Here’s my very biased take on where things stand at the close of 2008:
The never ending debate over the value of the hospitalist model is moot. Research on hospitaists’ impact on outcomes and efficiency has been inconclusive and is likely to remain so, given that large comparison groups against which to study the model are shrinking fast and will soon be nonexistent.
The security of our niche is based not on any measurable value, but on the mass exodus of traditional practitioners from the hospital. The resulting expansion in hospitalist jobs has outpaced growth in the work force. The trend shows no sign of abating. The current economic crisis will only serve to accelerate this exodus. The inflation of salaries may moderate, but hospitalists’ jobs should remain secure.
Larger threats to the hospitalist movement are turnover and burnout. Although we lack hard data on the magnitude of the problem it is widely apparent. This creates challenges for leaders in hospital medicine who are poised to define the ultimate direction of the movement. Hospitalists are increasingly being asked to go beyond the limits of their training by caring for all hospitalized patients regardless of illness. Moreover, their role as expert clinicians is increasingly threatened by pressure to become business and administrative solutions.
This emerging jack-of-all-trades model for hospitalists is a departure from the original notion of doctors devoting all their professional time caring for inpatients in the realm of their specialty (usually internal medicine) who, because they ascended a steep learning curve, developed unique expertise in hospital medicine. The old model attracted me to the field almost a decade ago because of its promise of professional satisfaction. The new model will be palatable for many of the short timers and moonlighters who increasingly make up the work force of hospital medicine but may not attract the career hospitalists needed to sustain and grow hospital medicine as a specialty.
Wednesday, December 31, 2008
Top 10 issues in hospital medicine for 2008, issue 2: patient safety and the culture of blame
Just as the quality movement has led to a culture of shame, the safety movement has exacerbated a culture of blame. That’s pretty ironic given that the seminal document of the patient safety movement, IOM’s To Err is Human, viewed the culture of blame as counterproductive and sought to mitigate it. This statement is from the executive summary of the book:
Why did this unfortunate and unintended consequence come about? It’s an example of what happens when a nuanced and highly complex issue gets thrown into the arena of unenlightened and uninformed public debate. Policy wonks distort it. Media spin it egregiously. Trial lawyers take notice.
We’ve seen the consequences this year. CMS’s ill-conceived and manifestly unfair never events policy went into effect, redefining many unavoidable events in hospitals as errors. With such redefinition comes a strong implication of widespread institutional and individual blame. The idea of patient harm as a “never event” has also spawned a new legal principle in which any patient harm is prima facie evidence of negligence, leading to more law suits and a shift in the burden of proof. Ready for the next malpractice crisis?
The focus must shift from blaming individuals for past errors to a focus on preventing future errors by designing safety into the system. This does not mean that individuals can be careless. People must still be vigilant and held responsible for their actions. But when an error occurs, blaming an individual does little to make the system safer and prevent someone else from committing the same error.
Why did this unfortunate and unintended consequence come about? It’s an example of what happens when a nuanced and highly complex issue gets thrown into the arena of unenlightened and uninformed public debate. Policy wonks distort it. Media spin it egregiously. Trial lawyers take notice.
We’ve seen the consequences this year. CMS’s ill-conceived and manifestly unfair never events policy went into effect, redefining many unavoidable events in hospitals as errors. With such redefinition comes a strong implication of widespread institutional and individual blame. The idea of patient harm as a “never event” has also spawned a new legal principle in which any patient harm is prima facie evidence of negligence, leading to more law suits and a shift in the burden of proof. Ready for the next malpractice crisis?
