Thursday, November 20, 2014

Do doctors find MOC helpful? Is it important to patients?

Not according to this survey.

Severity assessment in pulmonary embolism: a need for consistency

As it does for many conditions, severity assessment of pulmonary embolism guides treatment. Severity assessment for PE is more important than ever these days because treatment options have multiplied. There are now many more decision points than we had just a few years ago. Now under discussion, for example, is the question of which patients can be discharged early or even undergo the entirety of their treatment as outpatients. The approval of target specific oral anticoagulants adds another decision point. Which patients with PE are candidates for those agents? Recent discussions have asked the question of whether there exists a subset of patients with acute PE who don't need to be treated at all. A clinical trial now in progress seeks to address that question. The question regarding how long to anticoagulate patients for secondary prevention is not as open and shut as it was just a few years ago. This is illustrated by a reading of the most recent ACCP guidelines. The same is true regarding indications for IVC filters. Meanwhile the debate about selection of patients for thrombolytic therapy rages on and has recently been complicated by promising studies looking at half dose thrombolytic therapy for a variety of patients with pulmonary embolism.

For us to make sense of all the new evidence and treatment options severity classification becomes important. The problem is this area is evolving too and has become inconsistent across the published literature. I'm going to be blogging about some of the new treatment options in the near future. But in order to have a meaningful discussion it is first important to define the terms of severity classification. What follows is my attempt to review some of the history of PE classification and outline the topic as it stands now, however confusing.

Back in the day it was pretty simple. The binary decision was whether to treat conventionally (with unfractionated or low molecular weight heparin) or to use thrombolytic therapy. It was based on whether the PE was associated with normal blood pressure or hypotension respectively. PE with hypotension correlated with obliteration of 50% or more of the activity on radionuclide perfusion scanning, which was an ancillary criterion. There followed a rising awareness of patients who were normotensive but had a large clot burden and evidence of acute right ventricular dysfunction as measured by biomarkers and/or imaging which consisted usually of echocardiograhy as well, in some centers, as ascertainment of the ratio of right ventricular to left ventricular diameter on CT angiography. With the addition of this intermediate category we then had 3 categories which became known as massive, submassive and hemodynamically normal.

Treatment discussions regarding pulmonary embolism have centered around this classification. For massive PE there has been a fairly strong consensus in favor of thrombolytic therapy in the absence of contraindications. Submassive PEs are the subject of controversy with divided opinion on whether to treat with thrombolysis or conventional heparin therapy with the weight of opinion favoring the latter. Hemodynamically uncomplicated PEs according to the recent thinking are those that could be treated with conventional anticoagulation and considered for early discharge or even outpatient treatment.

With the publication of recent papers suggesting yet another treatment method, half dose thrombolytic in conjunction with anticoagulation, the discussion has been complicated further because these papers have used yet another classification, which stratifies pulmonary emboli into severe, moderate and (by implication) mild forms. The problem is, this new classification does not translate well into the traditional one because it uses criteria (mainly anatomic) that are not analogous. This is illustrated by the MOPETT trial and the more recent drip, dose and discharge (DDD) paper. Here are the definitions form the DDD paper:

Moderate PE was regarded as presence of symptoms plus objective evidence of PE, defined as 70% involvement of a pulmonary artery or 2 lobar or 4 segmental branches plus hemodynamic stability. Severe PE was defined as systolic blood pressure less than of equal to100 mm Hg plus all other features of moderate PE; saddle pulmonary embolism; or involvement of greater than 70% of the main pulmonary artery (PA) with thrombus, irrespective of blood pressure.

MOPETT did not define severe PE because those patients were not studied. The definition of moderate PE was along the same lines as in DDD with a slight variation:

“Moderate” PE was defined as the presence of signs and symptoms of PE plus computed tomographic pulmonary angiographic involvement of greater than 70% involvement of thrombus in greater than or equal to 2 lobar of left or right main pulmonary arteries or by a high probability ventillation/perfusion scan showing ventillation/perfusion mismatch in greater than or equal to two lobes.

In order to have a meaningful discussion of the rapidly emerging literature and treatment options for pulmonary embolism it is important to keep these definitions in mind. In the future we need some sort of a consensus.

Neuraminidase inhibitors for influenza: what does the evidence really show?

