Management of intracerebral hemorrhage following TPA for ischemic stroke

If there are any effective reversal treatments there is no good evidence to guide their use according to a systematic review in JAMA Neurology.

A discussion of the paper in Medpage Today notes the need for better evidence. The discussion says guidelines address the problem of TPA related cerebral hemorrhage, though based on low level evidence and expert opinion. The piece links to the current guidelines for the management of ischemic stroke. Those guidelines, however, only briefly mention TPA related hemorrhage and for management of this complication refer the reader to these guidelines for management of cerebral hemorrhage. They in turn, however, do not specifically address TPA related hemorrhage though they do address head bleeds related to oral antithrombotic agents.

Clinical trials to see if nutty ideas work

Don't laugh, because our tax money has been paying for such “research” for years. A recent paper outlines a little of the history, gives some examples and calls for it to stop.

From the opening of the paper:

A new phenomenon in clinical trials has arisen over the past 20 years. Complementary and alternative medicine (CAM) or integrative medicine (IM) modalities based on principles that bespeak infinitesimally low prior probability of success or that even violate well-established laws of physics and chemistry are being tested in randomized clinical trials (RCTs). CAM proponents frequently justify such RCTs by arguing that they will finally settle once and for all which CAM or IM modalities do and do not work. Our response is that this is a misguided viewpoint that has led to the infiltration of pseudoscience in academic medicine.

The authors give some examples which illustrate the absurdity of what's going on, then move to a discussion of the role of evidence based medicine, stating:

Evidence-based medicine (EBM) assumes that treatments do not reach the stage of RCTs without having amassed sufficient preclinical evidence to justify the effort, time, and expense of RCTs, as well as the use of human subjects.

Indeed that must have been the assumption of the founders of EBM in 1992 when the movement was launched. It must never have occurred to them that nutty ideas would someday be the subject of clinical trials. Hence the processes of EBM had no formal mechanism to distinguish sense from nonsense. Who knew, early in the movement, that such a mechanism would be needed? But, as illustrated in the paper, the assumption proved to be naïve thus exposing a major failure of EBM. I addressed that failure here and in several other posts.

Doing clinical trials to study implausible claims appears to be a violation of the Declaration of Helsinki, as the authors point out:

Indeed, so integral to this process is biological plausibility based on preclinical data that the Declaration of Helsinki [8] states, ‘medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, as appropriate, animal experimentation’.

The full text of the paper is available for free and is worth reading in its entirety for all the richness there.

Dean Ornish on lifestyle medicine

The idea behind lifestyle medicine, that a multifaceted program of hygienic (non pharmacologic) measures can help prevent or even treat many chronic diseases, though not new, continues to gain traction. It's an area of great interest to me and recently Dean Ornish's piece in Medpage Today caught my eye. From the post:

We tend to think of advances in medicine as a new drug, laser, or surgical device, something high-tech and expensive. Yet, the simple choices we make in what we eat and how we live have a powerful influence on our health and well-being.

True as that may be there are questions that need to be addressed about the science behind lifestyle medicine. First, lifestyle medicine represents a bundle of interventions. There are many bundles in medicine. If a bundle is proven to work we still may not know about the efficacy of its individual components until we study them individually. Some components may even prove to be harmful. A very recent example of this was the unbundling of early goal directed therapy. We'll never succeed in unbundling something so complex as lifestyle, yet we need to learn more about which of its individual components are most helpful and which ones are not so helpful or even harmful.

In the case of Ornish, a good deal of his work is beset with small numbers, methodologic issues and questionable assumptions. Despite these concerns I read his post with great enthusiasm until I came to this stopping point:

These lifestyle changes include:

A whole foods, plant-based diet (naturally low in fat and sugar)

stress management techniques (including yoga and meditation)

Hmmm, so yoga is part of the Ornish bundle. But this takes us way beyond scientific concerns about bundling into a whole new arena. Yoga is a complex philosophical and religious system that makes certain supernatural claims. If Ornish had merely mentioned its material aspects (stress management, low impact exercise, etc) without mentioning yoga itself my reaction would have been different. But to promote yoga as a specific system with benefits beyond the generic effects of exercise and relaxation, as Steve Novella once pointed out, implies magic. When magic is mixed with science you get pseudoscience. Apparently Ornish's interest in the magic arts doesn't stop with yoga.

