...two current reviews. One is detailed in physiology and management but is only available online with subscription [1]. The other is a practical clinical review that is freely available online [2].
The six minute walk test (6MWT) is often cited in studies and guidelines. To do one, try the American Thoracic Society published guideline [1]. They recommend a 100-foot hallway.
Results are measured in meters walked. For healthy older adults the mean distance in six-minutes was around 630 meters in one study. How much of an increase in distance suggests improvement? One study suggested that "...for individual patients with COPD, an improvement of more than 70 m...after an intervention is necessary to be 95% confident that the improvement was significant."
The benefit of measuring brain natriuretic peptide levels in dyspneic patients presenting to an emergecy room is reviewed online in BMJ [1, 2].
To estimate the civilian death toll doctors from Johns Hopkins Bloomberg School of Public Health and the College of Medicine of Al-Mustansiriya University in Baghdad surveyed 30 clusters of 30 households; 6300 people. [1, 2, 3]. Full-text online after free sign-in. This much-broadcast study estimates 100,000 deaths from January 2002 to March 2003. Research in the time of war cannot be easy. To critique methodology may seem to deny the tragedy of human loss.
Methodology
People who were surveyed knew the purpose of the survey. Unclear is how many of the reported dead family members were engaged in combat activity. Confirming deaths was problematic, often not asked for by surveyors to avoid "triggering violence" in those surveyed.
Asking or Inciting?
"Interviewers were initially reluctant to
ask to see death certificates because this might have
implied they did not believe the respondents, perhaps
triggering violence. Thus, a compromise was reached
for which interviewers would attempt to confirm at least
two deaths per cluster. Confirmation was sought to
ensure that a large fraction of the reported deaths were
not fabrications."
Combatants or Civilians. Both?
"Many of the Iraqis reportedly killed by US forces could
have been combatants. 28 of 61 killings (46%) attributed
to US forces involved men age 15–60 years, 28 (46%)
were children younger than 15 years, four (7%) were
women, and one was an elderly man."
An Admonishment.
"This survey shows that with modest funds, 4 weeks, and
seven Iraqi team members willing to risk their lives, a
useful measure of civilian deaths could be obtained.
There seems to be little excuse for occupying forces to
not be able to provide more precise tallies. In view of the
political importance of this conflict, these results should
be confirmed by an independent body such as the
ICRC, Epicentre, or WHO."
King Pharmaceuticals has limited its fulfillment of methimazole (Tapazole) indigent requests. Propylthiouracil (PTU) is a less expensive alternative [1, 2]. Locally PTU is $12.00/100 tablets.
B12 (cobalamin) deficiency can respond to oral replacement [1]. 1000 micrograms per day by mouth can treat pernicious anemia.
David Blumenthal reviews "Doctors and Drug Companies" in this week's New England Journal of Medicine [1]. Not a new topic, but goodwill and more are still easily bought with flattery or a small gift.
And then there are rofecoxib (Vioxx, gabapentin (Neurontin), levoxyl (Synthroid) and other pieces of history [2, 3, 4, 5].
...can be a complication of liver metastases [1].
Brown recluse spider images [1, 2, 3, 4]. These images give a better sense of size. (Normal leg extension reportedly the size of a quarter. Body said to be one-half inch.)
One page describes the range of the spider (Cincinnati being on the northeastern edge.)
What are the diagnostic criteria for Marfans (family history, aortic aneurysm, lens subluxation, long-limbed habitus)?
...I have asked our library for a copy of a recent review. [De Paepe, A. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62(4):417-26] Fibrillin testing seems not to be used diagnostically, lacking sensitivity and specificity.
Aortic Surgery
When is aortic surgery warranted?
...Another paper followed outcomes for 675 patients with Marfans after aortic root surgery [2]. An aortic route diameter of 5.5-6 cm indicated surgery even without symptoms. Images of aortic surgery in Marfans can be found online [3]
Diagnosis in Adulthood
Mayo clinic has published a series of Marfan's diagnosed in patients 32 years of age or older [4]. (Higher prevalence of aortic disease.)
