What it takes to adopt good ideas

A New Yorker article by Atul Gawande highlights the importance of spending time and talking about good ideas on a person-to-person basis as the best way to help innovations take hold.  Specific innovations that are discussed include the introduction of anesthesia, the control of germs/Lister’s theories of sepsis, adoption of oral rehydration solutions, and preventing hypothermia in newborns. The link to the article and a brief video review on the Colbert report:

Tell me about your mother

The following except from the New York Times (nyti.ms/1cvUprv ) by Haider Javed Warraich provides some useful advice when families members ask “What would you do if this were your mother?”  In pediatrics, the question is similar: “What would you do if this were your child?”

The patient was an elderly woman, admitted to our unit just a few hours earlier, with a breathing machine keeping her alive. We proceeded with the meeting as we were trained to do. We kept our elbows off the table, maintained eye contact (but not too much) and gave the family an update of where we stood.

A healthy family meeting, we’d been told, involved us speaking for about half the time, with the family speaking for the rest – venting, questioning, grieving and hoping, in no particular order. This meeting, though, was dominated by long periods of silence that unearthed the dull, low-pitched drone in the background.

The son, quiet for most of the meeting, broke the silence and, with a hint of anger and a big dollop of frustration, asked the one question I had dreaded being asked the most: “Doc, give it to me straight. If this were your mother, what would you do?”

While the patient-doctor interaction varies widely across cultures and continents, this question seems to be a universal constant…

From a patient or family member’s perspective, though, this question helps them make sense of the confusion, desolation and powerlessness that so often defines the hospital experience, which usually involves a full-on assault of numbers, jargon and ‘expert’ opinion. They are confronted with difficult choices, like whether they want to go ahead with a particular high-risk procedure or wait for the tincture of time to kick in…

Yet I still find this question hard to answer. See, my mother is the sort of person who spends two hours each day on the treadmill, even during vacations, so that she can eat to her heart’s content. Often described as a “fighter,” any additional moment she can spend with her children or future grandchildren would be worth the extra mile. My father, on the other hand, is someone who avoids getting his blood sugar level tested to evade medications and dreams of spending his last days in the quiet serenity of the village he grew up in. Thus my answer to the question would be very different, as it would be for anyone, depending on which parent you asked me about.

So I have come to believe that the right answer to the question, “If this were your mother, doctor…” is: “Tell me more about your mother.”

This response gives patients’ families the chance to think about their loved ones, about what they would value and what they would consider a good life, what they would think was worth fighting for if they were available to answer the question for themselves….And then, slowly, the family started sharing stories of the woman we had met only a few hours before, unconscious and intubated. She loved being independent, would hate for people to open doors for her or hold her hand as she tried to get up, they told us. She loved the sun, the beach. She loved walking, loved being out and about. She would never, ever want to go to a nursing home…

We then told them that based on a combination of her vital signs and lab values, as well as our clinical judgment, that while we could hope for some progress, it would likely not be enough to allow her any real shot at experiencing life outside a nursing facility again…

They turned to us and asked us to make her comfortable, and to turn off the breathing machine.

Related blog post:

Advice for doctors after the death of a child | gutsandgrowth

Global Disease Burden

In 1991, the World Bank and the World Health Organization launched the Global Burden of Disease Study.  A recent article reviews the key findings (NEJM 2013; 369: 448-57).

The goals of the study are to compare the burden of one disease with others; as such, it is “necessary to consider the age at death and life expectancy of persons affected by each disease and to take account of the degree of disability (eg. discomfort, pain, or functional limitations.”  A comprehensive measure of disability, disability-adjusted life-years or DALYs, was used for comparisons.

The study examined 291 types of diseases and injuries as well as 67 risk factors in 187 countries, looking at the years 1990, 2005, and 2010.

Findings:

  • In 2010, there were 2482 million DALYs which is a decrease of 0.6% from 1990.  On the basis of population growth, DALYs would have increased by 37.9% without improvements in disease burden.
  • Major causes of death in 2010: Ischemic heart disease-far ahead #1 (21.1% of deaths, 7850 thousand DALYs), Stroke (6.5% of deaths, 2574 thousand DALYs), Lung/airway cancer (6.1% of deaths, 3033 thousand DALYs), Alzheimer’s (5.9% of deaths, 2022 thousand DALYs), COPD (5.8% of deaths, 3659 thousand DALYs).
  • Global DALYs in 2010 (top ten -starting with #1): Ischemic heart disease, Lower respiratory tract infections, stroke, diarrhea, HIV-AIDs, Malaria, Low Back pain, Preterm birth complications, COPD, and road-traffic injury.
  • Top risk factors (starting with #1): High blood pressure, tobacco smoking (including 2nd-hand smoke), household air pollution, diet low in fruit, alcohol use, high body-mass index, high fasting plasma glucose level, childhood underweight, exposure to outside pollution, physical inactivity, diet high in sodium

Since 1990, there has been a shift.  “In general, communicable, maternal, neonatal, and nutritional conditions decreased in absolute terms.”  The main exceptions were HIV and malaria. Noncommunicable diseases, especially diabetes, have been increasing in terms of percentage and absolute numbers.

Another important change has been a relative increase in disability compared with premature death.  In addition, of the “top 25 causes of years lived with disability, only COPD, diabetes, road-traffic injury, ischemic heart disease, and diarrhea are also among the tope 25 causes of years of life lost.”  “What ails most persons is not necessarily what kills them.”

Bottom-line: While collecting this type of data has many potential limitations, the broad picture it provides should help inform policymakers with priorities for research and intervention.  This data also allows the US to benchmark its efforts compared to other countries.  For example, according to the authors, currently the US has the best global performance with respect to stroke and the worst with respect to lung cancer and Alzheimer’s disease; however, “data and analyses are lacking to elucidate the drivers of these changes in relative performance.”

Fewer Intern Hours & No Change in Patient Safety

Excerpt from Gastroenterology & Endoscopy News (Shorter Workweeks for Interns Do Not Promote Patient Safety) :

A policy to shorten the workweek for interns in the United States has failed to improve their quality of life and has possibly put patients at greater risk for medical errors, a new study has found (Sen S et al. JAMA Intern Med 2013;173:657-662).

The 2011 policy change, recommended by the Accreditation Council for Graduate Medical Education, capped at 16 continuous hours the longest shift a first-year resident could work in the hope that doing so would ease the strain on physician trainees.

But although the new rules have shortened the typical intern’s workweek from 67 to 64.3 hours, they haven’t encouraged residents to sleep more, helped them to avoid depression or increased their overall sense of well-being, the study found…The study was based on email surveys of 2,323 residents …entered training in 2009, 2010 and 2011, after the rule change.

“Given that increased sleep was a key [mechanism] through which the new duty-hour restrictions were intended to improve the health of residents, the lack of such an effect in the postimplementation cohort in our study is a cause for concern,” wrote the authors, led by Srijan Sen, MD, PhD, a psychiatrist at the University of Michigan in Ann Arbor. “Designing work schedules that account for circadian phase and explicitly training residents on practices to increase sleep time and improve sleep quality may be necessary.”

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

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

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

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

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

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)

“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.
Related link: