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Archive for the ‘Medical Studies’ Category

Thrombolytic Use in Ischemic Stroke

Sunday, January 26th, 2014

Brain CTUse of thrombolytic therapy in ischemic stroke is a perennial hot topic. Chances are that you will have as many people swearing AT the idea as you have swearing BY the idea of using thrombolytics for acute strokes. That fact alone should demonstrate that there is no “standard of care” for thrombolytic use in ischemic strokes.
If reasonable board certified doctors can’t agree that the risk of tPA outweighs the benefit of using tPA, how can there be a “standard” for using it?

I could go through the data and discuss the pros and cons of each trial studying thrombolytic use, but Dr. David Newman has done a far better job than I could ever hope to do and his analysis of thrombolytic therapy in acute ischemic stroke is published on TheNNT.com. In summary, of the available studies on thrombolytics up to March 2013, Dr. Newman found …
Two studies showed a marginal benefit in using thrombolytics
Four studies showed a demonstrable harm in using thrombolytics
Six studies showed no benefit from using thrombolytics

Back in 2011, EP Monthly asked for opinions on thrombolytic use for acute ischemic stroke in its now-defunct Standard of Care project, but those important data were never published or made available to the people who voted.

The debate over tPA use came to a head last year when ACEP representatives met with experts in the field of ischemic stroke, including representatives from ACEP and AAN and developed a policy which was then reviewed by representatives from the Society for Academic Emergency Medicine, the Emergency Nurses Association, the American College of Physicians, the Neurocritical Care Society, the American Academy of Family Physicians, the National Stroke Association, and the American Stroke Association.
The final “evidence based” policy advocated “offering” tPA to acute ischemic stroke when certain criteria were met (.pdf file).  This recommendation was given a “Level A” status, meaning that it constituted

Generally accepted principles for patient management that reflect a high degree of clinical certainty (ie, based on strength of evidence Class I or overwhelming evidence from strength of evidence Class II studies that directly address all of the issues).

Needless to say, there was a lot of discussion after these “evidence based” “guidelines” were published.

Some people questioned whether this “evidence based” policy would create worse patient outcomes. Others were concerned that the guidelines, even though they contained a disclaimer, could create legal liability when not followed. Still others wondered whether this clinical policy was even helpful in determining a course of action since there was no “consensus” statement, only an “evidence based” policy.

Then the British Medical Journal advocated using a healthy “skepticism” in reviewing the data since almost all of the study authors had either direct or indirect ties to companies that manufactured thrombolytics:

for one of the guidelines recommending alteplase, seven of eight panel members had ties with industry: three had direct relationships with companies that market alteplase, while four had links with an educational foundation wholly funded by industry, whose president and founder was an outspoken advocate for alteplase on acute stroke. The remaining author had resigned from the panel six years earlier

Even more troubling is that several of those authors allegedly did not disclose their ties to the manufacturers in the publication of the clinical guidelines (which, if true, would constitute an ethical violation). See table below – taken from this article.

Thrombolytic Author Conflicts of Interest and Disclosures

EM Literature of Note Blog weighed in on the issue, stating:

Whichever side of the expand/limit tPA in acute stroke debate you fall upon, the issues of sponsorship bias, one-sided panelists on a still-controversial practice, and lack of open peer review for the ACEP/AAN guidelines ought to be unacceptable.

Ten months later, ACEP just might be listening to some of the criticism. There is now a form on the ACEP web site where, for the next 60 days, ACEP members can comment on the thrombolytics in acute stroke policy and provide “supporting evidence” for their comments. These comments will then reportedly be presented to the ACEP Board.

http://www.acep.org/commentform/IVtPA-Stroke/

I encourage interested parties to go to the site and add their comments.

Unfortunately, we don’t know whether the comments will also be available for public view. That’s the reason for this post.

I’m asking two favors from the readers who have an opinion on this topic.

First, vote in the poll below. It will provide data that will hopefully be available for web searches far into the future.
Second, if you have an opinion or additional “justification” that you plan to enter on the ACEP site, please also enter it into the comment section below. In that way, the comments – both pro and con – will be available for public review and discussion.

