Timely Literature, Internal Medicine & Pediatrics

Therapy for Bronchiolitis?

2009-06-10T23:53:00.003-04:00

You could knock me over with a feather. I've watched bronchiolitis attack vulnerable infants over the last four years. There hasn't been much we could do. Supportive care? Nasal saline, intubate or NIPPV for respiratory failure, some people use oxymetazoline drops for the snotty noses thwarting the respiratory efforts of our little obligate nose breathers. Now it seems that there may actually be something helpful to offer. The literature is rife with randomized trials that fail to show that albuterol, racemic epinephrine, or steroids offer any benefits.

The fine folks at Cochrane published an analysis of 4 trials looking at nebulized hypertonic saline for acute bronchiolitis last fall. I have not been able to access the full text at home, because either I am too dim-witted to figure it out, or OSU doesn't subscribe to the most influential EBM resource available. Hopefully the former.

The bear of bronchiolitis is that it attacks the upper respiratory tract via snotty nose and it attacks the lower respiratory tract with more mucous and sloughed epithelium. This is a tough 1-2 punch for infants with little reserve.

Inhaled hypertonic saline has been used to augment airway clearance in CF over the last few years, so it only made sense to try it in infants. The 4 trials reviewed were small, so the total number of patients analyzed was small (254). They looked at both inpatients and outpatients and showed reduction in Length of Stay (LOS) by one day. They also found improvement in clinical score.

Well, according to the cochrane review and the 2007 paper from the journal of pediatrics, it evidently works. In the 2007 paper they gave it every 2 hours for 3 doses and then every 4 hours for 5 doses and then every 6 hours.

There doesn't seem to be a downside.

Anybody used hypertonic saline nebs for acute bronchiolitis?

POISE

2009-02-28T09:44:00.004-05:00

I spent a half day a week this month in preop clinic. While there, I took the time to go back and read the POISE trial that much ado was made about last year. POISE was a randomized placebo controlled, I believe double blinded study of extended release metoprolol in patients undergoing non-cardiac surgery. They had >8000 patients. MANY studies have shown the benefit of perioperative beta blockade in reducing perioperative MI, the internist's most feared perioperative complication.

POISE verified this finding, with reduction in nonfatal MI, but they discovered that more people died in the metoprolol group. Oops. What did they die of? Stroke. There was a 0.5% increase in stroke in the metoprolol group (statistically significant).

What the hell happened?

Well, if you look at their methods it is instantly obvious what went wrong. The treatment arm, whow as beta blocker naive, received a whopping 100 mg of extended release metoprolol 2-4 hours before their surgery. They chased it with another dose 6 hours postop, or earlier if they ad a HR > 80 or SBP >100. WOW! That's a lot of metoprolol for somebody who has never seen the drug before. 200 mg total of extended release metoprolol a day was then continued for patients that were able to tolerate it without severe bradycardia or hypotension. Gee, I wonder where the strokes came from? Any IM intern could have seen this coming.

Two take-home points here. Peri-operative betablockade doesn't need and shouldn't have the mega doses used in this trial. Also, if you have time before surgery, why not establish the drug for a week or two beforehand?

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60601-7/abstract

ACC/AHA 2007 guidelines for perioperative cardiovascular eval for non-cardiac surgery

Cough, Cough

2009-02-04T18:08:00.003-05:00

Well, sometimes it seems that nearly every patient you see in an outpatient clinic at this time of the year has a URI. I find myself constantly giving instructions that may or may not be helpful: "Use a cough suppressant with dextromethorphan", "Use a nasal spray with oxymetazoline either during the day so you can breathe and sound normal at work" (the way I do it) or "use a nasal spray with oxymetazoline at night so you can breathe and sleep". My personal favorite: "Drink plenty of water." These conversations are even more common now that cold medicine is essentially off the market for kids. So I embarked on a literature search to figure out if any of this stuff is really helpful. I searched for:

"upper respiratory infection" "supportive care" efficacy

and came up with the article I refer to here. I had heard of this study before, but I had never read it.

The authors at Pennsylvania State randomly assigned 105 patients to receive either buckwheat honey, dextromethorphan thickened and artificially flavored like honey, or nothing. It is not clear if the "nothing" syringe contained a placebo, but I suspect it did. The study population was kids 2-18 with a diagnosis of URI. They asked parents about the patient's coughing frequency, severity, bothersome-ness, affect on patient sleep, and affect on parent sleep. This was surveyed on presentation and diagnosis with the URI and again after treatment. In paired comparisons, honey was superior to "nothing" for cough frequency and combined symptom score. It was also "marginally significant" for child sleep and bothersome nature of cough. It was not significant for cough severity or parents sleep. No difference was detected between dextromethorphan and honey.

