Please Stop Using Azithromycin Indiscriminantly

There is a time and a place for a macrolide with a long half-life, and it is not empirically for pharyngitis.

And, it’s even less appropriate empirically for pharyngitis now that it’s been overused to the point where it’s nearly in the drinking water – because it can no longer be considered second-line for group A streptococcus for your penicillin allergic patients.

This is a case report and evidence review from Pediatrics that discusses two cases of rheumatic fever, both of which presented after treatment of GAS pharyngitis with azithromycin.  While rheumatic fever has been almost completely wiped out – there are so few of the RF emm types in circulation, that it’s almost nonexistent in the United States – there are still sporadic cases.  Macrolides are listed as second-line therapy for GAS, but single-institution studies have shown macrolide resistant streptococcus in up to 48% of patients.  Macrolide resistance varies greatly worldwide, from a low of 1.1% in Cyprus to 97.9% in Chinese children.

Why is macrolide resistance so high?  Azithromycin is the culprit; because it has such a long-half life, it spends a long time in the body at just below its mean inhibitory concentration, and preferentially selects for resistant strains.

Please stop using azithromycin.  Use doxycycline, or another alternative, when possible.  There has never been reported resistance to pencillin in GAS.

“Macrolide Treatment Failure in Streptococcal Pharyngitis Resulting in Acute Rheumatic Fever”
http://www.ncbi.nlm.nih.gov/pubmed/22311996

The Future of Medicine…is Defensive

At Northwestern University in Chicago, anyway – and probably externally valid to other institutions, as well.

This is a survey of 194 fourth-year medical students and 141 third-year residents regarding whether they observed or encountered “assurance” practice (extra testing of minimal clinical value) or “avoidance” practice (withholding services from patients perceived as high risk).  65% of medical students and 54% of residents completed the survey – decent numbers, but low enough to introduce sampling bias.

The numbers, of course, are grim – 92% of medical students and 96% of residents reported encountering “assurance” practice at least “sometimes” or “often”, while 34% of medical students and 43% of residents had encountered “avoidance” practice at least “sometimes” or “often” – nearly all of those being “sometimes”.  These behaviors are apparently learned from their superiors – approximately 40% of medical students and 55% of residents were explicitly taught to consider practicing defensive medicine.

Interestingly, medical students, internal medicine residents, and surgical residents all reported nearly identical levels of “often”/”sometimes”/”rarely” regardless of the behavior sampled – although surgical residents were more frequently taught to be defensive than medicine residents.

Must be a tough legal quagmire up in Chicago.

“Medical Students’ and Residents’ Clinical and Educational Experiences With Defensive Medicine”
http://www.ncbi.nlm.nih.gov/pubmed/22189882

Zolpidem and Benzodiazepines Will Kill You

Apparently!

Especially if you’re elderly.

It’s an interesting observational, statistically matched-control study using Electronic Health Records to monitor prescriptions of zolpidem (Ambien) and other benzodiazepines (Temazepam), commonly used as sleep aids, particularly in the shift-work population.

I think this graph pretty well sums up their results:

Blue lines are hypnotic-free, orange lines are patients taking hypnotics.  Downward slopes – exaggerated by the vertical scale – are bad.  An increased hazard for cancer was also found in patients prescribed hypnotics.

There are, of course, flaws with this study – but it is consistent with other published literature suggesting harms associated with hypnotic use.  The huge limitation of a study like this is controlling retrospectively for all the comorbid cofounders.  They attempt to do this statistically with a small set of comorbid disease, but it remains a limitation.

“Hypnotics’ association with mortality or cancer: a matched cohort study”
http://bmjopen.bmj.com/content/2/1/e000850

One-Man Crusade For Steroids In Spinal Trauma

The Cochrane Review regarding the efficacy of steroids in acute spinal cord injury, first published in 2002, has been updated for 2012.  The author’s conclusions: “Methylprednisolone sodium succinate has been shown to enhance sustained neurologic recovery in a phase three randomized trial, and to have been replicated in a second trial.”


