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Lucia is here too: Siblings of someone with PWS

The semester is almost over. My last blog assignment was due today! I can't stop blogging with out mentioning my niece Lucia Daniela. She probably wouldn't recognize me if she saw me in the street, because I've been living in the USA since she was born.  Just wanted to let her know that even though most of the blog has been about PWS and Luis Emilio, I wouldn't have any problem recognizing her anywhere.

Lucia Daniela picking fruits

I miss the fresh fruits from Nicaragua!! Save some for me Lucia Daniela

Luicia Daniela

Lucia Daniela

Growth hormone: is it a personal choice medication or medical necessity in patients with PWS?

Luis Emilio 5th birthday party!

Luis Emilio's Father (Hjalmar) I hope he gave the toy back!

The good news:  Luis Emilio’s growth hormone (GH) will no longer be paid out of pocket!! This has the whole family very happy.

To be fair:  I want to clarify that by no means did I mean to single out  Aetna health insurance, they just happen to be the first on a list of health insurances that were in alphabetical order. Another important point is that by no means is this a complete and thorough review of the evidence available.

My concern:
GH is the only drug approved by the U.S. Food & Drug Administration (FDA) for the treatment of Prader-Willi syndrome. I thought that if Luis Emilio can now get his medication for free in Nicaragua, patients in the USA are probably having their GH covered by their insurance as well. I looked at the Aetna 2011 Preferred drug pocket guide for Emory members and found that GH is a Tier 4  (personal choice) medication.  This insurance company technically covers the mediation. The patient will have to pay $100 co-pay though.

The same guide also states “Emory’s plan goal is to help keep the cost of prescription drugs affordable and provide you with access to the medications you need to stay healthy.” This brings up a lot of questions. Is $100 dollars affordable for most families? What makes a medication a personal choice? The most important question is:  Does the evidence show that growth hormone treatment (GHT) is needed in patients with PWS to stay healthy?

Lets look at some of the evidence:

We know the best evidence will be from randomized controlled trials (RCT).  One randomized study of twenty-five children with PWS, ages 4-37 months; found that the group that received GHT had: ¹

1. Increased Height
2. Improved language skills
3. Improved cognitive skills
4. Decrease body fat
5. Improved motor ability
6. One PWS subject experienced scoliosis progression.

If you are wondering about scoliosis and GHT, a RCT  found that GH treated children had similar onset of scoliosis and curve progression as randomized controls. ²

Another benefit of GHT found in a randomized, controlled GH trial in infants and prepubertal children (n=85) was:  ³

1. Improved HDLc/LDLc ratio. (Cholesterol)

GHT has also been studied in adults with PWS.  Forty-six adults with PWS were randomized to GHT or placebo treatment for 12 months in a double-blind trial and found that the group that received the GHT had:⁴

1. Decrease in visceral fat mass
2. Decreased abdominal fat mass
3. Decreased thigh fat mass
4. Increase muscle mass
5. Lean body mass improved
6. Total fat mass decreased
7. No major side effects were seen.

Not all studies that have been done on GHT in individuals with PWS are RCT. The results of these other studies add to the body of evidence in different ways:

1. They show consistency in the results. “Study findings that are replicated in different populations and by different investigators carry more weight than those that are not.” ⁵

Researchers compared 21 children (6-9 years old) treated with hGH for 6 years with 27 children of similar ages (5-9 years old) prior to treatment with hGH.  They found that PWS children treated with hGH demonstrated:⁶

1. Decreased body fat
2. Increased height
3. Greater motor strength
4. Increased high-density lipoprotein (good cholesterol)
5. Decreased low-density lipoprotein (bad cholesterol)

2. A study that followed 20 patient with PWS that received GHT proved a dose response: “The cumulative dose of rhGH over 10 years correlated inversely with the total body fat percentage” ⁷

Other concerns:

There have been concerns about Sleep disorders in patients treated with GH. One case report showed Obstructive sleep Apnea (OSA) developed after 6 months of treatment and resolved after stopping GH.⁸ Like I’ve mentioned in other post though, case reports are at the bottom of the list when it comes to quality of evidence.

