Self Care Pharmacy Blog

Archive for December, 2013


Protein Pump Inhibitors and Heart Disease Link

Tuesday, December 10th, 2013

By Yevgeniy Solokha, PharmD Student Cedarville University

Proton pump inhibitors (PPIs) are commonly used to prevent the symptoms and complications of gastroesophageal reflux disease (GERD).1 They work by reducing acid secretion in the stomach by inhibiting the gastric proton pump.2 With several products available over-the-counter (OTC), patients have also been able to use them for the self-treatment of heartburn and indigestion.3 Although these medications are effective, their long-term use has been associated with potentially serious health risks, including bone fractures and reduced magnesium levels in the blood.Not only that, but there has been some evidence suggesting that prolonged use of PPIs may also lead to heart disease.2

This association is the main topic of a recent study that has been published in the Circulation Journal of the American Heart Association. It has evaluated the effects of PPIs on mice and human endothelial cells using cell assays as well as blood samples collected from mice in vivo. The results show that PPIs lead to increased levels of asymmetrical dimethylarginine (ADMA) in the blood by inhibiting dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that breaks it down. This, in turn, prevents nitric oxide synthase (NOS) from generating nitric oxide (NO), which decreases the ability of blood vessels to dilate.The article essentially calls for the need to perform additional studies to evaluate whether the general population using PPIs may be at risk for heart disease.2 This is the main limitation of the study because the results cannot be easily extrapolated to humans. Also, there may be other factors that can contribute to this association.

A similar relationship between ADMA elevations and cardiovascular events has also been discussed in an article published in the Annals of Medicine.It proposed essentially the same mechanism as the one mentioned in this study. Another Danish cohort study set out to investigate a relationship between the use of PPIs and clopidogrel with cardiovascular events. It concluded that, “the increased cardiovascular risk associated with PPI use independent of clopidogrel is caused by unmeasured confounders”.5 Basically, this means that there must be something else going on which has not been accounted for. The main objective of the mouse study discussed above was to try to identify a possible mechanism for this observation. Since this association seems to be fairly new, the literature largely seems to be inconclusive on the subject.

I feel like it is still too early to tell whether there truly is a valid relationship between PPI use and heart disease because there have not been any randomized-controlled trials conducted in humans yet. For this reason, I would not change my self-care recommendation for the short-term relief of persistent heartburn and indigestion because OTC PPIs are indicated for a limited duration of therapy consisting of 14 days, after which they have to be discontinued for at least four months.3 Nevertheless, I think that the results of this study may be good to just keep in mind in case we encounter patients who may be on unnecessary prolonged use of PPIs. The possible heart disease association would simply be another reason to contact their physician about discontinuation. In this regard, I believe that pharmacists are located within a unique position within the healthcare system to make sure that patient safety remains a priority.

Would this knowledge impact your self-care recommendation regarding PPIs?


  1. Proton Pump Inhibitors for Gastroesophageal Reflux Disease (GERD). Available at: Accessed December 5, 2013.
  2. Ghebremariam YT, Lependu P, Lee JC, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845-53.
  3. Berardi RR, Kroon LA, McDermott JH et al. Handbook of nonprescription drugs, an interactive approach to Self-care. APhA Publications; 2006.
  4. Böger RH. Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond. Ann Med. 2006;38(2):126-36.
  5. Charlot M, Ahlehoff O, Norgaard ML, et al. Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study. Ann Intern Med. 2010;153(6):378-86.

Calcium Worth The Risk?

Tuesday, December 10th, 2013

By Jordan Long, PharmD Student Cedarville University

For years, calcium has been considered an essential nutrient to have in the daily diet. Intake of calcium is essential for many bodily functions including muscle contraction, nerve transmission, and bone remodeling.1 Some of the benefits from calcium are helping bone growth, prevent loss of bone density, and prevent osteoporosis development.2 But recent reports are questioning the actual efficacy in these different functions and if higher calcium levels could lead to adverse effects due to additional intake through supplementation.  These recent studies led the New York Times to post an article in April of 2013 stating that people should be Thinking Twice about Calcium Supplements.3 The article stated that not only is the efficacy of calcium supplementation in it’s prevention of bone fracture questionable, but calcium supplementation might be harmful. The views presented in this article are hard to believe, since calcium is a very common nutrient found in many foods found in the standard diet. However, recent literature is beginning to provide evidence to back up this view.

