Concern over MOC goes beyond the blogs

This just published article from Cleveland Clinic examines the evidence concerning MOC, its unintended consequences and the current status of the controversy. I don't have access to the full text but Dr. Wes provides a nice sampling here.

Growing resentment and misery over MOC

Dr. Robert M. Centor, the blog author at DB's Medical Rants, opines on this subject from time to time and did so again yesterday. He has a wide readership and his posts on topics such as this usually generate lively discussion. He talked around some questions in need of elaboration but unfortunately the comments on his site seem to be disabled at present, so I'll weigh in here. He raised the following issues:

Career long learning is essential.
All would agree with that premise, but Dr. Centor didn't address the real rub, which is the question of how best to promote and advance it and whose responsibility it is. Mature professionals realize that they as individuals know best how to direct their learning as opposed to some outsider such as the ABIM. That's inherent in the notion of self assessment. (Note that not even state licensing boards dictate the type of CME content doctors are required to learn).

MOC is not evidence based.
From his post:

These regulations have face validity to the regulators, but practicing physicians just see the time and hassle that each step creates. Regulators want us to practice “evidence-based medicine”, but they do not want to practice “evidence-based assessment”...

The ABMS goes much further than knowledge however. And these activities feel like busy work, and many physicians complain that these activities have no reasonable outcome data to support the hassles involved.

The process is counterproductive.
He wrote:

When the physician community loses faith in the process, then we should reconsider the process. Making physicians angry with the process seems counterproductive.

Dr. Centor is a good listener and feels the pain of the rank and file internist. But what does he plan to do about the situation? As Chair of the Board of Regents for ACP he is positioned to do a great deal. If ACP were to partner with AAPS in their effort it might tip the balance toward a favorable resolution of the struggle.


Meanwhile, as internists grow increasingly miserable the ABIM is digging in, holding fast to its policies and proposing even more hoops for docs to jump through such as this one:

ABIM could require candidates to achieve a perfect score on questions related to costs and redundant care as a requirement for admission to secure exams for initial certification or MOC.

More concerning than the latest requirements from the Board are the general trends. See where things are headed?

Paul Kempen responded here.

American Board of Internal Medicine to all the old farts out there: you're still certified for life---well, sort of

The push back against ABIM's Maintenance of Certification program (MOC) is growing by leaps and bounds. Most of this, as far as I can tell, is coming from docs who certified after 1990 and already had to recertify every 10 years but are now upset over the additional hoops created by ABIM for them to jump through. Missing from most of the discussions is how this affects the older docs who certified before 1990---who were “grandfathered” and told their certification was good for life. I'm afraid some of my older colleagues have slept through what happened. I wasn't aware of it until a few months ago.

So what am I talking about? Well, for the grandfathered internists who choose not to perform the “voluntary” recertification activities the Board is coming as close to de-certifying them as they can without actually taking the certification away and having to say “Sorry. We lied.”

How does it work? It's in the way they report your certification status. Go to their website and look up the name of a grandfathered colleague (this portion of the site is open to the public). Those not participating are designated as Certified but right under that it says Meeting Maintenance of Certification Requirements: No.

What will the public think? What will credentialing bodies think? While this will confuse some people it comes across loud and clear to most as nominally certified but not really certified.

For additional information see here.

Dalbavancin: about to be launched

A Dalvance drug rep will be bringing lunch to a hospital near you, and soon. So you might as well learn a little about it now. Here's a summary at Academic Life in Emergency Medicine. Here's more from Medscape ID.

You can think of dalbavancin as a second generation vanco but there are some unique properties, particularly its pharmacokinetics which enable once weekly dosing.

Dalvance is the first drug to benefit from the FDA's new fast track process for antibiotics. From the FDA bulletin:

Dalvance is the first drug designated as a Qualified Infectious Disease Product (QIDP) to receive FDA approval. Under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act, Dalvance was granted QIDP designation because it is an antibacterial or antifungal human drug intended to treat serious or life-threatening infections.

“Today’s approval demonstrates the FDA’s commitment to encouraging increased development and approval of new antibacterial drugs, providing physicians and patients with important new treatment options,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

As part of its QIDP designation, Dalvance was given priority review, which provides an expedited review of the drug’s application. Dalvance’s QIDP designation also qualifies it for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug and Cosmetic Act.

Here are a few of my questions and concerns:

There was a mild signal of liver toxicity in clinical trials.

