences. 

 

Because, at the risk of repeating myself, all drugs have side effects, and no medicine is 100% safe.