This has been the subject of controversy. Here is an evidence summary published in a recent issue of the Annals of Energency Medicine. From the article:

This Cochrane review demonstrates that oseltamivir shortens symptom duration by 21 hours in patients who receive the drug within 48 hours of symptom onset. Unfortunately, there is little information that can be inferred from current available data about hospitalization rates and neuraminidase inhibitors’ effectiveness in decreasing transmission rates of the influenza virus. However, the CDC continues to recommend neuraminidase inhibitors, using information based on observational studies that showed decreased hospital stays and severe outcomes such as ICU admissions or death in patients treated with oseltamivir.3

In the past, Cochrane reviews examining the effect of neuraminidase inhibitors were based on published clinical studies conducted by drug manufacturers; however, these studies were found to reflect only a small portion of the trials conducted and bore discrepancies with their clinical study report counterparts. For the first time in Cochrane history, this review attempted to remove the reporting bias seen in the previous reviews by analyzing the unpublished regulatory data from clinical study reports rather than relying on the published trials.4 Unfortunately, despite major efforts by the systematic review authors, they were unable to obtain much of the data from trials sponsored by the drug manufacturers.

So we have high level data in support of NI based on soft outcomes (time to symptom relief) and low level data in support of them for hard outcomes (severe complications, death). The debate about this has been heated and overhyped. The final answer is that it depends on your evidence quality threshold, your preferences and your values.

Performance and quality: more evidence of non evidence

From JAMA Internal Medicine:

Importance Hospitalization for acute medical illness is associated with increased risk of venous thromboembolism (VTE). Although efforts designed to increase use of pharmacologic VTE prophylaxis are intended to reduce hospital-associated VTE, whether higher rates of prophylaxis reduce VTE in medical patients is unknown.

Objective To examine the association between pharmacologic VTE prophylaxis rates and hospital-associated VTE.

Design, Setting, and Participants Retrospective, multicenter cohort study conducted at 35 Michigan hospitals participating in a statewide quality collaborative from January 1, 2011, through September 13, 2012. Trained medical record abstractors at each hospital collected data from 31 260 general medical patients. Use of VTE prophylaxis on admission, VTE risk factors, and VTE events 90 days after hospital admission were recorded using a combination of medical record review and telephone follow-up. Hospitals were grouped into tertiles of performance based on rate of pharmacologic prophylaxis use on admission for at-risk patients.

Main Outcomes and Measures Association between hospital performance and time to development of VTE within 90 days of hospital admission.

Results A total of 14 563 of 20 794 patients (70.0%) eligible for pharmacologic prophylaxis received prophylaxis on admission. The rates of pharmacologic prophylaxis use at hospitals in the high-, moderate-, and low-performance tertiles were 85.8%, 72.6%, and 55.5%, respectively. A total of 226 VTE events occurred during 1 765 449 days of patient follow-up. Compared with patients at hospitals in the highest-performance tertile, the hazard of VTE in patients at hospitals in moderate-performance (hazard ratio, 1.10; 95% CI, 0.74-1.62) and low-performance (hazard ratio, 0.96, 95% CI, 0.63-1.45) tertiles did not differ after adjusting for potential confounders. Results remained robust when examining mechanical prophylaxis, prophylaxis use throughout the hospitalization, and subsequent inpatient stays after discharge from the index hospitalization.

Conclusions and Relevance The occurrence of 90-day VTE in medical patients after hospitalization is low. Patients who receive care at hospitals that have lower rates of pharmacologic prophylaxis do not have higher adjusted hazards of VTE, even after accounting for individual receipt of pharmacologic prophylaxis.

Related commentary from ACP Hospitalist Weekly:

The findings suggest that "efforts to broadly increase rates of pharmacologic prophylaxis in non-critically ill general medical patients may not yield significant reductions in hospital-associated (VTE)," the authors wrote. Some of the past studies that found an association between using prophylaxis and lower VTE rates included patients with higher baseline risk of VTE like surgical patients, and patients with longer average lengths of stay than the typical medical service patient, they wrote. Many VTE experts and toolkits support an approach that would result in up to 95% of inpatients receiving prophylaxis, but "our study questions the wisdom of that approach," they wrote.

Unwise indeed. Moreover, guidelines for VTE prophylaxis in medical patients are sufficiently restrictive that it is unlikely that 95% of patients would be candidates. Performance driven initiatives tend to push the number higher than appropriate, however.

Wednesday, November 19, 2014

Gruber and stupid voters

Via FIRM. I wonder how many other policy makers feel that way and just didn't get caught. I wonder, too, how many of them feel that way about practicing physicians.  

