Category Archives: General Health

Linking diet, genes, and gut microbes to…heart disease

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A recent editorial (NEJM 2013; 368: 1647-49) helps explain the link between diet, genes, and gut microbes.  This editorial places in context a study, NEJM 2013; 368: 1575-84).  “The investigators found than dietary choline is metabolized by gut microbes to trimethylamine (TMA), which in turn is absorbed into the host bloodstream and metabolized in the liver to trimethylamine-N-oxide (TMAO).”  TMAO is thought to promote atherogenesis.

The study involved two phases.  In the first, using mass spectrometry, before and after suppression of gut microbes with antibiotics, they showed that a phosphatidylcholine challenge increased all choline metabolites; however, antibiotic use suppressed the formation of TMAO.

In the second phase, they looked at fasting plasma TMAO in relation to cardiovascular events in more than 4000 participants who underwent elective coronary angiography.  They identified an “independent, dose-dependent relationship between TMAO and the risk of a cardiovascular event.”

TMAO levels depend on the interaction between gut microbial production of TMAO which is affected by diet and by host genetic factors. The genetic factors are related to flavin-containing monooxygenases (FMO1 and FMO3); these enzymes oxidize TMA to TMAO are vary significantly in mice (and probably humans). With regard to diet, by limiting choline-rich foods (see links below regarding choline-rich foods) or by using probiotics, this may limit TMAO production and lower the risk of heart disease.

While these observations are intriguing, the mechanisms of TMAO in causing atherosclerosis and its primary function are unknown and much more information is needed to truly make these findings useful.  It is possible that TMAO is simply a biomarker of other factors.

One aside, the editorial states that our gut microbes contain “at least 100 times as many genes as our own genome.”

Take-home message: TMAO is a new potentially modifiable risk factor for atherosclerotic disease.

Related blog links:

Other related links:

Seeing is Believing

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As noted in a recent blog (Food Marketing Detectable on Functional MRI | gutsandgrowth), functional MRI is being studied for a number of applications.  Now, more data has emerged that a “pain signature” can be identified with this technology (NEJM 2014; 368: 1388-97).

Using a series of experiments, the authors enrolled 114 healthy participants and ultimately identified an imaging signature that was associated with heat-induced pain and increased nonlinearly with increasing stimulus intensity.  The first part of the study involved a machine-learning analyses after inducing physical pain by applying heat to the forearm of the participants.  The sensitivity and specificity were 94% or more in discriminating painful heat from nonpainful warmth, pain anticipation, and pain recall.  In the fourth part of the study, the authors showed that the signature response was reduced when an opiod analgesic (remifentanil) was administered.

Because this study enrolled otherwise healthy patients, the results cannot be extrapolated to other populations.  Nevertheless, it is likely that other painful conditions will have unique functional MRI signatures.

Pain is not easy to ascertain and obtaining functional MRIs is not likely to have a role in the near future as a clinical tool.  The concept of identifying a measurable pain biomarker though has been strengthened by this study.

Related blog entry:

Pain changes brain | gutsandgrowth

Why Social Media is Important for Doctors

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The following link is to a NY Times article and below are a few excerpts:

http://well.blogs.nytimes.com/2013/03/21/doctors-and-their-online-reputation/?smid=tw-nytimeshealth&seid=auto

 “While most doctors have come to terms with the fact that their patients routinely go online for information about what ails them, they remain uneasy about a more recent trend: the Internet is quickly becoming the resource of choice for patients to connect with, learn more about and even rate their doctors. And while many have used Facebook, Twitter, LinkedIn or online medical community sites like Sermo to engage with friends and colleagues, few have communicated with patients as, well, doctors. Most abstain for one simple reason: they aren’t sure how to be a doctor online.”
The link discusses a new book by Kevin Pho (KevinMD) and Susan Gay.  “In“Establishing, Managing and Protecting Your Online Reputation: A Social Media Guide for Physicians and Medical Practices,” “Dr. Pho and Ms. Gay offer highly organized key points, useful statistics and exuberant testimonials from doctors who have successfully leapt over the digital divide. There is plenty of practical advice, too, on topics ranging from what to post and when to engage, confer or rebuff, to how to decide what might be unethical or T.M.I. (Answer: ‘Can you say it aloud in a full hospital elevator?”)The book is an excellent and helpful resource. But what elevates it beyond the category of valuable how-to manual is the passionate call to arms that resonates from all those well-enumerated directions and clearly labeled diagrams. Like it or not, the authors warn, the Internet has profoundly changed the patient-doctor relationship, and doctors must embrace its effects on patient care — or risk losing their own influence.'”The article also notes that on the internet many individuals without any scientific background may have equal footing with recognized experts.  Another subject broached in this article is the issue of ranking physicians.”The biggest risk of social media in health care,” they conclude, “is not using it at all.”
Related website resources:

