Genocide in the Age of Globalization

The road to hell is paved with good intentions.

It doesn't get more disheartening than that.

I've decided to use my coveted day off curled up on my sofa reading "The Blue Sweater" by Jacqueline Novogratz, about her experiences educating and lending to micro-finance groups in East Africa, focusing on Rwanda.  Its incredible trying to grasp just how interconnected the world is today.  I recently finished reading "Black Hawk Down" by Mark Bowden, which had nothing and everything to do with the 1994 events in Rwanda.

Black hawk down was a disaster and, with 20/20 hindsight, the book reviews where mistakes were made and where things could have gone better in the planning process, yet in the final chapter, the author reviews the events and despite setbacks, the Somalis took a higher toll during the mission than the rangers did.  Despite this, Clinton withdrew troops following the "failed" mission and the United States is no longer directly involved in Somalia.  Horrifying images of American soldiers' bodies being dishonored in the streets of Mogadishu appeared in the media.  With this fresh in the minds of politicians and the American public, there was a sense of reluctancy to involve ourselves in international affairs, especially those in Africa.

Only months later, on April 6, 1994 a plane carrying the Hutu president of Rwanda and president of Burundi back from peace talks in Arusha was shot down as it flew into Kigali, killing both men.  That night, the genocide began to unfold.  In 100 days, roughly 800,000 people were murdered by people whom may have been their neighbors, relatives, or coworkers.

To this day it seems that Rwanda serves as a guilty conscience upon the international community, especially the United States.  Because of the delay in labeling the conflict as "genocide" and delay in international involvement, thousands of people were slaughtered.

It is now eighteen years later and, unfortunately, its seems that history has a cruel way of repeating itself.  The United States is now working to finally withdraw troops from Afghanistan and have only recently officially "ended" our involvement in Iraq, after roughly a decade of heavy military presence in both countries.  Our reasons as a nation for entering each nation were very different.

My knowledge of Iraq and its history are fairly limited, but I can say confidently that Saddam Hussain was not a good man  and hundreds of his own people were killed under his watch.  Post 9/11 the Bush administration played to our sentiments and even Democrats authorized the start of a new war in yet another Middle Eastern country.  It took almost a decade before we officially withdrew troops and left;  Americans had long growth tired of hearing of our involvement in a country that had initially posed little threat to ours and there had been a growing opinion that we should not have entered to begin with.

Not all international interventions have been this disastrous; in comparison, our involvement in Libya seems to have gone relatively smoothly, although I am gauging this on the fact that our involvement was short-lived and that I have not seen much about Libya in the news recently.

Libya aside, my question is, when is it right for the United States to involve itself in the domestic conflicts of other nations?

More recently has been the plight of the Sudanese.  Sudan is (was) an astonishing large and diverse country.  The north has an Arab majority which the south is predominantly tribal.  In Julie Flint and Alex de Waals book "Darfur: a new history of a long war" the authors criticize the international community for labeling the conflict in this region "genocide" because, they argue, it is far more complex.  Although Omar al-Bashir was most certainly aware of, and likely supported, the Janjaweed's atrocities, tribal conflict as well as conflict with neighboring Chad contributed to the suffering of the innocent.  Again, the United States involvement was limited, if not non-existant, in this conflict.

In July 2011, South Sudan gained its independence (http://www.goss.org/).  Tensions in Darfur have calmed and people are finally returning home and trying to rebuild (Darfur is located in Sudan, not southern).  However there has been recent blasts from the media over a "new" conflict erupting in the Nuba mountains, just north of the South Sudan border.  Unlike the ruling power in Khartoum, the Nubians are tribal and are targeted by the government for ethnic and religious reasons.

Today George Clooney was arrested for protesting outside of the U.S. Embassy for Sudan following the release of a youtube video made by Clooney and the ENOUGH project on March 13 http://www.youtube.com/watch?feature=player_embedded&v=p89OuPODBMM.  Op-Ed reporter for the New York Times, Nicholas Kristof, has also written a number of recent pieces on conflict in this area.

In the final shot of the Clooney video, Clooney stands over a dead body decaying in the sand and words appear on the screen: How many more bodies until the Nuba Mountains become the next Darfur?

Do I care?  One-hundred percent.  I think that the world is too connected to allow these kinds of atrocities to take place unnoticed by the global community and, as an American, I believe that every person on earth deserves the basic rights of food, health-care and free speech.  However as the international community demands that Omar al-Bashir be overthrown and taken to international court for atrocities he committed, I can't help but think that if we did get involved, could this be another Iraq? Also, I think that there are more cultural complexities to the Sudan than even I can fathom, it may take more than removing Omar al-Bashir to establish peace.

The only thing I feel I know for certain is that I don't know what the solution would be.

CHEST 2012 is blowing my mind.

After committing the 2008 guidelines to heart and four years of reverence as my holy book, the time has come to toss out the old and move onto the new; CHEST 2012 is here.

