Friday, May 26, 2017

Encephalopathy secondary to metronidazole


Here is a case presentation and brief discussion in NEJM (free full text). From the paper:

Encephalopathy associated with metronidazole use is an uncommon side effect of the medication. It typically manifests as dysarthria and gait instability. Risk factors include liver dysfunction and a prolonged course of metronidazole (typical cumulative dose, greater than 20 g). MRI of the brain is usually diagnostic and typically reveals a symmetric, enhanced FLAIR signal in the dentate nuclei of the cerebellum.


Thursday, May 25, 2017

Dabigatran versus warfarin and the risk of AKI



Background Whether dabigatran is associated with a lower risk of acute kidney injury (AKI) in patients with nonvalvular atrial fibrillation (NVAF) remains unknown.

Objectives The authors compared the risk of AKI in Asians with NVAF who were prescribed dabigatran versus warfarin.

Methods The authors analyzed patients enrolled in the Taiwan nationwide retrospective cohort study from June 1, 2012, to December 31, 2013. Dabigatran and warfarin were taken by 7,702 and 7,885 NVAF patients without a history of chronic kidney disease (CKD) and 2,256 and 2,089 NVAF patients with a history of CKD, respectively. A propensity-score weighted method was used to balance covariates across study groups.

Results A total of 6,762 (88%) and 940 (12%) CKD-free patients and 2,025 (90%) and 231 (10%) CKD patients took dabigatran 110 mg and 150 mg twice daily, respectively. Dabigatran was associated with a lower risk of AKI than warfarin for either the CKD-free (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.49 to 0.77; p less than 0.001) or CKD (HR: 0.56; 95% CI: 0.46 to 0.69; p less than 0.001) cohort. As the increment in CHA2DS2-VASc score (a risk score based on congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, aged 65 to 74 years, and female sex) increased from 0/1 to 6+ points, the incidence of AKI for the dabigatran group was relatively stable (1.87% to 2.91% per year for the CKD-free cohort; 7.31% to 13.15% per year for the CKD cohort) but increased obviously for patients taking warfarin for either CKD-free (2.00% to 6.16% per year) or CKD cohorts (6.82 to 26.03% per year). The warfarin group had a significantly higher annual risk of AKI than the dabigatran group for those with a high CHA2DS2-VASc score (greater than or equal to 4 for the CKD-free cohort and greater than or equal to 3 for the CKD cohort). Subgroup analysis revealed that among dabigatran users, those taking either low-dose or standard-dose dabigatran, those with a warfarin-naïve or warfarin-experienced history, those with or without diabetes, and those with CHA2DS2-VASc greater than or equal to 4 or HAS-BLED greater than or equal to 3 (risk score based on hypertension, abnormal renal and liver function, stroke, prior major bleeding, labile international normalized ratios, age 65 years or older, drugs or alcohol usage history) all had a lower risk of AKI than those taking warfarin.

Conclusions Among Asians with NVAF, dabigatran is associated with a lower risk of AKI than warfarin.


The future of CME


A NEJM Perspective piece on this topic opened with:

The point at which a clinician takes ownership of his or her own learning agenda is a pivotal moment in professional growth.

That sentence drew me into the article. The author, Graham T. McMahon MD believes there is a point in professional development where the clinician takes ownership of his or her continuing education. Self evident as that may be there are those who oppose this view, believing that CME content should be determined by external authority. That, for example, is the basis for the arguments of those few who defend Maintenance of Certification (MOC).

McMahon went on to elaborate on the benefits of self guided learning as opposed to that driven by others from afar:

Now that information is ubiquitous, simple information exchange has relatively low value; in its place, shared wisdom and the opportunity to engage in problem solving in practice-relevant ways have become key. Physicians seeking professional development can recognize when they’re actively learning and tend to embrace activities that allow them to do so. Education that’s inadequate, inefficient, or ineffective, particularly when participation is driven by mandates, irritates physicians who are forced to revert to “box-checking” behavior that’s antithetical to durable, useful learning.

So what are we to do? Much of the solution, according to McMahon, lies in the attitude of the learner rather than the CME offering:

A key element is self-awareness: professionals who know their own strengths and weaknesses are most likely to have a productive experience when they identify the types of activities that help them grow and then actively participate in them. There are many ways to increase self-awareness, such as taking a self-assessment quiz…

To become self-aware, we have to step out of the protective cocoon of self-confidence and become humble and open enough to assess both how we can best maintain what’s working and how we can grow further.


CME offerings, according to the author, are most effective when they are interactive and learner-centric. While this is a challenge in the traditional didactic format, he does not argue for the elimination of the didactic as some have proposed over the last several years. [1] [2]

All in all, the piece is respectful of differences in learning needs among physicians and supportive of them being in charge of their own individual educational agendas. A  concern I have, though, is this statement in the middle of the piece:

The regulators, too, need to evolve. By relinquishing the fixed structural requirements for health education and instead focusing on educational outcomes (rather than process and time spent), regulators and accreditors can create the right conditions for maximizing educators’ flexibility and promoting innovation. By creating a diverse system that can address even superspecialized needs, we facilitate choice among formats, activity types, and locations. I envision a future in which educational expectations and professional competency obligations are aligned and integrated and in which all physicians have an educational “home” that helps them navigate their continuing growth — so that education is intertwined with practice throughout their careers.

That sounds a little too much like the MOC we loved to hate a couple of years ago.


Wednesday, May 24, 2017

Viewpoint article in JAMA issue devoted to conflicts of interest


The article is available here as free full text. Here are a few points of interest.

Early on in the piece the author, Harvey V. Fineberg, MD, PhD, says:

An individual’s conflict of interest is not tantamount to saying her or his judgment is affected, nor does it constitute an accusation of bias or prejudgment. The presence of a conflict of interest is no judgment about the appropriateness or value of the relationship that engenders the conflict in a particular situation.