Choice of resuscitation crystalloid and mortality in sepsis

From a recent study:

Design: A retrospective cohort study of patients admitted with sepsis, not undergoing any surgical procedures, and treated in an ICU by hospital day 2. We used propensity score matching to control for confounding and compared the following outcomes after resuscitation with balanced versus with no-balanced fluids: in-hospital mortality, acute renal failure with and without dialysis, and hospital and ICU lengths of stay. We also estimated the dose-response relationship between receipt of increasing proportions of balanced fluids and in-hospital mortality.

Setting: Three hundred sixty U.S. hospitals that were members of the Premier Healthcare alliance between November 2005 and December 2010.

Patients: A total of 53,448 patients with sepsis, treated with vasopressors and crystalloids in an ICU by hospital day 2 including 3,396 (6.4%) that received balanced fluids.

Interventions: None.

Measurements and Main Results: Patients treated with balanced fluids were younger and less likely to have heart or chronic renal failure, but they were more likely to receive mechanical ventilation, invasive monitoring, colloids, steroids, and larger crystalloid volumes (median 7 vs 5 L). Among 6,730 patients in a propensity-matched cohort, receipt of balanced fluids was associated with lower in-hospital mortality (19.6% vs 22.8%; relative risk, 0.86; 95% CI, 0.78, 0.94). Mortality was progressively lower among patients receiving larger proportions of balanced fluids. There were no significant differences in the prevalence of acute renal failure (with and without dialysis) or in-hospital and ICU lengths of stay.

Conclusions: Among critically ill adults with sepsis, resuscitation with balanced fluids was associated with a lower risk of in-hospital mortality. If confirmed in randomized trials, this finding could have significant public health implications, as crystalloid resuscitation is nearly universal in sepsis.

A recent systematic review of health information technology

This updated systematic review on the effects of HIT recently appeared in the Annals of Internal Medicine. The focus was on meaningful use aspects, particularly clinical decision support and CPOE. A few studies looked at the effect of patients' access to their own EMRs. The results were mixed but tended to be positive. The vast majority of reports were on processes or very low level surrogates, with very few studies looking at meaningful clinical outcomes. Among those, however, were a couple of reports suggesting reduced mortality attributable to HIT.

Patient engagement in hospital medicine

A recent post on patient engagement for hospitalists offers these suggestions:

1. Encouraging patients to ask questions when they see their doctor every day
As simple as it sounds, this is not done nearly enough, and is a big missed opportunity to make a difference to patients’ understanding of their illness...

2. Giving patients all the knowledge they need about their medical condition
Writing details such as blood count numbers on the whiteboard at the end of their bed is one way to do this. In the future, patients will likely be able to pull up some of their own data on computers. The more that patients know, the more empowered they will be to make important health care decisions.

3. Involvement of families
Just as important as the patient, is the family. This is true for any patient who is too unwell to speak for themselves, and particularly applies to the elderly...

4. Involving the patient fully in the discharge process
The discharge process by its’ very nature is a risky endeavor. Typically there are medications that have been changed, tests pending, or even an uncertain diagnosis. All this at a time when the patient is still very frail. It is a crucial transition point, more important than almost any other to get right.

5. Follow-up care
All hospitalized patients must follow-up in a timely manner after being discharged. Nipping a potential problem in the bud can help reduce readmissions and potentially serious complications.

Those are great ideas although I have a problem with item 2. Few patients, even among the most intelligent lay persons, have the ability to interpret raw clinical data in a way that is useful for medical decision making.

Patient engagement is not a new idea. In fact, it's old school (I mean that in a good way). It was one of the key tenets of evidence based medicine, a movement launched in 1992. Because of its focus on the individual patient it does not work well with top-down, pathway driven or population based medicine.

The biggest barrier to this type of medicine is a lack of time as I pointed out before. [1] [2] Unintentionally, and to its potential embarrassment, the medical profession has increasingly attempted to circumvent the time problem by involving the discipline of palliative care as I once explained:

Palliative care is nothing more than good primary care. Or what an excellent internist or hospitalist should be doing. So yes, there is a definition for palliative care but it goes unspoken because the profession is, or should be, embarrassed by the fact that we need a “specialty” whose focus is to offload the rest of us from doing all those things that make for excellence in comprehensive care because we don't have the time.

Tuesday, November 18, 2014

Cholesterol efflux capacity correlates inversely with incident cardiovascular events

Study results were announced at AHA and published in NEJM.

IMPROVE-IT results announced

Here are the results presented at the AHA meetings as reported by Cardiobrief:

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial, presented Monday morning at the American Heart Association meeting in Chicago, randomized 18,144 high-risk patients within 10 days of an acute coronary event to either ezetimibe or placebo on top of a statin. These patients had LDL levels between 50-125 mg/dL, or between 50-100 mg/dL if on a prior cholesterol drug. Patients were followed for an average of six years. The trial ended after there were 5,250 primary endpoint events (CV death, MI, hospital admission for unstable angina, coronary revascularization more than a month after randomization, or stroke).