Studies have shown that calcium is essential for the increase of bone density in prepubescent children.4 Parents should highly encourage their kids to consume calcium in their diet to have strong bones. But the United States Preventative Risk Task Forces stated that there is currently insufficient evidence that the benefits from calcium supplementation over 1,000mg per day is worth the risk for the primary prevention of fracture in healthy, older woman. They also do not recommend taking less than 1,000mg a day of calcium supplementation, because it is not shown to decrease fracture at these low levels but increases risk of kidney stones.5 The National Institutes of Health recommends optimal calcium intake levels varying from 1,000mg to 1,300mg for anyone over the age of four, depending on age.1 Those numbers include the calcium from dietary intake and any calcium taken as a supplement. A lot of these studies are hard to compare and contrast their recommendations because of the high amount of variation in type of calcium supplementation and complementary supplementation, especially with vitamin D, which also plays an important role in the bones ability to absorb calcium.6

One of the primary concerns with calcium supplementation is that the risks of all cause mortality, attributed mostly to cardiovascular disease. A study observing all cause and cardiovascular mortality due to calcium found that there was an associated increase in all cause, cardiovascular, and ischemic heart disease mortality with people with an average intake of calcium above 1,400mg a day, but these results were not conclusive.7 A few other articles looking at the association of calcium and cardiovascular disease mortality found no hard evidence and said that no causality could be confirmed.8,9 Sadly, a limitation to the research of calcium effects is that randomized clinical trials might be unfeasible. The risks of high supplementation of calcium are to high and could be considered unethical to test for. But is the intake of calcium the issue? The National Institutes of Health states that calcium intake is not involved in the prevalence of cardiovascular issues, but the serum concentrations of calcium.1 Calcium serum concentrations are highly regulated by the body to obtain proper homeostatic balance, using the bones as a reservoir for excess calcium.10 But this balance could be thrown off by increased or decreased calcium intake over longer periods of time.  Even though there is some evidence that calcium supplementation could be reducing incidence of fractures, evidence is increasing regarding the incidence of cardiovascular issues.11

From the research, I would say that patients should be cautioned when thinking about taking a calcium supplement for an extended period of time. The New York Times pointed out some good points, people should try to stay away from supplements as much as possible.3 If someone is below his or her recommended daily value of calcium, higher intake of high-calcium food should be recommended. Some examples of foods that are high in calcium are milk, cheese, yogurt, kale, and spinach.1 The major thing causing problems in people that are taking calcium supplements is that they most likely have an adequate amount of calcium in there normal diet, and the additional supplement is putting them over the recommended daily amount. The supplements themselves might not be necessarily directly causing the higher risk of cardiovascular disease, but it is increasing the calcium levels above the recommended daily amount. People wanting to take calcium supplements should consult their local pharmacist or primary care provider to make sure it is appropriate. For another great resource, check out Dr. Mercola’s article on the relationship between vitamin K2, vitamin D, and calcium (Link found in references section below). It explains the proper balance of these dietary supplements and how to control your calcium levels through them.12

With all of these risks, do you know what your daily calcium intake is? Maybe it’s time you checked for yourself.




1. Dietary Supplement Fact Sheet: Calcium. Offices of Dietary Supplements of the National Institutes of Health Website. Accessed December 4, 2013.

2. Top Foods for Calcium and Vitmain D. WebMD Website. Accessed on December 4, 2013.

3. Thinking Twice about Calcium Supplements. New York Times Website. Accessed December 3, 2013.

4. Johnston, CC; Miller, JZ; Slemenda, CW; Reister, TK; Hui, S; Christian, JC; Peacock, M. Calcium Supplementation and Increases in Bone Mineral Density in Children. NEJM. 1992;327(2):82-87. Accessed December 4, 2013.

5. Vitamin D and Calcium Supplementation to Prevent Fractures in Adults. U.S. Preventative Services Task Force Website. Published February, 2013. Accessed December 4, 2013.

6. Calcium and Vitamin D; What you need to know. National Osteoporosis Website. Accessed of December 7th, 2013.

7. Michaëlsson, K; Melhus, H; Lemming, EW; Wolk, A; Byberg, L. Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ. 2013;346(228). Accessed December 4, 2013.

8. Bolland, M; Grey, A; Reid, I. Calcium and Cardiovascular Risks. Australian Prescriber. 2013;36(1):5-8. Accessed December 4, 2013.

