Tuesday, December 31, 2013

Nurses doing housekeeping chores

---including cleaning and decontaminating patient care areas. Hard to believe but true according to a TV news report.

A particularly rich piece of the corporate spin concerning the measure is found at 1:06 into the video with the reference to Florence Nightingale.

HT to the blogger at ofcourseitsaboutyou who said:

Especially insulting is the implication that Florence Nightingale would have wanted nurses to return to doing housekeeping in the hospital. Nightingale wanted nursing to move forward, not backward.

Vandy is pretty resource heavy and the place I'd least expect this to happen.

When I first saw the report I thought somebody was joking. But as I thought more I realized that this is not the first time health care workers have been pushed outside their professional boundaries. Doctors, for example, were asked to become secretaries with the rollout of CPOE. Few dared to call it out as it was so cleverly disguised as technology for the enhancement of patient safety.

Thursday, December 26, 2013

Baroreceptor failure

Here is a case report and brief review.

It can present with syncope, orthostatic hypotension, labile blood pressure and heart rate. Blood pressure is difficult to control and requires a special approach. Risk factors include neck irratiation (carotid sinus damage) and possibly chest irradiation (aortic arch baroreceptor damage).

When to suspect the diagnosis: the profile above in the context of a history of neck or chest irradiation or brainstem stroke.

Testing to confirm or exclude the diagnosis: no fixed algorithm. Exclusion of other causes. Tilt table testing may be helpful.

Full text at the above link.

Tuesday, December 24, 2013

Roth spots and little black bags

Here's another delightful essay by Herbert Fred.

With the demise of the little black bags (which were provided as gifts from the drug companies) came the end of routine use of the ophthalmoscope.

Patterns of cardiac arrest due to aortic dissection or aneurysm

From a recent study:

Materials and Methods:
Patients who were transported to this department from January 2005 to December 2010 and subsequently diagnosed with AD were included in this study. Patients with asymptomatic AD or those with AD that did not develop CPA were excluded. The AD was classified into four categories: Stanford A (SA), Stanford B (SB), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA)...
There were 24 cases of SA, 1 case of the SB, 8 cases of ruptured TAA and 9 cases of ruptured AAA. The frequency of males among all subjects was 69%, the average age was 72.3 years old and the frequency of hypertension was 47.6%. There was no ventricular fibrillation (VF) when the patients with AD collapsed. A loss of consciousness was the most common complaint. The outcome of the subjects was poor; however, three patients with SA achieved social rehabilitation. Two out of the three had cardiac tamponade and underwent open heart massage.
The current study revealed that mortality of cardiac arrest caused by the AD remains very high, even when return of spontaneous circulation was obtained. VF was rare when the patients with AD collapsed. While some cases with CPA of SA may achieve a favorable outcome following immediate appropriate treatment.

Friday, December 20, 2013

Excessive CVP levels and microcirculatory impairment

From BMC Anesthesiology:

We performed a post-hoc analysis of a prospective study in septic patients who were resuscitated according a strict non-CVP guided treatment protocol. Simultaneous measurements of hemodynamics and sublingual Sidestream Dark Field imaging were obtained 0 and 30 minutes after fulfillment of resuscitation goals. Data were examined for differences in microcirculatory variables for CVP less than or equal to or greater than 12 mmHg and its evolution over time, as well as for predictors of a microvascular flow index (MFI) less than 2.6.
In 70 patients with a mean APACHE II score of 21, 140 simultaneous measurements of CVP and sublingual microcirculation (vessels less than 20 µmeter) were obtained. (MFI) and the percentage of perfused small vessels (PPV) were significantly lower in the ‘high’ CVP (greater than 12 mmHg) group as compared to patients in the ‘low’ CVP (less than or equal to 12 mmHg) group (1.4 ± 0.9 vs. 1.9 ± 0.9, P = 0.006; and 88 ± 21% vs. 95 ± 8%, P = 0.006 respectively). Perfusion pressure (MAP–CVP) and cardiac output did not differ significantly between both CVP groups. From time point 0 to 30 minutes, a significant increase in MFI (from 1.6 ± 0.6 to 1.8 ± 0.9, P = 0.027) but not in PPV, was observed, while CVP and perfusion pressure significantly decreased in the same period. In a multivariate model CVP greater than 12 mmHg was the only significant predictor for a capillary MFI less than 2.6 (Odds ratio 2.5 (95% confidence interval 1.1-5.8), P = 0.026). 
We observed a significant association between a higher CVP and impairment of microcirculatory blood flow. Further research is needed to elaborate on our hypothesis generating findings that an elevated CVP may act as an outflow obstruction of organ perfusion.

Thursday, December 19, 2013

Interobserver variations in the interpretation of ECGs concerning for STEMI

From a recent study:
A cross‐sectional survey was performed consisting of 36 deidentified ECGs that had previously resulted in putative STEMI diagnoses. Emergency physicians, cardiologists, and interventional cardiologists participated in the survey. For each ECG, physicians were asked, “based on the ECG above, is there a blocked coronary artery present causing a STEMI?” The reference standard for ascertaining the STEMI diagnosis was subsequent emergent coronary arteriography. Responses were analyzed with generalized estimating equations to account for nested and repeated measures. One hundred twenty‐four physicians interpreted a total of 4392 ECGs. Among all physicians, interreader agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The sensitivity to identify “true” STEMIs was 65% (95% CI: 63 to 67) and the specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of accurate ECG interpretation for every 5 years of experience since medical school graduation (OR 1.06, 95% CI: 1.02 to 1.10, P=0.01). After adjusting for experience, there was no significant difference in the odds of accurate interpretation by specialty—Emergency Medicine (reference), General Cardiology (AOR 0.97, 95% CI: 0.79 to 1.2, P=0.80), or Interventional Cardiology physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P=0.15).
There is significant physician disagreement in interpreting ECGs with features concerning for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a suitable “stand‐alone” diagnostic test.

That last sentence may only be true when the popular formulaic approach to electrocardiographic interpretation is used. There are many well known STEMI mimics as well as examples of acute coronary occlusions that do not meet simplistic STEMI criteria (STEMI equivalents). Many such examples, recognizable by sophisticated observers, may have been ignored in this sample of physicians. The simplistic approach may be driven by todays STEMI performance incentives.