Primary endpoint events occurred in 34.7% of the control group versus 32.7% of the treatment group, representing a 6.4% reduction in risk (HR 0.936, CI 0.887-0.988, p=0.016). The investigators calculated that 50 patients would need to be treated for seven years to prevent one event.

The NNT of 50, when spread out over 6 years, is not huge. This represents a modest incremental benefit which is the best we would have reasonably hoped for given that the patients were already on statins and their baseline LDL levels were low.

The real impact of this study, in my view, is on the debate over whether LDL lowering matters. Findings about the pleiotropic effects of statins in recent years somehow led to the notion that LDL reduction was irrelevant. That simplistic thinking took hold despite lots of prior evidence that LDL reduction reduced cardiovascular events no matter by what means. Some even spun the new lipid guidelines as a debunking of the LDL hypothesis. IMPROVE-IT adds further support to LDL reduction.

Antibiotics for severe sepsis and septic shock: the earlier the better

Here are results from the Surviving Sepsis Campaign database confirming what we already knew.

Recruitment maneuvers in ARDS: systematic review and meta-analysis

From a recent paper:

Our database search identified ten RCTs (1,594 patients, 612 events) which satisfied the inclusion criteria. The meta-analysis assessing the effect of ARMs on in-hospital mortality showed a risk ratio (RR) of 0.84 [95 % confidence interval (CI) 0.74–0.95; I2 = 0 %], although the quality of evidence was considered to be low due to the risk of bias in the included trials and the indirectness of the evidence—that is, ARMs were usually conducted together with other ventilatory interventions which may affect the outcome of interest. There were no differences in the rates of barotrauma (RR 1.11; 95 % CI 0.78–1.57; I2 = 0 %) or need for rescue therapies (RR 0.76, 95 % CI 0.41–1.40; I2 = 56 %). Most trials found no difference between groups in terms of duration of mechanical ventilation and length of stay in the intensive care unit and hospital. The TSA showed that the available evidence for the effect of ARMs on in-hospital mortality is precise in the case of a type I error of 5 %, but it is not precise with a type I error of 1 %.

Although ARMs may decrease the mortality of patients with ARDS without increasing the risk for major adverse events, current evidence is not definitive. Large-scale ongoing trials addressing this question may provide data better applicable to clinical practice.

If an ICD is not proven beneficial early post MI why bridge with a life vest?

An interesting discussion at Cardiobrief.

Monday, November 17, 2014

Post marketing controversy over dabigatran

Questions have been swirling around the use of dabigatran in light of some recent post marketing data. These concerns were recently hyped by the blogger at Emergency Medicine Literature of Note in a post titled No Good Ever Comes of Dabigatran.

It revolves around two recently published papers on the post marketing experience. The news is not all bad.

First from JAMA Internal Medicine:

Importance It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.

Objective To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.

Design, Setting, and Participants In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.

Exposures Dabigatran users (n = 1302) and warfarin users (n = 8102)...

Results Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.

Conclusions and Relevance Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Then this from Circulation:

Methods and Results—We formed new-user cohorts of propensity score matched elderly patients enrolled in Medicare, who initiated dabigatran or warfarin for treatment of non-valvular AF between October 2010 and December 2012. Among 134,414 patients with 37,587 person-years of follow-up, there were 2,715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were ischemic stroke: 0.80 (0.67-0.96); intracranial hemorrhage: 0.34 (0.26-0.46); major gastrointestinal bleeding: 1.28 (1.14-1.44); acute myocardial infarction: 0.92 (0.78-1.08); and death: 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, where dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150 mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis.

Conclusions—In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death, and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with non-valvular AF. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

There's nothing shocking here that I can see. It appears that any excess bleeding attributable to dabigatran was driven by GI events, which we already knew from RE-LY. We also knew that the performance of most new drugs is better in clinical trials than in the real world.

As more post marketing experience comes in this story will continue to unfold for dabigatran and the other newly approved anticoagulants. There are no pat answers available at this point.

More from ACP Hospitalist Weekly.

Patient safety: where have we gone wrong?

