Friday, October 24, 2014

Does much of the blame for sarcopenia rest on the satellite cells of the fast twitch muscle fibers?

Well, at least some of the blame anyway.

Dr. LB Verdijk and coworkers at the Masstricht University in The Netherlands have published several articles contributing insights into at least some of what goes on with the age related loss of muscle size and strength.See here and here.

Their work deals with satellite cells (SC), so called because in their resting form they hang out on the periphery of skeletal muscle cells, wedged between the basement membrane and the sarcolemma.They are the muscle's stem cells. They are poised to multiply and to differentiate in myofibers when signaled by damage to the muscles which  includes strenuous exercise.

Their 2007 publication  gives a good summary in the article's title, "Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly" The authors did muscle biopsies in the lateral thigh in 80 elderly subjects (age 76 +/- 1 yr) and 80 twenty year olds. The proportion and mean cross-sectional area of type II fibers was reduced in the elderly  as were  the number of satellite cells per fiber .A similar pattern was not noted in the slow twitch (type I) fibers.The type II fibers were smaller and fewer in number and contained fewer satellite cells per fiber .

Now for the sorta  good news.

A more recent article from the same  research group in the Netherlands reported that a 12 week program of resistance exercise training significantly increased both muscle fibers size and satellite cell count in type II fibers in elderly subjects. This was part of a more comprehensive study which examined muscle fiber type and satellite cell content in 165 subjects in various age ranges. 49 of which were 70-86 years of age.Also a subset of elderly subjects took part in a 12 week resistance exercise program .Muscle biopsies after the training program demonstrated increased type II fiber size and satellite cell content.

It seems plausible that the satellite cell awakening induced by resistance exercise was instrumental in muscle cell growth.There are , of course, many other factors in the muscle loss of aging including loss of sex hormones,increase in inflammatory cytokines,inactivity,poor nutrition and loss of anterior horn cells,among others. Resistance exercise in the setting of adequate protein intake  is not the fountain of muscle youth but so far it seems the best we've got.

A final word.writing as someone who has run more ( much more ) than can be justified  based on reasonable  concerns of improving health .Running will not prevent sarcopenia. While running on level ground the quadriceps does little more than stabilizes the patella. I suppose running up hill may activate some type II fibers but basic jogging will not prevent the age related loss of muscle size and strength.



Tuesday, September 30, 2014

Can long standing endurance exercise training mitigate the loss of age related compliance of left ventricle?

With more evidence available to generate legitimate concern about an increased risk of atrial fibrillation with  many years of endurance exercise and papers about long time endurance athletes and the  much less likely risk of developing arrhymogenic right ventricular dysplasia (ARVD), some good news for the crazy, old long distance runners was very welcome.

Here is a link to summary of the paper by Dr. Paul Bhella et al. entitled "Impact of Lifelong Exercise "dose" on Left Ventricular Compliance and Distensibility"

Here is the authors'conclusion :

" Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this "dose" of exercise training may have important implications for prevention of cardiovascular disease."

Is there an age related decrease in left ventricular compliance.  According to a 1984 article by Rodeheffet et al the aging heart may be able to maintain cardiac output in the face of an age associated decrease in maximal heart rate by increasing stroke volume. See here for link. The older person relies more on an increase in end diastolic volume and riding the beneficial part of the Starling curve, but if the left ventricle become less compliant, which it is claimed it does as a function of age that adaptation would only work for a while.

Is the decrease in LV compliance due to just getting old or might it be due to lack of vigorous physical exercise. Dr. Armin-Zaeh and coworkers at the Dallas Based Institute for exercise and environment medicine  believe  it is the latter. See here.  My personal bias is obviously to agree with them. Here are the conclusions from the above linked article.


"In conclusion, a sedentary lifestyle is associated with a decline of ventricular compliance, leading to higher cardiac filling pressures and lower stroke volumes for a given filling volume compared with age-matched athletes or young individuals. Prolonged, sustained endurance training preserves ventricular compliance with aging and may be an important approach to reduce the probability of heart failure with aging."


A partial,apparent  counterpoint to the  above studies can be found here in this 2003 article by  P E Gates and co-authors whose analysis and summary minimized the importance of one of their own findings  ( namely that a standard measure of diastolic function (the A/e ratio) was higher in endurance trained subjects) and instead emphasized the value of the decreased arterial stiffness noted in long term exercisers.Either way it seems good news to long term endurance exercisers.

addendum: 10/1/14 Correction made on title, "Stiffness" changed to "Compliance"


Friday, September 26, 2014

Another chapter in "were you wrong then doctor, or are you wrong now?" this time regarding stenting of non culprit lesions.