Why then should we be worried about COI at all? The answer comes in the next paragraph (emphasis mine):

Some erroneously take a financial interest that qualifies as a conflict of interest to be an allegation that their thinking is tainted. They seek to defend their scientific integrity and adherence to evidence, and aver that the monetary payment they received or financial interest they hold could not possibly influence their scientific or clinical judgment. They may be right, and they miss the point. If a reasonable person would perceive that the financial circumstances could potentially influence their judgment, a failure to acknowledge and respond to the conflict of interest threatens to erode the trust that undergirds the value of professional judgment and expertise.

In short, it’s about the possibility that perceptions would be tainted. I’m looking for substance here and it’s a bit of a stretch. If the argument has any substance it is weakened by the postmodern view expressed a few paragraphs down:

If the presence of a conflict of interest is ultimately subjective—based on the judgment of a reasonable person—it is also situational, that is, dependent on the specific financial circumstances and relationship to the specific role of the person involved. The standards for adjudging a conflict of interest may also be bound by time and place, having different meaning in different cultures and at different moments in history.

The author addresses some of the many questions that arise in the management of COI. There appear to be no definitive answers:

What relationship to a payer and financial level triggers disclosure, discussion, and possible remedy? If not contemporaneous, for how long in the past is a financial relationship deemed relevant? Should the financial interests of a spouse, a parent, a minor child, and a sibling be considered as pertinent as those of the individual involved? In general, the answers to these questions should be guided by the reasonable person standard. To preserve public trust, it is better to lean toward more disclosure rather than less, while also protecting individual privacy and avoiding tangential matters. For example, the financial interests of a cousin or a niece are of less interest than those of a spouse or sibling.

On a refreshing note he takes an appropriately broad view of COI by not singling out industry, acknowledging many other types of financial conflicts as well as non financial conflicts.

The concluding paragraph says we need “disinterested expertise” (is there such a thing?) and reminds us once again that it’s mainly about perception:

Adherence to carefully considered, transparent, and evenhanded policies on conflict of interest can help physicians earn and maintain their trusted place in the minds of the public and policy makers.

What is conspicuously absent from the entire piece is a strong declarative statement that COI really does impair physician judgment let alone harm patients.


Sunday, May 21, 2017

Anticoagulant related nephropathy: huge problem, hugely under-recognized


From a commentary in JACC, here are some key points.

What is it?

Anticoagulant related nephropathy (ARN) is a form of AKI caused by systemic anticoagulation (generally over anticoagulation; in the original reports on warfarin the mean INR was in the mid 4 range).


What are the histopathologic findings?

Severe glomerular, and sometimes tubular, hemorrhage.


It's not just warfarin

Although originally described with warfarin and termed warfarin nephropathy it is now evident that other systemic anticoagulants (and probably any systemic anticoagulant) can cause it. The risk may be higher with warfarin than with the NOACs.


How do you diagnose it?

The difficulties in getting a renal biopsy in patients who are anticoagulated are obvious. Sometimes biopsy is done during a window of anticoagulant interruption. In other cases, if circumstances fit and there is no other plausible explanation “presumptive ARN” is diagnosed without a biopsy.


It is generally not reversible

According to the article, renal recovery tends to be poor.


During periods of excessive anticoagulation the risk is high

From the article:

To date, there have been 5 independent cohort studies...These studies show that the risk of ARN at the onset of coagulopathy is at about 20% overall and about 37% in patients with CKD (3).


According to the article the mortality is high, especially in CKD patients.


Saturday, May 20, 2017

Predicting ARDS mortality based on a simple clinical score


From a paper in Critical Care Medicine:

Objectives: Although there is general agreement on the characteristic features of the acute respiratory distress syndrome, we lack a scoring system that predicts acute respiratory distress syndrome outcome with high probability. Our objective was to develop an outcome score that clinicians could easily calculate at the bedside to predict the risk of death of acute respiratory distress syndrome patients 24 hours after diagnosis.

Design: A prospective, multicenter, observational, descriptive, and validation study.

Setting: A network of multidisciplinary ICUs.

Patients: Six-hundred patients meeting Berlin criteria for moderate and severe acute respiratory distress syndrome enrolled in two independent cohorts treated with lung-protective ventilation.

Interventions: None.

Measurements and Main Results: Using individual demographic, pulmonary, and systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we derived our prediction score in 300 acute respiratory distress syndrome patients based on stratification of variable values into tertiles, and validated in an independent cohort of 300 acute respiratory distress syndrome patients. Primary outcome was in-hospital mortality. We found that a 9-point score based on patient’s age, PaO2/FIO2 ratio, and plateau pressure at 24 hours after acute respiratory distress syndrome diagnosis was associated with death. Patients with a score greater than 7 had a mortality of 83.3% (relative risk, 5.7; 95% CI, 3.0–11.0), whereas patients with scores less than 5 had a mortality of 14.5% (p less than 0.0000001). We confirmed the predictive validity of the score in a validation cohort.

The score is explained in this piece in ACP Hospitalist Weekly:

The score the researchers chose had a minimum of 3 points and a maximum of 9, based on 3 variables: age in years (less than 47, 47 to 66, greater than 66), PaO2/FIO2 in mm Hg (Greater than 158, 105 to 158, less than 105), and plateau pressure in cm H2O (less than 27, 27 to 30, greater than 30). Seven other variables were evaluated for potential inclusion in the score but were not selected. Patients with a score greater than 7 were found to have an inpatient mortality rate of 83.3%, compared to 14.5% in patients with a score below 5, the study found.

Note that the score is only to be applied to the Berlin categories of moderate and severe ARDS.