Tuesday, December 30, 2008
Top 10 issues in hospital medicine for 2008, issue 3: confusing performance with quality
Dr. Robert Centor, an academic hospitalist, is Division Director of General Internal Medicine at the University Of Alabama School Of Medicine in Birmingham and Associate Dean for the Huntsville Regional Medical Campus. He is also a member of the ACP Board of Regents and past president of the Society of General Internal Medicine. He is perhaps better known to many of us as the blogger at DB’s Medical Rants. There he recently wrote a post titled Quality improvement is a misnomer in which he said:
The quality movement has largely failed due to widespread confusion between quality and performance. Why are performance and quality (real quality, things that matter in patient outcomes) fundamentally different? It’s all in the motivation. Real quality is driven by a desire to make a difference for patients, regardless of money or public perception. Performance, on the other hand, focuses entirely on public perception. As Dr. Robert Wachter said in his blog just the other day, performance is driven by shame and embarrassment. He also wrote:
Those words speak volumes. Think for a moment about hospitals doing cartwheels trying to improve their performance. It’s all about putting on a show. A natural consequence of hospitals’ excessive concern for perception is a nearly exclusive focus on publicly reported indicators. Therein lies the failure of today’s “quality” movement.
There’s nothing inherently wrong with publicly reported measures. The problem arises when hospitals focus on them to the exclusion of other measures which, though below the public radar screen, matter more. The result is that hospitals tend to ignore measures with the greatest potential to impact meaningful outcomes such as early goal directed therapy against sepsis and applied hypothermia after cardiac arrest, which have a NNT of about 6 for survival and good neurologic outcome, respectively. Many of the high public profile measures nowadays are either non-evidence based (rapid response teams), have a very poor bang for the buck (pneumococcal vaccine, NNT 50,000), have serious unintended consequences (the 4 hour antibiotic rule) or have failed to improve outcomes in the way they were promulgated (heart failure core measures).
If we want better health related outcomes we must focus on real quality, not performance. But with today’s explosion in web based reporting and hospitals scrambling to improve their image, don’t expect it to happen any time soon.
"Quality improvement" implies that patients will have better outcomes. Yet, few studies exist that show that improving performance measures really improves outcomes.
This model makes the unsubstantiated assumption that improving performance measures equates with improved outcomes, and thus we can label our efforts as quality improvement.
The quality movement has largely failed due to widespread confusion between quality and performance. Why are performance and quality (real quality, things that matter in patient outcomes) fundamentally different? It’s all in the motivation. Real quality is driven by a desire to make a difference for patients, regardless of money or public perception. Performance, on the other hand, focuses entirely on public perception. As Dr. Robert Wachter said in his blog just the other day, performance is driven by shame and embarrassment. He also wrote:
…hospitals are doing organizational cartwheels trying to improve their performance on the publicly reported indicators.
Those words speak volumes. Think for a moment about hospitals doing cartwheels trying to improve their performance. It’s all about putting on a show. A natural consequence of hospitals’ excessive concern for perception is a nearly exclusive focus on publicly reported indicators. Therein lies the failure of today’s “quality” movement.
There’s nothing inherently wrong with publicly reported measures. The problem arises when hospitals focus on them to the exclusion of other measures which, though below the public radar screen, matter more. The result is that hospitals tend to ignore measures with the greatest potential to impact meaningful outcomes such as early goal directed therapy against sepsis and applied hypothermia after cardiac arrest, which have a NNT of about 6 for survival and good neurologic outcome, respectively. Many of the high public profile measures nowadays are either non-evidence based (rapid response teams), have a very poor bang for the buck (pneumococcal vaccine, NNT 50,000), have serious unintended consequences (the 4 hour antibiotic rule) or have failed to improve outcomes in the way they were promulgated (heart failure core measures).
If we want better health related outcomes we must focus on real quality, not performance. But with today’s explosion in web based reporting and hospitals scrambling to improve their image, don’t expect it to happen any time soon.
Top 10 issues in hospital medicine for 2008, issue 4: emergency room handoffs
The handoff between the emergency room physician and the hospitalist is just one of several discontinuities in health care during which patients are vulnerable. Although it has been intuitively known for a good while it earned a place on this year’s top 10 list because of a new study documenting frequent occurrences of patient harm and near misses. This patient safety problem is one of competing agendas: poor communication and handoff errors are driven by administrative pressure on ERs to reduce their wait times and improve “throughput”.