 One study that looked at sleep disorders before starting GHT and 6 weeks after starting GHT found no significant changes in sleep-related disorders before and after starting GHT.  It would have been nice if this study would have been longer. In the case report it took 6 months before she developed OSA! 12 infants did have an increase in the frequency of obstructive events associated with either upper respiratory infections or a diagnosis of gastroesophageal reflux after starting GHT. After the upper respiratory infection or GERD resolved so did the increase in frequency of obstructive events. ⁹ 

Current available information argues against a cause and effect relationship between rhGH treatment and increase mortality. Dr. Phillip D.K. Lee reviews the evidence in regards to this relationship in detail and can be found at the web site:  http://www.gghjournal.com/volume22/2/featureArticle.cfm

My thoughts:

I don't know how health insurance companies determine if a medication is a "personal choice" and classify it as a higher tier. With out an alternative treatment available, I don't think this policy is helping their goal of keeping prescription drugs affordable for their clients. Based on the evidence available I think GHT is a medical necessity for patients with PWS. The benefits go beyond increased height.  Hjamar (Luis Emilio's father) can confirm how I pushed for GHT to be started for Luis Emilio.   It wasn't an easy task. I had to convince my family that the health benefits were greater then the risk; and that the benefits were worth the $300- $400 a week they had to pay out of pocket when he started therapy. 

I understand the insurance companies have to make these same decisions on a larger scale. They may feel that even though GHT  increases height, reduces body fat, improves language, motor and cognitive skills; patient's with out GHT are not at risk of becoming acutely ill or having a life threatening condition if they don't start treatment. Since lack of treatment does not put patients at risk of harm, it may be a personal choice to start treatment. 

If they can't afford it, it is not a personal choice all patients with PWS can make. Luis Emilio did have periods where GHT was discontinued because the medication was too expensive.

Bibliography: 
1. Myers SE, Whitman BY, Carrel AL, Moerchen V, Bekx MT, Allen DB. Two years of growth hormone therapy in young children with Prader-Willi syndrome: physical and neurodevelopmental benefits. Am J Med Genet A. 2007 Mar 1;143(5):443-8. PubMed PMID: 17103437.
2. de Lind van Wijngaarden RF, de Klerk LW, Festen DA, Duivenvoorden HJ, Otten BJ, Hokken-Koelega AC. Randomized controlled trial to investigate the effects of  growth hormone treatment on scoliosis in children with Prader-Willi syndrome. J Clin Endocrinol Metab. 2009 Apr;94(4):1274-80. Epub 2009 Jan 21. PubMed PMID: 19158197.
3. de Lind van Wijngaarden RF, Cianflone K, Gao Y, Leunissen RW, Hokken-Koelega AC. Cardiovascular and metabolic risk profile and acylation-stimulating protein levels in children with Prader-Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab. 2010 Apr;95(4):1758-66. Epub 2010 Feb 19. PubMed PMID: 20173020.
4. Sode-Carlsen R, Farholt S, Rabben KF, Bollerslev J, Schreiner T, Jurik AG, Christiansen JS, Höybye C. One year of growth hormone treatment in adults with Prader-Willi syndrome improves body composition: results from a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2010 Nov;95(11):4943-50. Epub  2010 Aug 11. PubMed PMID: 20702523.
5. Gordis, Leon. (2009). Epidemiology, fourth edition. Philadelphia, PA: Saunders Elsevier.
6. Carrel AL, Myers SE, Whitman BY, Eickhoff J, Allen DB. Long-term growth hormone therapy changes the natural history of body composition and motor function in children with prader-willi syndrome. J Clin Endocrinol Metab. 2010 Mar;95(3):1131-6. Epub 2010 Jan 8. PubMed PMID: 20061431; PubMed Central PMCID: PMC2841537.
7. Sipilä I, Sintonen H, Hietanen H, Apajasalo M, Alanne S, Viita AM, Leinonen E. Long-term effects of growth hormone therapy on patients with Prader-Willi syndrome. Acta Paediatr. 2010 Nov;99(11):1712-8. doi: 10.1111/j.1651-2227.2010.01904.x. Epub 2010 Jul 5. PubMed PMID: 20545932.
8. Nixon GM, Rodda CP, Davey MJ. Longitudinal association between growth hormone  therapy and obstructive sleep apnea in a child with Prader-Willi syndrome. J Clin Endocrinol Metab. 2011 Jan;96(1):29-33. Epub 2010 Oct 13. PubMed PMID: 20943780.
9. Miller JL, Shuster J, Theriaque D, Driscoll DJ, Wagner M. Sleep disordered breathing in infants with Prader-Willi syndrome during the first 6 weeks of growth hormone therapy: a pilot study. J Clin Sleep Med. 2009 Oct 15;5(5):448-53. PubMed PMID: 19961030; PubMed Central PMCID: PMC2762717.