It is pretty widely accepted that the patient safety movement has been a failure. The authors of this paper in the Annals of Internal Medicine cite a lot of reasons and conclude:

Good evidence exists that educating caregivers about safety science and improving safety culture is the foundation of improvement efforts. Of course, reliance on the line worker is a long-standing tenet of quality improvement across many industries. With the emerging evidence that safety is not improving and is too heterogeneous to be assessed by externally mandated measures, we conclude that external top-down efforts to measure safety should cease to expand. We should measure what matters by focusing on creating a positive safety culture, developing HIT tools to detect local safety problems, and training frontline caregivers to improve patient safety.

Pain management dogma and the opiate prescription epidemic

A recent post at Academic Life in Emergency Medicine talked about an epidemic of opiate prescriptions and the associated spike in mortality. The post and a related article in the Annals of Emergency Medicine focused primarily on the concerns of emergency medicine providers but it has more general applicability.

The article deals with multiple dimensions of the problem including the need for educational and even regulatory guidance. One point that particularly interested me has been the focus of many of my older posts this topic over the years which is that this epidemic got started with the “pain the fifth vital sign” initiative that began about a decade and a half ago. It's hardly coincidental that the opiate related fatalities started rising in 1999. The Institute of Medicine, the pharmaceutical industry and our own professional societies were among the many accomplices.

The “educational” piece of the campaign obfuscated the medical lexicon and elevated dogma over science. Worse, it was illogical. How, for example, could something so culturally driven and subjective as the symptom of pain be a vital sign? Nevertheless the campaign was so powerfully leveraged that administrators and physicians were wowed and cowed. Finally some are taking a more critical view of things. I recently posted this retrospective on some of the original tenets of the movement. A decade ago no one dared challenge them. Looking back now it would be humorous had the effects not been so devastating. From that post:

What still baffles me is why so many doctors accepted the biggest and most obvious load of nonsense, the idea that pain, long established in clinical medicine as a symptom, could suddenly become a sign. Even The Joint Commission and my own professional organization, the Society of Hospital Medicine (then known as NAIP) were serving the Kool-aid.

Other nutty ideas were promulgated:

Opiates are safe.
Uh huh. How's that working these days?

Doctors' concerns about opiate addiction are overstated; true opiate addiction is in fact rare.
Ten years or so ago if you pointed out narcotic seeking behavior you would be told, dismissively, that this was not addiction but pseudoaddiction. Pseudoaddiction, they said, was merely behavior exhibited by a patient whose pain was uncontrolled. Put another way, if your patient engaged in seeking behavior it meant you were not doing your job.

Pain can be measured.
Translate: pain is not subjective. Pain does not have emotional components. How many people knew that was a crock but were too intimidated to call it out?

No one should have to experience pain. Pain can be made to disappear from the planet.
Really? How about all those patients on chronic narcotics who have had their doses increased, time and time again, to ridiculously high levels, and are still suffering?

It's great to see that some people are finally saying enough is enough.

Dr. Wes on Annals of Internal Medicine editorial on Maintenance of Certification program (MOC)

Must read. Primary source.

Saturday, November 15, 2014

Sgarbossa rule: not just for LBBB?

The Sgarbossa rule has been extrapolated to ventricular paced complexes. As illustrated in this post from Dr. Smith's ECG blog it can also be applied to ventricular ectopic complexes, as seen in AIVR. The post presents a fascinating case with a lot of teaching points.

Friday, November 14, 2014

Can medical students learn point of care echocardiography with brief training?

From a recent study:

..The aim of this study was to assess the diagnostic value of bedside echocardiographic examinations performed with the use of pocket-size echocardiograph by experienced cardiologist and medical students...
All patients underwent bedside echocardiographic examination performed with pocket-size echocardiograph by two briefly trained medical students (n=90 patients) or cardiologist (n=30 patients). Major findings were recorded using a simplified questionnaire. Within 24 hours standard echocardiographic examination was performed in all patients by another cardiologist using a full sized echocardiograph. The study group was divided into 4 subgroups: A / B - first / second half of in-patients examined by students, group C - inpatients examined by cardiologist, group D- out-patients examined by students.
Results: The agreement between standard transthoracic echocardiography (sTTE) and major findings on bedside transthoracic echocardiography (bTTE) was fair to moderate (kappa 0.293-0.57) in group A, moderate to very good (kappa 0.535-1.00) in group B, good to very good (kappa 0.734-1.00) in group C and moderate to very good (kappa 0.590-1.00) in group D.
Conclusions: Pocket-size echocardiograph enables an expert echocardiographer to perform reliable bedside examinations. When used by briefly trained medical students it provides an acceptable diagnostic value with notable learning curve effect.

Via Hospital Medicine Virtual Journal Club.

Thursday, November 13, 2014