Ryan Radecki

Colchicine for Pericarditis: Do It

Anti-inflammatory treatment is the mainstay of therapy for pericarditis. Aspirin, NSAIDs, steroids – and now, colchicine. Used to treat inflammation related to gouty attacks, useful in other types of serositis, colchicine has been suggested as having value in pericarditis, as well.

This is a seven-year double-blind, randomized controlled trial between colchicine and placebo, added to usual therapy – which, in this case, was usually aspirin. Primary outcome was “incessant or recurrent pericarditis” – and, there’s no doubt in this trial the colchicine is successful and mostly harmless. With standard anti-inflammatory treatment 37% of patients suffered incessant or recurrent pericarditis within the 18-month follow-up period, compared with 16.7% of patients receiving colchicine. Colchicine had beneficial effect on symptom persistence at 72 hours – 40.0% vs. 19.2% – and was superior with remission at one week – 58.3% vs. 85.0%.

Adverse effects and drug discontinuation rates were essentially identical within the bounds of their relatively small sample size. I don’t see any particular reason to exclude appropriate patients from colchicine for acute pericarditis.

“A Randomized Trial of Colchicine for Acute Pericarditis”
http://www.ncbi.nlm.nih.gov/pubmed/23992557

Still Looking For Positive EHR Effects

Our health system just underwent an upgrade from the 2009 version of an EHR to the 2012 version. The color scheme is a little different. The painfully cluttered workflow is not significantly changed. I’m sure there are many Very Important Features – likely relating to burdensome documentation regulations – but, from a clinical standpoint, it still feels like we’re working with Windows 3.1.

But, we suffer this hacked together kludge because of the promise for tangible improvements in quality of care. One area that has markedly changed with the advent of EHR is the ability to obtain significant medical histories on our patients – without the need to rely on the imperfect patient interview. The hope of these authors was that, if they compared patients for whom they had complete records established in the EHR to patient who were EHR naive at their facility, they’d be able to demonstrate improvements in at leasts surrogate markers for patient-oriented outcomes.

Looking retrospectively at three EDs covering 13,227 patient visits, these authors found essentially statistical noise. Comparing multiple outcomes including hospitalization, ED LOS, quantity lab orders, and hospital mortality, they found inconsistently distributed variation that is more likely attributed to unmeasured confounders than any element of the EHR itself.

Like most folks using EHRs, I suspect there are small, difficult-to-measure improvements in healthcare delivery. Interoperability and centralized data sources would contribute vastly, I hope, to reduced testing and admission rates without adverse effects on outcomes. However, we’re still waiting for proof.

“The impact of electronic health records on people with diabetes in three different emergency departments”
http://www.ncbi.nlm.nih.gov/pubmed/23842938

“Distracting”, But Not Distracting

Cervical spine clearance is always a fun topic. Once upon a time, it was plain radiography, clinical re-assessment, and functional testing with dynamic radiography. Now, a zero miss culture has turned us mostly to CT – and, beyond that, even some advocate for MRI.

But, as far as clinical clearance of the cervical spine goes, we usually use the NEXUS criteria or the Canadian C-Spine criteria. One of the elements of the NEXUS criteria that is, essentially, subjectively defined is the presence of “distracting injury”. Many have questioned the inclusion of this element.

These authors looked at cervical spine clearance in the presence of “distracting injury”, which, for the purpose of research protocols, was essentially a fracture somewhere, an intracranial injury, or an intra-abdominal organ injury. They found, when assessing a GCS 14 or 15 trauma patient, even in the presence of these other injuries, clinical examination picked up 85 of 86 cervical spine injuries. One patient did not report midline cervical spine tenderness – with humerus and mandible fractures, as well as frontal ICH – and had a 2nd vertebrae lateral mass fracture.

So, clinical examination is mostly reliable in the presence of a “distracting injury”. I think the best interpretation of this study is “distracting injury” has to be determined on a case-by-case basis – one patient might be a reliable reporter in the presence of long-bone fracture, while another might need such a high level of pain control for initial management they are no longer aware of their cervical spine injury. It’s fairly clear it is reasonable to remove the cervical collar and forgo imaging for most patients who can be adequately clinically assessed.

“Clinical clearance of the cervical spine in patients with distracting injuries: It is time to dispel the myth”
http://www.ncbi.nlm.nih.gov/pubmed/23019677

Language Barriers as Overdose Risk

This is a simple study, but demonstrates an incredibly important risk – the effect on language barriers on subsequent prescription dosing errors.

These authors followed up English-speaking and Spanish-speaking parental dyads being prescribed acetaminophen at discharge from the Emergency Department. The discharge instructions were observed, and, following discharge, the parents were asked to repeat back their understanding of the correct weight-based dose of acetaminophen for their child.