It will probably be very expensive.

Given the many options for gram positive infections that we already have exactly where will this drug fit in?

The drug's approval is narrow in scope. What off label uses might be appropriate as we gain more experience?

Many patients with skin infections do not need MRSA coverage at all. That's a matter for clinical judgment.

I don't anticipate heavy usage of this drug. It's one more option, which is great.

The concluding comments of the Academic Life in Emergency Medicine post came across to me as a little hard line:

Even if the company adjusts the price to less than $100 per dose, hospital antimicrobial stewardship programs need to rationalize and limit the use of this new antibiotic for cases when cheaper non-inferior treatments have failed.

Rationalize? How rational is it to wait for treatment failure before considering another option that might be better for the patient? He goes on:

Advertisers’ persuasion of better compliance for “high-risk patients,” convenience, and non-inferiority, are not enough to challenge the standard care of SSTIs in the ED.

Not enough to even challenge standard care? It seems to me that the convenience advantage is pretty substantial. This is an illustration of the difference between two approaches to medicine: medicine by committee and evidence based medicine (EBM). The author of the post is advocating medicine by committee. It's incompatible with EBM because it proscribes two of EBM's essential components in decision making about whether to use dalbavancin: the individual patient's unique attributes, preferences and values and the judgment and expertise of the treating clinician.

Vancomycin, Zosyn and nephrotoxicity: should we be worried?

I hope readers will understand my using the name Zosyn instead of the more clunky piperacillin/tazobactam. I think the term “gone viral” well describes this concern. That is, the notion of the “nephrotoxic toxic vanc/zosyn combo” is spreading like wildfire (on the wards, via email, etc) though not so much through “official” media. It wasn't even mentioned in the nephrology or ID talks at the recent Society of Hospital Medicine national meeting. It's been difficult to find good information. But Academic Life in Emergency Medicine recently posted a topic review. As usual they did a great job. Their bottom line:

While there is no definitive link between pip-tazo and risk of AKI, there have been 5 different groups, with internal medicine and ICU patients, showing a possible association. To me, this adds one more reason to at least think twice about reflexively ordering pip-tazo for every sick patient.

In other words the evidence favoring the nephrotoxic association is low level but more and more is coming in in bits and pieces, adding to the concerns.

What I get tentatively from the available data, and this is just a hunch:

Vancomycin as nephrotoxic all by itself is a difficult sell for me. Maybe in patients who experience very high trough levels, but I don't know.

Zosyn as monotherapy appears to have nephrotoxic potential.

Vancomycin seems to potentiate the nephrotoxicity of Zosyn.

Antidotes for target specific oral anticoagulants: coming soon

Currently available options for reversal of TSOACs are limited. However, specific antidotes are in the pipeline and were the subject of this recent review.

They include:

PRT064445 (Portola Pharmaceuticals)

A recombinant Xa variant. Reverses anti Xa agents.


aDabi-Fab (Boehringer Ingelheim)

A humanized Fab fragment for reversal of dabigatran.


PER977 (Perosphere Inc and Daiichi Sankyo)

A small synthetic molecule which is a broad spectrum antidote, binding TSOACs, fondaparinux and low–molecular-weight heparins.

Update on the Surviving Sepsis Guidelines

This recent article in the Annals of Emergency Medicine is nothing new, and it is already a little out of date because it does not acknowledge the recent process trial results. But I have linked it here because it has a table that nicely compares and contrasts the current guidelines with the 2008 guidelines.

Vancomycin dosing: the right way and the wrong way

Current guidelines for MRSA targeted vanc dosing have been around for a while now and should be pretty familiar but inappropriate dosing is still a problem. “Hang a gram and call it a day” all too often prevails. This was the topic of an update at Academic Life in Emergency Medicine recently.

