2010 was a good year for biomarkers in hospital medicine

St. Louis City Hospital

Are you using biomarkers for all they're worth in your hospitalized patients? Here's a summary of new developments this year.

Procalcitonin

Procalcitonin has been validated for several roles in guiding the use of antimicrobial therapy, and stands poised to bring the concept of antibiotic stewardship to a new level. The major barrier is its lack of availability in real time in many hospitals. It has recently been approved for use in the US. I linked to a paper reviewing today's use of procalcitonin, here.

BNP and pro-BNP

The precise role of natriuretic peptides in guiding heart failure management remains a subject of controversy.   But the most interesting developments this year were in the area of expanded uses of natriuretic peptide measurement outside the management of heart failure. Perhaps the best known of these is risk assessment in patients with pulmonary embolism, discussed in several papers this year and in previous years.

Two new papers were of special interest this year. One looked at the kinetics of pro-BNP in acute onset atrial fibrillation. In cases where the time of onset of a-fib is unclear measurement of pro-BNP may help. Another paper, which I discussed here, reported preliminary evidence that the use of pro-BNP combined with a clinical risk assessment tool in patients presenting with chest pain produced outcomes equivalent to the conventional strategy of “rule out” followed by stress testing.

Lactate

The role of lactate measurement to assess septic patients' candidacy for early goal directed therapy was validated several years ago. This year produced new information on expanded indications for lactate, particularly the measurement of serial levels in critically ill patients. Two papers addressed this issue, which I linked and summarized here.

Hyponatremia in 2010---new and noteworthy

St. Louis City Hospital

When patients are hospitalized with hyponatremia, either as the principal problem or an incidental finding, the hospitalist is immediately faced with several questions. Does the patient have acute hyponatremic encephalopathy or not? Should the serum sodium be raised? How much and how fast? What is the best strategy to avoid osmotic myelinolysis?

Several important papers were published this year which may help refine the approach to the evaluation and management of hyponatremia. For acute hyponatremic encephalopathy bolus therapy with 100 ml at a time of 3% saline is gaining popularity and has sound rationale (see here).

The past year saw increased published experience with the use of desmopressin to blunt the rise in serum sodium and decrease the risk of myelinolysis, either reactively in situations of threatened overcorrection or proactively as part of the initial treatment, at least in cases of very severe, e.g. “double digit” hyponatremia.

One paper this year emphasized the special hazard of hyponatremia accompanied by hypokalemia and reminded us that correction of hyponatremia, and possibly even overcorrection, may result merely from efforts at potassium repletion.

Finally, two papers addressed the etiologic diagnosis of hyponatremia, pointing out that clinical volume assessment is difficult and discussing some fine points in the evaluation of serum and urine chemistries.

What were the most important issues in hospital medicine in 2010?

St. Louis City Hospital

It's popular right about now to look at the year in review. For the field of hospital medicine I have traditionally posted a top ten list. Although I'm dropping the top ten format this year (it tends to be artificial) I'm preparing some posts for the next few days on what I think the most important developments were in 2010. Among those are updates in safety, biomarkers, mechanical ventilation, cardiac function in critical illness and resuscitation. Stay tuned and look for the hospital sketch above.   

What's going on with the National Health Service?

The health system Don Berwick is in love with is anything but patient centered, and on the verge of a total melt down from the sound of this article from the Daily Telegraph.


HT SHS


Bob Wachter, meanwhile, has a different take (essentially that the Brits accept it, more or less, due to their inherent trust in big government and the elites, in a way that could never be so in the US).

Hospitalist comanagement of neurosurgical patients: loved by all and value neutral

One of my ortho colleagues gently taunts: “You're supposed to be the smart doctor. I'm just a dumb bone cruncher.” But I'm just as dumb about all that bone crunching surgical stuff as he claims to be about internal medicine. And so betwixt us both the bases get covered. Or so we hope.


Even in the days of old one of my close surgical colleagues and I were doing comanagement, long before anyone coined the term.  We didn't have cardiologists in those days, so I selected patients for pacemaker implantation and he performed the implants.  He would say "You take care of the tachyarrhythmias, I'll take care of the bradyarrhythmias."


Those are not very good definitions of hospitalist comanagement but it's about as precise as it gets. Which is why it's very difficult to draw conclusions from research evidence.


A recent issue of the Archives of Internal Medicine has published findings from the comanagement experience on the neurosurgical service at UCSF:

Results  During the study period, 7596 patients were admitted to the neurosurgery service: 4203 (55.3%) before July 1, 2007, and 3393 (44.7%) after comanagement began. Of those admitted during the postimplementation period, 988 (29.1%) were comanaged. After implementation of comanagement, no differences were found in patient mortality rate, readmission, or length of stay. No consistent improvements were seen in patient satisfaction, but strong perceived improvements occurred in care quality reported by nurses and nonnurse health care professionals. In addition, we observed a reduction in hospital costs of $1439 per admission.