This is an interesting conclusion to draw from an analysis of, essentially, only negative studies.  NASCIS 1 (1984) was statistically negative – but was discounted because the dosing was possibly too low.  NASCIS 2 (1990) was also statistically negative, except for pinprick and light touch at six months, which disappeared at one year.  The supposed positive outcome comes from a post-hoc analysis in which the patients who received their steroids between 3 and 8 hours after injury shook out to have a statistically significant improvements in motor score at six months and one year.  However, post-hoc subgroup analysis cannot be considered practice-changing evidence until confirmed in subsequent studies.  Otani (1994) was statistically negative for the primary outcome, but post-hoc analysis identified greater sensory improvement in the steroid group – which therefore implies greater motor improvement in the control group, as the overall combined neurologic scores were not different.  NASCIS 3 is not placebo-controlled.


There is also no mention in the Cochrane Review of adverse events – the only mention of the safety profile of high-dose steroids in the discussion section references a systematic review of high-dose steroids given to general surgical patients, both elective and trauma.  This is rigorously invalid, as the correct assessment of the safety profile of an intervention should be derived from the safety outcomes of the studies included in the analysis – nearly all of which had consistent, non-significant (underpowered) trends towards increased infectious complications.


Would it surprise you to discover that the author of the 2000, 2002 and 2012 Cochrane Review articles is the same first author of NASCIS 1, 2, and 3?

“Steroids for acute spinal cord injury.”

Discharging Bronchiolitis on Home Oxygen

This is another one of those window-to-the-future articles, where an enterprising department has taken a commonplace disease with a relatively high admission rate and tried to change the status quo.

As they note, bronchiolitis is the #1 cause of admission for children < 1 year, it accounts for 150,000 admissions annually, and costs $500 million.  One of the key clinical features that keeps otherwise well-appearing children in the hospital is hypoxia, specifically < 90% saturation by pulse oximetry as recommended by the American Academy of Pediatrics.

This is a retrospective chart review that essentially says “we did this and we like it.”  4,194 relevant charts were reviewed, 57% of which were discharged without home oxygen, 15% were discharged on oxygen, and 28% were admitted.  Of the discharged patients, 4% of the no-home-oxygen patients returned for eventual admission compared with 6% of the discharge-on-oxygen patients.  Overall, this led to a 25% relative decrease in admissions for bronchiolitis at their institution, compared to historical controls.

More confirmatory study is needed – it’s a little different at mile-high Denver than the rest of the U.S. – but this may be a promising way to reduce admissions for bronchiolitis.  It is also suggestive of what is likely the new future of cost-containment medicine, at least where the malpractice environment will tolerate it – an increasing proportion of higher-risk discharges with, in theory, closer follow-up that saves money in the long run.

“Discharged on Supplemental Oxygen From an Emergency Department in Patients With Bronchiolitis”
http://www.ncbi.nlm.nih.gov/pubmed/22331343

Ciprofloxacin is Better Than Cefpodoxime for UTI

…but don’t use either of them first-line.  And, of course, your mileage may vary based on local resistance patterns.


This study, in JAMA, is from Seattle, where their ciprofloxacin resistance in e. coli is extraordinarily low – only 4%.  Their e. coli resistance to cefpodoxime, a third-generation cephalosporin, was 8%.  They randomized 300 women with uncomplicated cystitis into, luckily, two rather similar groups – and found a 93% clinical cure rate for ciprofloxacin and an 82% cure rate with cefpodoxime.  Microbiologic cure rate at 5 days was 96% in the ciprofloxacin group and 81% in the cefpodoxime group.  And, then, there are a bunch of minor details in laborious text regarding the microbiology of the non-responders, but I’m not sure any of it’s actually relevant.  Seven women in the ciprofloxacin group required treatment for an “adverse effect” (nausea, headache, vaginal discomfort), compared with three in the cefpodoxime group.