TPA for acute ishcemic stroke: trends in usage

From the Get with the Guideline-Stroke database:

Methods and Results—We analyzed all AIS patients (n=1 9093 895) and those arriving less than or equal to 2 hours and treated with tPA less than or equal to 3 hours after onset (n=50 798) from 2003 to 2011 in the American Heart Association’s Get with the Guideline–Stroke (GWTG–Stroke). Categorical data were analyzed by Pearson χ2 and continuous data by Wilcoxon test. Intravenous tPA use less than or equal to 3 hours after onset increased from 4.0% to 7.0% in all AIS admissions and 42.6% to 77.0% in AIS patients arriving less than or equal to 2 hours and fully eligible for tPA (P less than 0.001). In univariate analysis, tPA use increased over time, especially in those aged greater than 85 years, nonwhite, and with milder strokes (National Institutes of Health Stroke Scale 0–4). Door-to-image time (median 24 versus 20 minutes) and door-to-tPA time (median 81 versus 72 minutes) also improved, with ≈65% of tPA-treated patients getting brain imaging less than or equal to 25 minutes after arrival. Multivariable analysis showed that with each additional calendar year, the odds that an eligible patient would receive tPA increased by 1.37-fold, adjusting for other covariates.

Slow uptake. In 2003, eight years post NINDS, only 42.6% of eligible patients were treated. By 2011, sixteen years post NINDS, it's up to 77%. If you present to an ER eligible for TPA, with each passing year your odds of getting treated increase 37%.

Thrombolysis for ischemic stroke has an interesting history. Its slow uptake in clinical practice is due in part to a massive and highly organized push-back from the discipline of emergency medicine. Maybe that's not entirely a bad thing. Contrast it with those treatments that were rushed to widespread implementation after a single clinical trial only to suffer a reversal.

RSV can cause severe disease in adults

Particularly the elderly according to this paper:

Methods. A retrospective cohort study was conducted on all adults (greater than or equal to 18 years) admitted to 3 acute care general hospitals in Hong Kong with virologically confirmed RSV infection during 2009–2011 (N = 607). Adults hospitalized for seasonal influenza during the period were used for comparison (n = 547)...

Results. The mean age of RSV patients was 75 (SD, 16) years; 87% had underlying conditions. Lower respiratory and cardiovascular complications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic obstructive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterial superinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively. Crude all-cause mortality was 9.1% and 11.9% within 30 days and 60 days, respectively; mean length of stay of survivors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superinfection, and elevated urea level and white blood cell count were independently associated with poorer survival. Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall outcomes of survival and length of stay were not significantly different from those in influenza.

Conclusions. RSV can cause severe lower respiratory complications in older adults, resulting in respiratory failure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.

Prehypertension is a risk factor

From a recent meta-analysis:

Methods

Databases (PubMed, EMBASE and the Cochrane Library) and conference proceedings were searched for prospective cohort studies with data on prehypertension and cardiovascular morbidity. Two independent reviewers assessed the reports and extracted data. The relative risks (RRs) of CVD, coronary heart disease (CHD) and stroke morbidity were calculated and reported with 95% confidence intervals (95% CIs). Subgroup analyses were conducted on blood pressure, age, gender, ethnicity, follow-up duration, number of participants and study quality.

Results

Pooled data included the results from 468,561 participants from 18 prospective cohort studies. Prehypertension elevated the risks of CVD (RR = 1.55; 95% CI = 1.41 to 1.71); CHD (RR = 1.50; 95% CI = 1.30 to 1.74); and stroke (RR = 1.71; 95% CI = 1.55 to 1.89). In the subgroup analyses, even for low-range prehypertension, the risk of CVD was significantly higher than for optimal BP (RR = 1.46, 95% CI = 1.32 to 1.62), and further increased with high-range prehypertension (RR = 1.80, 95% CI = 1.41 to 2.31). The relative risk was significantly higher in the high-range prehypertensive populations than in the low-range populations (χ2= 5.69, P = 0.02). There were no significant differences among the other subgroup analyses (P less than 0.05).

Conclusions

Prehypertension, even in the low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk factors.

Of particular interest, results of the analysis of low end versus high end prehypertension supports the long held view that a continuum of risk exists over a wide range of blood pressure extending down to levels many would consider “normal.” Although treatment implications are unknown accumulating evidence will no doubt expand the range of identified risk.

Related commentary here.

Subsegmental PEs: How important are they?

CT pulmonary angiography has opened up a can of worms. Although less sensitive than VQ scanning for clinically significant pulmonary emboli (based on the findings of PIOPED I & II) it often detects isolated subsegmental filling defects which do not correlate with clinical findings. In such a setting, according to the results of PIOPED II, the positive predictive value of CTPA is poor. This might occur if a peripheral filling defect is found as an “incidentaloma” when chest CT is done for some other reason or, more likely, when done indiscriminately following an inadequate pretest clinical assessment. In either case it's often a false positive.