Top 10 issues in hospital medicine for 2008, issue 5: what do we know about glycemic control in hospitalized patients?
Less than we thought we did this time last year, which wasn’t much. Since that time, non-evidence for strict glycemic control has been reported at such a dizzying pace I’ve barely been able to keep up with it. My posts from the past year are here, here, here, here and here.
At the close of 2008 what do we have to support glycemic control in hospitalized patients? Little more than observational studies, pathyphysiologic rationale and common sense. Based on such rationale, what we know reduces down to this:
Hyperglycemia is common in hospitalized patients, many of whom did not have a prior diagnosis of diabetes. It should not be ignored.
Sliding scale insulin should not be the sole means of glycemic control in hospitalized patients. Basal coverage should be included in the regimen.
Insulin drip protocols are appealing for ICU patients because of their rapidity of action, the flexibility they afford and the fact that subcutaneous insulin absorption is unreliable in hypoperfusion states.
Glycemic control does matter, but the best treatment targets are not known, and probably vary from one clinical state to another (sepsis, stroke, acute coronary syndrome, perioperative period).
At the close of 2008 what do we have to support glycemic control in hospitalized patients? Little more than observational studies, pathyphysiologic rationale and common sense. Based on such rationale, what we know reduces down to this:
Hyperglycemia is common in hospitalized patients, many of whom did not have a prior diagnosis of diabetes. It should not be ignored.
Sliding scale insulin should not be the sole means of glycemic control in hospitalized patients. Basal coverage should be included in the regimen.
Insulin drip protocols are appealing for ICU patients because of their rapidity of action, the flexibility they afford and the fact that subcutaneous insulin absorption is unreliable in hypoperfusion states.
Glycemic control does matter, but the best treatment targets are not known, and probably vary from one clinical state to another (sepsis, stroke, acute coronary syndrome, perioperative period).
Top 10 issues in hospital medicine for 2008, issue 6: weaning from ventilators is obsolete
---(with only a few exceptions). Despite this fact the term “weaning” remains popular in critical care. The new thinking is that most patients should not be weaned. Rather, on any given day they are either ready for extubation or they are not. The job of the clinician is to do a daily assessment for readiness.
While this fact has been known for over a decade it made my 2008 top10 list because of a pivotal study this year in which the assessment was validated as an integrated protocol combining the daily sedation interruption with the spontaneous breathing trial, resulting in a striking mortality benefit.
While this fact has been known for over a decade it made my 2008 top10 list because of a pivotal study this year in which the assessment was validated as an integrated protocol combining the daily sedation interruption with the spontaneous breathing trial, resulting in a striking mortality benefit.
Monday, December 29, 2008
Top 10 issues in hospital medicine for 2008, issue 7: emerging problems in the treatment of MRSA
We live with the fear that suddenly, one day, we will wake up to find vancomycin resistant Staphylococcus aureus (VRSA) in our community. Although rare reports of the sudden appearance of high level vancomycin resistance due to the vanA gene known to cause vancomycin resistance in enterococci have surfaced, the reality is that the major threats are different: vancomycin is gradually wearing out its welcome, by multiple mechanisms, while new strategies evolve. Hospitalists must be aware of these mechanisms and evolving strategies.
The mechanisms:
There are inherent weaknesses in vancomycin compared to beta lactam antibiotics. This relates to less effective killing action and a narrower therapeutic window for vancomycin. This is not a new problem, and accounts for higher mortality in MRSA infections (in which vancomycin is usually administered) than in MSSA infections (in which beta lactam antibiotics are used). This issue is reviewed here.
Vancomycin treatment failures increase in proportion to increasing MICs even well within the “sensitive” range below 2 mcg/ml.
Transient heteroresistance to vancomycin, in which small subpopulations of organisms show vancomycin MICs in the intermediate range, is common and may lead to treatment failure in patients whose isolates test “sensitive”.
Vancomycin tolerance, defined as a wide discrepancy between the MIC and MBC, may lead to treatment failure in patients whose isolates test “sensitive”.