The Difficulty with Drug Development

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Recent statistics from the pharmaceutical industry provide information about why it costs so much (1.2 billion dollars) to develop new medications.

  • Average time for experimental drug to go from lab to patients: 10-15 years
  • Only 5 in 5,000 compounds that enter preclinical testing make it to human testing
  • Only one of those five is approved for use in humans
  • Of approved drugs, only one in five makes more than the costs of development
  • FDA applications typically run more than 100,000 pages

Source: PhRMA Report 2012: Medicines in Development for Cancer

“I want a new drug …
One that don’t cost too much…
I want a new drug
One that does what it should
One that won’t make me feel too bad
One that won’t make me feel too good”

–Huey Lewis and the News: “I want a new drug”

Public Health Casualties: Collateral Damage in the War on Terror

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This week there is a fascinating editorial that I almost skipped because the title didn’t grab my attention: “Ensuring Public Health Neutrality” (NEJM 2013; 368: 1073-1075).

This commentary provides background by recollecting Red Cross relief flights to Biafra being shot down by the Nigerian government. “In the minds of some people, ..these attacks were justified by another clear violation of humanitarian neutrality: on at least one occasion, a plane painted with the Red Cross insignia was actually carrying weapons.”

Fast-forward to January 6, 2013.  12 deans of U.S. schools of public health sent a letter to President Obama protesting the conduct of a sham vaccination campaign as part of the hunt for Osama bin Laden.  Apparently, the CIA hired a Pakistani surgeon to go house to house vaccinating children but also drawing back a little blood in the syringe in order to analyze the DNA.  This ploy was not effective in the bin Laden compound as the surgeon’s team was kicked out.

So what are the consequences?

  • Pakistan has expelled foreign staff of the international aid agency Save the Children (Sept 2012)
  • Eight polio vaccination workers were killed (Dec 2012)
  • U.N. has suspended its polio-eradication efforts in Pakistan.  Pakistan is one of three countries where polio has not been eradicated (Nigeria and Afghanistan are the other two).
  • This undermines vaccination in Pakistan where 150,000 children die of vaccine-preventable illness each year.

Using physicians in this manner violates the Hippocratic Oath: “Whatever house I may visit, I will come for the benefit of the sick, remaining free of all intentional injustice.”

The authors note that “although some U.S. policymakers consider immediate national security concerns a higher priority than long-term global health efforts, the CIA’s false vaccination campaign in Pakistan may cause collateral damage with profound long-term implications for national security.  If every aid worker..is suspected of being a spy, the children..of the world will no longer have protection against our greatest killers.”

Public health neutrality –a different twist to think about while you are watching “Zero Dark Thirty.”

Related links:

New FDA warning for azithromycin (Zithromax)

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“The FDA is warning that a widely used antibiotic from Pfizer can cause rare but deadly heart rhythms in some patients. The agency is adding new warnings to the label of Zithromax, which is used to treat bronchitis, pneumonia and other infections.

Doctors should consider prescribing other antibiotics to patients at risk of heart problems, including those with irregular heartbeats or low levels of potassium or magnesium in their blood. Zithromax is popular because it often can be taken for fewer days than other antibiotics. The warning may prompt doctors to choose other options, though the new label notes that other antibiotics have similar effects on the heart.”