This has led to criticism of the overuse of CTA and questions regarding the significance of peripheral filling defects when the findings don't fit the clinical picture (see here and here).

It doesn't mean, however, that subsegmental defects are never important. What if the clinical findings do suggest PE? A recent study was cited by the bloggers at Academic Life in Emergency Medicine. From the paper (SSPE stands for subsegmental PE):

We analyzed 3728 consecutive patients with clinically suspected PE. SSPE patients were contrasted to patients with more proximal PE and to patients in whom suspected PE was ruled out, in regards of the prevalence of thromboembolic risk factors and the 3-month risks of recurrent venous thromboembolism (VTE) and mortality. PE was confirmed in 748 patients, of whom 116 (16%) had SSPE; PE was ruled out in 2980 patients. No differences were seen in the prevalence of VTE risk factors, the 3-month risk of recurrent VTE (3.6% vs 2.5%; P = .42), and mortality (10.7% vs 6.5%; P = .17) between patients with SSPE and those with more proximal PE. When compared with patients without PE, aged greater than 60 years, recent surgery, estrogen use, and male gender were found to be independent predictors for SSPE, and patients with SSPE were at an increased risk of VTE during follow-up (hazard ratio: 3.8; 95% CI: 1.3-11.1). This study indicates that patients with SSPE mimic those with more proximally located PE in regards to their risk profile and clinical outcome.

The key phrase in the above abstract is clinically suspected PE. If the peripheral filling defect fits the clinical picture it matters. If it doesn't fit, or is an incidentaloma, it's a different ballgame.

This paper raises broader questions about whether PE anatomy as assessed by CTA (i.e. clot burden, location) matters at all. Certainly we know from prior studies that hemodynamic findings and physiologic data (RV function, biomarkers) mean more than anatomy. A study from 2012 in Chest, for example, found no correlation between overall anatomic clot burden and clinical outcome. It did, however, in contrast to the Blood paper referenced above, find a correlation (though barely statistically significant) between location (proximal versus distal) and clinical outcome in the subset of hemodynamically stable patients (not in the overall cohort). More discussion on that paper can be found at PulmCCM.

Metformin associated lactic acidosis: what hospitalists need to know

Phenformin, an older generation biguanide and metformin's precursor, was in its last days on the pharmaceutical market during my training. It had caused hundreds, maybe even thousands of deaths from lactic acidosis before the FDA finally yanked it in 1978. In an unprecedented move the HEW secretary declared phenformin an “imminent hazard to the public health.”

So, naturally, when metformin was launched 17 years later, despite a purported lower incidence of lactic acidosis, its clinical use was approached with great caution and vigilance. Over time in the post marketing experience, in contrast to that observed with many other drugs, these cautions were relaxed as metformin proved to be a much safer and more forgiving drug than its predecessor.

Just how great, then, is the threat of lactic acidosis with metformin? That was the question of a recent study. Metformin associated lactic acidosis is very uncommon but can occur when metformin accumulates and is highly fatal. From the study:

All cases of lactic acidosis (pH, less than or equal to 7.35; arterial lactate, greater than or equal to 5 mmol/L) related to metformin accumulation (plasma level greater than or equal to 4 mcg/mL) from 2007 to 2011 were retrospectively reviewed. Erroneous ingestion and voluntary overdoses were excluded. Epidemiological, medical history, clinical and laboratory data were evaluated in all cases. Results. Sixty-six patients were included. Thirty-one patients (47%) had contraindication to therapy with metformin. All patients showed severe lactic acidosis (pH, 6.91 ± 0.18; lactate, 14.36 ± 4.90 mmol/L) and acute renal failure (creatinine, 7.24 ± 3.29 mg/dL). The mean metformin plasma concentration was 40.68 ± 27.70 mcg/mL. Metformin plasma concentrations showed a correlation, statistically significant even if not strong, with creatinine (p = 0.002, R = 0.37), pH (p less than 0.0001, R = - 0.43) and plasma lactate levels (p = 0.001, R = 0.41). Sixty-two (94%) underwent dialysis. Early mortality (before discharge from ICU) was 26% (17 cases)... 

Conclusions. Patients on chronic therapy with metformin may develop a mitochondrial-related toxicity that should be considered when patients present with lactic acidosis, renal failure, and frequently, a medical history of gastrointestinal manifestations during the days preceding the hospital admission.

