Tuesday, December 29, 2015

Fascinating ECG tracings

IV TPA for acute ischemic stroke

Here's a summary of clinical trials with a focus on time to treatment. Free full text.

Internal medicine lecture notes

Slideshare presentation here.

Biology and chemistry lectures

Update on dilated cardiomyopathy

This review draws on lessons from the Multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 trial. The review is titled The Natural History of Acute Dilated Cardiomyopathy. However, while the cases discussed here demonstrated acute clinical manifestations in their initial presentations, the diseases they represent may have been months or years in development, as acknowledged by the discussion at the end. And while the term “idiopathic” DCM was used to describe the patient population (patients with stress CM, systemic diseases known to produce CM, suspected ischemic etiology and tachycardia mediated DCM were excluded) specific causes are suspected in a significant number, the most common category being genetic. Viral myocarditis, once a wastebasket term for this syndrome, accounts for only around 10%.

The prognosis for this syndrome seems to be improving in the era of neurohumeral antagonists. From the review:

Mean initial LVEF was 24% ± 8% and increased to 40% ± 12% during treatment with ACE-I/ARB (82%), and a beta-blocker (94%). Transplantation-free survival at 1, 2, and 4 years was 94%, 92%, and 86%, respectively. This survival rate was substantially higher than the prior era.

The role of myocardial biopsy is diminishing and is now restricted to special situations:

Finally, endomyocardial biopsy is occasionally indicated in patients with ADCM. Current practice guidelines suggests that it is useful for patients with new onset cardiomyopathy in whom allergic/eosinophilic myocarditis, cardiac sarcoidosis, or giant cell myocarditis are suspected (17). The low diagnostic yield has led to a decline in its use (less than 10%) combined with the lack of proven efficacious therapy for lymphocytic myocarditis has led to substantial decrease in the use of this invasive technique. Biopsy can be useful for detecting treatable systemic diseases known to affect the myocardium such as sarcoid or eosinophilia..

Monday, December 28, 2015

The language of dermatology

Subjective aspects of chronic pain

The introduction to an article on chronic pain contains this statement on why pain was never a vital sign:

Pain is always subjective in that each individual learns the application of the word through their own experiences.

More from the article:

Cognitive and emotional factors have a critically important influence on pain perception and these relationships lie in the connectivity of brain regions controlling pain perception, attention or expectation, and emotional states. Imaging studies have confirmed that activity of afferent and descending pain pathways are altered by attentional state, positive emotions, and negative emotions among many other factors unrelated to the pain stimulus itself. The physiology of central pain amplification at the level of the brain takes into account these important connections. There are now numerous studies that demonstrate that patients with chronic pain have alterations in brain regions involved in cognitive and emotional modulation of pain (5). This complex interplay may explain why patients with long-term chronic pain develop anxiety and depression, but also why those with cognitive distortion and psychological distress are at increased risk for chronic pain and central amplification of pain.

These principles have been known in one form or another for decades. It is astonishing that health care professionals for a time acquiesced to a false dogma of pain as an objective and measurable parameter. This dogma and its consequences over the last 15 years represents one of the most shameful recent trends in medicine. The author puts it this way:

One of the most distressing recent developments in medicine is the explicit focus on eliminating pain — manifested as pain as the fifth vital sign and relief of pain being used to measure the quality of a health care facility.

The article points out that although pain is referable to some form of tissue damage there are, especially in the case of chronic pain, complex brain body relationships that come into play. Here are some examples given in the article:

Those patients with one pain condition are more likely to develop another, more centralized form of pain. For example, patients with inflammatory or degenerative joint disease, for example, are almost four times as likely to also have fibromyalgia, the prototypical musculoskeletal central pain amplification syndrome (7). Centrally maintained pain, in contrast to nociceptive or neuropathic pain, is usually multifocal, difficult to precisely localize, moves from site to site, and may have variable pain descriptions.

Chronic pain syndromes, such as chronic headaches, temporomandibular disorder, fibromyalgia, irritable bowel syndrome (IBS), interstitial cystitis/irritable bladder, pelvic pain, and others, cluster together in an individual (8) (Figure 2).

