Clinical Prediction Rule for Clostridium Difficile

Provided for information only; in no way can the use of such a tool supplant your clinical judgement and no warranty of any kind is made or implied

Pulmonary Hypertension

Today we discussed pulmonary hypertension.  Here are some follow up articles

First, see this post (though it is a bit old it touches on key points we discussed today and has some references)
http://internalvalidity.blogspot.ca/2008/12/day-144-pulmonary-hypertension.html

Pleural effusions due to right heart failure and pulmonary hypertension?
 
Pleural effusions without other clear cause are common in PH
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/21623177

Here is another article stating the same thing, written by Dr. LIGHT (i.e. light's criteria for exudate vs transudate fame)!   The majority are UNILATERAL (60%) and small (63%)
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/19395582

This is especially true in collagen vascular disease associated PH
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/21212140

What is the value of CT thorax in these patients?
 
An interesting review of the value of CT thorax in PH in terms of associated findings is here:
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/25523307

Referral to specialized clinics may be associated with better outcomes

http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/23568223

Associated editorial:
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/23568571


Finally, should we be more optimistic about the role of calcium channel blockers than I was in 2008?
 
The role of Calcium Channel Blockers in PH therapy is reviewed here
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/25666253

Case of the Week -- TTP

Please see previous post on Thrombotic Thrombocytopenic Purpura (TTP):
http://internalvalidity.blogspot.ca/2008/10/day-110-ttp.html

The ORIGINAL CASE REPORT by MOSCHCOWITZ in 1925 Archives of Internal medicine!
http://archinte.jamanetwork.com.proxy3.library.mcgill.ca/article.aspx?articleid=534853

2006 NEJM Review of the topic:

http://www.nejm.org/doi/full/10.1056/NEJMcp053024

Classic FFP in TTP paper (FFP is better than nothing):

http://www.nejm.org.proxy3.library.mcgill.ca/doi/full/10.1056/NEJM197712222972507

The Classic PLEX is better than FFP paper:

http://www.nejm.org/doi/full/10.1056/NEJM199108083250604

Drug-induced TTP:

http://www.ncbi.nlm.nih.gov/pubmed/25414441

HIV presenting as TTP (I've seen two!):

http://www.ncbi.nlm.nih.gov/pubmed/7926980

Risk of relapse in TTP:

http://www.ncbi.nlm.nih.gov/pubmed/7887549

Bonus -- approach to hemolytic anemia from my CMR teaching deck

http://chiefmedicalresident.blogspot.ca/2008/08/day-39-anemia.html

CIDP in Renal Transplant

Great case presented today

Here is the relevant reading:

Caused by tacrolimus:
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/25874089

Case series in solid organ transplant:
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/22577230

Due to CMV:
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/10489240

Review of drug induced CIDP and other similar neuropathies (mentions tacro!):
http://www-ncbi-nlm-nih-gov.proxy3.library.mcgill.ca/pubmed/12352008

Weekly blog - "Procalcitonin"

Today we discussed a case where the treating physician ordered a procalcitonin assay to decide whether or not the patient had a bacterial respiratory infection.  The result was (very) negative.  Nonetheless they continued antibiotics.  Was that the right decision?

This Lancet ID meta-analysis looks at the operating characteristics of the test.  There is a lot of heterogeneity of the pooled studies which is a caveat.  But to me, I'm not sure that a pooled sensitivity of 77% and specificity of 79% is all that impressive.

This would yield a positive likelihood ratio of 3.6 and a negative likelihood ratio of 0.27

If the patient has a 20% pre-test probability of bacterial sepsis the test would perform as follows:

Positive predictive value = 47%
Negative predictive value = 6%

(FYI the numbers for 10% and 30% are 28%/3% and 60%/12%)

Does that help you in the care of that patient?  Maybe if it is negative; however, it depends on the context and how ill the patient is and the consequences of being among the 6%.

FYI as of 2012 an estimate of the per unit cost was $10-15 for the test...  Given the volume of tests which would be (maybe unnecessarily) ordered in the emergency department each day it is no wonder that not all hospitals cover the test (ours does not at time of posting).  See technology assessment 2012 available online here.

Weekly blog -- "Ebola"

We discussed Ebola today.  Rather than blog I will shamelessly plug local work... See "Five things to know about Ebola"

Weekly blog -- "Aggressive lymphoma in an elderly patient"

Some take home reading:

This lancet oncology article discusses the challenges in treating elderly patients with hematological malignancies (link)

It also addresses "pre-chemo" treatment for DLBCL including corticosteroids for 7 days to be helpful in patients with poorer ECOG status to see if there is an improvement (but likely not helpful in ECOG 0-1)

For DLBCL reduced dose CHOP with full dose rituximab seems (on the basis of 2012 article) to be the best therapy for suitable patients.  Overall survival quoted in the article ranged from 35-56% at three years.

Standardized geriatric assessment may be helpful in deciding on a treatment strategy (link)

Burkitt's lymphoma may be another animal compared to other DLBCL -- with median survivals measured in months for patients over age 70 (link) ... And with CHOP-R 2 year progression free survival is less than 30%

HyperCVAD isn't tolerated by the majority of elderly patients.

EPOCH has not been tested in the elderly, but has been investigated with some success in the younger populations (link)

Really, a clinical trial is needed.

*****

On to rasburicase -- a pricy little addition to TLS management --

One way to reduce cost is to use less drug -- this meta-analysis suggests one dose may be as good as a full course (link) as does this smaller study (link) and this one where they saved 2 million dollars over 48 patients... (link)  There are more articles on this showing the same thing... (here too)

One could consider adding allopurinol after rasburicase (link) -- though it may not differ to single shot rasburicase

What was interesting is that in 2010 a Cochrane review in CHILDREN could not find an effect for the drug on renal failure or mortality (link)

A meta-analysis in ADULTS was performed (but not meta-analyzed due to heterogeneity) in 2013 which showed that uric acid goes down, but couldn't confirm hard outcomes either (link)

For a drug which costs up to $3600 per 7.5-mg vial (and you get 0.2mg/kg x 5 days if you follow the manufacturer's instructions) that is more than $30,000 per person treated (we pay much less if local data is believable)...  Amazing there is no better RCT data on this drug which is recommended for anyone with "high TLS risk, being >5%" or intermediate TLS risk (1-5%) with comorbidities.

For those interested in cost-benefit articles -- here is one on rasburicase (link) which makes a number of assumptions and states the drug is cost-effective...  I couldn't find the conflict of interest statements from the authors.  Also the cost of the drug modelled was only $2200 for adults (total course).   

Assuming the drug is only 3 times that price.  I'm pretty sure this would yield significantly different conclusions about its cost-effectiveness.  The CER for PREVENTION in ADULTS would be $120,000.

For treatment, that would depend on whether or not it works to prevent the downstream costs... and as I eluded to above, that is unclear.