But the more I dig into the body of the paper the more confusing it gets. There were lower costs in the post-comanagement as opposed to the pre-comanagement period (of only borderline statistical significance) but when comanaged patients were compared directly with non-comanaged patients (raw data not displayed in the paper) the comanaged patients had higher costs. To confuse things further, the authors say these were adjusted outcomes but in the same sentence imply that the difference was due to lower complexity in the non-comanaged patients. (OK, I'm very tired after a difficult few days of comanaging patients myself, so I may have missed something here).


And what about value? According to Skeptical Scalpel, quoting from an interview of one of the authors, the reimbursement to the comanagement service by the hospital was substantial.


Bob Wachter, one of the authors of the paper, gives an insider's view of the comanagement effort here.

Blackberry not working? There's help.

HT SHS.

Clostridium difficile update

Scanning EM of C diff

This review (free full text) was recently published in Southern Medical Journal.

Many C diff reviews have been published in the last few years. This one emphasized several points not covered in previous reviews:

Community acquired C diff is a newly emerging problem. Many patients have no history of recent prior antibiotic usage and lack other traditional risk factors.

C diff can occur in the setting of inflammatory bowel disease. IBD, in fact, is listed as a risk factor for C diff.

Mild disease can evolve into severe disease during treatment.

Leukocytosis may precede GI symptoms, so unexplained leukocytosis developing in a hospitalized patient may be a red flag.

C diff may present as acute abdominal symptoms without diarrhea.

Toxin assays have a sensitivity of only around 70%. Two negative toxin assays in a row, however, are associated with a high negative predictive value.

First recurrences are treated with the regimen to which the patient initially responded unless the recurrence is with severe disease in an patient previously treated with mild disease.

Subsequent recurrences are more problematic. Tapering regimens of vancomycin, pulsed dosing of vancomycin, vancomycin combined with rifampin, or vancomycin followed by rifaximin have been described.

Because alcohol based hand sanitizing agents are not sporicidal, hand washing with soap and water is recommended when caring for such patients.

Review of cardiac amyloidosis

Free full text from JACC:

Although no single noninvasive test or abnormality is pathognomonic of cardiac amyloid, case-control studies indicate that echocardiographic evidence of left ventricular wall thickening, biatrial enlargement, and increased echogenicity in conjunction with reduced electrocardiographic voltages is strongly suggestive of cardiac amyloidosis.

Via The Bottom Line.

Osteoporosis review

A very good review on evaluation, prevention and management.

Sensitivity of CT in subarachnoid hemorrhage?

It goes down about 10% per day after rupture.


Via The Bottom Line.

Loop diuretics for acute management of hypercalcemia?

Tradition based, not evidence based.

Another STEMI equivalent that's not technically a STEMI: posterior infarction

Some case examples with pointers on how to differentiate from ischemic ST depressions of “NSTEMI” from Dr. Smith's blog.

When are prophylactic anticonvulsants indicated?

A brief discussion at The Bottom Line.

Another SVT mimic

I recently mentioned 1:2 AV conduction. Here's another one: interpolated junctional extrasystoles. The authors considered 1:2 conduction in each case but it turned out to be junctional firing interpolated between sinus beats, leaving the sinus mechanism undisturbed, behaving as a parasystolic focus. An abrupt, exact doubling of the ventricular rate provides a clue.

Pylephlebitis as an unrecognized cause of septic shock

Case report in the Southern Medical Journal and brief discussion at The Bottom Line.

Why do hospitalists and IM house staff order PPIs?

Often for the wrong reasons in this study:

Sixty-nine percent of physicians reported prescribing SUP to greater than or equal to 25% of patients. In multivariable analyses, the following factors were associated with higher level of prescribing (greater than or equal to 25%) of SUP: fear of gastrointestinal bleeding (OR = 2.7, 95% CI 1.07, 7.28) and of the legal repercussions of not prescribing SUP (OR = 3.02, 95% CI 1.07, 8.56), whereas knowledge of SUP indications (OR = 0.39, 95% CI 0.20, 0.74) and concern about side effects (OR = 0.24, 95% CI 0.09, 0.61) were associated with low prescribing behavior. Level of training was not associated with prescribing rate. Less than half of respondents were able to identify a single side effect of proton pump inhibitor therapy.

ER-hopping drives up costs

I'm getting tired of going to Regional. Let's try St. Joe's tonight!


For many patients hospitals are like restaurants.


A new study in the Archives of Internal Medicine showed that such hospital-hopping is common and it drives up costs. And there's reason to believe it's unsafe. You can take for granted that medication errors will increase, and in this study patients who went to multiple ERs were more likely to be hospitalized overnight.