When answering the poll, keep in mind that the “standard of care” is what a reasonable physician would do under the same or similar circumstances. As noted on the defunct Standard of Care site, the standard of care is NOT “what the Best Practice would be, (arguably the top 5%); or what YOU would do (the top 25%); or or even what MOST physicians would do (the top 50%).”

The standard of care is the tipping point between “negligent” and “non-negligent” behavior. In essence, the question as asking whether a doctor has violated the standard of care and is therefore negligent and liable for damages if he or she does not administer tPA to an acute ischemic stroke victim.

Administering Thrombolytics for Acute Ischemic Stroke

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Please don’t forget to add comments in the comment section!

Facebook use in the Emergency Department

Friday, May 24th, 2013

New study shows that emergency department workers are on Facebook quite a bit. They spend an average of 4.3 minutes per hour on Facebook during day hours, which is just under an hour out of every 12 hour shift. However, during night shifts when the study hospital was busier, the staff spent an average of almost 20 minutes per hour — just on Facebook.

So are the results good news based on other studies showing that engaging in brief mindless tasks decrease worker fatigue and stress while increasing worker productivity and happiness? Or are the results bad news suggesting that patients aren’t getting full attention?

I also wonder about how the study determined active use of Facebook. Researchers set limits of 3 minutes for each interaction with Facebook, so someone checking their status for a few seconds would have been deemed to have spent 3 minutes on Facebook, as would someone who surfed Facebook for the entire shift. My guess based on my observation of computer use in my emergency departments is that the methods caused the times of use to be overestimated.

And the study also reminds us of another important point … when you’re on a work computer, what you’re doing is being watched.

Are You Better Than 83% of Radiologists?

Friday, February 15th, 2013

Fascinating study about missing obvious findings on CT studies, based on another study about selective attention. In the cited study, 83% of radiologists missed the abnormal findings on the first CT image.

Don’t ruin it for anyone else, but how many of you caught all the abnormalities on the CT scan below? For those who aren’t used to looking at chest CT scans, I included a fairly “normal” CT chest cross section (except for the small nodule) at approximately the same level on the bottom for comparison (credit here).

Abnormal CT

ct-scan

Does ED overcrowding affect outcomes or costs?

Tuesday, December 11th, 2012

Does ED overcrowding affect patient outcomes or costs?

This study from Annals Emergency Medicine (.pdf) suggests so.

However, the study used times that hospital was on ambulance diversion as a measurement of overcrowding.  When a hospital diverts ambulances, that action may demonstrate overcrowding or may also be due to CT scanner being down or other non-volume-related reasons. And just because a hospital is not on diversion doesn’t mean that there aren’t beds lined up in the hallways to cope with overcrowding. So the study is trying to draw associations between metrics that may be only marginally related.
In addition, the study excluded many rural hospitals that did not keep ambulance diversion data. There are many studies showing that mortality in rural areas is higher than mortality in urban areas. Had rural hospitals been included in the study data, it is conceivable that the rural hospitals which tend not to go on bypass may have decreased or eliminated the difference in death rates between “overcrowded” times and “normal” ED volumes.
I certainly don’t agree with the authors that their data “support the perception of ED crowding as a marker of poor quality of care.” I’m all for decreasing ED overcrowding and I agree that ED overcrowding should be viewed as an important public health priority … but using cost, mortality, and length of stay as measures of “quality” care? Seriously?
That’s the Kool-Aid that CMS is trying to get us to drink. Sorry, I’m not thirsty.

Just because you call a pig a cat doesn’t mean it’s going to start meowing.

Watch all the unintended consequences that occur if we adopt cost, deaths, and length of stay as surrogates for “quality.”

How Long Before Zofran Gets Black Boxed?

Wednesday, December 5th, 2012

It has been a few years, but the FDA’s war on antiemetics (medications for vomiting) continues.