In the discussion section the authors correctly state:

However, the impetus for this study sprung largely from the notion that categorization of ECGs into dichotomous STEMI and not‐STEMI groups is often over‐simplified. This notion has importance particularly in respect to appropriateness criteria for STEMI team activation protocols. Many analyses of STEMI team activations categorize electrocardiographic ST segment elevations as a binary variable—present or not present. Such dichotomies fail to capture the graded nature of ST‐segment elevations and may grossly oversimplify the challenging task of diagnosing true STEMI patients from the much larger cohort of at‐risk patients presenting with chest pain or equivalent symptoms...
While these data speak to the difficult nature of discerning accurate from inaccurate STEMI diagnoses on the basis of ECGs alone, they also suggest that considering electrocardiographic ST elevations as a dichotomous variable for the purposes of catheterization activation protocols or appropriateness analyses may be insufficiently discerning.

The insufficiency of such a dichotomous approach is illustrated by outcomes and pathology data suggesting that the STEMI/NSTEMI distinction is baseless.

Clinical and electrocardiographic presentations of takotsubo cardiomyopathy

In this series physical stress was more often the trigger than emotional stress. All manner of electrocardiographic presentations were noted but anterior ST elevation and T wave inversion were most characteristic.

Wednesday, December 18, 2013

Certification and maintenance of certification: a critical look

Among the many assumptions that underlie the board certification (BC) and maintenance of certification (MOC) processes most are based on weak evidence or no evidence at all and others address the wrong questions. Here are a few:

A physician's knowledge wanes over time after training

That's generally accepted. There is a cerebral half life for many of the facts learned during training. The principle may not apply so much to knowledge in the physician's content area, which is reinforced by experience.

The process leads to better patient outcomes

There is weak evidence around this claim but it doesn't address cause and effect.

The public wants it

The statement is well supported by survey data but is it enough to justify the onerous and expensive process if evidence for real quality and outcome improvement is lacking?

An outsider (eg the specialty board) knows best the learning needs of the individual physician

A philosophical more than an evidential assumption, it's held up to ridicule by physicians “on the ground” while apparently holding sway with policy makers.

What does the evidence really say? Two reviews which address the question are noteworthy. This one from a couple of years ago was authored by officials of the ABIM and tends to be promotional although it cites much the same evidence noted in this recent and somewhat more objective review (related editorial here).

Here's the short version:

Patient outcomes

BC: Data on the correlation between BC status and patient outcomes are mixed. While some show a positive association the causality is unknown. It is equally likely that BC status and patient outcomes are linked by common factors inherent in the caliber of the physicians or their training programs.

MOC: The relationship to patient outcomes has not been specifically examined for MOC.

Processes of care

Both BC and MOC have been shown to correlate with performance metrics, but such metrics have not been validated as surrogates for quality or outcomes.

The more recent review has some interesting tidbits about participation in MOC. Participation among the leadership of internal medicine, even officials of the ABIM, was low! From the review:

We also calculated the recertification rate of the internal medicine leadership in various organizations using information collected from various websites in July 2009, which was approximately 20 years after the change in certification to a time-limited process. The initial ABIM task force on recertification has a recertification rate of 18% (3/17). The ABIM Board has a recertification rate of 20% (6/20). The editorial board for the Annals of Internal Medicine has a recertification rate of 9% (2/22). The ACP Governors have a recertification rate of 4% (2/54). The ACP Board of Regents has a recertification rate of 8% (2/26). The ACGME-RRC Internal Medicine Committee has a recertification rate of 0% (0/12). These are the statistics for internal medicine recertification only; the rates for recertification in subspecialty areas are slightly higher (Table 2). We repeated part of this analysis in June 2012. Twenty-six members of the ABIM board had lifetime certification, and six (23%) have voluntarily recertified. Thus, the participation by senior leadership in internal medicine has been unusually low; this seems surprising since many of these individuals promoted the initial process.

The editorial elaborates on this finding.

Monday, December 16, 2013

New cholesterol guidelines: a brave and wise departure from current practice?

Well, that's the claim made in a recent BMJ editorial on the new guidelines (HT to DB's Medical Rants). To recap, the emphasis of the new guidelines was to treat with fixed doses of statins based on patients' risk rather than titrating to goal. While this represents a shift from the old recommendations it is not a radical departure from current practice. The “set it and forget it” approach offered by the new guidelines was, I suspect, already common in clinical practice. Moreover, based on accumulating research evidence it is more common nowadays for patients suffering acute vascular events to be discharged from the hospital on high statin doses, without much attention to their baseline lipids, similar to those recommended in the new guidelines. What the document did, though, was codify this practice which, one would hope, will cause it to be more uniformly and systematically applied. So this will not result in the “tectonic shift” that the BMJ author has claimed.

Then he goes on to say this:

A spate of studies over the past few years contributed to an insight that had previously eluded the field. Cholesterol plays a key role in atherosclerosis, but its modification by drugs does not always produce the expected result. Drugs have thousands of effects and their influence on cholesterol concentrations does not convey their net effect on patient risk. Trials showed that lowering LDL-C and raising high density lipoprotein cholesterol did not necessarily lower risk.8 9 10 11

Those trials did not ask the simple question of whether pharmacologic alteration in lipid levels would reduce events. With the exception of one study which may be an outlier because it involved a novel class of drugs these trials essentially addressed whether adding a second drug would address residual risk after statin therapy. Older studies which did ask the simple question supported the lipid hypothesis and provided evidence that altering LDL and HDL cholesterol levels leads to a reduction in important clinical events. I reviewed those studies in yesterday's post.

I did find some good points in the editorial. For example the author makes this point which is fundamental in the application of clinical trials to the principles of evidence based medicine:

Also, the risk thresholds for treatment should be understood as recommendations and not dictums. For any individual, the decision about the worth of a drug treatment depends on how that person feels about potential benefits, burdens, and harms—something that no writing group can determine. Ultimately, the decision depends on our ability to provide patients with the knowledge and guidance needed to make high quality decisions about their treatment.

Then he makes this point about performance measures:

The new guidelines are also a cautionary tale about the premature translation of medical guidelines into performance measures. They highlight that the push to chase targets was based on speculation, not on direct trial evidence, and opened the door to the use of drugs that had not been fully tested.