Traditional vancomycin dosing regimens have resulted in low trough levels. This can lead to treatment failure, since vancomycin’s effectiveness is time dependent rather than peak concentration dependant.
Poor penetration of vancomycin in lung tissue, requiring trough levels several fold above MIC.
These concerns have led to a lowering of the vancomycin sensitivity breakpoints for MRSA.
Evolving strategies:
Aiming for higher vancomycin trough levels. Although newer vancomycin preparations have been considered relatively non toxic, recent trends in higher dosing may be producing nephrotoxicity.
Use of other older antibiotics such as trimethoprim/sulfa, clindamycin and tetracyclines. In contrast to HA-MRSA, CA-MRSA isolates are usually sensitive to these antibiotics. Their use as an alternative to vancomycin in serious MRSA infections has been limited, has not been validated in high level studies, and is controversial.
Newer agents. Linezolid has been suggested as an alternative to vancomycin for pneumonia. The jury is still out. Daptomycin has been found non-inferior in intravascular infections. It is not effective against pneumonia. Tygecycline has efficacy against MRSA but is not approved for a wide variety of clinical indications. Limitations are that it is bacteriostatic and may not be effective against infections in which bacteriocidal activity is required. Moreover, serum levels tend to be low, a possible limitation in bacteremic infections.
The mechanisms:
There are inherent weaknesses in vancomycin compared to beta lactam antibiotics. This relates to less effective killing action and a narrower therapeutic window for vancomycin. This is not a new problem, and accounts for higher mortality in MRSA infections (in which vancomycin is usually administered) than in MSSA infections (in which beta lactam antibiotics are used). This issue is reviewed here.
Vancomycin treatment failures increase in proportion to increasing MICs even well within the “sensitive” range below 2 mcg/ml.
Transient heteroresistance to vancomycin, in which small subpopulations of organisms show vancomycin MICs in the intermediate range, is common and may lead to treatment failure in patients whose isolates test “sensitive”.
Vancomycin tolerance, defined as a wide discrepancy between the MIC and MBC, may lead to treatment failure in patients whose isolates test “sensitive”.
Traditional vancomycin dosing regimens have resulted in low trough levels. This can lead to treatment failure, since vancomycin’s effectiveness is time dependent rather than peak concentration dependant.
Poor penetration of vancomycin in lung tissue, requiring trough levels several fold above MIC.
These concerns have led to a lowering of the vancomycin sensitivity breakpoints for MRSA.
Evolving strategies:
Aiming for higher vancomycin trough levels. Although newer vancomycin preparations have been considered relatively non toxic, recent trends in higher dosing may be producing nephrotoxicity.
Use of other older antibiotics such as trimethoprim/sulfa, clindamycin and tetracyclines. In contrast to HA-MRSA, CA-MRSA isolates are usually sensitive to these antibiotics. Their use as an alternative to vancomycin in serious MRSA infections has been limited, has not been validated in high level studies, and is controversial.
Newer agents. Linezolid has been suggested as an alternative to vancomycin for pneumonia. The jury is still out. Daptomycin has been found non-inferior in intravascular infections. It is not effective against pneumonia. Tygecycline has efficacy against MRSA but is not approved for a wide variety of clinical indications. Limitations are that it is bacteriostatic and may not be effective against infections in which bacteriocidal activity is required. Moreover, serum levels tend to be low, a possible limitation in bacteremic infections.
Acknowledgment: Several issues raised here were covered by Dr. James Pile in his presentation at SHM 2008, which was the inspiration for this post.
Top 10 issues in hospital medicine for 2008, issue 8: resistant gram negative infections
For most of the last two decades gram positive infections have been the focus of attention concerning antibiotic resistance. More recently gram negative resistance has begun to outpace the pipeline of antibiotic development.