However, neither of these agents should be considered first-line for uncomplicated cystitis.  Nitrofurantoin and fosfomycin are recommended as first-line therapy in the most recent guidelines, along with trimethoprim-sulfamethoxazole depending on local resistance.  After that, consult your local antibiogram to determine whether beta-lactams are viable, or whether a fluroquinolone or a third-generation cephalosporin should be your next option.


“Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial.”
http://www.ncbi.nlm.nih.gov/pubmed/22318279

Everyone Loves “Art”

Apparently, rather than spend a lot of money on the back-end with patient satisfaction initiatives, all you really need is soothing artwork in your ED waiting room.


This is a rather simple, prospective cohort study in which research associates observed the waiting room behaviors of waiting patients.  They observed several different behaviors, but mostly were interested in “disruptive” behaviors – fidgeting, aggressive behavior, pacing, getting out of seat, etc.  After initial observation, artwork of “natural beauty” along with a DVD of soothing nature scenes was introduced into the waiting room of the two EDs in the study.


And, essentially, the ED waiting experience appeared more pleasant, according to their surrogate measures of patient disruptive behaviors – significant improvements in reducing out of seat behavior, fidgeting, front desk inquiries.


So, art?  Probably good, although this is a relatively methodologically weak study.


“Impact of Visual Art on Patient Behavior in the Emergency Department Waiting Room.”
http://www.ncbi.nlm.nih.gov/pubmed/22325555

An Overblown Critique of CMS OP-15

OP-15 for imaging effectiveness in atraumatic headache is coming, vigorously opposed by many.  To date, most of the opposition has been in principle, or with specific clinical concerns.

This is a different approach to the problem – looking at whether the patients that CMS identified as “inappropriate” were actually appropriate exceptions.  This was a retrospective chart review of 748 charts that were referred back to 21 hospitals as “inappropriate” following a “dry run” of OP-15.  Based on individual chart review, the authors found documentation of one of the exclusion criteria in 489 of them – 479 based on the clinical criteria, and 35 based on administrative criteria (some met both).  They then look at those 259 patients for whom there is no CMS exception for their CT, and they claim that 136 of those were clinically warranted.  They therefore conclude that only 125 of the original 748 were accurately identified by this quality measure as inappropriate use of CT in atraumatic headache, and that this measure is garbage.

And, a quick Google News search finds an extensive parade of indignant headlines pulled from ACEP’s press release, condemning the measure.

But, this study misses the point.  It’s not CMS’ responsibility to comb through individual charts to find these exclusion criteria.  The onus is on clinicians and hospitals to ensure their documentation clearly expresses the indications for CT in those cases that meet the exclusion criteria, and the purpose of this dry run is to help hospitals identify where the information they are supplying to CMS is deficient.

Then, I expect CMS to take a low opinion of the additional patients in whom these authors felt the imaging was clinically warranted.  Of the 78 patients for whom the authors felt ACEP guidelines for imaging were met, 73 of them met only the Level C recommendation: >50 years of age with a new type of headache and a normal neurologic examination.  Then, there is another set of patients with headaches on warfarin, who had recent neurosurgery, or had known hydrocephalus that they claim are misclassified by CMS – but I can’t see how the misclassification isn’t on the documentation end, as headaches in all those patients should meet ICD-9 339.44 “Other complicated headache syndrome,” which is an exclusion to the rule as well.

So, even just on first pass, I’m not sure this is an effective tool with which to influence revision of OP-15.  I expect this measure to go into effect as planned – and it will be up to us to document appropriately and thoroughly, and then to monitor and demonstrate that compliance results in measurable patient harms.