Performance measures, while they appeal to guidelines and research evidence, do so without appropriate critical analysis and expertise which is one reason they ultimately fail.

Sunday, December 15, 2013

The new cholesterol guideline: is it really a paradigm shift?

There's a lot of misinformation flying around about the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Some of the popular distortions include the idea that the guideline authors threw away the LDL targets and sent a message that lipid lowering doesn't matter. That's not what the document says at all. Over and over in the guideline the authors acknowledge that cholesterol reduction is the goal of statin therapy. Heck the title of the guideline, as linked above, makes that pretty explicit! And while they de-emphasized specific targets they didn't throw them out altogether. What the panel did was recognize that major lipid lowering trials were not designed to test titrated dosing of drugs to particular targets. Accordingly the major recommendations of the document are based on patients' overall risk more than their lab values. In the nine years since the ATP update on lipid management we've learned a great deal about the pleiotropic effect of statins. But LDL reduction remains an important part of the story and the guideline writers acknowledge that. There's no new paradigm here. They are merely making the recommendations more respectful of historic clinical trial design. I think it's a mistake to extend the interpretation beyond that.

Last month Dr. Robert Centor, blogging ad DB's Medical Rants, expressed his approval of the new guidelines. I agree with him that we needed a more evidence based approach. But then DB makes this statement:

The brilliance of the new guidelines comes from the writing group understanding that lowering the cholesterol level does not improve important outcomes, but statins (discovered and popularized because they lower cholesterol) improve outcomes regardless of ones initial cholesterol. Other drugs that lower cholesterol or raise HDL do not improve important outcomes!

But wait a minute. There's a substantial body of research showing that lipid lowering reduces clinical events no matter how you do it. Though some of the studies have confounders, as a whole they point to the importance of LDL reduction. The Oslo study, though confounded by more smoking cessation in the intervention group, suggested a reduction in coronary events attributable to dietary reduction of cholesterol. The LRC trial showed a reduction in events attributable to LDL lowering by means of cholestyramine resin. Clinical trials of other non statin drugs also showed reduction events attributable to lipid lowering though confounded by the ability of those particular drugs to raise HDL cholesterol: the Coronary Drug Project (niacin), the WHO study (clofibrate); and the Helsinki study (gemfibrozil).

Sidebar: the Coronary Drug Project also serves as a reminder that we had comparative effectiveness research back in the 1960s. The concept is not new, only the name designed to serve political ends and give authors catchy options for their titles.

The importance of LDL in the pathogenesis of atherosclerosis has been established for a long time. Our understanding of how that works is more nuanced than it was decades ago. In our more complex understanding of atherosclerosis and new appreciation of the pleiotropic effects of statin drugs we realize more than before that the LDL concentration is not the whole story. But it remains an important part of the story.

Background: This review, though out of date for treatment recommendations, is a careful analysis of early trials establishing the lipid hypothesis and demonstrating improvement in meaningful clinical outcomes with diet and non statin drug treatments to lower cholesterol.

Saturday, December 14, 2013

Extracorporeal life support (ECLS)

This refers to either extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R), for a variety of indications but mainly ARDS. Here is a recent review.

The status of ECLS is evolving. In the 70s, following an early wave of enthusiasm for ECMO as treatment for ARDS, research evidence was disappointing. By the time of my early interest in critical care the idea was almost rejected out of hand. Subsequently it began to emerge as a rescue modality for ARDS in cases of therapeutic desperation. Technology improved and offered variations of the technique as additional options. Out of necessity considerable positive experience was gained during the 2009 pandemic. Also, as quoted from the review:

Also that same year, the conventional ventilatory support versus ECMO for severe adult respiratory failure (CESAR) study was published. The investigators used a “pragmatic” study design and were criticized for the inability to standardize mechanical ventilation management in the conventional care group.[30] Importantly, the CESAR trial demonstrated that protocolized care that included ECMO in an expert center for ARDS care yielded higher survival than the best standard care in tertiary intensive care units in the UK.[30]

Here is the CESAR study. It concluded:

We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability.

So ECLS is making its way into clinical practice. The Extracorporeal Life Support Organization has published guidelines. The indications section reads:

Acute severe heart or lung failure with high mortality risk despite optimal conventional therapy. ECLS is considered at 50% mortality risk, ECLS is indicated in most circumstances at 80% mortality risk. Severity of illness and mortality risk is measured as precisely as possible using measurements for the appropriate age group and organ failure. See patient- specific protocols for details. 
Most contraindications are relative, balancing the risks of the procedure (including the risk of using valuable resources which could be used for others) vs. the potential benefits. The relative contraindications are: 1) conditions incompatible with normal life if the patient recovers; 2) preexisting conditions which affect the quality of life (CNS status, end stage malignancy, risk of systemic bleeding with anticoagulation); 3) age and size of patient; 4) futility: patients who are too sick, have been on conventional therapy too long, or have a fatal diagnosis. See patient-specific protocols for details.

Friday, December 13, 2013

Adipose tissue: metabolically active, proinflammatory

This review from the Archives of Medical Science helps explain the cardiovascular consequences of the metabolic syndrome.

Thursday, December 12, 2013

Strengthened FDA warnings for Lexiscan and Adenoscan

New from the FDA:

The U.S. Food and Drug Administration (FDA) is warning health care professionals of the rare but serious risk of heart attack and death with use of the cardiac nuclear stress test agents Lexiscan (regadenoson) and Adenoscan (adenosine). We have approved changes to the drug labels to reflect these serious events and updated our recommendations for use of these agents. Health care professionals should avoid using these drugs in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions.

This was already reflected in the labeling but the warning has been strengthened. The risk is believed to be low, though the denominator is unknown. The last sentence in the quoted text is of concern, given a general perception that these agents should be safer in potentially unstable patients as opposed to dobutamine or treadmill exercise.

Tuesday, December 10, 2013

Therapeutic hypothermia after cardiac arrest: what’s optimum?

Results of two trials were presented at AHA.

In this one 33 C was no better as a therapeutic target than 36 C in terms of survival or neurologic outcome.

In the other study initiation of cooling pre-hospital was associated with greater incidence or re-arrest and need for diuretics but produced no survival or neurologic benefit.

