Author: Ryan Radecki

Sharp Things are the Best Medicine

Rather, they’re the best fake medicine.

This is a mildly entertaining review of placebo responses from migraine trials, looking to compare the effect size of various forms of placebo.  These authors identified 79 studies with appropriate response-to-therapy data for analysis, and evaluated the relative influences of pharmacologic therapy, cognitive-behavioral therapy, and acupuncture or surgery versus their placebo/sham versions.

Sham cognitive-behavioral therapy was ineffective and all the confidence intervals crossed unity.  Pharmacologic placebo was only superior to no treatment at all.  Then, sham acupuncture or surgery was superior to both no treatment and pharmacologic placebo.  Hence, the authors conclude the expectation of benefit is enhanced by the elaborate rituals associated with invasive therapies – and ought to be considered and cautioned against when designing trials that attempt comparisons between invasive and medical therapies.

Or, you could simply use this knowledge for evil – and conduct almost guaranteed-success non-inferiority trials for any manner of medically useless device for provision of symptom relief.

The choice is yours.

“Differential Effectiveness of Placebo Treatments: A Systematic Review of Migraine Prophylaxis”
http://www.ncbi.nlm.nih.gov/pubmed/24126676

No, You *Still* Don’t Need Antibiotics For That URI

A guest post by Justin Mazzillo, a community doc in New Hampshire.

Perhaps you’ve seen a case or two this year – a child brought to the emergency department for a cold lasting more than a day. Little Johnny’s parents dragged him in to see you at three in the morning, in hopes of obtaining the instant cure of antibiotics. 
These authors out of Washington and the United Kingdom conducted a systematic review to determine the duration of symptoms of earache, sore throat, cough and common cold in children less than 18 years of age. They included only trial arms that used no treatment, symptomatic treatment or placebo. Their findings include:
·      Symptoms of earache resolved by day three in 50% of patients and day seven to eight in 90%.  
·      Sore throat resolved in two to seven days.
·      General cough resolved by day 10 in 50% and day 25 in 90%. Symptoms of croup were gone in 80% by day two.
·      Bronchiolitis symptoms were gone in 50% by day 13 and estimated to be gone in 90% of patients by day 21.
·      Lastly, it took 10 days for 50% of symptoms of the common cold to resolve and 15 days for 90% to be symptom free.
The authors found this data to differ significantly from estimates by the UK National Institute for Health and Care Excellence and the US Centers for Disease Control. This information may go a long way in preventing parents from convincing doctors to put little Johnny on a myriad of antibiotics while his virus runs its course.
“Duration of symptoms of respiratory tract infections in children: systematic review”

http://www.bmj.com/content/347/bmj.f7027

A Rapid Response Fantasyland

Rapid response teams sound good in theory – specifically skilled nurses as back-up providers for floor emergencies, intervening and escalating patients in times of unexpected deterioration.  However, the largest cluster-randomized trial and multiple meta-analyses have failed to show any benefit to rapid response teams.

The response to this high-quality evidence?  Irresponsible conclusions based on low-quality retrospective data.

These authors have so much enthusiasm for their product – a rapid response team that proactively rounds on patients – they’re blind to the most obvious holes in their data.  They try to retrospectively compare pre- and post-RRT implementation outcomes, despite having essentially only data on floor codes.  And, backing up their main conclusion, floor codes are lower post-RRT proactive rounding – of course, floor codes were already trending downwards at the time of implementation.

What happened when the RRT intervened?  The same thing as all other studies show – they moved patients to a higher level of care.  How did patients fare in the ICU?  A third died or were transferred to hospice.  Utterly overlooked in the discussion, in which these authors praise their product and their RRT nurses profusely, is the end result of their RRT product appears to be an unchanged mortality – a simple shuffling around the location of in-hospital deaths.  Their title implies a result that is simply demonstrated nowhere in the article, yet they continue to lavish themselves with accolades right up through the final conclusion:

“Our study demonstrates proactivity and innovation as an overall approach to inpatient cardiac arrests  ….  Innovation stems from a dedicated managerial team who routinely evaluates trends in the code data and creatively seeks ways to prevent cardiac arrest from occurring.”