There was an accompanying editorial which, according to a post at The Poison Review, contains a lot of pearls. Unfortunately I am unable to access the full text but the Poison Review post lists a few of them:

Evaluate patients started (or continued) on metformin for contraindications to the drug.

Screen patients on metformin who present with a gastroenteritis-type syndrome or other conditions that predispose to dehydration for metabolic acidosis (my feeling is that an initial blood gas would be unnecessary since checking the electrolytes and anion gap should suffice).

Consider early hemodialysis in patients presenting with MALA — this would both help remove the drug and correct severe acidosis.

Add metformin toxicity to the differential diagnosis in appropriate patients suspected of having sepsis, mesenteric ischemia, or respiratory failure.

Know that metformin-induced metabolic acidosis does indeed exist, and that these patients are typically extremely ill.

Realize that with proper care these patients can survive, even if they’ve presented with amazingly low pH readings.

STEMI versus NSTEMI: misunderstood, misapplied, revisited

I have written a number of posts about the binary distinction of “STEMI versus NSTEMI” for acute coronary syndrome. In those posts I have cited many examples of unintended consequences of this terminology and developed the premise that it's an artificial distinction which is often misapplied. Despite some push back and numerous questions I stand by the premise. The idea is not original with me. It was this paper from a fewyears ago, which I have cited several times since, that first alerted me to the problem.

My last post on this topic, judging form a nice Facebook avalanche I received, garnered some attention. Now might be a good time to revisit the issue.

If the question stirs debate in some minds perhaps there are a few basic problems with “STEMI/NSTEMI” we can at least agree about as starting points:

The terms STEMI and NSTEMI are simple surrogates to denote complex pathologic processes.

Flaws are inherent in the simplistic use of surrogates even though they can be clinically useful at times.

STEMI and NSTEMI are descriptive terms which lead to diagnosis based on simple pattern recognition.

Diagnosis by pattern recognition tends to ignore complexities of electrophysiology which are clinically important.

While electrocardiographic patterns can provide powerful clues they do not equate to pathologic processes in simple fashion.

The late J. Willis Hurst, master clinician and teacher of electrocardiography, published many articles on the subject. In this one from the American Journal of Cardiology he offered several suggestions for addressing the problem. One was that the electrocardiographic interpretation should not stop with pattern description but go on to include a list (differential diagnosis) of conditions associated with the pattern.

STEMI is a surrogate for acute coronary occlusion. But when the above exercise in differential diagnosis is carried out acute coronary occlusion will appear in the interpretation of many NSTEMI electrocardiograms. This was illustrated in a post from a couple of years ago at Dr. Smith's ECG blog.

Here are some of the points he made in that post:

STEMI and NonSTEMI are arbitrary terms that may confuse the clinician.

"STEMI" should mean "coronary occlusion" (or near occlusion, without good collateral circulation -- in other words, it needs thrombolytics or emergent angiogram with PCI).

NonSTEMI should mean "MI without occlusion."

"STEMI-equivalent" is a good term for "coronary occlusion".

Many STEMI-equivalents have no significant ST elevation, as you may have seen from many of my posts.

In some STEMI-equivalents (posterior STEMI, lateral STEMI, posterolateral STEMI), ST depression is the only, or most visible, feature of the ECG.

These are points I have made many times before, often via citation from Dr. Smith's posts. The difficulty lies in the fact that when using the electrocardiogram for emergency decision making we need something simple that we can use at a glance. The unfortunate reality is that in today's performance driven world we've made STEMI/NSTEMI too simple.

Z-drugs, cognition and driving

The Z-drugs are the newer generation hypnotics zolpidem, zopiclone, and zaleplon. These drugs are increasingly reported to impair cognition and driving. The main safety consideration is time from ingestion. From a recent review:

Z-drugs are short-acting GABA agonists that reduce sleep latency without disturbing sleep architecture. Bizarre behavioral effects have prompted warnings on the prescription, dispensation, and use of Z-drugs. Psychomotor impairment, falls, and hip fractures are more likely to occur with Z-drugs that have longer half-lives, that are taken at higher-than-recommended doses and when mixed with other psychoactive substances including alcohol. Zopiclone and higher doses of zolpidem are more likely to cause anterograde amnesia than zaleplon. Z-drugs, especially zolpidem, are associated with complex behaviors such as sleepwalking, sleep-driving, and hallucinations. Patients taking zopiclone and zolpidem have an increased risk of motor vehicle collisions, over double that of unexposed drivers. Driving impairment occurs with zopiclone and higher doses of zolpidem but is unlikely to occur after 4 h post-zaleplon administration. The residual effect of Z-drugs on next-day cognitive and psychomotor performance has significant impact on lifestyle, safety, and occupational considerations, including motor vehicle and machine operation. The risk–benefit analysis of Z-drugs in the treatment of insomnia, particularly in the elderly, may not favor treatment due to the increased risks of falls and motor vehicle collisions.