Occasionally a trip to a different hospital is unavoidable but in general, if you want to do your part for the medical commons and make your hospital visit a safer experience don't hospital-hop!


Via Grunt Doc.

Pharmacovigilance

Southern Medical Journal has published a two part series on adverse drug reactions, available as free full text here and here.

Acute RV failure understudied and underappreciated

Here's a review from JACC. Full text available via Medscape here. We usually think of pulmonary embolism and RV infarct but there are many other causes. Management is not as straightforward as you might think, and goals of therapy may conflict with those of coexisting disease processes in the critically ill patient.

In which Thomas Stossel smacks down the arguments against physician-industry collaboration

Via Med Policy.

Update on short QT syndrome

This condition has gotten a lot of attention in the last few years, but as far as we know it's rare.

Interview with David Sackett, one of the EBM movement's founders

Although EBM (at least in its popular application) cannot evaluate the unscientific claims of CAM (you need SBM to do that) it is useful for evaluation of most of the clinical questions that arise in mainstream practice. And I wonder what David Sackett would say if asked about EBM's blind spot. Right off the bat in the interview below he swats away some of the concerns of EBM's detractors by saying that first and foremost it's about the patient and clinical expertise. It's these elements that must be combined with the “best external evidence.”


His review of EBM's history is interesting. The movement had its antecedents in the 1960s with the birth of the discipline of clinical epidemiology at McMaster University.

“The core of her appeal is her deep love for freedom”

Anne C. Heller on Ayn Rand.



Via Instapundit.

What do docs in the rank and file think of health care reform?

Here are some survey results released by the Physicians' Foundation:

• The majority of physicians (60%) said health reform will compel them to close or significantly restrict their practices to certain categories of patients. Of these, 93% said they will be forced to close or significantly restrict their practices to Medicaid patients, while 87% said they would be forced to close or significantly restrict their practices to Medicare patients.

• 40% of physicians said they would drop out of patient care in the next one to three years, either by retiring, seeking a non-clinical job within healthcare, or by seeking a non-healthcare related job.

• The majority of physicians (59%) said health reform will cause them to spend less time with patients.

• While over half of physicians said health reform will cause patient volumes in their practices to increase, 69% said they no longer have the time or resources to see additional patients in their practices while still maintaining quality of care.

Via Drugwonks.

Acupuncture: hard core woo

As long as we're on the subject, read Steve Novella's recent take down at Science Based Medicine.

EBM's blind spot

The Cochrane Collaboration, arguably the exemplar of EBM, is a good place to illustrate EBM's blind spot, a phrase used by Kimball Atwood at Science Based Medicine in his description of EBM's inability to evaluate implausible health claims in the arena of complementary and alternative medicine (CAM).


Here's the listing of Cochrane CAM reviews. Few if any of the treatments covered in these reviews have enough scientific plausibility or prior evidence to warrant a share of our research funds, let alone a systematic review. But the Cochrane reviewers refuse to call a nutty idea a nutty idea. Submit the wackiest fairy dust treatment you can think of to the folks at Cochrane for review. The worst they're liable to say about it is that there's not enough evidence out there to know whether or not it's a valid treatment, so research (or more research) is warranted.


So here are a few examples.


Homeopathic treatment for influenza. Promising, say the reviewers, although more research needed.


Homeopathic treatment for asthma. RCTs needed, of course.


Acupuncture to enhance in vitro fertilization. It works, declare the Cochrane reviewers. But, they say, more research is needed.


Acupuncture for acute stroke (and the mechanism doesn't seem to matter to the reviewers, evidenced by the fact that they lumped hemorrhagic and ischemic strokes, conditions with entirely different mechanisms, together). The reviewers are not sure whether it works and recommend larger and more “methodologically sound” studies.


Acupuncture for vascular dementia. RCTs are urgently needed, say the reviewers!


EBM has become an enabler of pseudoscience, and that's its grand failure. Atwood explains why in the above link and multiple other posts linked there, and I summarize the reasons briefly here. That's the fatal flaw Richard Smith and DB didn't mention in their otherwise informative and accurate criticisms of EBM.

Rabies Milwaukee protocol

The protocol and related resources can be accessed here. The protocol is complicated and counterintuitive. It relies on principles which differ from those of general critical illness. If faced with a potential case, familiarity with the protocol will help in deciding whether you have the resources to implement it in your own hospital or whether the patient should be shipped.


And here's a recent report in MMWR of a case reported in Virginia, following international travel.

Ictal asystole---when the brain stops the heart

It's an experiment of nature in the field of brain-heart medicine. It can result from a seizure in a patient with normal heart function. Via PACE.

Work hour limits shouldn't be just for residents

Old farts need rest too, says Bob Wachter in a guest post at Kevin MD, citing a recent study of radiologists (both residents and attendings) showing deteriorating accuracy with increased fatigue.