Managerial buzzword self-aggrandizing nonsense.

“Proactive rounding by the rapid response team reduces inpatient cardiac arrests”
http://www.ncbi.nlm.nih.gov/pubmed/23994805

The Shock Index is a Shockingly Poor Predictor of Peri-Intubation Arrest

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
This retrospective analysis of 410 patients undergoing RSI is a helpful reminder of how a statistically significant association does not implicitly translate into a clinically useful one.

The authors of this paper attempted to identify factors that would predict peri-intubation cardiac arrest using a cohort of patients requiring emergent intubation in a large urban emergency department. Specifically does the Shock Index accurately predict those who will suffer post-intubation cardiac arrest? The Shock Index (HR/systolic BP) is essentially an attempt to quantify a patient’s volume status and cardiac reserve into simple ratio. These same authors have examined this score’s ability to predict peri-intubation hypotension in the past and found similar predictive capabilities.

Given the pedigree of the authors (Dr. Alan Jones and company) it is no surprise their chart review methods were next to flawless. Using standardized data collection forms, a single trained extractor identified patients who underwent ED intubations over a one year period. To ensure inter-observer reliability, 10% of this data was randomly audited by a second extractor blinded to the trials hypothesis. Backwards stepwise regression was utilized to determine what factors were independently associated with peri-intubation cardiac arrest (defined as cardiac arrest up to 60 minutes after intubation).

In this cohort, the rate of cardiac arrest after intubation was 4.2%, or 17 patients. 10 out of these 17 events occurred within 10 minutes of the intubation and, in 15 of the 17 events the initial arresting rhythm was PEA.  As one would expect, patients who experienced peri-intubation cardiac arrest had faster a heart rate, lower blood pressure and more frequent incidence of pre-RSI hypotension. The only two metrics that were found to be independently associated with cardiac arrest were the patient’s body weight and pre-intubation Shock Index. The Shock index was found to have an odds ratio of 1.16 with a confidence interval ranging from 1.003 to 1.3. Put in another manner, it was found to have an AOC of 0.73, rendering it essentially clinically useless.

Given these test characteristics, if we were to use a Shock Index of 0.88 (as suggested by the authors) to determine who is at risk for peri-intubation arrest than we would be left unprepared for an unacceptable quantity of patient who will decompensate during the procedure. This should be inherently obvious, as a formula that incorporates only heart rate and systolic blood pressure is incapable of encapsulating all the many reasons a patient may code peri-intubation. Not to mention that this study does not tell us whether the patients whom the Shock Index identifies as “at risk” will actually benefit from our added vigilance and pre-intubation hemodynamic optimization. Or does the Shock Index merely highlights a spectrum of the more critically ill patients who will inevitably deteriorate despite our clairvoyant best efforts?

Tachycardic, hypotensive patients are at increased peril for peri-intubation arrest. Sicker patients, older patients, and patients with poor cardiac reserve are all at higher risk. Most importantly, the Shock Index does not accurately predict who will and will not arrest after intubation. Similar to tools meant to predict difficult airways (not accurate enough to depend on clinically), we must be prepared for peri-intubation arrest in the majority of the patients requiring emergent intubation. Once a patient reaches the critical juncture of requiring intubation, we should be aware of all the perils this procedure involves and plan accordingly.

“Incidence and Factors Associated with Cardiac Arrest Complicating Emergency Airway Management”
www.ncbi.nlm.nih.gov/pubmed/23911630

Remember: Tamiflu is Still Junk

It’s that season of the year again, and with the fatalities from the H1N1 strain returning to the news folks are clamoring for Tamiflu (oseltamivir).

And, there’s still no evidence it has any protective effect at reducing complications from seasonal influenza.  In these two studies, a systematic review and a meta-analysis, some small reductions in symptom duration in mild illness were outweighed by drug adverse events such as nausea, vomiting, and diarrhea.  There is no evidence of any decrease in severe complications of influenza.

Unfortunately, the heterogeneity of trials, irregularities in baseline characteristics, and incomplete peer review all impair knowledge translation of this relatively expensive outpatient medication.  You’re all hopefully aware of the BMJ’s ongoing open data campaign regarding Tamiflu.  The last update from July seemed to indicate independent access to higher-quality trial data had finally been achieved.  If there is a durable, beneficial effect attributable to osletamivir, perhaps we will soon know.  Given the lack of transparency to date, I’m not optimistic.