9. Van Hemelrijck, M; Michaelsson, K; Linseisen, J; Rohrmann, S. Calcium Intake and Serum Concentration in Relation to Risk of Cardiovascular Death in NHANES III. PLOS One. 2013;8(4): 1-9. Accessed December 4, 2013.

10. Marks, AR. Calcium and the heart: a question of life and death. The Journal of Clinical Investigation. 2003;1(5):597-600. Accessed December 4, 2013.

11. Reid, IR. Cardiovascular Effects of Calcium Supplements. Nutrients. 2013;5:2522-2529. Accessed December 4, 2013.

12. What You Need to Know About Vitamin K2, D and Calcium. Website. Published in December of 2012. Accessed on December 7th, 2013.

Is Aspirin a Viable Option for the Prevention of Dementia?

Saturday, December 7th, 2013

by Nick Daniels, PharmD student

Dementia is one of the most prevalent health issues facing the elderly today. The disease state is characterized as a decline in memory or thinking skills severe enough to reduce a person’s ability to perform everyday activities.1 It is heavily correlated with Alzheimer’s in that 60 to 80% of those affected by the disease also suffer from dementia.1 One study estimates that 13.9%, which accounts for roughly 3.4 million people, of the population in the United States who are 71 years of age or older are affected by the disease with numbers increasing steadily as they progressed in age, with it ultimately effecting over 37% of the population older than 90.2 The severity of the symptoms associated with dementia, and its prevalence among the elderly, makes it a critical problem for which a preventative solution must be found.

The article, “Aspirin may Prevent Dementia and Cancers, World’s Largest Study Shows” published by ABC News discusses how researchers working in Australia are trying to do just that. The study, involving the participation of over 15,000 healthy Americans and Australians aged over 70, is using aspirin as a preventative agent to stop the development of the disease state through a suppression of stroke incidence.3 Researchers involved with the ASPREE study are using the aspirin in this case in an effort to keep constant the flow of blood to all areas in the brain in hopes of preventing tissue necrosis, microinfarcts, caused by ischaemic stroke.3 Tissue necrosis in the brain would result in reduced ability to think thereby causing advancement in dementia.3 Researchers began this double blind clinical trial in January of 2010 and they are expecting a reliable primary outcome measure by August of 2016.4 This sample is expected to be the most large scale available in regards to measuring aspirin preventative outcomes for dementia.5

While the aforementioned study into this area seems promising given the proven cardiovascular benefits of moderate aspirin usage and the study’s statistical power provided by its large sample size, I would advise caution to patients looking to dive headfirst into this type of preventative plan thinking it will be the guaranteed answer to solving the problem of dementia. To this point there is just not enough of a sample base to prove that the benefits of aspirin usage for the prevention of stroke outweigh the negatives, such as stomach bleeding and increased risk of massive stroke due to advanced movement of blood through the brain, associated with the medication.6 Hopefully the study currently being conducted can bring to light the answers to some of these questions. To this point, being so early on in the study, only the initial speculation by the researchers is available.

Without further evidence that validates the effectiveness of aspirin use in the prevention of dementia I cannot recommend its use for this indication. A previous study done by the NHMRC Psychiatric Epidemiology Research Centre in Australia tracking aspirin’s potential in use for preventing dementia actually found no difference between control and study groups.In cross-sectional data obtained in the study, those who had been taking NSAIDs or aspirin performed no better on the cognitive tests after account had been taken of other confounding variables.7

There are a few reasons behind the questionable results of some of these studies. The most important is they fail to acknowledge that stroke related dementia is only a portion of the larger problem of dementia as a whole.1 As was mentioned previously, up to 80% of all cases of dementia can be related to the development of Alzheimer’s which is different than the microinfarct dementia addressed by these studies.1 Many articles, like the one published by ABC, have the potential to heavily exaggerate the applicability of research being done. This could serve to mislead the public into adopting preventative strategies that could be ineffective, and at worst detrimental to their health. Also, the sample size in the NHMRC study is much smaller which could affect its validity in comparison to the larger study currently being conducted. Results from the larger study should give a more accurate representation of the medication’s effectiveness. I feel the ASPREE study also limits itself through a constrained diversity of ages. It would be more advantageous to begin the study using individuals who were much younger than 70 in order to reasonably ensure that patients had not already experienced some of the symptoms of dementia onset.