Resident fatigue was the initial focus of the patient safety movement and even predated the IOM report by over a decade, as a result of the Libby Zion case. Have initiatives to address physician fatigue improved patient outcomes? Although we can't answer that question with data I'm sure the anecdotal evidence would be impressive, as any of us who trained in the pre-Zion era could attest.


I trained in the days of every third and every other night call when night float was not part of the lexicon. On your call day you went to work early and worked 36 hours straight. Maybe longer. You got home late on your post call day so your spouse could watch you sleep. You occasionally fell asleep while interviewing your patient---typically your sixth admission of the night, at 3 AM. The next day a malignant attending might chide you on the sloppy appearance of your hand written H and P. You didn't dare point out that you were just too tired. Too tired? they might ask incredulously. These anecdotes are comical. But what about mistakes with consequences for patients? How many of us really want to know?


Well, for residents, at least, things have changed. We've gone to the opposite extreme, perhaps even too far. The latest proposal is to require naps. It seemed silly to me in the first grade. I would welcome it now.


If efforts to reduce resident fatigue haven't meaningfully impacted patient safety maybe it's because of the unintended consequences or because no attempt has been made to address the equally important issue of fatigue on the part of practicing physicians. But as Bob points out this would be next to impossible to implement for those who practice in the eat-what-you-kill world of fee for service reimbursement.


So (and my conflict of interest here should be obvious) maybe hospitalists should be the next group to target. After all, many of them are treated as advanced residents anyway, and most are not paid by RVUs. For that to gain traction organized hospital medicine would need to set a standard. This might be a worthwhile project for the Society of Hospital Medicine.

Whither evidence based medicine?

It's been 18 years now since evidence based medicine (EBM) became a catch phrase. Richard Smith, a former editor for BMJ, reflects on the distortions and unintended consequences of EBM as a “movement” in this month's The Scientist.


David Sackett and others once tried, in their classic BMJ editorial, to explain what EBM is and what it isn't. But, 18 years later, among academics, policy makers and practicing physicians alike it seems anything but clear what it is and what it isn't. There is a pure notion of EBM out there somewhere, perhaps best stated in the opening sentence of the Sackett editorial---“It's about integrating individual clinical expertise and the best external evidence.” But in real world application it's all over the place as Smith explains.


That's why it's folly to suppose that some central authority can dictate “what works and what doesn't work” for every patient and somehow homogenize the Dartmouth Atlas maps by bringing doctors into “compliance with EBM.”


More from DB's Med Rants.

Hand washing compliance: real quality or just another performance metric?

First a disclaimer. I am a strong proponent of hand hygiene. I strive to be 100% compliant where I work. But the skeptical side of me sees flaws in the hand hygiene dogma. Tracking hand cleaning rates as a performance metric (not a JC or CMS measure yet but being done at many institutions) may have unintended consequences. Moreover, the claim that hand washing keeps hospitalized patients safe from infections is simply not true. Allow me to explain. But first watch this video on hand hygiene at Vanderbilt, a leader in quality and safety.



It's clear the folks at Vanderbilt are passionate about hand hygiene but how effective is the measure, really? Watch the video closely and keep in mind evidence cited by the CDC in its guidelines that a 15 second hand wash is needed, as well as evidence that pathogens can be transmitted via the stethoscope. The stethoscope, perhaps more than the hands, is a major point of physical contact with the patient.


None of the people seen on this video cleaned their stethoscopes. And while it was difficult to tell how long they took to wash their hands it appeared to be well under 15 seconds in most instances.


Making the rate of hand washing the sole metric (91% at Vandy as reported in this video) may distract attention from equally or more important measures such as the length of the hand washing activity and the rate of stethoscope cleaning.

Just about the last place I expected to find quackademic medicine

---was Vanderbilt University Medical Center. Quackademic medicine goes against Vandy's traditions. VUMC was a leader in the biomedical sciences. It was always a place where new ideas were welcome but where nutty ideas were just nutty ideas. I was aware that woo got its foot in the door of VUMC a year or so ago with the opening of the Center for Integrative Health. At the time though I thought it was mainly soft woo. Then the other day I found this:



Early in the video I was mildly encouraged that at least scientific plausibility was preserved with the mention of endorphin and serotonin release but about 1:39 in when he started talking about blocked chi it was all over. This is pure woo. If it can find a place at Vanderbilt it can find a place anywhere. The infiltration is nearly complete.

Rescue therapies for severe ARDS

Severe ARDS can be defined in various ways, usually by the lung injury score. In general it means you can't ventilate the patient with reasonable airway pressures and fractions of inspired oxygen.