Read more here: http://www.thenewstribune.com/2013/03/13/2511288/fda-issues-warning-about-zithromax.html#storylink=cpy

Also from previous FDA statement:
[05-17-2012] “The U.S. Food and Drug Administration (FDA) is
aware of the study published in the New England Journal of Medicine,
on May 17, 20121, that compared the risks of cardiovascular death in patients treated with azithromycin (Zithromax), amoxicillin, ciprofloxacin (Cipro), levofloxacin (Levaquin), and no antibacterial drug.  The study reported a small increase in cardiovascular
deaths, and in the risk of death from any cause, in persons treated with a 5-day
course of azithromycin (Zithromax) compared to persons treated with amoxicillin,
ciprofloxacin, or no drug. The risks of cardiovascular death associated with
levofloxacin treatment were similar to those associated with azithromycin
treatment.”  Thus, levofloxacin also was associated with an increased risk.
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Build the information medical highway and expect more traffic

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A recent article indicates that increased patient access to online records was associated with increased in-person and telephone contacts (JAMA 2012; 308: 2012-19).

Background (from study introduction): The Institute of Medicine’s report on “Crossing the Quality Chasm” indicated that electronic patient-physician messaging was a promising technology to improve quality and efficiency.  Furthermore, previous studies have suggested that 25-70% of all visits to physicians do not require face-to-face appointments.

Design: To explore this topic further, the authors performed a retrospective cohort study on the use of health care services between 2005-2010 at Kaiser Permanente in Colorado.  This study examined patients ≥18 years old and looked at health care utilization before and after initiation of MyHealthManager (MHM). Users of MHM were compared with nonusers.  And, both groups (users and nonusers) were examined with regard to their health care utilization before and after MHM rollout. The first 30 days before and after activation of MHM were excluded from analysis to minimize the effect of increased utilization at the initiation of MHM.

Results:

  • By June 2009, patient use of MHM had increased to 53.8%.  In total, 87,206 MHM patients were identified and 71,663 nonusers were identified for study participation. 
  • MHM users were slightly older and more likely to be female.
  • After initiation of MHM, the rate of office visits increased by 0.7 per member per year (p<0.001) and the number of telephone encounters increased by 0.3 per member per year (p<0.001).  
  • The authors breakdown this data based on age, absence of chronic disease, presence of specific diseases (diabetes, coronary artery disease, congestive heart failure).  In all of these scenarios, MHM users had increased visits after initiation of MHM.  Nonusers generally had the same or less visits at the same time.
  • Figure 2 shows that MHM and nonusers had identical health care utilization beforehand.  Afterwards, the MHM users maintained a parallel line of increased usage that was fairly consistent for a year after rollout.

Why did this happen?  The authors note that the result was contrary to their expectations.  They speculate that individuals may have increased their in-person use after developing additional concerns following their review of information online and that individuals may sign up who are already more likely to use services.  Online access, in these individuals, may facilitate access to more frequent visits.

I think this article points to a more pervasive miscalculation of the effect of information technology and health care utilization.  While electronic health records (EHRs) can help organize and communicate vast amounts of information, the proposition that they will ultimately reduce health care costs/utilization or improve efficiency is looking dubious.  In my opinion, the best we can hope for is that EHRs, when used optimally, will improve the quality of the care.  It is equally possible, however, that EHRs could result in more legible but less accurate information due to well-recognized issues like copy-forwarding with inadequate editing.

Related blog posts:

Global Justice and Vaccine Policy

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I definitely was piqued by the editorial titled “Global Justice and the Proposed Ban on Thimerosal-Containing Vaccines.” (Pediatrics 2013; 131: 154-156) I wondered how vaccine policy could affect global justice.

In high-income countries, vaccines have shifted increasingly to preservative-free single-dose vials.  Whereas in poorer countries, vaccines have continued to rely on multidose vials which frequently contain thimerosal as a preservative.  The move away from thimerosal which contains ethyl mercury “was a precautionary move in response to theoretical concerns, now known to be unfounded.”

Currently, a multinational environmental treaty is close to finalization and this treaty aims to restrict human and environmental exposure to mercury.  The World Health Organization and the broader public health community have recommended that thimerosal be exempt from the treaty to avoid disruption in the global vaccine supply.  However, some nongovernmental groups have objected to the use of thimerosal in poorer countries when it has been phased out in wealthier countries.

