Month: December 2017

Are We Getting Better at Controlling Epilepsy?

Many things in medicine have changed for the better in medicine over the last 30 years. Some “innovations” have resulted in unintended consequences and costs, and, unfortunately, a few have ultimately proven harmful.

And then some just haven’t changed.

This rather depressing look at anti-epileptic therapy comes from an observational cohort in Scotland, monitoring the various outcomes and seizure frequencies in epilepsy over the last thirty years. There has been an explosion of new options for control of epilepsy – at no small cost – and, one would hope newer would be better.

After following changes in therapy and outcomes in 1,795 patients across 30 years, starting in 1982, the unfortunate conclusion is: little improvement. Starting from an era of primarily carbamazepine, phenytoin and valproic acid, despite the addition of a wide variety of modern options, the proportion of patients with 1-year seizure freedom has not changed. The primary driver of this observation appears to be little change in successful control of refractory epilepsy, in which patients failing to be controlled on their initial agent – about half – remain difficult to control, regardless of changes or additions to therapy.

I would not go so far as to say no benefit is derived from newer agents, as this study does not delve into safety profiles, adverse effects, and other reasons for discontinuation. I suspect, unfortunately however, this generally mirrors results from across the practice of medicine – where expectations and perceptions of efficacy do not match reality.

“Treatment Outcomes in Patients with Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs A 30-Year Longitudinal Cohort Study”
https://jamanetwork.com/journals/jamaneurology/article-abstract/2666189

Treatment Failure, or is Treatment the Failure?

Acute respiratory tract infections – otitis media, streptococcal pharyngitis, and sinusitis – comprise virtually a laundry list for antibiotic overuse in self-limited conditions. Certainly, a subset of each of these conditions are true bacterial infections and, again, a subset of these have their resolution hastened by antibiotics – and, finally, a subset of those would have clinically important worsening if antibiotics were not used. Conversely, the harms of antibiotics are generally well-recognized,though not necessarily routinely appreciated in clinical practice.

This patient-centered outcomes study, with both retrospective and prospective portions, enrolled children diagnosed with the aforementioned “acute respiratory tract infections” and evaluated outcomes differences between those receiving “narrow-spectrum” antibiotics and those receiving “broad-spectrum antibiotics”. Before even delving into their results, let’s go straight to this quote from the limitations:

Because children were identified based on clinician diagnosis plus an antibiotic prescription to identify bacterial acute respiratory tract infections, some children likely had viral infections.

“Some children likely had viral infections” is a strong contender for understatement of the year.

So, with untold numbers of viral infections included, it should be no surprise these authors found no difference in “treatment failure” between narrow-spectrum and broad-spectrum antibiotics. Nor, in their prospective portion, did they identify any statistically difference in surrogates for wellness, such as missed school, symptom resolution, or pediatric quality of life. However, adverse events were higher (35.6% vs. 25.1%, p < 0.001) in the broad-spectrum antibiotic cohort, and this accompanied smaller, but consistent, differences favoring narrow-spectrum antibiotics on those wellness measures.

So, the takeaway: broad-spectrum antibiotics conferred no advantage, only harms. If you’re using antibiotics (unnecessarily), use the cheapest, most benign ones possible.

“Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections”

https://jamanetwork.com/journals/jama/article-abstract/2666503

Intravenous or Oral Analgesia?

Or, better translated, is the new, fancier option really superior?

In many cases, the intravenous option is superior than the oral alternative. Cephalexin, for example, reaches higher serum levels via intravenous administration. The oral versions of morphine and hydromorphone are not equivalent intravenously. So, what about acetaminophen/paracetamol?

It is already well-established (by the manufacturer) the intravenous version of acetaminophen reaches higher peak serum levels, and does so more quickly, than oral versions. This study, however, asks the question from a patient-oriented standpoint – does this actually provide superior pain relief?

The short answer is no. This small study analyzing 87 patients receiving intravenous or oral acetaminophen in a double-blind, double-dummy fashion found no difference in mean change in pain levels at 30 minutes.  This is consistent with the limited previous evidence, and reasonably suggests there is no justification for IV use when patients are capable of taking the oral alternative.

Interestingly, this same group recently presented these data in abstract form with 108 patients rather than 87, and using median pain score reduction rather than means. Their abstract results are consistent with these, but the discordant number of analyzed patients is odd.

“Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting: a prospective, double-blind, double-dummy, randomised controlled trial.”
https://www.ncbi.nlm.nih.gov/pubmed/29247042

Prescribing Opiates to the Entire House

Opiate prescribing has blossomed into an appropriately huge issue in the current medical landscape. A fair bit of thought now goes into evaluating individuals for their potential for use and misuse – including even state-mandated prescription database review.

But, this interesting analysis suggests it should not only be the individual recipient considered when prescribing – but the impact on the health of the entire household. These authors compared administrative health care claims from 12,695,280 patients with a family member prescribed opiates against 6,359,639 patients whose family members were prescribed a non-opiate analgesic. Within one year, 11.68% of family members of those prescribed an opiate subsequently received their own, compared with 10.60% in the non-opiate cohort. After statistical adjustment, the absolute difference narrowed somewhat, and the authors also report their sensitivity analysis cannot rule out invalidation of their findings by an unmeasured confounder.

Regardless, this fits with my anecdotal experience – where many patients coming in for musculoskeletal pain have used a family member’s leftover opiate medication for breakthrough pain control. Despite the underlying limitations from this statistical analysis, it certainly seems to have face validity. It is reasonable to consider not just the individual patient being prescribed opiates, but also the risk to the household as being a gateway to subsequent opiate prescribing for family members.