The American College of Cardiology recently retracted one of its magic five "Choosing Wisely" recommendations.In 2012 ACC had advised that in the setting of an acute coronary event one should only revascularize the "culprit artery".This is the artery thought to be responsible for the event and if other obstructions are detected the ACC said that there was evidence that the fix everything approach might be harmful.This advice was based on non randomized trials. Here is ACC's official statement.

Now apparently two randomized trials  suggest one should fix the other obstructions. Here is quote from ACC:

 “over the last two years, new science has emerged showing potential improvements for some patients in their overall outcomes as a result of complete revascularization.”

Larry Husten,prolific medical journalist whose Forbes article on this subject is linked above, really nailed it , quote:

" It seems to me that the medical organizations that produce guidelines should freely admit this lack of evidence for most recommendations. Then, instead of getting their panties all in a bunch trying to defend the indefensible– as we saw recently with the salt guideline– they could advocate for better evidence...So if they want to make the case for more data they will have to first acknowledge their ignorance.

Acknowledging ignorance seems the last thing  likely to emerge from the guidelines generating organizations.

In 1728, the three verdict system arose in Scottish Criminal cases.The accused could be found guilty,not guilty or not proven. So guilty, not guilty or admitting their ignorance and admitting we just can't say.


Being  a guideline author seems to confer immunity for having to say you are sorry.  The individual physician strives to do what is the right thing for his patient and hopes that what he does is right, the quality rule makers are able to summon up sufficient hubris to  presume to know what is good for everyone. Of course they frequently do not. Remember the beta blocker fiasco.



 


Friday, September 19, 2014

Are pediatric football concussions different from high school and college head trauma?

It would be nice to think so and a 2012 study by Maugans et al provides some data ( see here for full text) which suggests it may be the case. Eight young football players  (in a study of 12 athletes ) were studied early post concussion and at two subsequent times.The football players ages were : two 12 year olds,one thirteen year old,three 14 years olds and 2 aged 15.

Multiple Imaging techniques were used . The diffusion tensor imaging (TDI) tests were normal  as were conventional MRIs,and proton Magnetic resonance spectroscopy.

 This is in contrast to two studies in college and two studies in high school football players, none of whom experienced a concussion ,which showed decreased fractional anisotropy (FA) in certain white matter tracts and/or functional MR  abnormality in the dorso-lateral frontal cortex.See here for Talavage's article regarding functional MR changes in high school players.

.Further one study (Bazarian,  (see here for full text)) showed persistence of the TDI changes six months after the college football  season ended. Here is the authors' summary:

" we have demonstrated that a single football season of RHIs  [ repeated head impacts]without clinically evident concussion resulted in WM changes on DTI. These DTI changes correlated with multiple helmet impact measures and persisted despite 6 months of no-contact rest. This lack of WM recovery could potentially contribute to progressive, cumulative WM damage with subsequent RHI exposures. If this relationship is confirmed in longitudinal studies, efforts to limit the development of RHI-related WM changes by monitoring helmet impact measures, and further elucidation of modifiable factors that may influence WM recovery, could mitigate the long-term risk of CTE [chronic traumatic encephalopathy]."

Maugan's group did demonstrate decrease in  cerebral blood flow ( CBF) in the concussed subjects which tended to return to normal over a few weeks.The authors' conclusion;

"Pediatric SRC [sports related concussion] is primarily a physiologic injury, affecting CBF significantly without evidence of measurable structural, metabolic neuronal or axonal injury."

What might account for the apparent differences in brain scan results in the college and high school players and the younger athletes studied by Maugan.

Possibly the younger players have a  threshold for CNS symptoms given a head blow  that is lower that the  threshold for whatever tissue changes take place that are reflected in DTI findings.There are contradictory data regarding the question of whether younger brain are more or less susceptible to damage for head trauma.

While it has been shown that  some head  impact levels ( as measured by accelerometers in helmets) in  youth football may approach those demonstrated in high school and college they are on average lower.(see here for full text of article by Cobb, 2013 for detailed data of head impact forces ) Further, the total number of impacts in a season of high school or college practice and game time may be considerably more than in a season of youth football and it may be the cumulative effects is what drives the DTI changes and whatever underlying tissue changes that may occur.Also as the years pile up, youth football and then high school and then college and then for a few professional football the total  number of head impacts grows and it may be the long term cumulative effect of multiple sub-concussive plus the occasional concussive blow that  leads to CTE in a minority of football participants.A definitive link between the imaging findings on active players and the pathological changes seen in chronic traumatic encephalopathy has yet to be established.