In serious infections multiple studies [1] [2] [3] have demonstrated the effect on survival of including the causative pathogen in the initial (“empiric”) antibiotic selection. This generally means very broad initial coverage with two or more agents. For gram positives, vancomycin coverage has become knee jerk. Decision making for gram negative coverage is now more complex. The clinician must take into account changing trends in resistance mechanisms, a wide variety of antibiotics and local resistance patterns.
This review outlines newly emerging resistance threats. Extended spectrum beta lactamases (ESBLs) and carbapenemases along with other resistance mechanisms may result in resistance to all commonly prescribed antibiotics, necessitating consideration of alternatives such as tygecycline or the older and largely abandoned class of polymyxin antibiotics. (More information on the polymyxins can be found here).
ESBLs concentrate in the periplasmic space of gram negative bacilli and consequently may overwhelm the beta lactamase inhibitors present in two currently available antibiotic combinations. For this reason, and because ESBLs inactivate late generation cephalosporins, carbapenems are increasingly included in initial therapy. A carbapenem review is referenced here. Additional posts from last year with recent literature citations can be found here and here.
In serious infections multiple studies [1] [2] [3] have demonstrated the effect on survival of including the causative pathogen in the initial (“empiric”) antibiotic selection. This generally means very broad initial coverage with two or more agents. For gram positives, vancomycin coverage has become knee jerk. Decision making for gram negative coverage is now more complex. The clinician must take into account changing trends in resistance mechanisms, a wide variety of antibiotics and local resistance patterns.
This review outlines newly emerging resistance threats. Extended spectrum beta lactamases (ESBLs) and carbapenemases along with other resistance mechanisms may result in resistance to all commonly prescribed antibiotics, necessitating consideration of alternatives such as tygecycline or the older and largely abandoned class of polymyxin antibiotics. (More information on the polymyxins can be found here).
ESBLs concentrate in the periplasmic space of gram negative bacilli and consequently may overwhelm the beta lactamase inhibitors present in two currently available antibiotic combinations. For this reason, and because ESBLs inactivate late generation cephalosporins, carbapenems are increasingly included in initial therapy. A carbapenem review is referenced here. Additional posts from last year with recent literature citations can be found here and here.
Top 10 issues in hospital medicine for 2008, issue 9: palliative care
Hospitalists talk a great deal about palliative care even though no one seems to know (or articulate) exactly what it is. This year Bob Wachter described the success of the program at UCSF and this study demonstrated that palliative care programs save hospitals money. Nevertheless the concept remains poorly defined. This, as I explained in a recent post, is a source of confusion for clinicians and may be a barrier to more widespread adoption. Characterizations are variable, ranging from descriptions of terminal care to definitive care for a variety of illnesses. To confuse things further proponents use nebulous terms like patient centered as if they are unique to palliative care, but which should characterize medical care in general. (I’m reminded of the woo-meisters who hijacked the notion of the whole person for their own promotional use, but I digress). What the various descriptions of palliative care have in common are attributes all of health care aspires to: quality of life, symptom relief (palliation means helping things get better, after all), excellence and efficiency (avoiding high tech, expensive care for those who won’t benefit). Palliative care, then, is just good old fashioned doctoring. Why does it require a special service?
Several commenters, trying to help carve out a definition, merely talked around the concept. This one came close:
That still leaves COPD, dementia, cerebrovascular disease, heart failure, easily 90% of internal medicine, under the umbrella of palliative care. This is something the entire hospitalist service, not a just special team, should be doing.
Several commenters, trying to help carve out a definition, merely talked around the concept. This one came close:
The underlying premise is that the patient has a "life-limiting" disease (what used to be referred to as a terminal disease), but that unlike hospice, there is a role for palliative care early on in the disease course, mostly for symptom management and social & spiritual support, even as the patient receives disease-modifying or curative treatment concurrently….There are times when you would not get palliative care involved, for example, with a 20 year old patient with pyelonephritis or a 45 year old with an acute MI.
That still leaves COPD, dementia, cerebrovascular disease, heart failure, easily 90% of internal medicine, under the umbrella of palliative care. This is something the entire hospitalist service, not a just special team, should be doing.