A new wave in the uprising against maintenance of certification (MOC)

R. Mack Harrell, MD, president of the American Association of Clinical Endocrinologists (AACE), told Medpage Today that MOC in its present form must change and the status quo will not be tolerated. He and other internal medicine leaders attended an internal medicine summit last month in which they outlined their objections to the American Board of Internal Medicine (ABIM). A leader of the ABIM who was present said he'd take it back to the board. According to Dr. Harrell multiple subspecialty leaders are aligned with this effort and if a satisfactory answer is not forthcoming from the board they will begin work to develop alternative means to recognize doctors' efforts in lifelong learning.  

New York Times piece on Pradaxa (dabigatran)

It seems the folks at BMJ think they've uncovered a scandal in the approval and launch of Pradaxa. (What they actually “uncovered” was nothing of the sort although some bloggers have piled on with the idea). Based in part on the BMJ report the NYT ran a piece about the risks of Pradaxa. Dr. John M then gave the NYT article a nice smack down:

This purpose of this post is to clarify misstatements made in a recent New York Times article about the anticoagulant drug dabigatran (Pradaxa). The piece had three major inaccuracies, plus one thought-error from a cardiology leader.

I encourage you to read the rest of Dr. John's post for specific examples. This sort of thing is not unusual for NYT reporting on medicine nor is it unique to them. There's a problem that arises when a journalist tries to present a scientific topic to the general public: it gets dumbed down. Way, way down sometimes, for several reasons. Often journalists uncritically accept and run with popular myths (in the case in question, the myth that patients taking warfarin cannot eat certain green vegetables). Sometimes they gloss over important distinctions (in the case of the NYT piece the author either didn't know, or didn't care about the difference between relative risk and absolute risk). Perhaps most importantly scientific topics, when reported with the nuance and subtlety they deserve, lose a lot of their value as a “story.” This last reason, though no excuse for sloppy reporting, is a common. To report on medicine to the lay public is to take something that's arcane, tentative and sometimes ambiguous and make it interesting. It can be done but few journalists seem to take the effort required to pull it off well.

Antimicrobial treatment of infective endocarditis: an update

Article at journal site.

Full text via Medscape.

Undetectable high sensitive troponin I in PE

Associated with favorable prognosis in this study, and the potential for outpatient treatment.

Via Hospital Medicine Virtual Journal Club.

On role modeling

In a really interesting read in the journal Academic Medicine Dr. Jochanan Benbassat explains that role modeling, though vaguely defined and part of the “hidden curriculum,” is a powerful factor in medical education. We are well aware of its good aspects; we seek to emulate the traits of mentors we admire. But there are unintended consequences, says the author. The responses to role modeling are largely subconscious, somewhat emotionally driven, uncritical and even primitive. There are potential dangers. My own take is that the student's response to the role model involves the psychological defense mechanisms of identification and introjection. Early in the process of finding out who they are and what they are becoming as clinicians, students are uniquely susceptible. (These psychological mechanisms were explored with fascinating insight and great comical effect in Woody Allen's movie Zelig). The article explores ways students can mitigate the harmful effects through self reflection and critical thinking.

Filtered resources versus Google to answer clinical questions

Which approach is better? Findings from a recent study might come as a surprise:

Method: In 2011 and 2012, 48 internal medicine interns from two classes at Rutgers University Robert Wood Johnson Medical School, who had been trained to use three evidence-based summary resources, performed four-minute computer searches to answer 10 clinical questions. Half were randomized to initiate searches for answers to questions 1 to 5 using Google; the other half initiated searches using a summary resource. They then crossed over and used the other resource for questions 6 to 10. They documented the time spent searching and the resource where the answer was found. Time to correct response and percentage of correct responses were compared between groups using t test and general estimating equations.

Results: Of 480 questions administered, interns found answers for 393 (82%). Interns initiating searches in Google used a wider variety of resources than those starting with summary resources. No significant difference was found in mean time to correct response (138.5 seconds for Google versus 136.1 seconds for summary resource; P = .72). Mean correct response rate was 58.4% for Google versus 61.5% for summary resource (mean difference −3.1%; 95% CI −10.3% to 4.2%; P = .40).

Conclusions: The authors found no significant differences in speed or accuracy between searches initiated using Google versus summary resources.

Does this mean Google is as good as filtered “evidence based” resources? Not necessarily. The filtered resources available to the participants were quite limited, consisting only of First Consult, DynaMed and Wiley’s Essential Evidence Plus. Certainly not representative of the best selection in that category. Participants using Google landed on a wider variety of sites including the primary sources themselves: journal articles.

How many of the Google users hit on social media? None! Social media are rising in their perceived importance as resources for answering clinical questions and are increasingly being promoted through initiatives like FOAM and Blitter. But this study, though limited by being small, suggests that penetration remains low. So for now it would appear that most users who Google clinical questions end up in non social media resources although most who do land on social media do so via Google (at least for my blog). These trends are likely to change over time.