Although parents may feel some reassurance from Maugan's research, there is little to be reassured about in  the brain imaging studies of high school and college football players following a concussion free season as well as those studies on players with concussions.There is certainly little reassurance offered in this lengthy and detailed  article from Rolling Stone.There is an increasing about of research on the effects of football related head trauma ( as well as ice hockey) .One pundit, a retired football  player,commented  that it is the parents who really need their heads examined.

Addendum : Minor alterations in syntax and spelling and grammar done on 9.24.14.The original, unfinished version was published on 9/19/14 by mistake .

Thursday, September 18, 2014

Is the "triple aim of health care" analogous to the dual mandate of the Federal Reserve

Well, it can be argued that they are both unachievable and the execution of their aims and goals will require wise men such as the "Men of system" discussed by Adam Smith.

In 1977,  Congress, having accepted at least part of the theory of Keynesian economics, amended The Federal Reserve Act, with the passage of the Humphrey-Hawkins Act, stating the monetary policy objectives of the Federal Reserve as:

"The Board of Governors of the Federal Reserve System and the Federal Open Market Committee shall maintain long run growth of the monetary and credit aggregates commensurate with the economy's long run potential to increase production, so as to promote effectively the goals of maximum employment, stable prices and moderate long-term interest rates."

In other words, the Federal Reserve System is tasked by law to control inflation and maximize employment in spite of the fact, given the tools to which the system has access, that the two mandates might be incompatible.

Dr Don Berwick speaks of medicine's "triple aim"  ( as envisioned by the Institute for Health Care Improvement)  : Population health,the patient's experience and the per capita cost.The collective medicinal "we" should strive  to improve population health,the individual patient's experience and reduce the per capita cost.

I am reminded of a series of  articles in JAMA in 199 4by Dr. David Eddy ( "Rationing resources while improving quality" ) in which he promised to provide a means to improve quality of medical care and reduce costs. This was to be done by utilizing a utilitarian cost calculus.The idea was to do what was best for the group,the health care collective statistically, even though he admitted that in such a system there would be winners and losers but the utility to the former would out way the dis utility to the minority. Of course in this scheme quality had to be defined or redefined as  what is better for the aggregate. At least Eddy was candid about there being losers,in Berwick's utopian visions in the picture he paints there seem only to be winners.The population will do better, the individual patient's experience will improve and "we" will spend less money per patient. Everyone will do better and it will even cost less.What could possibly be wrong with that?

I believe that IHI's policy recommendations are basically Eddy's prescription adorned with a layer or two of management-speak verbiage dumped on the top to obfuscate what is really happening. When you improve population health care or outcome and simultaneously  decrease per capital costs, you essentially are doing a cost effectiveness analysis based on a statistical benefit to some group ( e.g. those covered lives in an ACO or HMO) regardless of what determent might befall some other  individuals in the group making the third aim of improving the  patient's experience little more than a fraudulent claim. This is population medicine dressed up in polite euphemisms designed to flimflam the members of the health care collective.

Both Dr. Robert Berenson and Dr. Harold Sox,former president of the American College of Physicians, are  perhaps more candid about about their visions for medical care in the country.

Berenson writing in 1998 in the Annals of Internal Medicine said.

"We propose that devotion to the best interests of each individual be replaced with an ethic of devotion to the best interests of the group for which the physician is personally responsible.

Berenson makes it clear that the individual's interest shoudl be trumped by the group's interest.


Dr Harold Sox, former president of the American College of Physicians, in his commentary regarding "population medicine"  made it clear that in shifting funds from managing one disease to another would involve for at least a few generations results in some not receiving treatment so others might enjoy some type of preventive measures. That would be quite an "experience" for those who might have to forgo some treatment.

Quoting Sox's  November 12, 2013 JAMA commentary:

 "Planning to optimize population health will mean determining the frequency,causes and consequences of he common medical conditions in a population and devising strategies for dealing with them over a lifetime. "...
resources must be allocated across program to prevent,detect and treat disease and its risk factors. "...One reasonable principle to move resources from groups of patients less likely to benefit to groups more likely to benefit...

With the application of this utilitarian calculus there will be winners and losers which Sox seems to admit implicitly the following paragraph.