“The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.”
http://www.ncbi.nlm.nih.gov/pubmed/23565231

“Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials.”
http://www.ncbi.nlm.nih.gov/pubmed/22997224

The Great Chocolate Question

Continuing our mini-Christmas sabbatical from serious business, yet again Science has asked an important question.  And, yet again Science has the answer – chocolates don’t survive very long on medical wards.

In the BMJ’s annual Christmas collection, this “covert” observational study evaluated the median time Cadbury Roses and Nestle Quality Street chocolates survived from their arrival on the wards.  The boxes were opened within an average of 12 minutes, and were half-consumed within 2 hours.  Roses appeared to be preferred to Quality Street, based on median survival time.

Important science; previously known as Sweet Consumption of Famished Faculty – a Limited Observational Trial; SCOFF-A LOT.

“The survival time of chocolates on hospital wards: covert observational study”
http://www.bmj.com/content/347/bmj.f7198

Biphasic anaphylactic reactions – How long should we observe?

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

ED Nurse: “You want to watch that allergic reaction for 6 hours? Seems like a long time.”
ED MD: “Yeah, I know but I want to make sure they don’t have a biphasic anaphylactic response.”
ED Nurse: “When does that usually happen?”
ED MD: “Well, uh . . . I’m not sure . . . hey did anyone see that 90 year old with dizziness yet? I should go see her now.”

If this conversation seems familiar, you’re not alone. We’ve all been taught that patients with allergic reactions have a risk of recurrent reaction. What we fear, is an anaphylactic episode that improves, the patient goes home and then has recurrent anaphylaxis and dies. As a result, many of us have been taught that if the patient resolves, you watch them for 4-6 hours and if they remain okay, they can go home.

However, when you look at the literature, it shows that the biphasic reaction can be delayed. It can occur anywhere from 5 minutes up to 3-4 days out. So what is the optimal duration of observation?

Enter this retrospective, chart review from the University of British Columbia. The researchers found 2,819 patients with allergic reactions at two institutions (496 classified as anaphylaxis) and the scoured databases for representations within 7 days. They further separated out those patients with clinically important biphasic reactions. Overall, there were five patients (0.18%) who had clinically important biphasic anaphylactic responses in seven days. Of these, two had immediate biphasic anaphylaxis during their initial Emergency Department visit and three experienced a delayed response up to six days out of their initial visit. Two of the biphasic reactions were in patients initially presenting with anaphylaxis (0.40%) and three were in patients presenting with simple allergic reactions (0.13%).  There were no deaths identified.

The study has the typical limitations of any retrospective chart review. One major concern is that patients presented to EDs other than the original two sites. The researchers did, however, check the regional database for representations and checked the provincial database for mortality.

Although the study isn’t perfect, it suggests that the biphasic response may be lower than previously thought. Prior studies have shown biphasic reaction rates ranging from 3 – 20% (Tole 2007). As a result, some authors have recommended observation for up to 24 hours after an anaphylactic reaction. The truth is that there are no consistent recommendations about observation. The authors conclude that,

“although extended observation would be justified in patients with severe or protracted anaphylaxis, the added costs and resource use involved in routine prolonged monitoring of patients whose symptoms have resolved may worsen ED crowding while likely adding little to individual patient safety.”

While it’s hard to recommend changing practice based on a retrospective study, this is the largest study done on the subject and offers very reassuring numbers. The bottom line is that clinically important biphasic reactions are rare (less than 1%) and can occur days after the initial reaction. There is no 100% safe observation period. After symptom relief, and decision for discharge, patients should be given epinephrine auto injectors and taught how to use them. Any potential inciting allergens should be removed and follow up should be arranged with an allergist. With a clinically important biphasic response rate < 0.5%, extended observation seems to be unnecessary.
References
Grunau BE et al. Incidence of Clinically Important Biphasic Reactions in Emergency Department Patients with Allergic Reactions or Anaphylaxis. Ann of EM 2013. ePub http://dx.doi.org/10.1016/j.annemergmed.2013.10.017

Tole JW, Lieberman P. Biphasic Anaphylaxis: Review of Incidence, Clinical Predictors and Observation Recommendations. Immunol Allergy Clin N Am 2007; 27: 309-26.
http://www.ncbi.nlm.nih.gov/pubmed/17493505

God Bless Us, Everyone

So says Tiny Tim, from the Dickensian Christmas fable – or, more familiarly, from the Disney production on the same theme.