Based on a related discussion at Medpage Today therapeutic hypothermia remains an important intervention. However we have yet to find the sweet spot in terms of optimal timing and “dose” of the intervention.

Monday, December 09, 2013

Immediate blood pressure lowering in ischemic stroke

In patients with acute ischemic stroke not receiving thrombolytics, the guidelines for years recommend avoidance of antihypertensive therapy up to levels of 220/120 (permissive hypertension). High level evidence to guide clinicians in one direction or the other, however, was lacking. The recently published CATIS trial (presented at AHA and published in JAMA) addressed the question:

Objective To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge.
Design, Setting, and Participants The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013.
Interventions Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033)…
Results Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (−12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (−7.2%) in the control group within 24 hours after randomization (difference, −5.5% [95% CI, −4.9 to −6.1%]; absolute difference, −9.1 mm Hg [95% CI, −10.2 to −8.1]; P less than  .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, −9.3 mm Hg [95% CI, −10.1 to −8.4]; P less than  .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93).
Conclusion and Relevance Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge.

There are no findings from this new trial to indicate change from current guideline based practice.

Sunday, December 08, 2013

Another novel anticoagulant scores against warfarin

ENGAGE AF was presented at AHA and published in NEJM:

We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding…
Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes.

The interpretation of the results is complex. Here is a related discussion in Medpage Today.

Friday, December 06, 2013

Pitfalls in the evaluation of patients for B12 deficiency

From a recent study:

Methods This retrospective study reviewed the electronic medical records of 192 patients initiated on intramuscular vitamin B12 injections.
Results Only 12 patients had objectively documented hematologic responses: decrease of mean corpuscular volume by greater than or equal to 5 fL with stable or improved hemoglobin. Another 5 patients had equivocal hematologic responses. There was one plausible neurologic response. Thus, only 18 (9.4%) of 192 patients had data supportive of a clinical response. In these 18 patients, the baseline serum B12 level was less than or equal to 107 pg/mL; only 3 patients also had a baseline serum methylmalonic acid level, which was greater than or equal to 1.29 μmol/L in all 3 patients.
Conclusions Currently, only a small minority of patients initiated on intramuscular vitamin B12 supplementation derive any meaningful clinical benefit. Furthermore, current testing recommendations for vitamin B12 deficiency are usually not followed.

The authors make several suggestions to improve diagnostic accuracy:

Reserve B12 testing for patients with a clear clinical indication.

Avoid reliance on a single test.

Laboratories should perform reflex testing of MMA levels and IF antibodies when low B12 levels are detected.

Hematologic responses should be followed during treatment and if the expected response does not occur evaluation for other conditions should be carried out.

Wednesday, December 04, 2013

Financial struggles for hospitals

---will continue in 2014 according to a recent Moody's Investors Service report. The report was linked by Danielle Scheurer over at The Hospitalist Leader. She wrote:

Moody’s Investors Service predicts the financial outlook for US not-for-profit hospitals will be no better in 2014 (and which has been negative since 2008). They expect hospitals will continue to see tight margins, as revenue will not keep up with expenses..
Overall, for hospitalists, this will have to translate into a continued and fierce focus on Value (Quality / Cost) for all of us, to maintain feasible operating margins within our hospitals..

Of course this goes back beyond 2008. Hospitals have struggled for decades and it just steadily gets worse. The biggest tsunami for hospitals happened in 1984 with the advent of DRGs. It's just been a gradual continuum of more and more intrusive regulation and financial challenges ever since. Obamacare, whatever ultimately becomes of it, will likely just be another phase of that continuum. It will be disruptive but probably not as disruptive as what we saw in 1984.

But people lose pieces of their memory. I recall sitting in a large conference room in 1983 or 84. The speaker, talking about the advent of DRGs, warned the audience: “Doctors, you are about to be held accountable for providing high quality health care efficiently and at a low cost.”

Fast forward to 1994. Despite the demise of the Clinton health care plan managed care had already adopted the model and was poised to advance like a steamroller. And there was another conference room, another speaker who said: “Doctors, you are about to be held accountable for providing high quality health care efficiently and at a low cost.”

Fast forward to about a month ago in a conference room at the Hyatt, at UCSF's hospital medicine course. Bob Wachter, course director, stood up and spoke those same words. As if it was something new.

Reports like this remind me to try and be a better steward of medical resources. The unfortunate consequence for hospitalists has been the redefinition of core skills from clinical to business.

Tuesday, December 03, 2013

Electronic medical records

For a number of years now electronic medical records (EMRs) have been promoted by politicians and policy experts who know little about clinical medicine on the ground. Alongside this have appeared publications which purport to show beneficial clinical effects of EMRs. Virtually all of those, however, have reported low level and unvalidated surrogates for quality. The evidence that's out there does not convince that EMRs improve meaningful clinical outcomes. Dr. Robert Centor, the blogger at DB's Medical Rants, recently wrote a post about the unfulfilled promise of EMRs. Much of what he said concerned how they undermine diagnostic accuracy, a point with which I heartily agree and plan to elaborate on in a future post. But he concluded with this:
EHRs could help medical care. Currently it is only making physicians more busy work.

Much of the busy work he was referring to comes from what is known as computerized physician order entry (CPOE). CPOE was touted for various reasons as a process for enhancing patient safety and reducing errors. Again there was only soft and flawed surrogate evidence in support of that claim. But the main thing to understand about CPOE is that it is nothing more than shifting the workload of order processing from the traditional ward secretary to the physician. Unlike the ward clerks, though, doctors lack secretarial skills. Sure the reduction in secretaries saves hospitals money. But whether it improves patient safety by taking a link out of the chain of process or jeopardizes patients by removing a layer of safety (the secretary, usually more skilled in the processing and administrative aspects of implementing orders) is unknown.

Computerization of medicine is great in the abstract. Superficially it's a can't miss idea. That's why people in leadership who are removed from direct patient care can't understand our hesitation and our many objections. The unintended consequences are huge and difficult to navigate. Someday we will learn to use the EMR for all it is worth. Only then can we be confident that patients are better off as a result. It may take another decade.

Sunday, December 01, 2013

The TACT diabetes substudy: How far can the apple fall from the tree?