Rescue therapies are modalities considered unproven in that they haven't been validated by high level evidence. As measures of last resort for the patient who cannot be managed by other means, however, they may offer the only hope for survival. Rescue therapies were reviewed in a recent issue of Critical Care Medicine and include recruitment maneuvers, high PEEP, high frequency oscillation, inhaled nitric oxide, prone positioning, corticosteroids and extracorporeal life support.

Anxiety and COPD outcomes

From Thorax:

Results COPD was associated with a greater risk of anxiety in multivariable analysis (OR 1.85; 95% CI 1.072 to 3.18). Among patients with COPD, anxiety was related to poorer health outcomes including worse submaximal exercise performance (less distance walked during the 6-min walk test: −66.3 feet for anxious vs non-anxious groups; 95% CI −127.3 to −5.36) and a greater risk of self-reported functional limitations (OR 2.41; 95% CI 1.71 to 3.41). Subjects with COPD with anxiety had a higher longitudinal risk of COPD exacerbation in Cox proportional hazards analysis after controlling for covariates (HR 1.39; 95% CI 1.007 to 1.90).

I don't have the full text of this paper, and I wonder if they controlled for continued smoking. Nicotine is a powerful anxiolytic for some COPD patients.


Via Clinical Cases and Images.

"It is not the effect on individuals that is presently at issue -- it is the authority of Congress to compel anyone to purchase health insurance"

---said a federal judge today in a ruling upholding Virginia's challenge to Obamacare.

Right ventricular infarction---clues from the standard 12 lead

This electrocardiogram was presented in a case discussion at the Prehospital 12-Lead ECG blog. This patient had changes of acute inferior STEMI. Generally, right sided precordial leads are used to diagnose RV MI. However, clues suggesting the diagnosis are present in this standard 12 lead, one being the minimal ST elevation in lead V1, the other being the fact that the greatest magnitude of ST elevation occurs in lead III, the inferior lead which most reflects changes in the right ventricle.

In the treatment of obesity it's not just diet and exercise

Sleep may be the missing ingredient.

Hematologic toxicity of linezolid

This study was based on a medical record review from an academic VA medical center:

Patients. Four hundred forty-four patients (mean age 63.7 yrs) who received 544 courses of linezolid from 2004–2007.

Measurements and Main Results

The frequencies of grade 1–2 and grade 3–4 thrombocytopenia were 7.6% and 5.2%, respectively. Grade 3–4 anemia developed in 18.8% of courses; each of the patients had baseline grade 1–2 anemia. Linezolid was discontinued because of toxicity in 35 (6.4%) of the 544 courses. Independent variables associated with grade 3–4 thrombocytopenia included a baseline hemoglobin level of less than 10.5 g/dl, presence of immunosuppression, and a baseline platelet count of 50–99.9 × 103/mm3. Independent variables associated with development of grade 3–4 anemia included presence of a cardiovascular condition, urologic condition, immunosuppression, and a baseline platelet count of 50–99.9 × 103/mm3. Other toxicities reported with linezolid included diarrhea (6.6% of courses), followed by nausea (4.4%) and vomiting (4.0%).

Conclusion. The overall rates of thrombocytopenia and anemia for patients receiving linezolid were found to be higher than those in phase III clinical trials. 

Evaluation of the patient with hypokalemia---a systematic approach

This review is part of the American Journal of Kidney Disease Acid-base and electrolyte teaching case series.

Does early goal directed therapy matter? A point-counterpoint

In response to a study published in Chest showing a disturbing low rate of adherence to early goal directed therapy (EGDT) at a large medical center, editorials expressing opposing views were presented in the same issue.


First Dr. Emanuel Rivers, principal investigator in the landmark EGDT study published almost a decade ago, defended the protocol. He cited the very strong basic science rationale that had been developed long before the EGDT trial. He also noted, as I have many times before in this blog, the many studies over the ensuing years after the trial that replicated its findings.


The counterpoint editorial was written by Dr. Gary Schmidt from the pulmonary-critical care section at the University of Iowa. His was largely and argumentum ad populum: adherence to EGDT is low; this must reflect informed skepticism; therefore EGDT is not validated. He did point out evidence that lactate guided therapy may be a surrogate for serial measurement of ScvO2. At least one study, however, found that lactate levels were complementary to the measurement of ScvO2. Finally, he noted three trials in progress which are examining various components of EGDT:

These include the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial (1,600 subjects), the Protocolized Care for Early Septic Shock (ProCESS) trial centered in Pittsburgh (1,935 subjects), and the Protocolised Management of Sepsis (ProMISe) trial in the United Kingdom (1,260 subjects).

The results of multiple studies which replicate Rivers' original findings are compelling and I doubt that these three trials will negate EGDT in any way. More likely, by examining individual components of EGDT they will provide better understanding and insight, and perhaps some tweaks that will refine early hemodynamic resuscitation of septic patients.