English-speaking parents: 25% dosing errors
Spanish-speaking parents: 54% dosing errors

Firstly, these are both too high – despite a standardized chart given to parents. Observation of discharged indicated providers only explicitly identified the dose of acetaminophen for parents 37% of the time.

Secondly, it’s clear an extra level of care needs to be taken when language barriers present themselves. The dosing error risk remained significant whether adjusted for health literacy, income, or preferred language of discharge instructions.

We can, and need, to do better.

“Parental Language and Dosing Errors After Discharge From the Pediatric Emergency Department”
http://www.ncbi.nlm.nih.gov/pubmed/23974717

Nothing Reliably Predicts Infected Stone

…but the obvious predictors are, well, obvious.

Ureterolithiasis sounds miserable. Luckily, it is typically self-limited, temporary, and results in minimal lasting morbidity. However, infected ureterolithiasis is a higher-risk clinical syndrome – and, even worse, infected, obstructed ureterolithiasis is a potential urologic emergency. Thus, suspected infected ureterolithiasis certainly ought to be considered for imaging.

In this review of consecutive patients with suspected ureterolithiasis, 7.8% had concomitant urinary tract infection verified by urine culture. Female, fever, and history of urinary tract infection were fair predictors of UTI, and increasing levels of pyuria and nitrates on urinalysis were strong predictors. Overall, the presence of greater than 5 WBCs/hpf on microscopic examination was 86% sensitive and 79% specific for UTI. No predictive feature was universally present, and specificity could be increased only at significant cost to sensitivity.

So, UTI complicating ureterolithiasis is uncommon and inconclusively diagnosed – but the strongest predictors are the obvious ones we’ve been accounting for already.

Fun tidbit: Stone size ranged from 1 to 50mm. 50mm!

Somewhat-related plea: These folks performed CT on ~90% of patients. Many cases of ureterolithiasis can be diagnosed to reasonable certainty simply on clinical grounds. Stop the cost/irradiation madness!

Somewhat-related plea #2: There isn’t any proven pro-expulsion therapy. All the tamulosin trials are small, manufacturer-sponsored, and non-compelling. IV fluids also don’t help. If the benefits aren’t proven, then all you have left are costs & potential harms.

“Association of Pyuria and Clinical Characteristics With the Presence of Urinary Tract Infection Among Patients With Acute Nephrolithiasis”
http://www.ncbi.nlm.nih.gov/pubmed/23850311

Suture Everything Closed

Management of dog bites still exhibits significant variability. Antibiotics, traditionally generally prescribed, are only selectively necessary. Another element of mythology, primary closure of wounds for optimal cosmesis, is the subject of this trial.

These Greek authors randomized 182 patients to either primary suturing or non-suturing of traumatic bite lacerations. Obviously, the lacerations receiving primary closure had much improved cosmetic outcome. The infection rate of suturing was 9.7% vs. 6.9% without, and this study was underpowered to confirm whether this small difference occurred by chance alone. The main predictor of subsequent infection was treatment >8 hours after injury. All patients, unfortunately, received local scrubbing with povidone-iodine and were prescribed amoxicillin/clavulanic acid, neither of which were likely helpful.

I think it’s absolutely reasonable to approximate wound edges for dog bite lacerations after gentle and thorough cleansing. This study doesn’t provide any truly conclusive guidance for wounds >8 hours old – as they had similarly poor outcomes, regardless – other than to offer information to patients on their sub-optimal prognosis.

“Primary closure versus non-closure of dog bite wounds. A randomised controlled trial”
http://www.ncbi.nlm.nih.gov/pubmed/23916901

ACEP/AAN Guideline Writers Respond

Some of the authors of the new ACEP/AAN clinical policy have responded to the BMJ report discussing conflict-of-interest in guidelines, focusing on the science behind the tPA portion.

If you haven’t already visited, it’s truly a star-studded sort of discussion, with David Newman, Jerome Hoffman, Robert Solomon, Jeffrey Saver, Stephen Messe, Peter Sandercock, and James Grotta, among others.

“NEXUS Chest” Decision Instrument

Low-yield radiography in the setting of trauma is pervasive and costly, but, unfortunately guidance regarding appropriateness is poor. The NEXUS group previously derived a chest imaging decision instrument, and this newly published article describes the validation study.

The good: 98.8% (CI 98.1-99.3%) sensitivity for any thoracic injury on imaging, and 99.7% (CI 98.2-100%) sensitivity for injuries of major clinical significance.

The really, really bad: 13.3% (CI 12.6-14.1%) specificity for thoracic injury or 12.0% (11.3-12.6%) specificity for major significance.