To review …

Bendectin was the first antiemetic to be taken off the market after famous plaintiff attorney Melvin Belli sued Merrell Dow Pharmaceuticals. No credible evidence was ever found that Bendectin caused birth defects as the plaintiff attorneys alleged, yet Merrell Dow removed bendectin from the market to avoid further lawsuits.
Droperidol was another great nausea medicine that got the FDA’s dreaded “black box” because it allegedly caused QT prolongation. See commentary here.
Then the FDA went after Tigan suppositories. Remove them from the market, it demanded.
Compazine was next to get the dreaded “black box” kiss of death.
Then came Reglan, which joined the “black box” club due to a risk of tardive dyskinesia. Interesting that one of the medications that has been used to treat tardive dyskinesia is another antiemetic … Zofran.
Phenergan was next. In Wyeth v. Levine, a Vermont jury decided that drug labeling warning against intra-arterial use wasn’t strong enough. The resulting black box warning struck fear into the hearts of hospital risk managers everywhere. By the way, how many of you knew that Phenergan is an antihistamine and, like Benadryl, can be used as a local anesthetic?

It appears that not enough people were scared off by the previous FDA warning on Zofran, though.

Now, the FDA has decided the 32 mg IV dose of Zofran has the “potential for serious cardiac risks” and is demanding removal of all 32 mg IV Zofran doses from the market. Those same cardiac risks – QT prolongation – were used to get droperidol black boxed, so it is only a matter of time until Zofran gets its scarlet letter from the FDA.

Personally, I would like to see the FDA’s studies on Zofran … and all the other antiemetics for that matter. I seriously doubt many of the claims.

In the meantime there’s always Aprepitant. That’s only $100/dose (in 2004). Plus … the FDA won’t determine that it’s bad for your health for at least another 10 years – about the time it goes off patent.

Stretching the Definition of “Quality”

Thursday, October 25th, 2012

Attribution: http://www.everystockphoto.com/photographer.php?photographer_id=12419

It seems as if some members of the American Academy of Pediatrics have determined that emergency physicians aren’t performing enough useless tests on teenage girls.

According to a study presented at this year’s AAP conference, only 19 percent of the 77 million girls between ages 14 and 21 that were examined in emergency departments between 2000 and 2009 received pregnancy testing. Subgroup analysis showed that only 42% of those patients complaining of abdominal pain received pregnancy testing and only 28% of those patients exposed to radiation that could cause birth defects received a pregnancy test.

In an American Academy of Pediatrics news release, the researchers, including study author Dr. Monika Goyal, found it “particularly concerning” that rates of pregnancy testing were low even among females with potential reproductive health complaints or with exposure to “potentially teratogenic” radiation (i.e. may cause birth defects) such as chest x-rays or CT scans.

First, note how Dr. Goyal and company mention nothing about the indications for performing pregnancy testing in the emergency department. In other words, they’re bashing emergency physicians for failing to order a test when they haven’t even described when the test should be ordered.

I’m sure that Dr. Goyal’s study didn’t look at repeat visits or specific patient histories. If they’re reporting on 77 million patient visits, they must be using aggregate data. Another problem with the study is that aggregate data doesn’t take into account all of the instances in which a pregnancy test may not be indicated in a female teen.
If the patient had a negative pregnancy test in the doctor’s office two days prior to her current visit, another pregnancy test probably isn’t warranted. If a patient who is known to be pregnant is also having abdominal pain, a pregnancy test is probably a waste of time and money. Patients with epigastric pain or “heartburn” probably don’t need pregnancy tests. Should we get pregnancy tests on every patient with classic UTI symptoms? I don’t.

It’s pretty ridiculous to call the lack of pregnancy testing “particularly concerning” without saying what the “concerns” were. Did the researchers find any cases of bad outcomes due to lack of pregnancy testing in the 77 million cases that they reviewed? I’m sure there will be a few, but then a thorough researcher would then analyze thoses cases to determine whether the bad outcome was due to a failure to perform a pregnancy test. This study did nothing of the sort.

I was also surprised by the specious logic that patients having a chest x-ray performed should have pregnancy testing performed because chest x-rays “may” cause birth defects. The amount of radiation in a chest x-ray is equivalent to the amount of background atmospheric radiation people experience just being alive for 10 days. It is also equivalent to the amount of radiation that someone taking two roundtrip flights from Washington DC to Los Angeles would absorb. Read more about it on Wikipedia if you’re interested. Calling for more pregnancy testing because chest x-rays may be “teratogenic” is like demanding that all women take a pregnancy test before taking a cross-country flight on an airplane because the increased radiation exposure in the upper atmosphere may be just as “teratogenic.”
Whoops. Better not give the TSA any ideas.