There is much more. The article is available as free full text.

Basic genetics

Use of levofloxacin in patients with long QT intervals

The risk may be overstated and was very low in this study.

Managing complications of TPA in ischemic stroke

The most feared complication is ICH. Less well appreciated is orolingual angioedema. This free full text review provides a summary of what little is known.

Thursday, December 24, 2015

Remission of adult ADHD

From a recent study:

Method A 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.

Results Retention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (less than 4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54–25.45, p less than 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04–1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).

Wednesday, December 23, 2015

How long should we treat with oral anticoagulants after VTE?

This question has been asked many times and in many ways through the years. Despite that, as the authors of a new study open their paper:

Importance The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain.

More from the paper:

Design, Setting, and Participants Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers.

Interventions Warfarin or placebo for 18 months.

Main Outcomes and Measures The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months.

Results After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups.

Conclusions and Relevance Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy.

From a related piece in ACP Hospitalist Weekly:

The authors noted that their primary outcome included 2 outcome measures that may not have been clinically equivalent, that newer anticoagulants were not examined, and that D-dimer levels were not used to guide therapy, among other limitations. However, they concluded that an additional 18 months of warfarin treatment in patients with first unprovoked PE improves outcomes versus placebo, although the improvement was not sustained after anticoagulant treatment was discontinued.

"Our results suggest that patients such as those who participated in our study require long-term secondary prophylaxis measures," the authors wrote. "Whether these should include systematic treatment with vitamin K antagonists, new anticoagulants or aspirin, or be tailored according to patient risk factors (including elevated D-dimer levels) needs further investigation."

Tuesday, December 22, 2015

Admitting ICU diagnosis is a poor predictor of infection

According to a recent study:


We studied a cohort of critically ill patients admitted with clinically suspected sepsis to two tertiary ICUs in the Netherlands between January 2011 and December 2013. The likelihood of infection was categorized as none, possible, probable or definite by post-hoc assessment. We used multivariable competing risks survival analyses to determine the association of the plausibility of infection with mortality.


Among 2579 patients treated for sepsis, 13% had a post-hoc infection likelihood of “none”, and an additional 30% of only “possible”. These percentages were largely similar for different suspected sites of infection. In crude analyses, the likelihood of infection was associated with increased length of stay and complications. In multivariable analysis, patients with an unlikely infection had a higher mortality rate compared to patients with a definite infection (subdistribution hazard ratio 1.23; 95% confidence interval 1.03-1.49).


This study is the first prospective analysis to show that the clinical diagnosis of sepsis upon ICU admission corresponds poorly with the presence of infection on post-hoc assessment. A higher likelihood of infection does not adversely influence outcome in this population.

There are some important lessons from this study. Though we often have to aggressively give antibiotics “just in case” in severely ill patients, who often have undifferentiated presentations, many of these will turn out not to be infected. This speaks for the importance of diligent efforts to de-escalate. In order to facilitate rapid initiation of antibiotics, remember that sepsis is defined clinically. That is, the definition requires only that infection be suspected, not established. It is a clinical syndrome more than it is a diagnosis (in much the same way ARDS is a syndrome rather than a specific diagnosis). The findings in this paper provide one more illustration of how unrealistic it is to expect clinicians to assign a specific diagnosis on the front end even though that is what the coders would like us to do.

Monday, December 21, 2015

Is saline toxic? More evidence to add to the pile.

From a recently published large propensity-matched cohort study:


This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98 %) received 0.9 % saline whereas 1706 (2 %) received a calcium-free balanced solution as the primary fluid.


There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27 % vs. 1.03 %, P less than 0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P less than 0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P less than 0.001). No differences were found in acute renal failure.


In this large electronic health record, the predominant use of 0.9 % saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials.