Sunday, December 28, 2008
Top 10 issues in hospital medicine for 2008, issue 10: How should hospitalists respond to the pseudoscientific invasion?
Suppose an integrative medicine consult service is introduced at your hospital with plans to offer Therapeutic Touch, Reiki, acupuncture and Tai Chi. You are the medical director of the hospitalist program. The CEO, knowing that your program accounts for most of the consult requests and hoping for a nice revenue stream from the new service, asks for your support. What do you do?
While integrative medicine programs commonly offer harmless treatments whose modest benefits are self evident (relaxation modalities, music therapy) these tend to be mixed with other claims which are scientifically unsound. As hospitalists we are (or claim to be) all about ethics and scientific integrity. As quackery spreads throughout mainstream academic and community medical institutions like cancer the individual hospitalist is increasingly likely to confront the issue.
At the organizational level there has been little discussion. I have attended one hospital medicine course sponsored by a large academic institution which promoted non-evidence based alternative medicine. The Society of Hospital Medicine has been silent. It’s time to take a stand.
Tolerance for the promotion of quackery in mainstream medicine is a violation of fiduciary duty.
While integrative medicine programs commonly offer harmless treatments whose modest benefits are self evident (relaxation modalities, music therapy) these tend to be mixed with other claims which are scientifically unsound. As hospitalists we are (or claim to be) all about ethics and scientific integrity. As quackery spreads throughout mainstream academic and community medical institutions like cancer the individual hospitalist is increasingly likely to confront the issue.
At the organizational level there has been little discussion. I have attended one hospital medicine course sponsored by a large academic institution which promoted non-evidence based alternative medicine. The Society of Hospital Medicine has been silent. It’s time to take a stand.
Tolerance for the promotion of quackery in mainstream medicine is a violation of fiduciary duty.
Top 10 issues in hospital medicine for 2008
About this time every year I compile a top 10 list of issues I think were important for hospitalists. This listing is subjective and very biased. As in past years it covers both organizational and clinical issues in hospital medicine. It will be presented as a series of posts, in more or less reverse order of importance, over the next few days.
Saturday, December 27, 2008
Friday, December 26, 2008
Liberation from mechanical ventilation in patients with neurologic disorders
Protocol driven assessment for liberation from mechanical ventilation is well established for patients with respiratory failure, but relatively little has been written concerning patients with neurologic impairment. Patients with impaired consciousness present special problems with regard to clearance of secretions and ability to maintain an airway. The November issue of Critical Care Medicine reports an assessment tool for patients with neurologic disorders.
Update in the treatment of pressure ulcers---nothing to get excited about
A gazillion treatments are promoted for pressure ulcers but according to this JAMA review none of them, including nutritional supplements, are evidence based.
Wednesday, December 24, 2008
Wake up and breathe!
The benefits of spontaneous breathing trials and sedation interruptions (spontaneous awakening trials) in mechanically ventilated patients have been known for years. A recent pivotal study showed that combining both trials in an integrated protocol provides additional benefits including decreased mortality. One of the study authors discussed the practical aspects of the integrated protocol, popularly known as the wake up and breathe protocol, in a recent Medscape interview.
Patient falls
An article in ACP Hospitalist profiles the aggressive multidisciplinary efforts of several institutions to reduce fall risks. Their success? One effort reduced falls by 27% (note that’s not 100%). Another resulted in 143 consecutive fall free days. (Impressive, but somebody fell on day 144). Falls as a never event? Absurd.
Tuesday, December 23, 2008
Does Michael Jackson have alpha-1 antitrypsin deficiency?
The story’s been all over the blogs today. Fox news says the story’s fake, that Jacko’s fine. Even if true it’s sloppy reporting. This post is typical:
The posts also say Jackson desperately needs a lung transplant.
While it’s true alpha-1 has extrapulmonary manifestations and disease associations (cirrhosis, necrotizing panniculitis, dementia) there’s no link to visual loss or bleeding. The statements, lacking in internal consistency, are offered without explanation.