Proton pump inhibitors and the risk of spontaneous bacterial peritonitis

From a recent study:

Aim

To determine whether PPI use increases the risk of SBP using a large cohort.

Methods

This retrospective cohort study included 1965 cirrhotic patients with ascites diagnosed between January 2005 and December 2009. The SBP incidence rate was compared between the PPI and non-PPI groups before and after propensity score matching to reduce the effect of selection bias and potential confounders. Multivariate analysis was conducted to confirm the association of PPI use with SBP.

Results

After excluding 411 patients, 1554 were analysed. Among them, 512 patients (32.9%) were included in the PPI group. The annual SBP incidence rate was higher in the PPI group than in the non-PPI group (10.6% and 5.8%, P = 0.002) before matching. Indications for PPI use and dose of PPI were similar between patients with and without SBP. In the propensity score matched cohort (402 pairs), the SBP incidence rate was also higher in the PPI group than in the non-PPI group (10.8% vs. 6.0%, P = 0.038). Multivariate analysis revealed that PPI use (Hazard ratio 1.396; 95% confidence interval, 1.057–1.843; P = 0.019) was the independent risk factor for SBP.

Conclusions

Proton pump inhibitor use significantly increases the risk of spontaneous bacterial peritonitis in cirrhotic patients with ascites. Proton pump inhibitor use should be undertaken with greater caution and appropriately in patients with cirrhosis.

Via Hospital Medicine Virtual Journal Club.

AKI related to cardiac surgery

An article link and concept map at Nephron Power.

Alcohol induced hypertension

Free full text review.  

Markers of fitness and all cause mortality

This study looked at outcomes of a population of patients with no known cardiovascular disease who underwent exercise testing. We wouldn't do such testing on health subjects nowadays but these data were gathered from 1993 to 2003:

Methods and Results We examined conventional cardiovascular risk factors and exercise test parameters in 6546 individuals (mean age 49 years, 58% men) with no known cardiovascular disease who were referred to our clinic for exercise stress testing between 1993 and 2003. The association of exercise parameters with mortality was assessed during a follow‐up of 8.1±3.7 years. A total of 285 patients died during the follow‐up period. Adjusting for age and sex, the variables associated with mortality were: smoking, diabetes, functional aerobic capacity (FAC), heart rate recovery (HRR), chronotropic incompetence, and angina during the exercise. Adjusting for cardiovascular risk factors (diabetes, smoking, body mass index, blood pressure, serum total, HDL, LDL cholesterol, and triglycerides) and other exercise variables in a multivariable model, the only exercise parameters independently associated with mortality were lower FAC (adjusted hazard ratio [HR] per 10% decrease in FAC, 1.21; 95% confidence interval [CI], 1.13 to 1.29; P less than 0.001), and abnormal HRR, defined as failure to decrease heart rate by 12 beats at 1 minute recovery (adjusted HR per 1‐beat decrease, 1.05; 95% CI, 1.03 to 1.07; P less than 0.001). The additive effects of FAC and HRR on mortality were also highly significant when considered as categorical variables.

Conclusion In this cohort of patients with no known cardiovascular disease who were referred for exercise electrocardiography, FAC and HRR were independently associated with all‐cause mortality.

Update on valvular heart disease

A concise free full text review in the American Journal of Medicine.

RCT of dexmedetomidine for severe alcohol withdrawal, as adjunctive to benzodiazepines

This is the first RCT I know of looking at dexmedetomidine for alcohol withdrawal:

Design:  Prospective, randomized, double-blind, placebo-controlled trial.

Setting:  Single center; medical ICU.

Patients:  Twenty-four adult patients with a Clinical Institute Withdrawal Assessment score greater than or equal to 15 despite greater than or equal to 16 mg of lorazepam over a 4-hour period.

Interventions:  Patients received a symptom-triggered Clinical Institute Withdrawal Assessment protocol with lorazepam and were randomized to dexmedetomidine 1.2 μg/kg/hr (high dose), 0.4 μg/kg/hr (low dose), or placebo as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms.