The other day in the doctors lounge a colleague asked me if I had heard about a new study presented at AHA showing a benefit of chelation therapy in diabetics. I'm not big on sound bite medicine and often don't get around to reading, let alone blogging about such things for a month or more. So I told him no I hadn't, but it had better be an improvement over the recent TACT study, which I thought was seriously flawed.

I found it Saturday over morning coffee. And no, it was not an improvement over TACT. It was merely a subgroup analysis of TACT itself. Most of you have heard the buzz by now so I'll cut straight to the study, which was simultaneously published in one of the Circulation journals. Here's the link. From the paper:

Methods and Results—Patients received 40 infusions of EDTA chelation or placebo. A total of 633 (37%) patients had diabetes mellitus (322 EDTA and 311 placebo). EDTA reduced the primary end point (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina; 25% versus 38%; hazard ratio, 0.59; 95% confidence interval [CI], 0.44–0.79; P less than 0.001) for over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI, 0.39–0.88; adjusted P=0.002). All-cause mortality was reduced by EDTA chelation (10% versus 16%; hazard ratio, 0.57; 95% CI, 0.36–0.88; P=0.011), as was the secondary end point (cardiovascular death, reinfarction, or stroke; 11% versus 17%; hazard ratio, 0.60; 95% CI, 0.39–0.91; P=0.017). However, after adjusting for multiple subgroups, those results were no longer significant. The number needed to treat to reduce 1 primary end point over 5 years was 6.5 (95% CI, 4.4–12.7). There was no reduction in events in non–diabetes mellitus (n=1075; P=0.877), resulting in a treatment by diabetes mellitus interaction (P=0.004).

Conclusions—Post–myocardial infarction patients with diabetes mellitus aged greater than or equal to 50 demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. However, they do not constitute sufficient evidence to indicate the routine use of chelation therapy for all post–myocardial infarction patients with diabetes mellitus.

The hype surrounding this paper will be misleading. Before I get to that, some other links of interest. Here is a discussion piece from the Heart.org, now part of Medscape Cardiology (free full text after registration). The piece is less than appropriately critical of the study but does provide some details for those without full text access to the original paper. Also found at the Medscape site is this article by Dr. John Mandrola (who blogs at Dr. John M). I think Dr. John is way too kind to the study and his tone, as reflected in the title Chelation Therapy: Promising for Diabetic Patients but Disruptive to the Medical Establishment is a little incendiary. From his introductory comments:

Based on this analysis of TACT, only six patients with diabetes had to be treated with chelation to prevent one adverse outcome. That's less than half the NNT when statins are used in patients with diabetes and established vascular disease—an uncontroversial indication.

Yet the medical establishment is overcome with doubt.

What does he mean by the medical establishment? If he means an organized body of leaders in medicine who stand for good ethics and scientific integrity, put me in that camp. That medical establishment has good reason to be upset about TACT. But perhaps Dr. John means something different. He says:

One of the doctors whom I hold in highest regard sent this to me in relation to the establishment:

The machine depends on people being sick to function. If people take control of their own health, the machine falls apart. And it is a billion-dollar business. Who wouldn't aggressively denounce anything that threatens it?

The disruption wrought by the new cholesterol guidelines pales in comparison to the angst surrounding chelation therapy.

Dr. John is talking around a very serious accusation: that professionals in mainstream medicine don't want patients to get well and stay well by taking charge of their own health. It's a somewhat conspiratorial idea but popular enough. The suggestion is that doctors in conventional medicine don't want their patients to be empowered. Is that what he really meant?

How should we interpret the study? First the usual objections. Be cautious about basing treatment recommendations on just one trial. PROWESS and many other studies taught us that lesson. (And keep in mind that TACT is just one in the face of several prior studies all of which were negative). Moreover we all know the hazards of subgroup analysis.

But more telling is a look at the peculiarities of TACT itself. With the publication of the original study in JAMA there was a companion editorial by Dr. Steve Nissen that was appropriately critical. He said:

Execution of a high-quality RCT requires skilled investigators and study coordinators who understand these critical scientific principles. For TACT, more than 60% of patients were randomized at enrolling centers described as complementary and alternative medicine sites. Many of these centers have websites that describe their services, which include an array of unproven therapies ranging from stem cell therapy to regrow breasts after mastectomy, high-dose intravenous vitamin C to treat cancer, and use of cinnamon for treating diabetes to treatment of influenza with antimicrobial essential oils or homeopathic remedies (while warning patients not to undergo immunization). Other sites offer chelation to treat or cure a variety of conditions including autism in children. A common theme of these centers is evident—they appear to attempt to appeal to vulnerable patients who have challenging diseases by offering a variety of unscientific and unproven therapies. Whether a high-quality RCT can be performed at such sites is questionable.

For an in depth look at what Nissen was referring to this article by Atwood and colleagues is a must read. It reviews prior negative studies and exposes what was really going on with TACT and, I believe, is prerequisite to understanding the findings. It's compelling reading and what you get from it is that TACT was badly (and in my reading of the paper, hopelessly) flawed. That's why I ask in title of this post how far the apple of the diabetes substudy can fall from the tree of TACT.

What's the take-home message? Here's Dr. John's:

It would be a huge mistake to dismiss this science because chelation does not conform to preconceived notions or because it is practiced outside the mainstream of medicine. Let's not forget about the patients with this terrible disease. It's not as if we have good treatments for them.

The authors have completely and thoroughly answered all questions posed to them. The trial has been repeatedly inspected and vetted in two prestigious peer-reviewed journals. Both the critics and TACT authors agree that it is too early to recommend chelation therapy. But surely the signal of benefit is strong enough to warrant confirmatory trials. It is time to replicate these findings.

I agree with him that this represents insufficient evidence to change practice. I also agree we shouldn't dismiss something just because it's outside mainstream. But the concerns about TACT are more basic. They are about ethics and scientific standards. My take on the study is not as optimistic as Dr. John's.

Not only was TACT just one positive trial in the face of several negative studies (a Bayesian analysis, I suspect, would be unfavorable) but it was an anomaly. It's hard to read the Atwood paper and not come away thinking this trial was uniquely flawed. Whether the findings of the TACT substudy even warrant further research could be vigorously debated.

Lactate monitoring in critical illness

Free full text review.

Saturday, November 30, 2013

Gastric antral vascular ectasia (GAVE)

Here is a case report and mini-review.

