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The things patients bring in


My favorite patient encounters almost always involve the patient bringing in something they found in a newspaper or magazine. The best ones are fully annotated with the patients thoughts and comments. Typical subjects are: alternative medicine, vitamins, noni juice (don’t get me started), new tests or scare mongering articles about drugs I have prescribed.

The other day one of my patients brought in a list of the 50 most prescribed medications according to the AARP. Jackpot.
I have transcribed the data into excel so I could abstract some of the data. The raw excel file is here.
I have three charts from the excel file that are interesting, the first is just a graph of the number of prescriptions with the retail cost overlaid. Can you spot the brand name drugs:
I then simplified the data by removing the noise from the individual drugs and used the indications for each drug. Here is that data by number of prescriptions and then by cost:
You can see the disruption caused by the brand name drugs which catapult PPI (ulcer/heart burn medications) from 5% of the prescriptions to 17% of the cost and take statins (cholesterol) from 9% of the prescriptions to 18% of the cost. Can you imagine how the chart looked before Zocor (simvastatin) went generic?
There are no insulins on the list, so I wonder if there other absences.
What does it say about the U.S. that 3 of the top 6 indications for therapy are pain, depression and anxiety?
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Geriatric nephrology hits the NEJM

The introduction references the following study and states that in 1999:
  • Nursing home residents represented 4% of the people starting dialysis
  • Nursing home residents represented 11% of the people initiating dialysis over the age of 70
  • First year mortality is 35% for patients older than 70
  • First year mortality is 50% for patients older than 78
The investigator used the USRDS and The Minimum Data Set, a database of nursing home residents that all Medicare and Medicaid certified nursing homes must participate contribute to. The study cohort consisted of people who were in the nursing home prior to starting dialysis. Patients were included if they had a functional status assessment prior to initiating dialysis. This resulted in a cohort of 3,702 residents.
Functional status was measured by grading the following skills on a scale from 0 (total independence) to 4 (dependence):
  1. eating
  2. dressing
  3. toileting
  4. maintaining personal hygiene
  5. walking
  6. getting up out of a chair
  7. moving around in bed
Increases in scores A second measure of functional status, MDS-ADL, was also used. Demographic, co-morbidity data was collected from the Form 2728 genereated by the nephrologist at the time of the initiation of dialysis.
200 patients were excluded from the analysis because they failed to have a funcrional status assessment prior to starting dialysis. These patients were healthier than the study cohort. I don’t feel this is a critical bias as this represented a rather small fraction of the cohort. My guess is the results of this study fairly represent the population of dialysis nursing home residents.

The key points are beautifully rendered in two charts. The first shows the mortality of the cohort following the initiation of dialysis:
The bars represent the timing of the ADL assessment. The dotted line is cummulative mortality. The red arrow is the half-life of this population. Half the cohort is dead before 9months!
Looking at the mortality alone one must wonder if the patients are receiving any survival benefit from dialysis. It is hard to imagine the mortality is much worse if they didn’t get dialyzed.
The meat of the article is in next graph that shows the distribution of functional status every 3 months. It goes back a year prior to initiating dialysis and follows forward for the first year after initiating dialysis. Patients demonstrate a stable functional status until the 3 months prior to starting dialysis. In the three months prior to initiation there is some subtle decreases in functional status but that really accelerates as soon as they start dialysis.
The combined end points of death and deterioration are shown in a bleak graph:

What a depressing study, both mortality and morbidity. It forces nephrologists to question the role of dialysis in nursing home residents. This is a population that does terrible on dialysis.
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After 20 years of learning I still get clinical scenarios that are total blanks

I have a patient who had an Type B aortic dissection from her left subclavian artery to somewhere south of the renal arteries. She was managed medically. Today, a decade removed from the aortic dissection, she was admitted with recurrent expressive aphasia. As part of that work-up she received a carotid doppler that did not show carotid narrowing as we were looking for but rather a carotid tumor.
She received a CT angiogram of her neck to evaluate the tumor. The CT scan revealed bilateral upper lobe pulmonary emboli. As far as we can assess these have been asymptomatic. I told her we are going to anticoagulate her but and she refused on the basis that it could worsen her dissection. The dissection was still present on the most recent CT scan.
What a bazaar scenario:
  • Decade old type B aortic dissection
  • recurrent TIAs
  • carotid bulb tumor
  • bilateral pulmonary embolism
  • patient belief that anticoagulation is bad for patients.
Here is a review of conservative aortic dissection management from the Annals of Thoracic Surgery.