Saturday, December 19, 2015

Renewed interest in oxygen toxicity

In the 1970s, 80s and 90s we were obsessively concerned about oxygen toxicity in patients mechanically ventilated for ARDS. Over time since then those concerns were gradually forgotten and up until very recently largely ignored, and for no good reason. Only in the last year or two has there been a major resurgence of interest. This recent review highlights the consequences of oxygen toxicity in the lungs and other organs.

Friday, December 18, 2015

Nonceliac gluten sensitivity

Here's a free full text review from Mayo Clinic Proceedings. What is conspicuously absent from an otherwise excellent article is acknowledgement of the controversy of whether this entity is even real. On that question there is a great post at Science Based Medicine. From that post:

The idea that gluten sensitivity is real and widespread goes far beyond the current scientific evidence, and the well-established facts of celiac disease. Time will tell if gluten avoidance follows the path of Candida, and other dietary fears and fads that preceded it. But it doesn’t need to. Given the protean nature of CD, symptoms cannot be dismissed as nocebo effects: A CD diagnosis needs to be ruled out before NCGS is even contemplated. Going gluten-free in the absence of a proper medical evaluation may not be directly harmful, but it complicates a diagnosis. Moreover, it can be expensive, and difficult to maintain 100% avoidance – essential with CD, but not established as necessary with NCGS. Besides, who really wants to cut out all gluten-containing products if they don’t need to? Until better diagnostic criteria are established, the N of 1 trial is probably the most science-based (if impractical) approach: single-blind challenges to measure for subjective or objective symptoms. Our challenge in dealing with dietary fads as health professionals is to recognize that some of our patients are suffering, and evaluate them in a science based way: without dismissing the symptoms, and without advocating dietary transformations that may be unnecessary.

Thursday, December 17, 2015

Microbiology of community acquired pneumonia

Here are some surprising findings from a recent study published in NEJM:


We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen.


From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radiographic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age.


The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria.

Wednesday, December 16, 2015

Institute of Medicine report on cardiac arrest

The IOM report on cardiac arrest was released on June 30. A summary of the report in JAMA is here. The report calls for improvements in data reporting, public education, EMS capability, accreditation standards, quality improvement initiatives, research funding, translating evidence into practice, and the establishment of a national collaborative.

Unfortunately the report is badly out of date in that it ignores the spectacular results or research by Ewy and his Arizona colleagues reported over the past decade. In a recent summary of that research Ewy wrote:

Decades of research and ongoing reviews of the literature led the University of Arizona Sarver Heart Center Resuscitation Research Group to conclude in 2003 that the national guidelines for patients with primary cardiac arrest were not optimal. Therefore, we instituted a new, nonguidelines approach to the therapy of primary cardiac arrest that dramatically improved survival.

You can go to the link and read the rest. That single paragraph, in my opinion, contains more pertinent information on the current state of resuscitation care than the entire 240 page IOM report.

Directory of FOAM and related sites

Tuesday, December 15, 2015

Medical marijuana: the latest trend in herbalism

A while back Dr. David Gorski wrote a series of posts at Science Based Medicine on medical marijuana as “ the new herbalism.” In the introductory post he discussed the scientific problems with herbalism in general and I think he really nailed it with this:

I also pointed out that, although herbalism is the most plausible (or perhaps I should say the least implausible) of modalities commonly associated with “complementary and alternative medicine” (CAM) or “integrative medicine”, it still exhibits a number of problems, the biggest of which is what I like to call either the delivery problem or the bioavailability problem. In brief, herbs, when they work, are adulterated drugs. The active ingredient is usually a minor constituent, embedded in thousands of other constituents that make up herbs, and it’s almost impossible to control lot-to-lot consistency with respect to content or active ingredients given how location, weather, soil conditions, rainfall, and many other factors can affect how the plants from which the medicines are extracted grow and therefore their chemical composition. To demonstrate the concept, I pointed out that it’s much safer and more predictable to administer digoxin to a patient who needs its activity on the heart than it would be for the patient to chew on some foxglove leaves, given that the therapeutic window (the difference between the doses needed to produce therapeutic effects and the lowest dose that will cause significant toxicity) is narrow.

It's basic. It's a major premise, a starting point for discussions of herbal medicine.