Interesting stuff. Maybe I should be comfortable recommending honey for cough. They go on to hypothesize about how this might actually work. There are theories about sweetness leading to reflex salivation, secretion of airway mucous, and a "demulcent effect" in the pharynx and larynx. There is also a theory about these secretions improving mucociliary clearance in the airway via an expectorant mechanism.

LINK

Statins role in CAD

2009-01-18T19:44:00.004-05:00

The chiropractor for whom my mom works tried to dissuade my dad from continuing to take statins based off an article: "Dr. Julian Whitaker's Health & Healing-Your Definitive Guide to Wellness Medicine".
Dr. Whitaker's claim is that MI's are caused from inflammation and have nothing to do with cholesterol. Recent research is finding that the role of inflammation is much more involved than originally thought. So Dr. Whitaker has some validity in his claims.
http://content.nejm.org/cgi/content/abstract/336/14/973
http://circ.ahajournals.org/cgi/content/full/105/9/1135

However extensive research still shows that cholesterol plays a role in CAD.

http://jama.ama-assn.org/cgi/content/abstract/285/4/430
http://content.nejm.org/cgi/content/abstract/344/26/1959
http://jama.ama-assn.org/cgi/content/abstract/282/24/2340

The last link is a meta-analysis of Medline articles from 1966 to 1998 on CAD and statins.

Furthermore, Dr. Whitaker's references are a bit concerning: Business Week, 2 science articles-1 from Biofactors and 1 from Circulation (seemingly valid), and a book.

Finally, statins not only help reduce cholesterol, but also help reduce inflammation, which could be another factor in which they are helping to reduce MI's. So be it cholesterol or inflammation, research has shown that statins continue to lower MI's.

"Dr. Julian Whitaker's Health & Healing-Your Definitive Guide to Wellness Medicine". June 2008. Vol. 18; no. 6; pp. 1-3

Soy Beans

2009-01-05T21:42:00.000-05:00

So remember studying for Step 1 and having to know that vegetarians are at an increased risk for B12 deficiency? Well, I came across an article talking about the benefits of soy beans. If fortified w/cobalamin as some soy products are, it looks like being a vegetarian isn't so "risky" and actually beneficial.
To make this article peds related...I found it interesting that babies on soy formula can have decreased absorption of iron or thyroid hormone supplementation. Furthermore, soy contains tyramine so could cross react with MAOI's.
Key points from article:

Advantages:
-reduce cholesterol, LDL, and TG levels.
-reduce menopausal hot flashes
-reduce bone turnover-->improve bone mineral density
Disadvantages:
-diarrhea (common)
-Rare:menorrhagia, amenorrhea, HA, dizziness, MSK complaints

Article from American Family Physician, Vol 79, No. 1, Jan. 1, 2009
Michelfelder, Aaron J., MD. "Soy: A complete Source of Protein", pp. 43-47

Burnout and Suicidal Ideation among U.S. Medical Students

2008-12-28T09:03:00.000-05:00

I came across this article in the Annals a few months ago. I have been tapped to lead an electronic journal club in January, and this is the article that I will be using. If anyone has any input that they want included in the discussion, lets hear it.
Linky
I know the authors from medical school and have a great deal of respect for them. I exciteded to give it a critical read and will post my thoughts here soon. I will say though, that I know these are huge issues for some medical students.

Cats, Toxoplasmosis, and Pregnancy

2008-12-11T19:42:00.000-05:00

The other night, my vet student roommates lectured me that we "human medicine" doctors need to stop scaring people about pregnant women getting toxoplasmosis from changing garfield's litter box. They claimed that kittens are the only ones to shed it in their feces. So I had to find some proof and here are the articles supporting their claim. In the limited time I spent, I didn't find an article specifically talking about kittens vs. cats, but this is just some of the articles that popped up on OMIM.

Sources of toxoplasma infection in pregnant women: European multicentre case-control study

This was a case control study performed in 6 European cities using 252 pregnant women w/either acute infection or w/IgM for anti-Toxoplasma gondii and 858 controls. Risk factors for infection included undercooked lamb, beef,or game, contact with soil, and travel outside Europe and theUnited States and Canada. Contact with cats was not a risk factor.