And, these numbers are probably subject to some limitations, considering about half the patients only received chest x-ray, rather than chest CT. That said, the injuries missed by x-ray are not likely of major clinical significance – and the patients selected for x-ray alone in the run of standard practice were likely selected for a low pretest probability of serious injury, regardless.

The authors suggest their instrument, despite it’s terrible specificity, still represents a valuable rule-out option, theorizing that even the small reduction in imaging this rule represents is beneficial. However, as we’ve covered before, one-way decision instruments are subject to cognitive bias and use as two-way rules, which may paradoxically increase imaging – although, in trauma, it’s hard to imagine a way to order more. Careful adoption of this instrument will be required – perhaps only after clinical evaluation as a screening decision-support question in the CPOE, asking one last time if the patient possibly meets this very-low-risk criteria prior to ordering.

The exclusion from very-low-risk criteria, by the by:

Older than 60 years
Rapid deceleration mechanism (fall >20 ft, MVC >40mph)
Chest pain
Intoxication
Abnormal mental status
Distracting painful injury
Tenderness to chest wall palpation

“NEXUS Chest – Validation of a Decision Instrument for Selective Chest Imaging in Blunt Trauma”
http://www.ncbi.nlm.nih.gov/pubmed/23925583

Post-Arrest Catheterization Delusions

We have, yet again, another favorable publication espousing the benefit of cardiac catheterization after cardiac arrest. There is not a great deal of ambiguity regarding the management of post-arrest STEMI. However, the cohort these authors examine – those without obvious cardiac cause for arrest – is harder to to judge.

Unfortunately, this article is the same level of evidence as the prior publications in this field – by which I mean, practice change followed by retrospective, observational case-series. These authors look back at their cohort cohort of VT/VF that was not STEMI – a reasonable initial stratification based on presenting rhythm and likely association with acute coronary syndrome. Of 269 patients meeting this definition, 122 underwent early catheterization and 147 did not. The outcomes were more favorable in the cohort that underwent catheterization, and thus, the conclusion:

“In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality.”

But, these authors are unable to pin down exactly what element of post-arrest care in the catheterization lab leads to this decreased mortality. Only 26.2% of patients undergoing early catheterization had a lesion amenable to intervention (the authors call this level of incidence “high” – hum), and intervening on a coronary lesion conferred no specific survival advantage. Therefore, it’s not the PCI that benefited these patients. There was an increased incidence of post-resuscitation shock in the catheterization cohort, and these underwent left-ventricular support more frequently – which may or may not have resulted in improved outcomes. Furthermore, the median time to therapeutic hypothermia in the catheterization cohort was an hour faster as well – suggesting this baseline difference in treatment may have influenced cognitive outcomes.

Unfortunately, retrospective studies like this suffer critically from selection bias – patients in the arm receiving cardiac catheterization may have had other unreported features favorable for cognitively intact outcomes, leading clinicians to treat them differently/more aggressively. It would be inappropriate to generalize this observational association with causation and send all post-arrest to catheterization. Certainly, some subset of VT/VF arrest benefits from early cardiac catheterization, but this study unfortunately does little to delineate which.

“Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI”
www.ncbi.nlm.nih.gov/pubmed/23927955‎

Guidelines For Sale

In a world of complex and sometimes conflicting literature, many physicians and professional societies rely on experts to synthesize the evidence and produce general guidelines supporting best practices. To evaluate the potential for sponsorship bias, these authors perform a cross-sectional study of recently published national and international guidelines associated with the greatest healthcare expenditures.

In line our with our recent coverage of the BMJ investigative report, 75% of guideline committee members disclosed relevant financial conflicts of interest. The astute reader may judge for themselves whether these most frequently reported COIs are relevant:

ADHD: manufacturers of methylphenidate HCl and atomoxetine
Alzheimers disease: manufacturers of solanezumab and donepezil HCl
Anemia/CKD: manufacturer of darbepoetin alfa
Asthma: manufacturers of fluticasone propionate and montelukast sodium
Bipolar/depression: manufacturers of duloxetine, olanzepine, sertraline, and ziprasadone.
Cholesterol: manufacturers of simvastatin and rosuvastatin
COPD: manufacturers of budesonide & fometerol, tiotropium bromide, and fluticasone propionate
Hypertension: manufacturers of irbesartan, losartan, and amlodipine besylate/benazepril HCl
Myocardial infarction: manufacturers of rosuvastatin, rivaroxaban, and alteplase
Multiple sclerosis: manufacturers of interferon beta and terifunomide
Rheumatoid arthritis: manufacturers of certolizumab pegol, adalimunab, and abatacept

I’m sure these guidelines reliably provide funding-agnostic recommendations. We might as well just have a bidding war between drug companies to vie for favored product status.

“Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry: A Cross-sectional Study of Common Conditions in the United States”
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001500