Avoiding IV contrast hazards: facts, myths, FAQs

Here's a great podcast andaccompanying notes from ercast. For further reading here's the American College of Radiology's Manual on Contrast Media. TMI for a quick read but a useful reference to have.

New evidence on IVC filters: low level but compelling

From a recent large database of patients with unstable PE:

Results
Among 21,095 unstable patients with pulmonary embolism who received thrombolytic therapy, in-hospital all-cause case fatality rate was lower in every age group who received a vena cava filter in addition to thrombolytic therapy (P = .0012 to less than .0001). Patients aged greater than or equal to 81 years showed the greatest absolute reduction of case fatality rate with filters (19.3%). Among 50,210 unstable patients who did not receive thrombolytic therapy, case fatality rate also was lower in every age group who received a vena cava filter (all P less than .0001). Patients aged greater than or equal to 81 years with vena cava filters showed the greatest absolute risk reduction of case fatality rate (27.7%).

Conclusion
Vena cava filters are associated with a reduced in-hospital all-cause case fatality rate in unstable adults with pulmonary embolism, irrespective of age.

This use of IVC filters is common and there is wide practice variation. It is not considered strictly evidence based, the only clearly recognized indication being a patient with acute proximal DVT and an absolute contraindication to systemic anticoagulation. The evidence quality of the findings presented above is low but at least suggests that many of the clinicians appearing to practice non-evidence based medicine (by filling in for non-evidence with clinical judgment) were right all along.

May-Thurner syndrome

Here is a case report and brief topic discussion from the SHM 2014 abstract presentations. This condition is easily overlooked but its diagnosis has treatment implications. From the abstract:

May-Thurner syndrome is due to significant compression of left common iliac vein between right common iliac artery & lumbar vertebral body. It’s clinical prevalence is 2-3% of all lower extremity DVT’s and it results in intimal hyperplasia causing anatomical obstruction & stasis. It is commonly seen in women between the ages of 20-50... 

Although May-Thurner syndrome is a rare cause of DVT, it can cause recurrent episodes of DVT, PE, Chronic venous insufficiency & life threatening thrombosis. Clinicians should look for May-Thurner syndrome in young women between ages 20- 50 (even though they are on OC pills) who present with extensive Left leg DVT as Catheter directed thrombolysis, angioplasty & stenting can cure the condition.

Hospitalization increases the risk of gout attacks

In this study.

Intravenous interferon-beta-1a (FP-1201): promising pharmacotherapy for ARDS?

From the Lancet RespiratoryMedicine:

Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35–45%), but no eff ective pharmacotherapy exists. Production of anti-infl ammatory adenosine by ecto-5ȸ-nucleotidase (CD73) helps maintain endothelial barrier function. We tested whether interferon-beta-1a (IFN-beta-1a), which increases CD73 synthesis, can reduce vascular leakage and mortality in patients with ARDS...

We then tested the safety, tolerability, and effi cacy of intravenous human recombinant IFN- beta-1a (FP-1201) in patients with ARDS in an open-label study (comprising dose-escalation and expansion phases). We recruited patients from eight intensive care units in the UK. Eligible patients were aged 18 years or older, had ARDS, and were being treated with assisted ventilation. We established an optimal tolerated dose (OTD) in the first, dose-escalation phase. Once established, we gave all subsequently enrolled patients the OTD of intravenous FP-1201 for 6 days...

By day 28, 3 (8%) of 37 patients in the treatment cohort and 19 (32%) of 59 patients in the control cohort had died—thus, treatment with FP-1201 was associated with an 81% reduction in odds of 28-day mortality (odds ratio 0·19 [95% CI 0·03–0·72]; p=0·01).

It's only a phase II trial and it looks too good to be true. If it is confirmed in high level studies it will be a breakthrough in the treatment of ARDS.

Via Respiratory Therapy Cave.