Measurement and Main Results:  High-dose and low-dose groups were combined as a single dexmedetomidine group for primary analysis with secondary analysis exploring a dose-response relationship. The difference in 24-hour lorazepam requirements after versus before study drug was greater in the dexmedetomidine group compared with the placebo group (–56 mg vs –8 mg, p = 0.037). Median differences were similar for high dose and low dose. The 7-day cumulative lorazepam requirements were not statistically different between dexmedetomidine and placebo (159 mg vs 181 mg). Clinical Institute Withdrawal Assessment or Riker sedation-agitation scale scores representing severe agitation (13% vs 25%) or moderate agitation (27% vs 22%) within 24 hours of initiating study drug were similar for dexmedetomidine and placebo groups, respectively. Bradycardia occurred more frequently in the dexmedetomidine group versus placebo group (25% vs 0%, p = not significant), with the majority of bradycardia occurring in the high-dose group (37.5%). Study drug rate adjustments occurred more often in the dexmedetomidine group compared with the placebo group (50% vs 0%, p = 0.02). Neither endotracheal intubation nor seizure occurred in any group while on study drug.

Conclusions:  Adjunctive dexmedetomidine for severe alcohol withdrawal maintains symptom control and reduces lorazepam exposure in the short term, but not long term, when using a symptom-triggered protocol. Monitoring for bradycardia is needed with dexmedetomidine but the occurrence may be lessened with low dose. Further study is needed to evaluate the clinical impact of dexmedetomidine.

Macrolides and mortality in critically ill patients with community acquired pneumonia

From a recent systematic review and meta-analysis:

Conclusions:In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines.

The inappropriate conflation of medical stewardship and distributive justice

This piece from a few months ago in the Southern Medical Journal challenges the group think of today's policy makers. It's a must read. It makes the point that the clinician's responsibility is to the individual patient, not the medical commons. Excellence in the care of the individual patient, of course, includes eliminating waste in terms of the excesses (nonbeneficial or even harmful care) which could be categorized as low value. And while such good stewardship will have the collateral effect of easing the burdens of resource allocation the physician's job is to treat the patient, not society. Here are a few gems from the article:

A professional commitment to distributive justice in the clinical context unavoidably undercuts the core historical commitments of medical professionalism. This is because physicians owe a fiduciary duty to the individuals under their care...

The idea of converting waste into value and having physicians (rather than “government”) take the lead in doing so, is intrinsically attractive, to say the least; yet it is important to keep in mind that the collateral benefits procured through prudent care are just that. Clinicians owe a fiduciary duty to the patient, not the world.

Heparin induced thrombocytopenia (HIT): the essentials

Well summarized in this little blurb.

Graves orbitopathy

From a recent review:

Graves orbitopathy (GO) is an autoimmune disorder representing the most frequent extrathyroidal manifestation of Graves disease...GO is an inflammatory process characterized by edema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat...Encouraging smoking cessation and achieving euthyroidism in the individual patient are important. Simple treatment measures such as lubricants for lid retraction, nocturnal ointments for incomplete eye closure, prisms in diplopia, or botulinum toxin injections for upper-lid retraction can be effective in mild cases of GO. Glucocorticoids, orbital radiotherapy, and decompression/rehabilitative surgery are generally indicated for moderate-to-severe GO and for sight-threatening optic neuropathy. Future therapies, including rituximab aimed at treating the molecular and immunological basis of GO, are under investigation and hold promise for the future.

ACC membership survey on MOC

Via Dr. Wes:

Nearly 90 percent of respondents opposed the changes to the American Board of Medical Specialty (ABMS)/American Board of Internal Medicine (ABIM)'s new Maintenance of Certification (MOC) requirements, citing, among multiple concerns, higher than expected costs. Nearly a third of respondents indicated that the changes will affect their future career plans and will likely accelerate career decisions such as early retirement, part-time work, or transition to non-clinical work. Approximately one-quarter of physicians in practice for 15 years or more specified that early retirement was a probable outcome.

Dr. Wes also pointed out the lack of evidence that MOC improves outcomes.

Early discharge or outpatient treatment of pulmonary embolism: a summary of the evidence

Which patients are candidates? The short answer that comes to mind is “walky talky patients without DVT.” That, of course, is simplistic, with several risk assessment tools and many clinical judgment considerations that apply. The approval of TSOACs for PE will bring this option to the table more often. There is the potential for great cost savings. Here is a review of the topic.

ER use as a function of PCP access in the VA system

From the JGIM:

DESIGN AND PATIENTS:

A longitudinal retrospective study of 627,276 patients receiving primary care from 6,398 primary care providers (PCPs) nationally within the Veterans Health Administration (VHA) in 2009. We tracked weekly changes in PCP-level appointment availability.

MEASUREMENTS:

The number of a PCP's patients who went to the ER in a given week.