"It will take several generations to realize the benefit of investments in disease prevention.In the short run, these investments may draw resources away from the tests and treatment of some sick people.In the long run, diseased prevention and better low-cost technology could reduce the outlay for treatment."

If Berwick's, triple aim is something other than  the utilitarian approach of Eddy,Berenson and Sox I wish someone would explain. It is the old wine in newly labeled bottles, this time labeled "enhanced patient experience" and the platitudinous "patient centered care" when really it is the greatest good for the greatest number as judged by cost effectiveness calculation and the real winners are the third party payers and their fellow travelers. . 






Sunday, August 31, 2014

The effects of multiple sub-concussion head blows in football

Two research  groups have demonstrated brain imaging findings in collegiate football players over the course of a season.Importantly these abnormal findings occurred in players who did not experience a concussion..While concussions occurring at all levels of football competition has finally attracted some long overdue attention,more recently the significance of so called " sub-concussive" head blows is under scrutiny.

Bazarian et al studied 10 college football players over the course of one season. ( "Persistent Long Term cerebral White Matter Changes after Sports related Repetitive Head Impacts. Plos one 9(4),e94737)

 Head impacts were recorded and measured by helmet accelerometers and brain imaging was done preseason, immediately post season and six months after the end of the season. Imaging was done by the diffusion tensor technique (DTI).This MR technique can demonstrate abnormalities in the white matter and can visualize connections of fiber tracts between different parts of the brain.Current theory regarding traumatic brain injury is that axons are stretched with resultant micro damage.These changes are not detectable by conventional MR while DTI is capable of detecting abnormalities associated with so-called mild brain trauma.

White matter changes were noted in these players none of whom sustained a clinically evident concussion.
The changes in most players,but not all, were also seen in the six month followup images. Evidently in some cases the 6 month period with no head impacts allowed recovery or at least return to the pre season scan pattern.. There was a correlation between number of head impacts and DTI findings. The DTI changes were not correlated with changes in cognitive testing or tests of balance.The authors state that it is not known whether the changes noted represented damage per se or recovery and beneficial plasticity. The number of head impacts ranged from a low of 431 to 1850.Multiple head impacts occur regularly in lineman while quarterbacks and wide receivers are more at risk for more severe single hits and concussions.
 

A possibly encouraging  finding in the Bazarian study  is that none of players demonstrated any scan abnormalities at the beginning of the season.One would expect that if these findings were to persist for very long periods of time (longer than 6 months) that these players who likely played football for a number of years by this time would have shown some abnormality from repeated head blows.

Another TDI imaging study was published by TW McAllister ( Effect of head impact of diffusivity measures in a cohort of collegiate contact sports athletes, Neurol. 10:1212/01Dec 11 2013.) There was at least one important difference from Bazarian's results. Quoting the authors from this study which involved 80 varsity football and ice hockey players and 79 non contact sports participants:

 "The magnitude of change in corpus callosum MD (mean diffusivity) was associated with poorer performance on a measure of verbal learning and memory."

What are the underlying tissue changes corresponding to the DTI patterns? No one knows whether they represent damage to the axon and or the myelin  sheath and/or edema. See here for a comprehensive discussion of the DTI technique and findings in head trauma.

Regardless of the exact relationship between imaging findings and the tissue changes, it is difficult  to argue that subjecting (allowing) young brains to sustain multiple hits can be anything other than potentially harmful.Although recent emphasis on concussion and chronic traumatic encephalopathy (CTE) has lead to some rule changes in the direction of limiting to some degree head blows and rules regarding management of concussions ( when to be allowed to return to play etc) ,every Friday night tens of thousand of young men hit each other repeatedly in the head and are cheered on by hundred of thousands of football fans and parents. For now the dogs continue to bark while the caravan moves on.


ADDENDUM:9/4/14 and again on 9/24/14
Much to no one's surprise a similar study has been published involving measurement of head impact forces and DTI changes in a high school football team over the course of a season. (Devenport,EM et al, "Abnormal white matter integrity related to head impact exposure in a season of high school varsity football"
J of Neurotrauma 2014 Jul 14, published ahead of print) .There was a significant linear relationship between their measured impact force and DTI changes as well as relationship between DTI measurements and changes in a memory test.







Wednesday, August 13, 2014

What would happen if Choosing Wisely became the medical "law of the land"?