Eye Findings
The Cleveland Clinic looked at final diagnosis in 75 patients referred to opthalmology for assessment of possible Marfan's Syndrome [5]. (Average age 23.5.) 78% of suspected Marfan's cases referred with eye symptoms did have lens subluxation and a final diagnosis of Marfan's. Two of six self-referred patients (having learned of the diagnostic possibility through publicity) ultimately were diagnosed with Marfan's syndrome.
Palm offers a helpful list of tips for better use of their interface [1].
The Kerry & Bush measured proposals for the uninsured are reviewed in a free article online in the New England Journal of Medicine [1]
One interesting point compares the ten-year costs of the uninsured plans to the ten-year costs of the Medicare drug bill.
Ten-Year Costs (billions)
$500 Medicare Drug Bill
$630 Kerry Uninsured Plan
$90 Bush Uninsured Plan
Number Uninsured Covered (millions)
27 Kerry
2.4 Bush
Kerry's plan provides insurance for 27 million of the 45 million uninsured. Bush's plan extends coverage to about 2.4 million people. Doing the math (my math, not the article's) this would work out to ten-year costs per uninsured person covered of: Bush $37,500 and Kerry $23,000.
As in the 1960's when Medicare was passed is it easier for our society to see the needs of the elderly than those of the uninsured? The Medicare drug bill meets less political resistance than a plan for the uninsured. (Are the uninsured less visible? Is it a matter of personal responsibility? Is it easier to imagine that we all get old?) [2]
Of those who were uninsured for the whole year, nearly 90% have a family member who was employed full-time or part-time during the year.
Ralph Nader's plan was not reviewed in this NEJM article but it can be found online [3]
At our P&T meeting we talked about whether celecoxib (Celebrex) as well
as rofecoxib (Vioxx) will be shown to be associated with increased risk
of myocardial infarction--a class effect.
Coxibs, Heart Risk, and Physiology
Garret FitzGerald reviews this association this week in a pre-release
article in New England Journal of Medicine [1]. He is concerned that both coxibs raise the risk of cardiovascular disease by inhibiting prostaglandin I2. (To paraphrase, he says that prostaglandin I2 is the predominant cyclooxygenase product in endothelium. It inhibits platelet
aggregation, causes vasodilatation, and prevents the proliferation of
vascular smooth-muscle cells in vitro.)
"The individual cardiovascular effects of prostaglandin I2 in vitro
contrast with those of thromboxane A2, the major COX-1 product of
platelets, which causes platelet aggregation,vasoconstriction, and
vascular proliferation. Whereas aspirin and traditional NSAIDs inhibit
both thromboxane A2 and prostaglandin I2,the coxibs leave thromboxane
A2 generation unaffected,reflecting the absence of COX-2 in platelets."
"Thus, a single mechanism, depression of prostaglandin I2 formation,
might be expected to elevate blood pressure, accelerate atherogenesis,
and predispose patients receiving coxibs to an exaggerated thrombotic
response to the rupture of an atherosclerotic plaque."
Coxibs, FDA and the Marketplace
In a second article the history of the clinical research into the
heart-risk of coxibs and FDA oversight is reviewed by Eric Topol [2].
A Related Subject (Class Effects of Statins)
Speaking of class effect of drugs, at the end of our P&T Meeting
mention was made of the story of cervastatin (Baycol) and this statin's
withdrawl from the market in 2001 for rhabdomyolysis. The FDA site reviews that old story [3].
A prospective NIH study of the biochemical and cognitive effects of
statins is underway, coordinated by the University of California San
Diego. The concept of that study, and an good review of statin adverse
effects, can be found online [4].
This week's JAMA has this image of aquaporin proteins, and a brief review of recent progress [1]. Dr. Peter Agre won last year's Noble Prize in medicine for this serendipidous find. The article speculates as to aquaporin's role in cataracts, congestive heart failure, diabetes insipidus, etc.
Wednesday 9:00 Conference discussed a young woman with postural orthostatic tachycardia (POTS) worsened by pregnancy [1,2,3,4]. Curiously she had a past episode of optic neuritis.
Optic neuritis can be associated with the multiple sclerosis [5]. Multiple sclerosis can be associated with autonomic abnormalities [6, 7]. While multiple sclerosis can remit with pregnancy [8] I seem to recall a "demyelinating disease of pregnancy" (I will look for evidence of this [9]). How these come together in a particular individual is unclear. MRI could help, or complicate.