Is stealing always a crime?

I talked to my family in Nicaragua this weekend and the topic of how they were punishing Luis Emilio when he takes food he was not suppose to eat came up. Because he is still a toddler we haven’t had to face the legal problems young people with PWS can have when they steal food. It is heartbreaking to read stories like: “An eleven-year-old girl is arrested for stealing food from her neighbor’s freezer”.  We know that people with PWS always feel hungry. Anyone who felt like they were starving to death would also have a hard time controlling the urge to steal something to eat. Is punishing Luis Emilio going to make any difference in his behavior?

In a quick Google search today I found a few case studies on the effects of behavior therapy in food stealing in patients with PWS.  One study “ found that verbal reprimands, delivered contingent upon eating prohibited foods, were sufficient to decrease the food stealing of a girl with Prader-Willi syndrome.”¹ This was in a supervised environment in a hospital. We really can’t say this will make any difference in the real world, or that it will help other people with PWS.

If we look at how scientific evidence is categorize based on the quality of its source, case reports are at the bottom of the list. They are still important. Based on this report, a larger study can be proposed. If behavior therapy really works we can replicate the findings in different studies and in different populations.

In the mean time, should the laws be different for people with PWS? Is stealing always a crime?

Reference:

1. Maglieri KA, DeLeon IG, Rodriguez-Catter V, Sevin BM. Treatment of covert food stealing in an individual with Prader-Willi syndrome. J Appl Behav Anal. 2000 Winter;33(4):615-8. PubMed PMID: 11214035; PubMed Central PMCID: PMC1284283.

Getting back to the research question!

PWS is found in people of both sexes and all races worldwide. Luis Emilio was born and is currently living Nicaragua.

I have been blogging about PWS in hopes to contribute to the Prader-Willi Syndrome on the Move awareness initiative. Can blogging really increase awareness though? Life can get pretty busy. Especially if you have a family member with PWS that requires physical therapy, office visit to multiple specialists, in addition to the usual things most of us have to do on a regular day. We want to make sure that family members and friends interested in increasing awareness are investing their time in things that are really making a difference. One of the benefits of using the Internet to increase awareness is the number of potential people that will be exposed to the blog. The down side is, it makes it very difficult to measure the effect of our efforts. 

Study design: I propose doing a cross sectional study to explore the relationship between blogging about PWS and awareness about the signs and symptoms seen in patients with PWS. Participants in the study will fill out a short survey that will evaluate their level of knowledge about PWS and the level of exposure to this blog. This will allow us not only to determine if there is any relationship between blogging and awareness, but it will also allow us to determine the proportion of the population that is exposed to the blog.

Study population: Students enrolled in the principals of epidemiology class at MU during the spring semester of 2011. This blog is part of an epidemiology project. Part of our assignment is to read other students blog. Students are not required to read everyone’s blog. This makes it a convenient population to study because we can expect to have students that have read the blog and students that have not read the blog.

Exposure variable: Number of post about PWS the student read from the blog:  sonia-lookingforhappiness.

Outcome Variable: Percent of questions answered correctly about the signs and symptoms in patients with PWS.

Sample size: Because the study population is relatively small we can afford to survey the entire class. The proportion of students exposed to the blog and the effect size, if any, found in this study can be used for calculation of sample size in future studies on this subject that may have a larger study population.

Limitations of the study:

1. We are measuring the exposure and the outcome at the same time and therefore we cannot determine a temporal relationship. It may be that students with increased awareness about PWS were interested in reading the blog.

2. The exposure variable is subject to recall bias.  Students may not remember how many post they read or if they read the blog at all. This may also lead to misclassification. For example, a student may not remember that he skimmed through a couple of post at the beginning of the month and be classified in our study analysis as a non-exposed student.

3. Although our goal would be to survey the entire class. Students may decide not to participate in the study. This can lead to selection bias. Students that have increased awareness about PWS would be more likely to complete the survey weather or not they read the blog.

4. Participants in the study would be graduate students, many with a health background; hence generalizability of the results to the general population is limited.

5. There are multiple known confounders that we would need to control for.  For example: the different levels of medical knowledge in students in the class. If only the students with a health background read the blog, a higher percent of correct answers on the survey may not be related to the blog at all!

6. The study doesn’t measure the effect it has on other readers that are not in the class!

Do you think that blogging increases awareness?