As health care professionals it is important to spread awareness in regards to dementia and the potential benefits, or shortcomings, of various preventative measures. Do you believe the limited base of evidence available for aspirin usage in the prevention of dementia is enough to warrant its use for this indication? What future do you believe the medication has in the prevention, or treatment, of neurodegenerative diseases?


[1] What is Dementia? Available at: Published June 28, 2013. Accessed December 2, 2013

[2] Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1-2):125-32

[3] Ogilvie, Felicity. Aspirin may Prevent Dementia and Cancers, World’s Largest Study Shows. ABC News. Published November 28, 2013. Accessed December 3, 2013.

[4] Nelson M, Accessed December 6, 2013.

[5] ASPREE Study. Available at: Accessed December 6, 2013.

[6] Paikin JS, Eikelboom JW. Cardiology patient page: Aspirin. Circulation. 2012;125(10):e439-42.

[7] Henderson AS, Jorm AF, Christensen H, Jacomb PA, Korten AE. Aspirin, anti-inflammatory drugs and risk of dementia. Int J Geriatr Psychiatry. 1997;12(9):926-30.

Are you “Pro” Probiotic Supplements?

Thursday, December 5th, 2013

by Heather Evankow, PharmD student

In recent years, the popularity of probiotic supplements has risen. Probiotics are bacteria that help maintain the natural balance of organisms (microflora) in the intestine.1 The idea of probiotics is not a new concept. The idea was first developed around 1900 by the Nobel Prize-winning recipient Elie Metchnikoff. Metchnikoff theorized that the fermented milk products Bulgarian citizens ingested were a major factor in their longer life spans when compared with other countries.2 It was not until the year 1989 when R. Fuller popularized the term “probiotics”.3 Today, probiotics can be seen in the news claiming to improve the immune system, aid in skin health, defend against depression, clear up a bloated gut, prevent urinary tract infections, and even delay allergies.4

The Daily Herald recently released the article, Probiotics are all the rage, and experts say there are results behind the hype. The author, Gabriella Boston, Boston combines the opinions of several healthcare professionals to emphasize the health benefits behind the evolving topic of probiotics.

The first healthcare provider, Megan McCusker, is a dermatologist who believes probiotics are an important treatment therapy for treatment of anything from acne to psoriasis.4 While the Federal Drug Administration (FDA) does not approve any health claims for this supplement, McCusker could recommend 5-20 billion units per day depending on the patient’s needs. There were no clinical research references to show how McCusker developed these recommendations.

A nutritionist Boston featured, Jared Rice, also believes in the benefits of probiotics. Rice has not observed any downsides with his patients taking probiotics, but still advises patients to seek medical attention before taking high doses. Rice believes it is essential to buy the healthiest probiotic supplement. Also, he believes it is important to create a probiotic-friendly body by eating whole grains, bananas, and onions while steering clear of nondigestible carbohydrates.4 Unfortunately, there was no data referenced to confirm the benefits of Rice’s claims.

Ebeth Johnson, a nutritionist and chef, also gave her expert advice for this article. She believes this probiotic trend is here to stay. She encourages incorporating probiotics into your diet by consuming unpasteurized miso, live cultured pickles, tempeh, unsweetened kefir and yogurt, and kombucha teas.5 It is unclear how Johnson came up with these supplement sources. In addition, she also did not mention any specific research to validate the quality of these sources.

While the experts in Boston’s article seem confident in their recommendations of probiotics supplements, the clinical research is still limited for probiotics. The varieties of strains make it problematic in understanding the health benefits.

One of the most researched probiotic strains is Lactobacillus rhamnosus GG (LGG). LGG has been proven to help pediatric patients with pain-related gastrointestinal (GI) disorders in many clinical studies.5 In a 2011 meta-analysis, researchers systematically searched for randomized controlled trials assessing LGG supplementations in children with functional dyspepsia (FD), irritable bowel syndrome (IBS), abdominal migraine and functional abdominal pain (FAP).5 The major limitations for this analysis included incomplete outcome data and the number of trials with a small sample size. The results revealed a decrease in severity in pain with the overall study population and the IBS subgroup.5 The frequency was also decreased in the IBS subgroup.