“Association of Household Opioid Availability and Prescription Opioid Initiation Among Household Members”
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2664515

Atraumatic Spinal Needles are Less Traumatic

It’s a tautology!

In a solid “not news, but newsworthy” systematic review and meta-analysis published in The Lancet, these authors pooled data from 110 trials comparing conventional (“cutting”) spinal needles with “atraumatic” ones. The atraumatic ones, after all, are thought to result in less tissue damage and corresponding complications. The perceived downside to the atraumatic needles, however, is related to potentially decreased procedural success.

In short, none of the results favor the conventional needles.  The sample sizes for each measure ranged from 24,000 patients to 1,000, with most right in the middle of the range.  These authors evaluated incidence of such complications as post-procedural headaches, need for analgesia, need for epidural blood patch, nerve root irritation, or hearing disturbances. With regard to procedural success, these authors evaluated the traumatic taps, first attempt success, and overall procedural failure rate.

The magnitude of reduction in various complications was wide, but consistent. In an absolute sense, any post-procedural headache associated with use of atraumatic needles was from 12% to 7%, and the need for epidural blood patch decreased from 2% to 1%.  With regard to any reduction in procedural success, no signal of difference was observed.

The authors accurately report there is low awareness of the advantages of the atraumatic needles among clinicians. These data, even if not novel, at least are published on an adequate platform to improve awareness of the superior alternative.

“Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis”
https://www.ncbi.nlm.nih.gov/pubmed/29223694

What Does the ACC Say About OAC Reversal?

Just in case you were curious ….

Conventional tests useful for ruling out clinically relevant levels contributing to bleeding risk:

  • Dabigatran – a normal Thrombin Time or sensitive activated partial thromboplastin time (aPTT).
  • Factor Xa-inhibitors – None.

If you have access to Anti-Xa specialized assays, they can be used to measure the level of activity for the Factor Xa-inhibitors.

Managing OAC-associated bleeding:

  • Warfarin – 4-factor prothrombin concentrate complexes (PCCs) at weight-based dosing between 25 units/kg and 50 units/kg based on INR.
  • Dabigatran – Idarucizumab.
  • Factor Xa-inhibitors – 4-factor PCCs at 50 units/kg.

The authors also suggest use of PCCs as second line for idarucizumab, but this is likely to be fruitless and the evidence is very weak. Hemodialysis is also an option for removal of circulating dabigatran in a narrow set of clinical scenarios.

The authors also mention andexanet alfa and ciraparantag as potentially useful adjuncts at some point in the future, but no specific clinical role has yet been defined.

“2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants”
http://www.onlinejacc.org/content/early/2017/11/10/j.jacc.2017.09.1085

Retiring Steroids for Hives

This is one of those perfectly unglamorous, yet infinitely practical sorts of topics we encounter in everyday Emergency Medicine. I must see a patient with urticaria, almost always without known underlying trigger or etiology, nearly every other shift. They are itching furiously, and, well – it’s an Emergency!

In true “don’t just stand there, do something!” fashion, I’ve done what I can to help. This typically means “something stronger”, something not over-the-counter, and is usually a dose of dexamethasone to augment antihistamine therapy.

This small trial of 100 patients randomized patients with uncomplicated urticaria to levocetirizine (a H1 receptor-blocker) plus 40 mg of prednisone for four days, or levocetirizine plus placebo. Patients were assessed at several subsequent time points for “itch score”, rash recurrence, and other adverse events – and the winner is: placebo! There was no obvious difference or trend favoring those patients receiving steroids.  There is, however, always the potential for Type II error with such a small sample, but when a positive outcome is difficult to demonstrate, the magnitude of effect is not likely to be large.

Interestingly, they screened 710 patients in order to enroll 100, with 412 not meeting inclusion criteria. These exclusions were mostly evenly distributed between the following criteria: angioedema or anaphylaxis, use of antihistamines or glucocorticoids prior to the ED visit, and rash of greater than 24 hours duration. These limitations do limit the generalizability of these findings, considering their study cohort was ultimately only about one-fifth of all comers. It is probably still reasonable to suggest from a Bayesian sense, at least, steroids should be assumed not to have value in somewhat wider a population than explicitly testing here, but this is not definitive.

“Levocetirizine and Prednisone Are Not Superior to Levocetirizine Alone for the Treatment of Acute Urticaria: A Randomized Double-Blind Clinical Trial”

https://www.ncbi.nlm.nih.gov/pubmed/28476259

Out of the Way!

The mobile stroke unit is the new, malignant, extravagant reaction to the “Time is Brain” mantra. However, not all locations are endowed with such an embarrassment of resources.

This very brief report details a systems approach in Mashhad, in Northeast Iran. In 2015, these authors reported only 1.2% of all strokes received treatment with IV tPA, and their analysis indicated prehospital delays were their primary issue. Rather than take the CT to the patient, their far more entertaining solution was simply to clear a path. To relieve delays from chronic traffic congestion and gridlock, they designed an online control system for all traffic lights to be activated based on the severity of the emergency medical condition. Green lights in a continuous path from the incident location to the medical facility help activate traffic flow to allow ambulances room to maneuver. These authors report their successful implementation reduced prehospital transfer time by 50%, although absolute measures are not reported.

Now, they do mention their next step is to report on improvements in patient-oriented outcomes. However, unless the traffic is truly catastrophic, I expect improvements in anything but process surrogates will be difficult to detect.

“Time is brain: An online controlling of traffic lights can save lives”
http://emj.bmj.com/content/early/2017/11/24/emermed-2017-206888