Disease associations include cirrhosis and rheumatic diseases particularly systemic sclerosis. The terminology surrounding GAVE tends to be confusing. Watermelon stomach is a subtype of GAVE associated more with the rheumatic diseases. Portal hypertensive gastropathy, with which GAVE may be confused, is a separate entity.

Friday, November 29, 2013

The Avandia hype: cooler heads prevail

As reported in Medscape:
The US Food and Drug Administration (FDA) is lifting restrictions on the prescribing and use of the diabetes drug rosiglitazone (Avandia, Avandamet, Avandaryl, GlaxoSmithKline) on the basis of recent data that demonstrate no elevated cardiovascular risk.
"Although some scientific uncertainty about the cardiovascular safety of rosiglitazone medicines still remains, in light of the new re-evaluation of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, our concern is substantially reduced," the FDA said in a statement.

Finally a more sober assessment. The issue of Avandia and cardiovascular disease was hyped in 2007 when this meta-analysis came out. I tried to apply some perspective but in no time the hype took on a life of its own.

One of the authors of the meta-analysis (Dr. Steve Nissen) didn't seem to mind. In fact, he threw a little fuel to the fire, saying in an interview that Avandia deaths would dwarf the carnage of 911. And his meta-analysis didn't even show a statistically significant increase in deaths attributable to Avandia.

The potential for macrovascular harm from older diabetes drugs had been known for decades but was never hyped in this manner. The screaming was so loud it was hard to have a nuanced discussion though I tried, here and in other posts.

Wednesday, November 27, 2013

Monday, November 25, 2013

Type of bundle branch block and incident risk of heart failure

From a report in Circulation: Heart Failure:
Methods and Results—Cox’s regression was used to evaluate hazard ratios with 95% confidence intervals for HF among 65 975 participants of the Women’s Health Initiative (WHI) study during an average follow-up of 14 years…
Compared with women with no BBB, LBBB, and intraventricular conduction defect were strong predictors of incident HF in multivariable-adjusted risk models (hazard ratio, 3.79; confidence interval, 2.95–4.87 for LBBB and hazard ratio, 3.53; confidence interval, 2.14–5.81 for intraventricular conduction defect). RBBB was not a significant predictor of incident HF in multivariable-adjusted risk model, but the combination of RBBB and left anterior fascicular block was a strong predictor (hazard ratio, 2.96; confidence interval, 1.77–4.93). QRS duration was an independent predictor of incident HF only in LBBB, with more pronounced risk at QRS greater than or equal to 140 ms than at less than 140 ms. QRS nondipolar voltage (RNDPV) was an independent predictor in both RBBB and LBBB and, in addition, in LBBB, QRS/STT angle and ST J-point depression in aVL were independent predictors.

Saturday, November 23, 2013

The Sunshine Act: What’s it all about?

Here’s a nice free full text summary in NEJM explaining its effects on physicians. The article mentions ways physicians can participate in the process and further the cause of transparency. If you really want to get on board with transparency here’s the Facebook challenge: next time you attend a drug company sponsored event, check in. Mention that you are attending a sponsored event and include a brief description of the food and beverages.

Friday, November 22, 2013

Prone ventilation in severe ARDS

Up until publication of this study in NEJM prone positioning was reserved as a rescue modality. This study however showed a robust improvement in mortality when prone ventilation was used selectively for patients defined physiologically as having severe disease.

Thursday, November 21, 2013

Fungal meningitis following epidural steroid injections

Here are two recent reports from NEJM about the outbreak, traced to a compounding pharmacy [1] [2].

Of interest:

61 deaths were reported.

Strokes, mainly posterior circulation territory, were reported as complications.

This was the largest outbreak of health care related infection ever reported in the US.

Two organisms, Aspergillus fumigatus and Exserohilum rostratum, were identified in clinical infections.

Fungal infections of the CNS may be prone to chronicity and relapse, so final outcomes remain unknown in many patients.

Wednesday, November 20, 2013

Can we prevent ARDS?

According to a recent review prevention is based on early recognition and management of risk factors. Consideration of certain risk factors suggests various preventive strategies, most of which are not based on high level evidence:

Low tidal volume mechanical ventilation
This is of proven benefit for patients with established ARDS who require invasive mechanical ventilation. What about mechanically ventilated patients who do not have ARDS? The review cites evidence that in such patients it is an effective strategy. This evidence has been accumulating for awhile and I summarized it back in 2010.

Prophylactic PEEP
Although “5 of PEEP” is almost a default setting for mechanically ventilated patients these days the evidence on whether it prevents lung injury is mixed.

Fluid management
Direct evidence is not available concerning fluid management as a preventive strategy. If the cutoff for defining ARDS is arbitrary and lung injury exists along a continuum, one might infer benefit based on findings in patients with established ARDS. It is well known that a conservative fluid strategy is beneficial in such patients.

Appropriate sepsis care
Sepsis is a well known precursor to ARDS. Although the particular outcome of ARDS has not been specifically examined, early application of the sepsis bundle is known to improve general outcomes. ARDS is sometimes a late consequence of sepsis. Halting the sepsis progression early might be a preventive measure.

Transfusion strategies
No such strategies have been studied in controlled trials for prevention of ARDS. However, given the increased recognition of transfusion associated lung injury (TRALI), a restrictive transfusion strategy, as is now generally recommended for hospitalized patients, is appealing.

Tuesday, November 19, 2013

Altitude related illness

The topic was recently reviewed in NEJM.

High altitude pulmonary edema, acute mountain sickness and high altitude cerebral edema were discussed. High altitude cerebral edema is a serious condition which can be fatal, and exists on a continuum with acute mountain sickness.

Monday, November 11, 2013

HbA1c, QTc and mortality in DM2 patients with foot ulcers

In this study A1c levels below 7.5 and long QT intervals were associated with increased mortality. There is a poorly understood association between lengthened QT interval and DM which I have cited in previous posts.

Sunday, November 10, 2013

Langerhans cell histiocytosis

This mysterious and somewhat rare condition was formerly given a variety of confusing names. Here is an update.

Saturday, November 09, 2013

Friday, November 08, 2013

Emerging echinocandin resistance in Candida glabrata

From a recent report:

Results. Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19–58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence.
Conclusions. Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.