Dr. Rivers offered a rebuttal in which he questioned the equipoise of continued trials. Dr. Schmidt countered once again.

Combination antibiotics in early septic shock---synergistic effect?

In hospital medicine there exists a dialectical tension between the idea of “antimicrobial stewardship,” which encourages restricted use of antibiotics, and that of “adequately broad spectrum therapy” in which combinations of antibiotics are advocated for a variety of reasons.


The best discussion I've found on the purported reasons for combinations of antibiotics (some of which are better clinically validated than others) is in Mandell's ID textbook, Part I Chapter 18. Reasons for combination therapy include coverage of the likely spectrum when the pathogen and/or its antimicrobial sensitivity is unknown. The most time honored and clinically accepted example of this is meningitis. Sepsis and pneumonia are emerging as increasingly important examples in this category, given recent data that mortality is reduced when the spectrum is covered at the initiation of therapy as opposed to adding drugs later in the course as microbiologic data become available. (Shoot first, ask questions later). Another reason for combination therapy is prevention of emergent resistance. The best validated example is treatment of tuberculosis. A third reason is antimicrobial synergy. The most universally accepted example of this is the treatment of enterococcal endocarditis.


So the title of an article in the September issue of Critical Care Medicine is a little deceiving: Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: A propensity-matched analysis. My first reaction was that this is something we already knew based on the reason cited above. But that's not what this study was about. It compared monotherapy with an agent to which the offending pathogen was proven to be susceptible to double coverage by agents having different mechanisms of action, to which the pathogen was susceptible. From the paper:

Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with β-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p less than .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26];p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days.

So now there are two reasons to use combination antibiotic therapy with the initiation of treatment of septic shock: adequacy of coverage and synergy.


A related editorial discussed general issues related to combination antibiotic therapy in a variety of settings. The editorial cites a lot of data and deserves a careful read.

Upper extremity DVT secondary to PICC insertion

The risk was about 3% in this study.

Renal tubular function

This is from the American Journal of Kidney Disease Core Curriculum series. Free full text. Not light reading.

Gurgling and hospital acquired pneumonia

Gurgling during speech or quiet breathing noted at any time during hospitalization was a powerful predictor in this study.

The myth of 98,000 patients

It's been just over a decade since the Institute of Medicine (IOM) dropped a bomb with the publication of its patient safety report To Err is Human. Many believe the report to be a scholarly scientific work. After all, the IOM is a subsidiary of the National Academy of Sciences. In reality it was a massive publicity stunt. Head on over and check out my guest post at Kevin MD (and the interesting comment thread there) where I argue that the report may have done more harm than good for the cause of patient safety.

Pneumococcal vaccination for adults: Is it time to switch?

To the conjugate vaccine, that is, especially now that the 13-valent vaccine is available. It is much more effective in preventing pneumococcal disease than its weak sister the polysaccharide vaccine, whose major role is the enhancement of hospital report cards. If you really want to impact pneumococcal disease what should you do? Give the conjugate vaccine off label? A recent article in Chest discusses the ins and outs.

New appropriateness criteria for cardiac CT

These are just out. Free full text. Included are criteria for both CTA and cardiac calcium scoring.

Emergency treatment of COPD: high flow oxygen and mortality

A recent BMJ paper reported:

Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting...

Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.

In their discussion section the authors concluded:

However, resources for an aggressive campaign of education will still be needed to change the “more is better” oxygen culture that may ignore the potential dangers of hyperoxia.

The more is better oxygen culture may be driven in part by overconfidence in pulse oximetry. COPD patients who are decompensated may have respiratory acidosis which shifts the oxy-hemoglobin dissociation curve to the right due to the Bohr effect. This causes hemoglobin to unload oxygen to tissues more readily, resulting in a lower saturation for a given PO2. Knee jerk reactions to such low saturations, however well intended, may have adverse consequences.

Incidence of Takotsubo cardiomyopathy peaks on Monday

Via the American Journal of Emergency Medicine.

Initial assessment and treatment of severe asthma

Tips from the Medscape Viewpoints series.

Antiplatelet therapy after intracerebral hemorrhage

Patients who have recovered from ICH may have indications for antiplatelet therapy. How often is this done? Is it safe, weeks or months later? These questions were addressed in a recent study published in Stroke.

Results—There were 417 ICH patients who survived to discharge. Of these, 120 patients were prescribed subsequent antiplatelet medicines (28.8%). The median time from discharge to antiplatelet use was 14.8 months (range, 2 days–7.5 years). Among all survivors, there were 14 recurrent ICH (rate, 9.7 per 1000 patient-years; 95% confidence interval [CI], 5.3–16.4), 29 subsequent ischemic strokes (rate, 20.6; 95% CI, 13.8–29.6), and 40 subsequent ischemic strokes or myocardial infarctions (rate, 28.7; 95% CI, 20.5–39.0). Hazard ratios associated with antiplatelet exposure were 1.07 (95% CI, 0.24–4.84) for recurrent ICH, 0.23 (95% CI, 0.03–1.68) for ischemic stroke, and 0.72 (95% CI, 0.25–2.02) for ischemic strokes or myocardial infarction.