We examined all case records for acute (less than 2 weeks) type B aortic dissection treated at The Mount Sinai Hospital since 1985. The review identified 68 patients, 42 male and 26 female, with ages ranging from 32 to 96 years (mean, 65.5 years)…

… Follow-up ranges from 0 to 112 months (mean, 31 months). Medical therapy consisted of aggressive antihypertensive and “antiimpulse” therapy. Patients with unremitting pain or uncontrollable hypertensiondespite this regimen underwent early operation. Urgent operation was also performed for rupture or significant aortic dilatation (greater than 5 cm). Recently, malperfusion, initially an indication for operation, has been relieved using percutaneous catheter fenestration [1–3]…

No difference was found in one or five year survival when the cohort was divivded by the timing of the surgery. No attempt was made to look at the year of enrollment and whether that a difference in survival.

Another case series: Management and long-term outcome of aortic dissection. (Full Text). Mixes Type A and B patients.

I could find no evidence to support the patient’s belief that she should avoid anticoagulation.

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Pharma and Medical Education

Jose Arruda, Chief of Nephrology, UIC Medical Center
I was excited to see Dr. Arruda on the schedule to speak at our fellowship. This is one of the best aspects of being an academic nephrologist; we get prominent nephrologists from around the country to speak to our department.
When I saw the title of his lecture was A New Approach to Hyponatremia, I knew we were going to get the vaptan story (PDF).

Otsuka is pushing tolvaptan (Scamsca™) hard. We are getting detailed a lot, and I hear that the cardiologists are also getting an earful. Honestly, the data looks a little thin to me. The drug is the most reliable method for tackling persistent SIADH. But that’s rare. In my experience, usual care fixes almost every case of hyponatremia within a day or two. There are a minority of cases that don’t respond quickly. These episodes of persistent hyponatremia worry me. Unfortunately, tolvaptan doesn’t feel like a good option for these patients. We know from the SALT studies that a week after you stop the drug the sodium equals the control group and the drug costs $300 per day (average wholesale price (PDF), retail price). I find it hard to prescribe a $9,000 per month drug for chronic therapy. I’ll stick with salt tablets, furosemide and water restriction.

Arruda’s lecture was on tolvaptan and the first slide was giving some background on hyponatremia and he commented that “I hate this slide.” I can’t imagine putting together a presentation and flying 500 miles to present it and loathing the very first slide.
It is illustrative of what is wrong with academic nephrology. Dr. Arruda hates the first slide in his deck. Why doesn’t he remove/fix/change the slide? Because the slide deck has been vetted by the FDA and Otsuka’s lawyers. He can’t change it. He has signed a contract saying he won’t change it. Dr. Arruda gave a solid, thoughtful lecture to our department, but he did that in spite of the materials he was using. He spent considerable time just talking about the pathophysiology of sodium and did a better job than most at avoiding being a mere shill for Otsuka.
Our nephrology program, and I suspect others (most?) rely on the generosity of pharma companies to bring scientists to our program but we pay by letting the drug companies supply the slides. Tragically, those slides are vetted by people uninterested in education and devoted to meeting the conflicting demands of both the marketing and legal departments.
Dr. Arruda seems like a good guy and is a highly respected nephrologist but the only way we could get him to come to Detroit was on Otsuka’s dime and they were able to control the message.
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Highest PTH

Intact PTH of 3,420.7 in a dialysis patient. Calcium 9.7 phos 6.1. On 18 mcg of paricalcitol q treatment and cinacalcet 90 mg daily. Patient is getting excellent dialysis with eKt/V of 1.69 on 210 minutes of dialysis.

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Articles that changed the way I practice: Sodium intake, hypertension and mortality