RESULTS:

Among all PCPs, being absent from patient care for the week had no effect on whether that PCP's patients used the ER in that week (incident rate ratio (IRR) 0.997, p = 0.70). However, among PCPs who were near-sole providers of care, a PCP's absence for a week or more had a statistically significant effect on ER visits (IRR 1.04, p = 0.01). The percentage of a PCP's weekly appointment slots that were fully booked (booking density) had no significant effect on whether their patients used the ER in that week among all PCPs. However, among near-sole providers of care, a 10-percentage point increase in the booking density changed the IRR of ER visits in that week by 1.005 (p = 0.08) and by 1.006 on weekdays (p = 0.07).

CONCLUSIONS:

Patients' access to their PCP had a small effect on whether those patients used the ER among PCPs whose patients rarely saw another PCP. Among other PCPs, there was no effect of PCP access on ER use. These results suggest that sharing patient-care responsibilities across PCPs may be effective in improving access to care and decreasing unnecessary ER use.

I don't have access to the body of the paper but I wonder if this data set included patients who got frustrated and hopped down the street to the nearest community hospital ER. I bet it didn't.

aVR, the Rodney Dangerfield lead

Lead aVR is beginning to get a little respect but still doesn't get the respect it deserves. Here is a recent review.

Recent attention to aVR has focused on arrhythmia diagnosis, pericarditis and ACS. Many recent publications emphasize ST elevation in aVR during ACS as a sign of global ischemia due to left main coronary artery involvement. As the review points out, however, the situation is more complex. From the abstract and introduction:

The 12-lead electrocardiogram (ECG) is a crucial tool in the diagnosis and risk stratification of acute coronary syndrome (ACS). Unlike other 11 leads, lead aVR has been long neglected until recent years..ST-segment elevation in lead aVR can be caused by (1) transmural ischemia in the basal part of the interventricular septum caused by impaired coronary blood flow of the first major branch originating from the left anterior descending coronary artery; (2) transmural ischemia in the right ventricular outflow tract caused by impaired coronary blood flow of the large conal branch originating from the right coronary artery; and (3) reciprocal changes opposite to ischemic or non-ischemic ST-segment depression in the lateral limb and precordial leads. On the other hand, ST-segment depression in lead aVR can be caused by transmural ischemia in the inferolateral and apical regions.

Background from some prior posts:

[1] [2] [3]

Cardiovascular genetics

This update discusses some of the many single nucleotide polymorphisms (SNPs) found in genome wide association studies to be risk factors for cardiovascular disease. Some operate through known mechanisms (e.g. lipids, hypertension) and others, such as 9p21, by unknown mechanisms. From the article, here are the key points:

The genetic risk variants for CAD are very common, occurring on average in 50% of the population with a frequency varying from 2% to 91% (Table 1).

The relative increased risk of each genetic variant is small, averaging 18% with an odds ratio varying from 2% to 90%.

For CAD as well as other common polygenic disorders, multiple genetic risk variants are inherited by everyone. Those at high genetic risk for CAD have a greater genetic risk burden due to inheritance of a greater number of common risk variants, as opposed to inheriting one or more genetic variant of high risk. In a CARDIoGRAM analysis of 23 genetic risk variants for CAD, the average number inherited per individual (case or control) was 17, varying from a minimum of 7 to a maximum of 37.

Most of the genetic risk variants for CAD are located in DNA sequences that do not code for protein. This means the risk variant mediates its increased risk for CAD directly or indirectly through regulation of DNA sequences that do code for protein.

All DNA genetic risk variants need only be assessed once, since one’s DNA does not change over one’s lifetime nor do genetic risk variants vary with time, meals, drugs, or gender.

Sudden pulmonary edema, shock and a tricky ECG

Dr. Smithpresented a case of acute severe mitral regurgitation due topapillary muscle rupture. I thought it was worth posting here because there were a lot of pearls. The patient presented in extremis with no immediately apparent reason why, but after adding up the ancillary clues it could hardly be anything else. Also, a repeat 12 lead ECG done minutes later clarified some aspects of what was going on, a great illustration of the Corey Slovis rule “One ECG begets another.”

Fecal Microbiota Transplant as treatment for C diff

A review in the American Journal of Gastroenterology.

Free full text from Medscape.

Cotrimoxazole: indications, dosing and precautions in critically ill patients

I found this review worth posting because the information it contains is hard to find anywhere else. It is available as free full text and is worth bookmarking for reference.

When we think of Bactrim in the critical care unit we usually think of Pneumocystis. However, Stenotrophomonas and Nocardia are also potential indications.

Ascorbic acid to prevent contrast induced kidney injury

Recent promising treatments for prevention of contrast induced AKI include statins and ischemic preconditioning. Now ascorbic acid can be added to the list.

Oral anticoagulants in patients with atrial fibrillation: which drug, which patient?

Free full text review.