Another hopeful probiotic strain is Streptococcus thermophilus VSL #3. A multicenter, randomized, placebo-controlled, double-blind, crossover study has shown VSL #3 to be successful and safe in helping the lives of children with IBS.6  59 patients from ages 4-18 years of age completed the study with no untoward adverse effects reported. Researchers found no significant difference was found in the stool pattern of patients, but abdominal pain, abdominal bloating, and family life disruption were all significantly more effective to the placebo.6

Have you had any encounters with probiotic supplements? Comment and share your experiences. Please include the main therapy goal, specific probiotic strains, and the dosage.

If you have had no experience with probiotics, based on the information above, would you personally try probiotic supplements? Share your rational.


1. “Probiotics – Topic Overview.” WebMD. Healthwise, 04 FEB 2011. Web. 29 Nov 2013. <>.

2. Parvez, S. and Kang S. “Probiotics and their fermented food products are beneficial for health.” Volume 6. Web. 29 Nov. 2013. <>.

3. Ouwehand, A., S. Salminen, and E. Isolauri. “Probiotics: an overview of beneficial effects.” Vol 82.Issue 1-4 (2002): 279-289. Web. 29 Nov. 2013. <

4. Boston, Gabriella. “Probiotics are all the rage, and experts say there are results behind the hype.” Daily Herald. N.p., 28 Oct 2013. Web. 29 Nov 2013. <>.

5. Horvath, A., P. Dziechciarz, and H. Szajewska. “Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood.” Alimentary Pharmacology & Therapeutics. Vol 6.Issue 12 (2011): 1302-1310. Web. 29 Nov. 2013. <>.

6. Guandalini S., G. Magazzu, and A. Chiaro. “VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study.” J Pediatrics Gastroenterol Nutr. 2010 Jul;51(1):24-30. Web. 04 Dec. 2013.

Over the Counter Probiotics May Be Able to Sooth Baby’s Colic

Thursday, December 5th, 2013

by Mallory Martin, PharmD student

This article posted by the BBC, “Probiotics ‘soothe some babies with colic’”,1 explores an option into easing or possibly preventing your baby’s colic. The article describes an analysis of 12 studies looking into probiotics as a treatment for colic. The analysis was done by a team of scientists in Australia and reported in the Jama Pediatrics Journal. However the article didn’t cite where in the journal this article was found. This seemed uncharacteristic and it made it difficult to evaluate their findings. All this aside, their findings were quite exciting because although colic is not a harmful condition to babies and resolves itself after 3-4 months1, it can be quite stressful for caretakers. An option for soothing baby’s colic would be highly valued for this reason.

When attempting to sooth colic, parents can be scared away by ambiguity, not wanting to give something to their baby unless it is proven. “Research shows” is a phrase that may be thrown around a lot, but what people really want to know is whether a treatment is safe for their child and if it is effective. Taking these people into consideration and with the incomplete citation by the BBC article, I wanted to explore several articles published on this topic in an attempt to come to a conclusion on whether or not to recommend probiotics for colic.

Probiotics must first be understood on their own before exploring them as a treatment for colic. Probiotics are a mixture of different microorganisms that when orally ingested are considered to have several overall health benefits.1 The word itself means “promoting life”.2 They generally have very low risk in normal adults because the cultures so closely resemblethe natural flora of the gut. 3 Probiotics are also naturally present in food. Some foods that contain probiotics are fermented vegetable such as sour kraut and most commonly yogurt.2 Probiotics contain many different types of bacteria but among the most common is Lactobacillus reuteri. It is this strain of bacteria that is considered to have the most health benefits. 2

Certain health benefits have been discovered with probiotic use. Probiotics, L. reuteri specifically, has been shown to lower LDL levels, kill bacteria that causes tooth decay, lessen the harmful effects of gingivitis, and lower your likelihood of developing episodic diarrhea or traveler’s diarrhea. Some reports even show that this bacterium can lessen a child’s risk of developing eczema through probiotic-filled breast milk. Studies in women’s health showed that it may help balance the bacteria present in the vagina and lower the risk of yeast infections, bacterial vaginosis, and urinary tract infections. Some additional benefits include its ability to reduce upper respiratory infections when compared to placebo, provide relief to baby’s colic, and reduce bloating and gas.2