Why Thimerosal Should be Exempt from this Ban:

  • No credible scientific evidence of any risk to human health from thimerosal
  • Vaccines with thimerosal are used in >120 countries to immunize ~84 million children every year.  It is estimated that these vaccines save 1.4 million children every year.
  • Potential vaccines affected include hepatitis B, tetanus, and diptheria-tetanus-pertutsis
  • “Although there are other preservatives…, none are yet viable alternatives to thimerosal”

The individuals and organizations who have opposed thimerosal come from wealthier countries and would not suffer the consequences of a potential ban.  “Where’s the justice in that?”

Related references:

  • Pediatrics 2013; 131: 149-151. Public health experts recommend the ongoing use of thimerosal as a preservative.
  • Pediatrics 2013; 131: 152-153.  Provides context for previous AAP joint statement on thimerosal in 1999.

Related blog entry:

Vaccine successes and ambitions | gutsandgrowth

Aptly titled “The Cost of Technology”

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A brief commentary in JAMA makes some real useful observations regarding the effects of the electronic medical record on patient care (JAMA 2012; 2497-98).   The article describes a drawing by a 7-yer-old girl of her doctor who has an outstanding reputation among his peers.  Yet, in the drawing he is staring at the computer, and his back is to the patient.

The author notes that “when a physician focuses on a patient with complete attention, this simple act of caring creates a connection between two human beings. Almost immediately, the patient begins to feel, well, cared for, and this becomes a first step toward helping that person feel better.”

The computer is now a third player in this dynamic.  We “find ourselves entering more and more data while we are trying to listen to and talk with our patients.”  “By default, the patient moves down to second place…it is becoming the new reality.”

Physicians have to develop electronic records that allow us to record our thinking and improve efficiency so that we have more time to communicate with patients.  Can this be accomplished?

Related blog entry:

Smoking-related mortality

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“The time is always right to do what is right.”  Martin Luther King

When it comes to almost any situation, including smoking cessation, this quote is probably appropriate.  The hazards of smoking are detailed in recent several articles/editorial (NEJM 2013; 368: 341-350, 351-64, 389-90).

In the first article, the authors reviewed smoking-cessation histories from 113,752 women and 88,496 men.  All participants were older than 25 years and interviewed between 1997-2004.  These participants were from a cohort in U.S. National Health Interview Survey (NHIS).  The NHIS is a nationally representative cross-sectional health survey.

The second study involved large populations from the Cancer Prevention Study I (CPS I) which started in 1959 and CPS II which started in 1982.  These were prospective studies followed the mortality associated with smoking.  In all, the populations of these two studies exceeded 1.2 million.

What were the key findings?

1. The benefits of smoking cessation were noted in all age groups.  Those who quit between 25-34 years of age lived 10 years longer.  Those who quit between 35-44 years of age lived 9 years longer. Those who quit between 45-54 years of age lived 6 years longer. Those who quit between 55-64 years of age lived 4 years longer.

2. Smokers mortality worsened compared to the general population over a 50-year period. During the three time periods (1959-65, 1982-88, 2000-10), the mortality dropped by 50% in the overall study population.  However, female smokers mortality remained unchanged and male smokers experienced only a 24% reduction.

Specific hazard ratios (HR) for a large number of conditions are detailed in these studies.  For example, among men, the HR for death due to lung cancer was 24.97 in the contemporary cohort.  Due to the nature of these large cohorts, there are many limitations and it is difficult to draw conclusions about a specific threshold in terms of amount of smoking.  However, the conclusions may actually underestimate the effects of smoking due to undersampling of certain high risk populations, like incarcerated persons and those with mental illness.

The editorial notes that more women die from lung cancer than breast cancer.  Yet, due to smoking’s stigma, there are no ‘race for the cure’ promotions.  In addition, increasingly smoking is a behavior concentrated in persons of lower social status.  As such, it “risks becoming invisible to those who set health policies and research priorities.”

Even Nick Naylor might consider a career change if he read these studies (Thank You for Smoking (film) – Wikipedia, the free encyclopedia).