Another practical issue is that lead aprons block x-ray radiation. Often x-ray techs and/or doctors will just have a potentially pregnant patient put a lead apron over her abdomen while an x-ray is performed rather than obtaining a pregnancy test. Of course such actions would be “particularly concerning” because no pregnancy test was done.

In the AAP news release, the study’s author stated that the “findings underscore the need to develop quality improvement interventions to increase pregnancy testing in adolescent girls in the emergency department, especially among those with higher risk of pregnancy complications.”

Translation: This study has failed to show that failure to perform pregnancy testing has any relation to quality of care or that it has caused harm to even one patient.

Conclusion: This study was a complete waste of time and money.

FDA’s Latest Deadly Drug: Codeine

Thursday, August 16th, 2012

Get ready for more governmental regulation of opioids and maybe even some black box warnings added to the prescribing information for c0deine-containing drugs … just for everyone’s safety, of course.

According to this FDA Special Bulletin on Safety Information, three pediatric deaths and one case of respiratory depression were documented in the medical literature after children took codeine-containing compounds. The etiology for the deaths was allegedly because the children had a variation in their cytochrome P450 enzyme that caused the codeine to break down faster into morphine, high levels of which, according to the FDA, “may be fatal.” If your child or your patient is an “ultra-rapid metabolizer” of codeine, he or she could DIE.

The FDA also published a “Drug Safety Communication” that disclosed the studies on which its recommendations were based.

One case cited by the FDA as “proof” that codeine can kill you involved a 2 year old child with sleep apnea who underwent tonsillectomy and adenoidectomy and who died three days after surgery. At autopsy, the child had elevated levels of codeine and morphine in his system, had aspirated food particles, and also had bilateral pneumonia. No mention of how much codeine the patient’s parents gave the child, only of the dose that was prescribed. No mention of how bilateral pneumonia or aspiration in a young child can be deadly. The researchers concluded that the elevated morphine levels “may” have contributed to the child’s death. The FDA wants you to believe that there was a causal connection there.

Another article cited by the FDA was from the same authors who now found three additional cases of children who died after having tonsillectomy/adenoidectomy and were prescribed codeine. I didn’t purchase the article, but I also am assuming that there were no controls for dosing of the medication, only for prescription of the medication. In other words, I doubt that the researchers would be able to tell whether the parents accidentally just gave the child too much medication as opposed to whether some genetic variant caused higher than normal blood levels of the medication at normal doses.

I also did a PubMed search for “children codeine p450” and also “pediatric codeine p450“.
There was one Canadian case report of a mother who was an “ultra rapid metabolism phenotype” whose breastfed child had fatal opioid intoxication after the mother used codeine.
There was another case report from Canada of a 5 year old girl who died from hydrocodone overdose when she was taking both clarithromycin for an ear infection and valproic acid for seizures. The medications decreased metabolism of the drug and she also had a genetic defect that decreased the metabolism of the drug.
None of the other articles that I found mentioned pediatric death due to an interaction between opioids and cytochrome P450.

Now, based on 4 deaths out of likely hundreds of millions of codeine prescriptions, the FDA is “currently conducting a safety review of codeine” and is recommending that doctors use low doses of codeine for patients in pain or that doctors just use another medication completely for children in pain. The FDA also recommends that caregivers monitor patients for signs of opioid toxicity. These recommendations are already in the prescribing information for Tylenol with Codeine.

Oh, and the FDA also notes that doctors can always perform “FDA approved” genetic testing to see if children have the gene responsible for rapid metabolism of codeine.

I can’t help wonder what motivation the FDA has to issue this warning about 4 deaths in tens or even hundreds of millions of prescriptions that were hypothesized to have been caused by this mechanism. It’s not like codeine is a new drug or that the cytochrome P450 pathway is a new discovery. Why now?

Trying to justify the FDA’s existence/budget? Getting a cut of the fees for approving the genetic testing? Getting fees for some new pain medication so that it can be approved for use in pediatric patients? Something just doesn’t make sense.