Species based therapy of candida infections may no longer be enough.

Thursday, November 07, 2013

Novel (target specific) oral anticoagulants: pharmacokinetics and drug interactions

This post contains some more of the key points from Dr. Tracy Minichiello's talk at the recent UCSF Hospital Medicine conference along with additional material I've gathered including this review.

First a little background about CYP3A4 and P glycoprotein. CYP3A4 is an important enzyme affecting drug bioavailability and metabolism. Drugs (including the TSOACs) and food (notably grapefruit) may interact via CYP3A4. Unfortunately comprehensive lists of interacting drugs are difficult to find and popular consumer resources may not be updated concerning the TSOACs. I did find this article helpful (click on the pdf link for free full text). It is a bit dated but does contain a long list of applicable drugs. Given the lack of current and comprehensive references your best bet may be to use one of the on line interaction checkers such as the one available via UpToDate.

P glycoprotein is the other big player. P glycoprotein is an ATP-binding cassette (ABC) transporter which extrudes substances out of cells and thus plays a role in drug disposition and bioavailability. All three currently approved TSOACs are susceptible to interactions involving the protein. Again, because comprehensive lists of interacting drugs are not readily available the use of an interaction checker may be necessary. Some background can be found in this paper.

Below are a few of the basics about the kinetics of available TSOACs.

Routes of elimination:

Dabigatran (Pradaxa) 80% renal
Rivaroxaban (Xarelto) 30-60% renal (60% total but half of this is of an inactive metabolite).
Apixaban (Eliquis) 25% renal

Degree of protein binding:

Dabigatran (Pradaxa) 33% (HD effective for removal)
Rivaroxaban (Xarelto) 95% (HD ineffective for removal)
Apixaban (Eliquis) 87% (HD ineffective for removal)

Drug interactions:

Dabigatran (Pradaxa) Via P glycoprotein
Riaroxaban (Xarelto) Via P glycoprotein and CYP3A4
Apixaban (Eliquis) Via P glycoprotein and CYP3A4

Though focused on pulmonary embolism this review is also helpful concerning some of the general aspects of the pharmacokinetics and pharmacodynamics of TSOACs.

Tuesday, November 05, 2013

Novel oral anticoagulants

---which by the way are now referred to as the target specific oral anticoagulants (TOACs)---were the topic of the first talk at the UCSF Hospital Medicine course. Tracy Minichiello, MD, Professor of Medicine at UCSF, covered some pearls and practical aspects of using these agents.

Here I will provide a few basic points about the labeling from her talk along with some additional information from external links.

The agents approved in the US are dabigatran (Pradaxa), rivaroxaban (Xarelto) and Apixaban (Eliquis). All three are approved for non valvular atrial fibrillation. Xarelto has the additional approved indications of VTE prevention and treatment. Elimination is 80% renal for Pradaxa, 30-60% renal for Xarelto and 25% renal for Eliquis.

Renal labeling for Eliquis is unusual and applies only if one of two other characteristics is present:

age greater than or equal to 80 years
body weight less than or equal to 60 kg
serum creatinine greater than or equal to 1.5 mg/dL

No data are available for patients with clearance below 15 or on HD.

Renal labeling for Xarelto is problematic because it is complex (varying significantly based on which indication) and is not contained in its entirety in some readily available references (eg Micromedex and Rxlist). The creatinine clearance cutoff below which use is contraindicated is 30 for for VTE treatment and prevention and 15 for a fib. For VTE treatment or prevention no renal adjustment is called for within the allowable range of renal function though for VTE prevention (only) at clearance of 30-50 the labeling says “use with caution.” (Does that mean we throw caution to the wind for other indications?). For a fib with clearance of 15-50 reduction to 15 mg daily is called for.

Adjustment of Pradaxa to half dose (75mg bid) is recommended for clearance of 15-30. More aggressive renal adjustment recommendations apply if certain interacting drugs are administered. See product labeling for those details. As with Eliquis, no information is available for patients with clearance below 15 or on HD.

Labeling for interacting drugs as well as other practical aspects of the use of TSOAC drugs covered in Dr. Minichiello's talk will be discussed in subsequent posts.

At first glance the TSOACs look like “cleaner” drugs with greater ease of use as compared to warfarin. What I learned from Dr. Minichiello's talk and break out session is that this is not necessarily true despite some advantages. You need to know a great deal about the pharmacokinetics of these agents in order to use them confidently and competently.

Monday, November 04, 2013

The Mediterranean diet protects against CKD

I never cease to be amazed. From a recent report:

Results Compared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered.
Conclusions Adherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such a diet could improve outcomes (independent of other healthy lifestyles) in CKD patients.

Saturday, November 02, 2013

Hospital medicine CME

Today I'm in San Francisco having just completed UCSF's 17th Annual Hospital Medicine course. First a shout-out to Bob Wachter, course director, for putting together another great meeting. Offerings of this quality are getting harder to find because for the last decade they have been under attack by the CME thought police. The CME thought police operate under several wrong headed assumptions a few of which I'll mention here:

Industry sponsored CME is corrupt and can't be good. This meeting is one of many counter examples.

CME should not take place in a nice relaxing setting. Resort-based CME is now considered a no-no by many institutions which have discontinued their off campus activities.

CME is only worthwhile if it can be tied in a measurable way to physician behavior. And a close corollary..

Didactic CME should be abandoned because it cannot be linked directly to measurable outcomes. Though the benefits of traditional didactic CME are not as concrete as the thought police would like my own career long learning experience strongly convinces me of its value.

Many attendees Tweeted the conference. I was not among them. For me Tweets are a little too sound-bitey to do justice to the course content. But unlike the CME thought police I respect differences in learning needs among individuals and make no presumption about what style of information sharing is best for others. So if Tweets work for you search #UCSFMHP13 and find Tweets aplenty from the conference.  I may blog portions of the content once I have some down time if I'm still as pumped up and expansive as I am now.

Inverse relationship between length of stay and readmission rate for heart failure

From a report in Circulation: Heart Failure:

Patients treated in countries with longer lengths of stay for heart failure hospitalizations had significantly lower rates of readmission within 30 days of randomization. Findings were similar among sites in the United States, where each 1-day increase in the mean length of stay at the site level was independently associated with a lower risk of all-cause and heart failure readmission.