Choosing Wisely (CW) is an initiative or campaign lead by the American Board of Internal Medicine Foundation (ABIMF) to change the thinking of physicians and patients so that the choice of  medical tests and treatments are chosen  wisely in such a way as to greatly reduce waste of resources and harm to the patient.

It began as an apparent low-key program to simply have the physician and her patient sit down together and have conversation about what needed to be done in a particular patient's case and it continues in part to be marketed as such. So, if for example that a given test, e.g. MR of the lumbar spine,might not be ordered if it were the case that an MR in that stylized scenario had not been shown to be helpful.The patient would be subject to possibly harm of a false positive tests and the possible cascade of more testing,etc etc.

However in the two years since the launching of CW ( at the time of this writing) several policy experts and wonks have envisioned a much more full bodied, authoritative and coercive role  for the pronouncements announced under the CW brand.  It is this expanded role for CW that I refer to as the medical law of the land.. From simply reducing waste and  harm a second wave of CW is to reducing "low value" services,however that may be defined

So based on some of these experts' recommendations, what would the medical landscape look in the era in which the decisions of Choosing Wisely ,would be much more than the suggestions or recommendations,which is how they are sometimes presented  and  instead be  determinative in regard to the reimbursements of third party payers, private and public as well being used in decisions regarding maintenance of certification and other mechanisms to decrease medical costs.

Consider the comments of Dr Robert Benson Jr.,President Emeritus of the ABIM and ABIMF  writing on the ABIMF blog with bolding of words added by me:

" CMS, which has the ultimate negotiating position in the form of reimbursement for Medicare services, could only accept negotiated bundled charges. It could also refuse payment for non-compliance with the Choosing Wisely recommendations."...ABIM could require candidates to achieve a perfect score on questions related to costs and redundant care as a requirement for admission to secure exams for initial certification or MOC."

So, a candidate for ABIM certification would have to properly quote the Choosing Wisely rules recommendations before he even gets to take the certification ofrMOC examination.

This recent commentary by Dr N.E. Morden and her co-authors from Yale and Harvard tells the same story.

"..physician-endorsed low-value labels will probably be leveraged to these purposes. [cost containment and quality measures]...We believe that if such efforts are designed and applied carefully they should be embraced as a promising method for reducing low-value services."

...linking the lists ( of tests and procedures not to do ) to specialty specific maintenance of certification act activities such as practice audits and improvement tasks could also advance their dissemination and uptake at very low cost."

"...Choosing Wisely items should also be incorporated into quality-measurement efforts such as Center for Medicare and Medicaid Services Physician Quality Reporting  ...linking low value service use to financial incentives ( translate penalties )  .. should accelerate ...into practice changes."

So payment for physician services,quality ratings,and maintenance of board certification are linked to adherence to the "recommendations" of  CW.

In this proposed choosing wisely world the deciders at CW assume a very powerful position.Various special interest groups stake holders would have great incentive to lobby the CW leaders,to do what they could to direct the "recommendations". Physicians would have to follow the CW guidance or risk loosing certification let alone payment for services. As bound as physicians would be to the  dictates of the CW authority how much trust could a patient have that his physician is acting in his ( the patient's) best interests .Making CW the medical law of the land would be a giant step toward the collectivization of medicine and destruction of the traditional physician patient relationship.

Of course, all of those sky-is-falling comments are in stark contrast to what one would read on the websites promoting the CW campaign.. There we hear  marketing phrases such as "ensuring the right care at the right time" and doing reasonable, sensible things and involving the patients in the decision process. Mom and apple pie with ice cream on the pie is the image floating above  the CW advertising efforts, but when one reads the comments of Benson and Morden et al  that outlines what they want to do,a different, darker side of CW is visible.So what is it: an idealized physician-patient collaborative effort or advocacy for  an alarming  level of medical care hegemony lead by select members of the higher echelons of the progressive medical elite who seem to believe that carrots are not enough .The ABIMF and the Robert Wood Johnson Foundation are spending millions of dollars convincing the public and members of the medical profession that Choosing Wisely is a collaborative,thoughtful movement that just wants to ensure that patients get the right care at the right time while the President Emeritus of ABIM(F) and some policy wonks from Yale and Harvard talk a markedly different game.

Today's trial balloons may well become tomorrow's policies and governing rules about how medicine is practiced and it will not be all about the right treatment at the right time.It will be about the most cost effective means of achieving quality adjusted life years as that is valued by someone other than those trying to live those years.



Addendum: Minor changes in grammar and style made on 10/8/14