Conclusions—Antiplatelet prescribing was common after ICH. Subsequent ischemic strokes or myocardial infarctions were more common than recurrent ICH. Antiplatelet prescribing did not appear to have a clinically significant impact on outcomes measured. Despite being contraindicated, antiplatelet use wasnot a major hazard for recurrent ICH.

The risk of recurrent VTE after stopping therapy

---varies according to whether there was a transient risk factor or not, and by the nature of the transient risk factor. From a new study in the Archives of Internal Medicine:

Annualized recurrence rates were calculated and pooled across studies. At 24 months, the rate of recurrence was 3.3% per patient-year (11 studies, 2268 patients) for all patients with a transient risk factor, 0.7% per patient-year (3 studies, 248 patients) in the subgroup with a surgical factor, and 4.2% per patient-year (3 studies, 509 patients) in the subgroup with a nonsurgical factor. In the same studies, the rate of recurrence after unprovoked VTE was 7.4% per patient-year. The rate ratio for a nonsurgical compared with a surgical factor was 3.0 and for unprovoked thrombosis compared with a nonsurgical factor was 1.8 at 24 months.

Conclusions  The risk of recurrence is low if VTE is provoked by surgery, intermediate if provoked by a nonsurgical risk factor, and high if unprovoked. These risks affect whether patients with VTE should undergo short-term vs indefinite treatment.

Can the patient fall in the hospital really be a never event?

Although it's been administratively defined as a never event and hence a “medical error” the premise has never been based on evidence. In the latest study an intensive process improvement tool reduced falls only modestly. Patients still fell.

TZDs in diabetes: risks, benefits, practical aspects of use

A Medscape video presentation.

Wide anion gap acidosis in acetaminophen overdose

I've recently mentioned other renal complications of acetaminophen ingestion: wide gap acidosis in therapeutic use and AKI with overdose. Now a paper in the American Journal of Emergency Medicine describes wide gap acidosis in overdose. It was seen in 41% of patients in their series, occurred early in the course, resolved in a day or so and did not predict outcome. These patients tended to have elevated lactate levels and the mechanism may differ from that of wide gap acidosis associated with therapeutic use.

STEMI changes can be fleeting

Here one minute, gone the next, as illustrated by this post from Dr. Smith's blog. It's just one example of why the current classification of MI into STEMI and NSTEMI has poor pathologic and clinical correlation.

Blue journal podcasts

This is the podcast archive from the American Journal of Respiratory and Critical Care Medicine. Access is free.

New data regarding the effect of the hospitalist model of care on length of stay

Although it has been widely believed that the hospitalist model of care reduces hospital length of stay one of the largest and highest quality studies comparing hospitalist and non-hospitalist care, which showed no differences in utilization, was suppressed and not included in any of several systematic reviews on the subject. Thus, up to now, the data have been mixed and the overall effect of hospitalist care was not known.

But a newly published study of a large Medicare database tips the balance of evidence in favor of the hospitalist model. It showed not only a reduced length of stay but an increase in the magnitude of the effect over time through 2006:

RESULTS: In multivariable analyses controlling for patient and hospital characteristics, differences in LOS associated with hospitalist care increased from 0.02 fewer days in 2001/02 to 0.22 days in 2003/04 to 0.35 days in 2005/06. For 2006 admissions, differences in LOS were greater in older patients and patients with a higher diagnosis-related group (DRG) weight. The differences were three times as great for medical as for surgical DRGs, with greater differences in LOS at nonprofit than for-profit hospitals and at community than teaching hospitals.

Boosters of the movement have been making this claim for years. Only now do they have the weight of evidence behind that claim.

Free full text at Medscape.

In which a New York Times columnist

---makes fun of Republican fears of rationing, then criticizes Arizona for rationing. So is she furrit or aginnit?


More from Wesley Smith.

Session at U.N. climate control convention opened with prayer to the Mayan Moon Goddess

No, I'm not making this up. Via Secondhand Smoke.

Practical aspects of using dabigatran

A Medscape video presentation.

Sleep apnea---what the hospitalist needs to know

This article in Today's Hospitalist is a compilation of links to primary literature and pearls from HM 2010 sessions.

Formulating clinical questions and searching with PubMed

With the ready availability of easy to use secondary sources like UptoDate is PubMed searching becoming a lost art?


Apparently not for the IM residents at NYU. Here's a nice summary.