As several physician-historians have done before, this short piece explores the malady afflicting Tiny Tim in the context of industrial London.  Because Dickens tended to very accurately portray phenotypic manifestations of illness – Pickwickian Joe, the epileptic Monks, the dwarf Jenny Wren – the character depictions give realistic insights into the travails of the working poor.  Was it cerebral palsy?  Simple malnutrition?  Or something more exotic like renal tubular acidosis?

Regardless the diagnosis, the treatment of the time would have been the same:  cod liver oil.

May your Christmas be merrier than that.

“Environmental Factors in Tiny Tim’s Near-Fatal Illness”
http://archpedi.jamanetwork.com/article.aspx?articleID=1107722

Uninjured Children are Uninjured, and Other Tautologies

In America’s culture wars (e.g., War on Drugs, War on Women, War on Christmas, etc.), few rise to the magnitude of the Emergency Physician vs. the consultant surgeon.  The disagreement in necessity of CT radiography for minor trauma is well-documented, and even surgeons themselves admit to possibly overdoing it in their valorous quest for zero-miss.

This study has the conclusion we’d like to see – but not the evidence needed to fully support it.  These authors from Denver performed a retrospective review of 174 pediatric trauma team activations, specifically evaluating the incidence of CT-identified injuries for four categories of patients.  The cohort these authors focus on for their conclusions are those with no apparent injury and no abnormal vital signs, but were imaged (presumably, considering this is retrospective) based on “mechanism of injury”.  Of the 66 patients who received any kind of CT imaging in the absence of objective indications, zero serious injuries were identified.

However, this MOI-indicated CT group was not exactly uninjured – over a third had a long bone fracture, and 9% had a skull fracture.  In a group of children whose average age is 7, of whom half have a significant injury, it is hard to quibble retrospectively with the indications for each CT individually – even if all were ultimately negative.  There is an obvious hint of truth that, yes, if MOI is the overriding justification for CT, it will result in an embarrassingly low incidence of true injury.  In the end, this study only shows us we need to continue advancing our development of clinical evaluation instruments to improve yield and cost-effective care.

“Mechanism of injury alone is not justified as the sole indication for computed tomographic imaging in blunt pediatric trauma”

Follow the Money

The sun is coming up – in 2014 the Sunshine Act will further illuminate just how much money is being hemorrhaged in healthcare to support the profit motives of pharmaceutical and device providers.  However, increased transparency has become more prevalent – including a few companies posting grant award registries to their websites.  These 14 companies, and their distribution of funds in 2010, are the focus of this brief report in JAMA.

Considering this is just a subset of a little more than half the top drug companies in sales from 2010, the numbers are more than a little staggering: $657M distributed, with over $100M from Roche/Genentech alone.  Medical communication companies received 26%, followed by academic medical centers with 21%, then disease-targeted advocacy organizations with 15%.  But, this report focuses only on the MCCs – considering their role in knowledge translation to the average clinician and consumer.

The largest beneficiary/offender?  Medscape/WebMD.  $20M in grant awards from just this subset of 14 drug companies – suggesting pharmaceutical corporation “donations” represent a significant portion of their $500M annual revenue.  It might be most appropriate to label every news post on their site as “sponsored content” or “special advertising section”.  This brief report further evaluates the privacy policies of these MCCs, and determines physician behavior collected by their sites is likely redistributed for profit back to various industry players.

Pharmaceutical and device manufacturers are not charities.  Executives from these companies, despite what their public relations department would have you believe, are not sitting in strategy meetings discussing altruistic giving for the good of health.  These financial outlays are investments in marketshare and mindshare, and ought to be viewed for what they are – corrupting influences contributing to the degradation of cost-effective care.

“Medical Communication Companies and Industry Grants”