“Assessment of Medicare’s Imaging Efficiency Measure for Emergency Department Patients With Atraumatic Headache”
http://www.annemergmed.com/webfiles/images/journals/ymem/FA-JDSchuur.pdf

Unneeded Stents Are Bad And Bad For You

Well past a decade into the stent era, there’s finally a growing recognition and furor over the costs and potential harms of unnecessary stenting.  While interventional cardiologists are great for the bottom line of hospitals, a few high profile cases have demonstrated that PCI and stenting might be performed more than indicated.


And, not only is it costing those patients more in procedural billing, it’s likely harmful to them as well.


This concept of “Fractional Flow Reserve” has been developing in cardiology literature to better evaluate whether a stenotic lesion is actually significantly impairing the perfusion of myocardium.  These authors, part of a French cohort study called “DEFER,” are following up prior studies showing FFR-guided selective stenting for left main disease is reasonable, and looking back at what they call “small vessel” coronary disease – LAD, RCA, and LCx.


This is, unfortunately, a retrospective analysis, and there are huge differences between the groups that underwent angiography-guided PCI and the group that underwent FFR-guided PCI – but not enough difference to account for the additional hazard ratio acquired by the angiography-guided PCI.  Angiography-guided PCI, in their propensity-score adjusted hazard ratio, still had significant associations with increased non-fatal MI and future revascularizations during their five-year follow-up period.  Indeed, the FFR-guided PCI group that did not find any vessels requiring intervention did outstanding – suggesting this perfusion-based strategy might be better for ensuring the benefits of stents do not outweigh the risks.


“Long-Term Clinical Outcome After Fractional Flow Reserve−Guided Percutaneous Coronary Revascularization in Patients With Small-Vessel Disease”
http://www.ncbi.nlm.nih.gov/pubmed/22319067

Is Midazolam Really Superior to Lorazepam?

Or, more accurately, is it reasonable to perform an intramuscular injection of midazolam rather than an intravenous injection of lorazepam for seizure-like activity in the prehospital setting?

Almost certainly.

In fact, some folks are taking this article and claiming that intramuscular midazolam is superior to intravenous lorazepam, that it’s a “game changer.”

Well, let’s not go crazy here.

As with any piece of literature, the more vocal the giddiness I see perpetuated about the internet, the more cautious I am with rushing to judgement.  It is, of course, a very well-designed, prospective, double-dummy, randomized, non-inferiority comparison between midazolam and lorazepam.  The aim of the study is, essentially, to show that, even though midazolam is not typically as rapidly effective at terminating seizures, the time difference is made up by intramuscular route versus the time required for an IV start.

What’s kind of odd that I see in this article is that nearly a third of the lorazepam group did not receive the benzodiazepine portion of the intervention – and they compare it to the midazolam group in which all but 5 patients received the intervention.  When their primary outcome is the number of folks who arrived seizure-free in the Emergency Department – it seems as though the 7% absolute difference between the two groups could be easily explained by the fact that a third of the lorazepam group didn’t receive an intervention.  Most of the lorazepam group had the intervention withheld because they stopped seizing of their own accord at the time of enrollment, with a minority having the intervention withheld because IV access could not be obtained.

And, the differences favoring midazolam are hard to pin down whether it’s actually medication superiority, or something different about the seizures.  42 patients in the lorazepam group failed to stop seizing after additional therapy, compared with only 22 in the midazolam group – is this a difference in efficacy, or a difference in the underlying disease process – which appears to be more resistant to any therapy, including rescue, in the lorazepam group?

But, in any event, this just nitpicking against the superiority argument, and not the non-inferiority argument.  From a clinical standpoint, it is clearly safe and effective to use intramuscular midazolam for seizures in the prehospital setting.  However, what I’d prefer to see is a similarly powered trial of intranasal midazolam, which takes all the injection risks for patient and provider out of the equation during the seizure.  This is a good first step, but I think we can make effective treatment even safer if intranasal can be shown non-inferior as well.

“Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus”
http://www.nejm.org/doi/full/10.1056/NEJMoa1107494