The degree of evidence in support of the medical use of marijuana is somewhere between slim and none, so why such wide acceptance? As Dr. Gorski suggests:

Indeed, more than twenty states, plus the District of Columbia, have legalized medical marijuana. They’ve done so on the basis of a political movement among patients that make pot sound like a miracle drug that can help when no other intervention can. And it’s more than that. Medical cannabis has been touted as a near-panacea for everything from pain to chemotherapy-induced nausea to HIV- and cancer-induced cachexia to even curing cancer itself. Yes, there’s a lot of hype out there, and there are a lot of claims that sometimes go viral on various social media, even though the evidence to support the claims is often, to put it mildly, less than rigorous.

It's just another example of how, when issues of science are determined in the arena of public discussion hype all too often wins.

Although I'm not a proponent of legalization of marijuana for recreational use it is hard to disagree with Gorski's position:

Again, I believe that marijuana should be legalized, regulated, and taxed, just like alcohol and tobacco. If marijuana is going to be approved for use as medicine rather than for recreational use, however, the standards of evidence it must meet should be no different than any other drug, and for the vast majority of indications for which it’s touted medical cannabis doesn’t even come close to meeting that standard.

Put another way, an argument for legalization for recreational use has far more integrity than an argument for medical use.

Dr. Gorski summarizes the evidence in this manner, and this comports with what I have seen:

Overall, the evidence base, from my interpretation, ranges from nonexistent (most indications) to suggestive (anti-inflammatory), to fairly good (ant-emetic). However, most of the good clinical trials didn’t use marijuana cigarettes as most patients get them, but rather either purified cannabinoids (or synthetic analogues) or cannabis cigarettes spiked with varying amounts of THC. Indeed, all of these studies tend to suggest that purified drugs from cannabis or synthetic drugs based on compounds designed to mimic either endocannabinoids or cannabinoids from marijuana will be the future. I realize that that’s not what medical marijuana activists want to hear.

So all this is not to say that cannabinoids have no medical potential. Indeed they do. They have intriguing biologic effects that warrant investigation. But all scientific indications point to pharmaceutical grade cannabinoids rather than medical cannabis. As Gorski further states:

In any case, if one were going to decide on a drug delivery device for cannabinoids, one could hardly design a worse device than burning the leaf and inhaling the gases, where the active drug is just one of hundreds of products of combustion, all loaded with particulate matter and tar.

The failure of performance measures

Understanding of performance is beset by obfuscation of the language. For purposes of clarity it is helpful to remind readers of recent deceptive changes in health care terminology reminiscent of Orwell's Newspeak Dictionary.  Important to this discussion are “quality” which is gradually replacing the more meaningful and descriptive term “performance” and “value based purchasing” which has all but replaced “pay for performance.”

A recent review of performance measure failure suffers from some of this confusion but is otherwise a useful read. Here are a few important points to keep in mind in reading this article:

Performance, considered by many to be a surrogate for quality, has never been validated as such.

Attempts to use performance for leverage have come in two forms: payment incentive and public reporting.

Originally, officially promulgated performance measures (by Joint Commission and CMS) were limited in number. Many more were adopted voluntarily, “in-house,” by various local health systems. A large number of those are being added to the list of nationalized (and mandatory) measures under the Affordable Care Act.

Some performance measures failed because they were adopted based on somebody's big idea and scant evidence, only to be later refuted by higher level trials. Those are the focus of the article.

Others were based on good evidence but still failed to help patients because the unintended consequences of “report cards” countered any benefits inherent to the measures themselves (eg heart failure core measures, the pneumonia antibiotic rule).

Not all of the measures have been proven harmful (some have) but none have been proven to benefit patients.

Monday, December 14, 2015

Can you give norepinephrine through a peripheral vein?

The answer may depend on where you practice. We have no research data to guide us. Only case reports appear in the literature. This post at ScanCrit offers a common sense approach that would allow peripheral infusions for limited amounts of time with certain precautions applied.

Stat CT angio for every stroke?

Free full text.

Understanding the A-a gradient