Of course, now if sometime in the future a young patient dies from an alleged codeine overdose, there will be some newspaper article published and some lawsuit for millions of dollars in damages filed alleging that if only the negligent doctor had paid attention to the FDA warnings and performed CYP2D6 genotyping, the patient would probably still be alive today.

And people wonder why doctors practice defensive medicine.

 

UPDATE
Congratulations to the Wall Street Journal, NY Times, Washington Post, ABC News, Bloomberg News, NPR, and the Boston Globe for feeding into the hysteria. Hat tip to EM Today from ACEP for the links.

Antibiotics Kill, Probiotics Heal

Sunday, May 20th, 2012

Two interesting studies were published recently.

First was a study in NEJM showing that the beloved ZeePack that so many people think will clear their boogers and resolve their cough instead increases the risk of death. During the 5 days that they took Zithromax (azithromycin), patients had almost a threefold increase in risk of cardiovascular death and almost a twofold increase in death from any cause. Patients who took Levaquin (levofloxacin) had the same increased risk of death as those who took Zithromax. The risk for death was significantly higher in patients who had preexisting heart disease.
Perhaps this may be related to the increase in death associated with higher patient satisfaction scores?
Also interesting that there was not an increase in death for patients using amoxicillin and Cipro. Makes me wonder whether “atypical” bacteria (which aren’t killed by amoxicillin or Cipro but are killed by Zithromax and Levaquin) provide some beneficial effect in the human body.

Which serves as a good segue to the second study.

A study in JAMA showed that probiotics significantly decrease the incidence of diarrhea that occurs when taking antibiotics.

I happen to be a proponent of probiotics for a number of medical problems. A couple of weeks ago I was offered the opportunity to review a new book about probiotics and will put up a review in the near future … when I finally get the time to read it.

Microbial Armageddon

Wednesday, May 9th, 2012

Any patient who demands a ZeePack for a runny nose, who wants amoxicillin for sinus congestion, or who wants Levaquin to “keep this bronchitis from developing into pneumonia” needs to read this Bloomberg article.

We are heading toward a situation where people die from infections that no antibiotics can treat. The article discussed one infant in a pediatric ICU that died because the infection that the child developed was resistant to all antibiotics used for treatment. Six similar incidents occurred during the course of 16 months. Estimates are that 100 million people in India have been colonized with organisms carrying the genetic mutation. Medical tourism in India is decreasing as a result.

Even the director of the CDC cites the situation an example of why we have to limit antibiotic prescriptions: “We are looking at the specter of untreatable illness.”

Oh, and remember how the Centers for Medicare and Medicaid Services assert that if hospitals don’t give antibiotics to every single pneumonia patient within 6 hours of arrival – even though a large proportion of pneumonias are viral in nature – that the hospitals are falling outside of “quality” guidelines? Our government’s own “quality” guidelines may be contributing to the looming microbial Armageddon in this country.

Medicaid Recipients Twice as Likely to be ED Patients

Friday, March 16th, 2012

A study just published in the Annals of Emergency Medicine shows something that many people suspected: Patients with Medicaid (i.e. government “insurance”) tend to use the emergency department much more often than patients with private insurance.

After studying 230,000 participants in the National Health Interview Survey, the researchers found that Medicaid patients were more than twice as likely to use the emergency department as their privately-insured counterparts. When barriers to timely primary care were added into the picture (including difficulty reaching doctor on telephone, difficulty obtaining timely appointment, long waits in the physician’s office, limited clinic hours, and lack of transportation), emergency department utilization increased significantly. 40% of Medicaid patients had used the emergency department more than once in the prior year. 51% of Medicaid patients with one barrier had more than one ED visit in the prior year and 61% of patients with two or more barriers had more than one ED visit in the prior year.

I’m sure that there are other reasons for the higher than normal emergency department utilization, the biggest one being lack of a disincentive for using emergency departments versus primary care physicians.

The article concluded that “Expansion of Medicaid eligibility alone may not be sufficient to improve health care access.”

Insurance doesn’t equal access. Wonder where I’ve heard that before ….

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