I’d wager the claim is fake. Too goofy to be true.
Halperin says Jackson is battling an inherited condition called A1AD — alpha-1 anti-trypsin deficiency — where those affected by it lack a protein that helps protect the lungs. Halperin says that due to the ailment, Jackson “can barely speak” and that the “vision in his left eye is 95 percent gone.”
And while the breathing woes are surely something to worry about, Halperin claims that “it’s the bleeding that’s the most problematic part. It could kill him.”
The posts also say Jackson desperately needs a lung transplant.
While it’s true alpha-1 has extrapulmonary manifestations and disease associations (cirrhosis, necrotizing panniculitis, dementia) there’s no link to visual loss or bleeding. The statements, lacking in internal consistency, are offered without explanation.
I’d wager the claim is fake. Too goofy to be true.
Sunday, December 21, 2008
Intensive glycemic control in critically ill medical and surgical patients
Add this paper to the litany of negative studies.
On a related note, this paper in the same issue of Critical Care Medicine showed adverse cerebral metabolic effects of intensive glycemic control in patients with severe brain injury, which correlated with increased mortality.
On a related note, this paper in the same issue of Critical Care Medicine showed adverse cerebral metabolic effects of intensive glycemic control in patients with severe brain injury, which correlated with increased mortality.
Glycemic control and macrovascular outcomes in DM 2: the VADT
This was presented at a meeting a while back, but just published on line in NEJM:
Though a bit disappointing it’s no surprise, and consistent with what we already knew, that intensive glycemic control had no impact on macrovascular outcomes over the first 5 years or so of treatment. It was mildly surprising that microvascular disease was not impacted. What we recently learned from the long term follow up of the UKPDS was that it may take up to 10 years to realize beneficial clinical outcomes. If the FDA insists on “hard” clinical outcomes the development of new diabetes drugs may be doomed. A related editorial in the Journal of Clinical Endocrinology and Metabolism makes the same point here.
The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene.
Results The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications.
Though a bit disappointing it’s no surprise, and consistent with what we already knew, that intensive glycemic control had no impact on macrovascular outcomes over the first 5 years or so of treatment. It was mildly surprising that microvascular disease was not impacted. What we recently learned from the long term follow up of the UKPDS was that it may take up to 10 years to realize beneficial clinical outcomes. If the FDA insists on “hard” clinical outcomes the development of new diabetes drugs may be doomed. A related editorial in the Journal of Clinical Endocrinology and Metabolism makes the same point here.
Friday, December 19, 2008
Speaking of thrombolytic therapy for patients presenting in cardiac arrest
This just came out in NEJM:
Of note, patients initially suspected of having PE were not randomized and give open label thrombolytic therapy. Patients presenting in cardiac arrest with PEA as the presenting finding should be considered for thrombolytic therapy.
In a double-blind, multicenter trial, we randomly assigned adult patients with witnessed out-of-hospital cardiac arrest to receive tenecteplase or placebo during cardiopulmonary resuscitation…. the data and safety monitoring board recommended discontinuation of enrollment of asystolic patients because of low survival, and the protocol was amended. Subsequently, the trial was terminated prematurely for futility after enrolling a total of 1050 patients… We did not detect any significant differences between tenecteplase and placebo in the primary end point of 30-day survival (14.7% vs. 17.0%; P=0.36; relative risk, 0.87; 95% confidence interval, 0.65 to 1.15) or in the secondary end points of hospital admission (53.5% vs. 55.0%, P=0.67), return of spontaneous circulation (55.0% vs. 54.6%, P=0.96), 24-hour survival (30.6% vs. 33.3%, P=0.39), survival to hospital discharge (15.1% vs. 17.5%, P=0.33), or neurologic outcome (P=0.69). There were more intracranial hemorrhages in the tenecteplase group.
Of note, patients initially suspected of having PE were not randomized and give open label thrombolytic therapy. Patients presenting in cardiac arrest with PEA as the presenting finding should be considered for thrombolytic therapy.
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