Its absolutely amazing how much additional evidence has become available in four years and to see just how much has changed.  Although my work cut out for me, in reviewing the guidelines, it makes it easier to review what the experts recommend, rather than trying to go through all the trials and piece together recommendations myself.  When guidelines wait too long to provide updates, in the end, they end up discrediting themselves *cough* JNC7 *cough*

Less than a year out a pharmacy school, I still have trouble wrapping my head around some of these recommendations.  Have I become this set in my ways?

Let's look at CHEST.

Warfarin:
Warfarin can be initiated the same day that LMWH/fondaparinux/UFH is started for the treatment of VTE .  Pharmacy school hammered into my head the mantra "no loading dose, no loading dose, no loading dose" however new recommendations suggest that patients should be given 10mg of warfarin for the first two days, then dosing after that should be based off the change seen in the INR.  This recommendation seems to apply for any indication for warfarin start.  This will push the patient into range faster, examples given showed patients more likely to get to range a day ahead of patients dosed conventionally.

Rebuttal: First and foremost, I would have to review the individual trials to see if patients were dichotomized by age, but it is unclear if the guidelines are recommending 10mg for two days across the board, including our 80 year old grandmas.  I would like to see data specific to the elderly before following along.
Secondly, irregular dosing makes it more difficult to establish a starting weekly dose outpatient.  From my brief experiences in managing patients in an outpatient warfarin clinic, I have had the most difficulty dosing patients who received highly variable dosing in the hospital, which can end up meaning overshooting or undershooting their INR.

Despite this recommendation by the consensus guideline, I doubt that many of the anticoagulation pharmacists at my facility will buy into it.  The Navajo tend to be slower to respond to warfarin but much more sensitive.  For anticoagulation pharmacists across the Navajo Nation, it is hypothesized that there may be a gene that contributes to this, but we have no way of knowing which patients will be more likely to respond in certain ways.  Despite how slowly the INR budges in the first few days, some of the patients end up shooting up to incredibly high INRs in the second week.  Very little medical research is done on Native Americans (it doesn't take a rocket scientist to figure out why they may be adverse to the idea considering the history with white America) so again, I have no data to support this, but using a loading dose in this population may be more dangerous than using it in other populations.

Dabigatran.
Dabigatran 150mg twice daily is recommended over warfarin for patients with atrial fibrillation with a CHADS score of one or higher.

Dabigatran was approved for atrial fibrillation based off the results from the RE-LY trial, which only looked at 110mg twice daily or 150mg twice daily and excluded patients with a creatinine clearance less than 30mL/min.

I am so excited about the new anticoagulants, and if you understand warfarin, its not difficult to understand why.  Warfarin is a difficult drug.  But the fact of the matter is, these new drugs are relatively unknown.  It is difficult for me to consider recommending an expensive, new drug that has been studied limitedly over the gold standard of anti-coagulation that has been proven effective time and again in clinical trials.  Am I afraid of the unknown? To be honest, yes.  I know what to expect from warfarin, but I'm not entirely sure of all the risks I bestow on a patient by recommending dabigatran.

Furthermore, it is interesting that the guidelines specifically recommend only the 150mg twice daily dosing for patients with "good" renal function.  The 75mg twice daily dose was never studied in clinical trials and many of the new precautions with bleeding are specific to patients with impaired renal function, despite being on the lower dose.  A New Zealand study published in the New England Journal examined a series of case reports regarding bleeding with dabigatran showed that patients with low body weight, low renal function, and older age were at greater risk.  Furthermore, the makers of dabigatran recommend that the INR fall below 2.0 for patients previously on warfarin before starting, which may not always be adhered to.

"But dabigatran did not have that caveat; I think the government wanted it be used. They saw it as a good replacement forwarfarin and wanted as many people as possible to switch. The uptake was very quick—too quick. Doctors were very keen to prescribe it, and everyone got carried away."  Dr. Harper, the primary investigator, tells HeartWire (www.theheart.org).

To my knowledge, only two patients are taking dabigatran at my facility but are taking the 75mg twice daily dose (not according to my recommendation).  One of the patients was switched as a result of variable INR due to non-compliance.  This patient is not going to be anti-coagulated if she is non-compliant with her dabigatran, the difference is that we may not know the difference until she strokes out.

To summarize, I disagree with CHEST's "blanket-statement" recommendation and think that dabigatran should be recommended on a case-to-case basis and the greatest folly I see in the recommendation of the switch to dabigatran is to recommend it in patients who are non-compliant with warfarin.  Patients that refuse to take their anticoagulants will not be anti-coagulated.

Aspirin.
I have a couple of beefs with recommendations regarding aspirin in the new guidelines.