Renal effects of bactrim

1) It inhibits tubular secretion of creatinine. This results in a very mild rise in creatinine shortly after the beginning of treatment. There's no associated rise in the GFR. This is a benign condition.
2) Interstitial nephritis.
3) Hyperkalemia. It's an ENac inhibitor and this can have consequences, particularly in the elderly.


Via Renal Fellow Network.

The 2009 influenza pandemic---is it over?

Probably, according to the speaker at NYU Internal Medicine Grand Rounds recently, as reported in the Clinical Correlations blog. Some novel 2009 pandemic flu is still around alongside this year's seasonal H3N2 strain. All appear to be sensitive to  oseltamivir and zanamivir. The pre-pandemic seasonal H1N1from last year, which was resistant, is gone for now.

Emergency uses of glucagon

---are covered in two blog posts (here and here) from My Variables Only Have 6 Letters.

You blog, maybe you tweet

---but do you TILT?


TILT was created by the originator of the TRIP database. It takes social networking to the next level. Users can maintain an on line learning log, sort of a portfolio, and share it with others.


It's all explained here.

The safety of statin drugs in patients with abnormal liver function tests---the GREACE study

A post-hoc analysis of the GREACE study, published in Lancet, looked at the use of atorvastatin in patients with abnormal liver function tests. These patients were believed to have non alcoholic fatty liver disease (NAFLD). The study revealed findings in line with previous reports suggesting that statin drugs are safe in patients with elevated transaminases, at least those who do not have acute or symptomatic liver disease. But there was more. The patients with abnormal liver tests experienced a greater reduction in cardiovascular events attributable to atorvastatin than those with normal liver tests. Finally, patients with abnormal liver tests treated with atorvastatin had improvement in liver function whereas those not treated had worsening.


A related blog post containing the Lancet press release can be found here.

Propofol infusion syndrome

The propofol infusion syndrome was discussed at Nephron Power along with some links. I found helpful reviews here, here, here and here.


Because the syndrome has a high mortality even after appropriate treatment is initiated, early recognition should be helpful. Early red flags include escalating pressor requirements (a situation which might be easily overlooked since propofol infusion syndrome often develops in patients who are critically ill and already have fluctuating pressor requirements), hypertriglyceridemia and elevated CK. Two of the reviews mentioned the occasional development of new ECG abnormalities resembling the Brugada pattern.


Management consists of stopping propofol and general supportive care. There's nothing very specific about the supportive care except a suggestion that carbohydrate deprivation should be avoided, since patients with propofol infusion syndrome seem to have a problem with beta oxidation of fatty acids.

Lithium intoxication

This topic was briefly discussed in a post at Renal Fellow Network. The principal question in management is often when to resort to emergency dialysis. The answer is generally sooner rather than later, particularly in chronic or acute on chronic toxicity. Ultimately the nephrologists will need to make that decision, and it's wise to get them involved early.


It bears mention that there is a syndrome of irreversible neurotoxicity.

No respect, no respect at all for hospitalists

Image source: Wikipedia.
Creative Commons license 3.0.
Attribution:  Jim Accordino

It's not that they aren't liked. Referring docs and hospital staff love them. But as DB pointed out in one of his recent posts, hospitlaists are increasingly being regarded as advanced residents. It wasn't always that way. At the inception of the movement hospitalists were appreciated mainly for their clinical expertise in the uniquely complex aspects of the care of very ill inpatients. At the time the name of their professional organization, the National Association of Inpatient Physicians (NAIP) better reflected that. Since then clinical expertise has been devalued as hospitalists have increasingly been viewed as business solutions and providers to off-load the clerical work and rounding duties from other services. As hospital medicine has devolved into the Swiss Army knife model it has become a mile wide and an inch deep. The Society of Hospital Medicine has, unfortunately, pushed the field in this direction.

I'm sure that in his travels and speaking engagements DB interacts with a large cross section of hospitalists. One gets the sense from his post that hospital medicine is becoming less professionally satisfying for many of them.

Neuronotes

Nifty animations and more.

What is osmotic nephrosis?

Osmotic nephrosis is the histopathologic counterpart of the syndrome known as colloid-induced kidney injury. It can be caused by a number of intravenous infusions commonly used in clinical medicine. Referring to an originally purported mechanism (osmotic injury) subsequently refuted, osmotic nephrosis is a misnomer. The actual mechanism (to an oversimplification) is the formation vacuoles containing the offending substance, in proximal tubular cells, via pinocytosis. Known causative agents include mannitol, IVIG and hydroxyethyl starch.


Excellent reviews can be found here and here. The first review addresses mainly the histopathologic changes and mechanisms of injury. The second review is relevant to the colloid versus crystalloid debate because it points out the potential renal toxicity of some colloid preparations.


Via Nephron Power.

Novel recreational drugs

They're coming out so fast no one can reasonably expect to keep up. Here's a review of three of them with links to some drug culture resources for updates.