Saturday, March 10, 2012

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

Thursday, March 8, 2012

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

Tuesday, March 6, 2012

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.

"Hypnoticsassociation with mortality or cancer: a matched cohort study"
http://bmjopen.bmj.com/content/2/1/e000850

Sunday, March 4, 2012

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."