Article found on: http://www.bmj.com/cgi/content/full/321/7254/142?view=full%26pmid=10894691

Prevention of toxoplasmosis in pregnancy: knowledge of risk factors.Kravetz JD, Federman DG.

Study was done to compare the knowledge of ocer 100 ob's, internists and fp's when counseling expectant mothers on risk factors for toxoplasmosis. It was found that ob's were more likely to give the appropriate information, but all groups "inappropriately advised avoidance of all cat contact".

Article found on OMIM taken from Infect Dis Obstet Gynecol. 2005 Sep;13(3):161-5.

palivizumab for RSV

2008-12-02T21:42:00.000-05:00

Tis the season. We spend a lot of time and money getting Synagis (Polivizumab) for our most at-risk patients. How much benefit is there to be gained here?

Two trials, one from the IMpact-RSV Study Group published in Pediatrics in September of 1998, and one from the Cardiac Synagis Study Group, lead author, our own Timothy Feltes, established the role of polivizumab in preventing morbidity in high risk pediatric populations.

1. IMpact-RSV trial Cliff's Notes

Palivizumab is a humanized mouse monoclonal IgG antibody against the F protein of RSV.

In the study, 15 mg/kg IM polivizumab or placebo was administered monthly for 5 months to infants with GA less than or equal to 35 weeks who were <6 mos of age or infants <24 mos with BPD.

It was double blinded and placebo controlled.

They showed a 55% reduction in hospitalizations for all comers.

For premature infants, this reduction was 78%, and for the BPD group it was 39%.

2. Feltes paper Cliff's Notes

Congenital Heart disease had been excluded from the original polivizumab studies.

The last drug for RSV (RSV-IGIV) had increased mortality in congenital heart disease patients.

This was hypothesized to be secondary to increased viscosity.

Study patients were hemodynamically significant CHD patients <24>

This was a double blinded placebo controlled trial.

Relative reduction in rate of hospitalization of 45% was shown in the polivizumab group.

Duration of hospitalization and duration of oxygen therapy during hospitalization were also shown.

No associated adverse events were noted.

Congenital Heart Disease

2008-12-02T07:13:00.000-05:00

Anybody know any good congenital heart disease web resources?
I've found Yale's to be helpful.

Strong enough to get your ring around the collar, but not to cause dermatitis.

2008-11-23T20:03:00.000-05:00

Little has been published on the effects of laundry detergents. However, physicians and Uncle Buck always ask if you have changed laundry detergent when you get a rash. So a multicenter study was conducted to evaluate the validity of this old adage. The study for allergic contact demratitis (ACD) involved the placement of 2 patch tests-a granular detergent and a liquid one. Reactions to other chemicals like fragrances and nickel were compared to the laundry detergent reactions. Over 700 patients volunteered, but only 5 had a postitive patch test to either or both detergents. 2 of these 5 patients could be evaluated further. Further testing showed that in 1 of the 2, reduplication of the dermatitis could not be elicited. Meanwhile, the other had a reaction to the controls and the detergents. For more details on the study and others like it, check out the citations below.

Information from:

Allergic contact dermatitis to detergents: a multicenter study to assess prevalence.

Belsito DV, Fransway AF, Fowler JF Jr, Sherertz EF, Maibach HI, Mark JG Jr, Mathias CG, Rietschel RL, Storrs FJ, Nethercott JR.

Division of Dermatology, University of Kansas Medical Center, Kansas City, KS 66160-7319, USA.

Study can be found at:

J Am Acad Dermatol. 2002 Feb;46(2):200-6. Links

Comment in:

OMIM

2008-11-19T20:46:00.000-05:00

Just a reminder that OMIM is a great resource for information about genetic syndromes. I have found myself referring to it for both IM and Peds information.

For example,
Sandhoff Syndrome, which is clinically similar to tay-sachs

You get a decent clinical summary with references as well as the genetics.

Any other online genetics resources that people know of?

Who thought that botulinus intoxication was a good thing?

2008-11-13T21:28:00.000-05:00

After having a CP patient with severe hypertonia, I wanted to find some treatment options and found this study to be interesting. After starting a registration program for all CP patients in Sweden in 1994, several treatment studies began. These studies are linked to the following article.