I have long been skeptical towards the party line that salt intake is a driver of high blood pressure, as I wrote here and here. Though hypertension is nearly unheard of in primitive cultures with sodium intake below 50 mmol/day (1.6 g day), increasing sodium intake has modest effects on blood pressure. Three mm of systolic per 100 mmol of sodium (2.3 grams) according to the Intersalt Study (PDF). This 3 mm of systolic agrees with the change in blood pressure in the DASH-Sodium trial. Similar effect size has been documented in meta-analysis:
  • A 2002 meta-analysis by Lee Hooper of 11 trials of at least 6 months duration found a 1.1/0.6 mmHg reduction from a 35 mmol (810 mg) reduction in sodium intake.
  • A broader meta-analysis published in JAMA in 1998 looked at 114 trials and found a reduction of 3.9/1.9 in hypertensive patients and 1.2/0.3 in normotensive participants.
Despite these seemingly modest results all of the clinical practice guidelines on hypertension have adopted sodium restriction as a key part of blood pressure control:
My position when talking with patients about dietary modifications for high blood pressure had been to mention sodium restriction and weight loss but focus on the DASH diet (PDF) and exercise. But this strategy has recently evolved as I became aware of a pair of studies, one by Cook et al which strengthened the sodium argument and one by Larry Appel which weakened his own DASH research.
The Rise of Sodium
The article by Nancy Cook is a follow-up on the Trial of Hypertension Prevention I and II. These were randomized controlled trials of patients with high normal blood pressure which tried to determine which lifestyle modifications were effective. Patients randomized to sodium reduction were given individual and group counseling sessions on how to reduce sodium in the diet. After 18 months the patients in the TOHP I reduced sodium intake by 44 mmol/day (1 g sodium) and blood pressure fell 1.7/0.8 mmHg. In TOHP II, after 36 months, sodium intake was reduced by 33 mmol/day (750 mg of sodium) and blood pressure fell 1.2/0.7. The decreases in blood pressure in both studies are unimpressive.
Cook went back to these studies, 10 years after TOHP I and 5 years after the completion of TOHP II, and looked at the rate of cardiovascular events (primary outcome: MI , CVA, CABG, PTCA, CV Death). They found a 25% reduction in events in patients in the low sodium group (p=0.04) that increased to 30% reduction when the study was adjusted for baseline sodium excretion and weight. These results are incredible to me, modest reductions in sodium intake that were achieved through patient education had negligible effects on blood pressure but dramatic benefits on morbidity.

The strengths of this evidence comes from two lines of reasoning:
  1. It is a randomised trial. Even though the current data comes from an observational extension of the original RCT, this does not change the fact that we are looking at two groups that were orignially randomized.
  2. This is a study which looks cardiovascular events rather than blood pressure or other intermediate outcomes.
The fall of the DASH
The DASH Trial (Appel 1997) used a diet rich in fruits and vegetables to provide increased fiber and potassium along with other trace minerals. Low-fat dairy products provide increased calcium while keeping the diet low in saturated and total fat. Participants randomized to the DASH diet were served meals with 4-5 servings of fruit, 4-5 servings of vegetables, 2-3 servings of of low fat dairy and <25%>

The results were dramatic:
  • Decreased blood pressure of 5.5/3.0 mmHg
  • Decreased in hypertensives 11.4/5.5 mmHg
  • Maximal blood pressure response occurred after only 2 weeks

The primary weakness in the DASH trials is that I’m not going to provide my patients with all of their food. It is not a clincally relevent intervention. As physicians, all we can do is educate and cousel on diet. Appel did a follow-up study where he did just that and the DASH was no longer so impressive.
The PREMIER Trial randomized patients to three groups:
  1. Control group with no interventions
  2. Standard advice: 18 face-to-face meetings to go over weight loss, and strategies to reduce sodium and alcohol consumption
  3. Standard + DASH: 18 face-to-face meetings with the same contant as the standard group with additional counseling on adopting the DASH diet
Counseling resulted in significant weight loss of 5 kg in both experimental groups versus loss of 1 kg in the control group. There was no difference in physical activity, but physical fitness did improve from baseline all three groups. They didn’t find a reduction in alcohol or sodium intake however there was good separation in the potassium intake with the greatest increase in potassium in the DASH group as would be expected. Both of the experimental groups had greater reductions in blood pressure than the control group. 40% of the patients randomized to the Standard advice and 48% of the patients in the Standard + DASH were able to lower their blood pressure below 120/80. This difference was not statistically significant.

There was no improvement in blood pressure control with the addition of the DASH diet over counseling patients on established risk factors.
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Most insulting/funny sentence ever from a consulting doc

I have a new patient that I inherited from a former colleague. She came to me with a letter from her ophthalmologist addressed to the patient that she was suppposed to give to her primary care doctor and nephrologist.

Here is the money quote:

I am going to give you a copy of Harrison’s textbook to look for secondary causes of hypertension.

When the patient came in she didn’t have the book so I have no idea how to re-run her work-up of secondary hypertension (which had been done multiple times in the past).

Hey asshole, next time you have a bad outcome on one of your patients I’ll make sure I send you a copy of Clinical Ophthalmology: A Systematic Approach. What a dick.
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I just gave the world’s greatest lecture on diabetic nephroapthy

It was incredible. The residents, who usually sleep through the second half of noon conference, were completely charged up and by the end of the lecture were holding up lighters and chanting my name. I dove from the stage and was passed around like a Rock God.
Here is the lecture in powerpoint format to download. You can also see the Slideshare but they mangle the animations so if you want to really feel the educational frenzy download the .ppt.