For patients that have undergone hip fracture surgery, there is a strong recommendation for clot prevention therapy for at least 10-14 days, out to 30 days.  Patients can use LMWH, UFH, fondaparinux, warfarin or... aspirin? really? aspirin?  It almost seems hypocritical especially because aspirin has not been recommended as sufficient clot prophylaxis in other scenarios.  LMWH is still recommended first line, and honestly I would need to see the full length VTE prophylaxis guideline to fully file my complaint on this one, but... really? aspirin?

Aspirin is recommended for anyone over the age of 50 WITHOUT symptomatic cardiovascular disease.  Aspirin is cheap and prevents clots.  In the early years of pharmacy school, I was told to give aspirin to anyone over the age of 50 AND to anyone with diabetes, regardless of age.  However, after presenting on the ADA/AHA/ACCF 2010 and U.S. Preventive Service Task Force 2009 guidelines, I began to change my mind.

The majority of trials looking at aspirin for primary prevention did not reach statistical significance additionally, practitioners are beginning to think twice about using aspirin because there absolutely is an increased risk of bleed associated with its use.  Both guidelines focus on weighing the risk of bleed against the risk of having an event.  The Task Forces break down the recommendation by age, and recommend aspirin for age cohorts based on the man's risk of CHD and the woman's risk of stroke. Check the document for the specific recommendation, but to ball-park it, use aspirin in patients ages 60-79 when man's risk of CHD is greater or equal to 10% or woman's risk of stroke is greater of equal to 10% (recommendation for use in patients ages 50-59 starts at a lower risk level ~5%).  The Task Forces do not make a specific recommendation for ages of either gender above the age of 80 due to significantly increased risk of bleed.

ADA is easier to follow but can only apply to patients with diabetes.  For men over 50 and women over 60 with an additional risk factor (smoking, hypertension, hyperlipidemia, family history premature CVD, or albuminuria) low dose aspirin is recommended.   Controlled risk factors are not counted.

The CHEST 2012 recommendation to use aspirin in any patient over 50 almost seems archaic in light of recommendations made recently by other major medical organizations.  The ADA and Task Force guidelines are fairly similar; the CHEST recommendation creates a major discrepancy among other major guidelines.

So

I may not agree with everything in the new guidelines, I may be wary to change my ways, but the great thing about the medical field is that is always changing.  A professor told me that she had been taught NEVER to use a beta-blocker in any patient with heart failure, now it is the standard of care.  These discoveries that completely change clinical practice occur on a year to year basis.  I think the best we can do is educate ourselves, read the literature, and keep an open mind.  Despite my complaints/rebuttals, I love my new CHEST which if filled with a plethora of fabulous recommendations and will help us to guide therapy to improve patient care.

References:
pending (please excuse my unprofessionalism), CHEST exec summary, Chest Anticoagulants, CHEST therapy for VTE disease, USPSTF 2009, ADA/AHA/ACCF 2010, http://www.theheart.org/article/1363757.do

The girl and the peach

I wrote this some time ago, back in September, a lot has been going on.  I feel much more settled in my new home and work environment, but I still need to set aside time to collect my thoughts.

The girl and the peach.

I was also talking to the ER pharmacist today.  We went out to breakfast at Denny’s then tried on boots.  She had worked there during her residency for three months.  The docs and nurses didn’t always like having a pharmacist there.  The ER is small and cramped.  It is often overflowing and beds are set up in the walk ways as needed.  Less critical patients are often moved out of beds and into chairs.  Space is limited.

Besides the trial of becoming accepted as a useful resource in an already crowded area came the emotional toll of seeing good people or children coming in hurt and sometimes permanently damaged from preventable circumstances.  The story that has been told to me repeatedly by ER pharmacist is the story of the girl and the peach.

A young girl (2 years old? 6 years old?) was being watched by her grandmother.  Her parents had gone out for the day.  She was eating a peach.  A slice of the peach slid down her throat.  She was choking.  Grandma called the parents.  They were still in town shopping.  They would be home later.   Grandma knew no first aid.   She didn’t even know enough to try to hit the girl on the back to help her to get it back up.  As the little girl slowly lost oxygen, she became tired.  Grandma told her to go lie down and get some sleep.

When the parents came home hours later, the girl was still sleeping and now, unresponsive.  They moved her into the truck and drove the the ER.  By the time she had gotten there, she had had the peach lodged in her throat for hours already.  She was blue and unresponsive.  As the doctors pounded on her tiny chest and struggled to get breathing tubes down into her throat, they saw a tiny heart rate come back.

A child’s heart is very resilient, the pharmacist told me.  It will keep beating even after they’re gone.

The little girl was probably already gone long before she came into the ER, but they continued to struggle to save her life.

Eventually, the heart monitor showed only a flat line.  She was gone.  She died because she had choked on the soft flesh of a peach and her family was so uneducated about basic first aid that the only recommendation her grandmother had given her was to go lie down in her room.

We all cried that day, she told me.