A study in southern Sweden was initiated to analyze the development of spasticity with age in all children with CP from 0 to 15 years during the period 1995-2006. Measurements of muscle tone in the gastrocnemius-soleus muscle according to the modified Ashworth scale were analyzed. The CP subtypes were classified according to the Surveillance of Cerebral Palsy in Europe network system based on 6218 examinations in 547. The degree of muscle tone increased up to 4 years of age, but decreased each year up to 12 years of age. The same tendency is seen in all spastic subtypes. The findings may have implications both for clinical judgement and for research studies on spasticity treatment.

The original article citation is: BMC Musculoskelet Disord. 2008 Nov 6;9(1):150.

Who gets HUS from E. coli 0157:H7?

2008-11-10T12:15:00.001-05:00

We have an interesting patient on the service who has E. coli O157:H7. How can we predict who will get HUS?

I didn't find much on this question. A google scholar search for "predict HUS 0157" turned up this article. It is a quick and dirty study of 15 kids with 0157:H7, 5 with HUS, and 10 without. They looked at fever, vomiting, abdominal pain, tachycardia, and dehydration, and there was a significant p. value associated with dehyrdration at presentation and development of HUS.

Joishy, M. and Jauhari, P. and Mathew, A.A. and Rangarajan, T. "Can we predict the development of haemolytic uraemic syndrome in the early stage of Escherichia coli O157 infection?"Archives of Disease in Childhood, (2008) 93:2 180.

This article refers to this article, which is a nice review of 10 studies looking at the association between leukocytosis and development of HUS. A number of these studies were pediatric.
Anjay MA, Anoop P, Britland A, " Leukocytosis as a predictor for progression to haemolytic uraemic syndrome in Escherichia coli O157:H7 infection, 2007 Sep;92(9):820-3.

Cliff's:
Leukocytosis is a reliable early risk predictor
Absence of leukocytosis also has reliable NEGATIVE predictive value.

Schwachman-Diamond Syndrome

2008-11-08T07:34:00.000-05:00

Schwachman-Diamond Syndrome was the topic of the question of the day yesterday, and my team and I bombed it badly. First I accused our chief resident of inventing the syndrome, but it turned out that the syndrome is real. The Diamond of Schwachman-Diamond fame is indeed the same Diamond as that of Diamond-Blackfan fame.

A quick google scholar search on Schwachman-Diamond Syndrome and the 2nd hit found a review article from 2002.

Cliff's Notes:

The syndrome classically has three fundamental features:

1. pancreatic insufficiency
2. leukopenia
3. metaphyseal dysostosis

It is the 2nd most common cause of pancreatic insufficiency in children (behind CF), and the third most common cause of inherited bone marrow failure behind Fanconi's anemia and Diamond-Blackfan.
It is autosomal recessive.
It is associated with MDS and AML
Patients are susceptible to viral/bacterial/fungal infections secondary to a qualitative and quantitative immunodeficiency
The pancreatic insufficiency is secondary to acinar maldevelopment
Half of patients have the metaphyseal dysostosis , most commonly of the femoral head, and most commonly asymptomatic.
Life expectancy is >35 years.

The original article citation is:
Shwachman, H., Diamond, L.K., Oski, F.A. & Khaw, K.-T. (1964) The syndrome of pancreatic insufﬁciency and bone marrow dysfunction. Journal of Pediatrics, 65, 645–663.

Pediatric Clostridium difficile colitis

2008-11-08T06:35:00.000-05:00

We don't look for C. diff much in kids because kids don't get c. diff disease very often. In fact, simply having C. difficile is more often a sign of carrier status than of active disease. When we diagnosed a little girl on my service with c. diff, I thought I would see what I can learn. There is not much on pediatric C. difficile. I found the following:

McFarland, LV. “Pediatric Clostridium difficile: A Phantom Menace or Clinical Reality?.” Journal of pediatric gastroenterology and nutrition, v. 31 issue 3, 2000, p. 220.

High Points:

In the article, McFarland points out a number of pediatric c. difficile outbreaks. She separates positive C. difficile tests into four categories: "1) asymptomatic carriage, 2) acute and protracted diarrhea, 3) colitis (pseudomembranous colitis [PMC], fulminant colitis, toxic megacolon, and non-PMC colitis), and 4) recurrent infections."

Pediatric C. difficile may or may not be antibiotic associated.

High risk antibiotics are clindamycin, amoxicillin, ampicillin, and 2nd/3rd generation cephalosporins (our patient had had separate courses of two of these in the last month!).

I would add that the spores are not killed by alcohol hand rub, so soap and water is your friend in a C. difficile patient's room.

There was also a reasonably solid review article in the NEJM at the end of October this year.