The authors cite the unintended consequences of DRGs:

Since 1984, when the current reimbursement model was introduced in the United States, there have been strong incentives to reduce lengths of stay to maximize hospital profitability. The consequent reduction in hospital lengths of stay has been accompanied by increases in postdischarge readmission rates,17 which may have resulted in greater overall costs among patients with heart failure.

Friday, November 01, 2013

Strategies associated with reduced heart failure readmissions

From a recent study:

Strategies that were associated with lower hospital RSRRs included the following: (1) partnering with community physicians or physician groups to reduce readmission (0.33% percentage point lower RSRRs; P=0.017), (2) partnering with local hospitals to reduce readmissions (0.34 percentage point; P=0.020), (3) having nurses responsible for medication reconciliation (0.18 percentage point; P=0.002), (4) arranging follow-up appointments before discharge (0.19 percentage point; P=0.037), (5) having a process in place to send all discharge paper or electronic summaries directly to the patient’s primary physician (0.21 percentage point; P=0.004), and (6) assigning staff to follow up on test results that return after the patient is discharged (0.26 percentage point; P=0.049).

Thursday, October 31, 2013

H7N9 influenza: are we close to a pandemic?

According to this analysis in BMC Medicine the human-to-human transmission efficiency is below the threshold. A decline in the growth of cases has followed closure of live bird markets.  

Wednesday, October 30, 2013

Combining esmolol and nor epi in septic shock?

Recently published in JAMA:

Importance  β-Blocker therapy may control heart rate and attenuate the deleterious effects of β-adrenergic receptor stimulation in septic shock. However, β-Blockers are not traditionally used for this condition and may worsen cardiovascular decompensation related through negative inotropic and hypotensive effects...
Results  Targeted heart rates were achieved in all patients in the esmolol group compared with those in the control group. The median AUC for heart rate during the first 96 hours was −28/min (IQR, −37 to −21) for the esmolol group vs −6/min (95% CI, −14 to 0) for the control group with a mean reduction of 18/min (P less than .001). For stroke volume index, the median AUC for esmolol was 4 mL/m2 (IQR, −1 to 10) vs 1 mL/m2 for the control group (IQR, −3 to 5; P = .02), whereas the left ventricular stroke work index for esmolol was 3 mL/m2 (IQR, 0 to 8) vs 1 mL/m2 for the control group (IQR, −2 to 5; P = .03). For arterial lactatemia, median AUC for esmolol was −0.1 mmol/L (IQR, −0.6 to 0.2) vs 0.1 mmol/L for the control group (IQR, −0.3 for 0.6; P = .007); for norepinephrine, −0.11 μg/kg/min (IQR, −0.46 to 0.02) for the esmolol group vs −0.01 μg/kg/min (IQR, −0.2 to 0.44) for the control group (P = .003). Fluid requirements were reduced in the esmolol group: median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h(IQR, 4038 to 4775) for the control group (P less than .001). We found no clinically relevant differences between groups in other cardiopulmonary variables nor in rescue therapy requirements. Twenty-eight day mortality was 49.4% in the esmolol group vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; P less than .001).
Conclusions and Relevance For patients in septic shock, open-label use of esmolol vs standard care was associated with reductions in heart rates to achieve target levels, without increased adverse events. The observed improvement in mortality and other secondary clinical outcomes warrants further investigation.

This is very promising but I'm not ready to try it at home, just yet. Yes, it does warrant further study.

More discussion at Medpage Today.

Tuesday, October 29, 2013

Beverage choice and the risk of kidney stones

From a recent paper:

Results The analysis involved 194,095 participants; over a median follow-up of more than 8 years, 4462 incident cases occurred. There was a 23% higher risk of developing kidney stones in the highest category of consumption of sugar-sweetened cola compared with the lowest category (P for trend=0.02) and a 33% higher risk of developing kidney stones for sugar-sweetened noncola (P for trend=0.003); there was a marginally significant higher risk of developing kidney stones for artificially sweetened noncola (P for trend=0.05). Also, there was an 18% higher risk for punch (P for trend=0.04) and lower risks of 26% for caffeinated coffee (P for trend less than 0.001), 16% for decaffeinated coffee (P for trend=0.01), 11% for tea (P for trend=0.02), 31%–33% for wine (P for trend less than 0.005), 41% for beer (P for trend less than 0.001), and 12% for orange juice (P for trend=0.004).
Conclusions Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk.

Monday, October 28, 2013

What's unhealthy about obesity?

Inflammation, mainly. This fascinating article discusses inflammation as a key determinant of unhealthy versus healthy obesity and its role in driving all the nasty components of the metabolic syndrome.

Sunday, October 27, 2013

H7N9 influenza: what we know so far

The Annals of Internal Medicine recently reviewed the topic.

Points made in the review:

The virus produces severe disease.

Population immunity is unlikely.

It appears to be sensitive to commonly available antiviral agents.

Human to human transmission potential is unknown.

Saturday, October 26, 2013

Hypertension in the ICU

This review discusses definitions of acute hypertensive syndromes, the relevant pathophysiology and treatment approaches.

Friday, October 25, 2013

The antibiotic development pipeline for gram negative infections: how's it going?

According to the recent report from IDSA (free full text) there's been some progress but not nearly enough. There are a few drugs in phase 3 trials but they do not address all the emerging threats.

Thursday, October 24, 2013

Antiarrhythmic drugs for resuscitation from cardiac arrest

A recent systematic review and meta-analysis took another look. New research has not changed what we've known for years:

Ten randomized controlled trials and seven observational trials were identified. Amiodarone (relative risk (RR), 0.82; 95% confidence interval (CI), 0.54 to 1.24), lidocaine (RR, 2.26; 95% CI, 0.93to 5.52), magnesium (RR, 0.82; 95% CI, 0.54 to 1.24) and nifekalant were not shown to improve the survival to hospital discharge compared with placebo, but amiodarone, lidocaine, and nifekalant were shown to be beneficial to initial resuscitation, assessed by the rate of return of spontaneous circulation and survival to hospital admission, with amiodarone being superior to lidocaine (RR, 1.28; 95% CI, 0.57 to 2.86) and nifekalant (RR, 0.50; 95% CI, 0.19 to 1.31). Bretylium and sotalol were not shown to be beneficial.