Although the results are promising, research in this area is not concrete. Probiotics may have both risks and benefits for different people. Risk for special populations, such as small children and older adults, is unclear since there is little to no research done on these groups.2 So far, healthy, full-term babies who have received high doses of probiotics have not presented with any negative effects.4 However there is some evidence that young children who are pre-term or not fully healthy, such as children with weakened immune systems, catheters or other medical devices inside them, may be at risk if taking probiotics.4 When considering L. reuteri in treatment of colic, one study by Savino concluded that it is inconclusive whether L. reuteri reduces colic but it appears to reduce levels of harmful E. coli. 5,6 Savino performed a follow up study after comparing L.reuteri with simethicone and compared the bacteria against a placebo in treatment of colic.7 This study had a better study design for its desired outcome because the infants involved were chosen based on Wessel’s Criteria, a more systematic approach than the first study. The results concluded that L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of baby’s colic and was well tolerated and safe.7 Some factors that could contribute to the varying results in these studies include the differences in the care the infants received in different homes and different study designs. An article put out by Fox News article reported on this as well. The conclusion was that probiotics may not be effective. However in young infants, they can potentially reduce risk of asthma and eczema.4 This positive effect, while unrelated, is something to consider when evaluating probiotics for your child.

Considering all this information, I would recommend probiotics as a means of treatment for infantile colic. The best option would be for a nursing mother to start a regimen of daily probiotics and allow the probiotics to transfer through the breast milk. However, L. reuteri is available for infants to ingest. Gerber has a colic relief drop that specifically has L. reuteri in it which includes sunflower oil. Gerber also has a powder for formula around 30 dollars for 24 ounces. BioGaia has a straight L. reuteri drop for around 20 dollars for 5 mLs. There are options. Even if it may not be 100% guaranteed to be effective, if your colicky baby is becoming too much to handle and you have tried many other options, I would say it is worth a try. Especially considering no bad effects have been found and several unrelated positive effects have been suggested. Probiotics would be a safe and natural way to go in your attempt to soothe your baby and get a good night’s rest yourself. Some may not agree with me. With the lack of research and uncertainty, risks could exist. Just because no negative effects have been found does not mean that it is completely safe. Would you take that risk with your own child?


1. Roberts, M. Probiotics ‘soothe some babies with colic’. The BBC. October 7, 2013. Accessed December 3, 2013.

2. Maier, R. Surprising Benefits of Probiotics. Healthine Web site. April 13, 2013. Accessed December 3, 2013.

3. Probiotics – Topic Overview. Webmd Web site. February 04, 2011. Accessed September 15, 2013.

4. Rettner, R. Are Probiotics Safe for Kids?. Livescience Web site. October 06, 2011. Accessed December 3, 2013.

5. Woznicki, K. Probiotics May Reduce Crying From Colic. Webmd Web site. August 16, 2010. Accessed October 15, 2013.

6. Savino F, Cordisco L, Tarasco V, et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics. 2010;126(3):e526-33.

7. Savino F, Pelle E, Palumeri E, Oggero R, Miniero R. Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics. 2007;119(1):e124-30.

Evidence for Supplement Use to Prevent Cancer or Cardiovascular Disease?

Wednesday, December 4th, 2013

By Tirhas Mekonnen, PharmD Student, Cedarville University

Dietary supplements have been used for various reasons. Dietary supplements such as ascorbate, vitamin E, and ß-carotene, are reducing agents and thereby, detoxify reactive oxygen intermediates in the laboratory.1 Researchers are studying to find out if consumption of food rich in these antioxidant compounds could potentially reduce the risk for certain types of cancers as well as other chronic health problems like cardiovascular disease.  However, clinical trials with antioxidants as dietary supplements have failed to show clear beneficial effects.1

This article on Medpage Today by Todd Neale discussed a systematic review that investigated the use of mineral and dietary supplementation for primary prevention of cardiovascular disease or cancer.2 The review evaluates 24 randomized, controlled trials and 2 cohort studies that examined the benefits and harms of using vitamin and mineral supplements for primary prevention of CVD, cancer, or all-cause mortality in healthy individuals without known nutritional deficiencies.3 The study found that except for two clinical trials, there was only “a small borderline-significant benefit” from multivitamin supplements on cancer (but only in men), limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or cardiovascular disease”.3 Although the review looked at many studies there are some limitations.

One of the limitations is that the review included short term studies that analyze the use of dietary supplements.3 However, those short-term studies may not confirm or indicate the outcomes of chronic use of dietary supplements. For example, the median follow up time of the study titled, “Randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals” was only for seven and half years.4 The review also consists of studies done in various countries. However, poor eating habits, tobacco use, consumption of alcohol, and many other variables may differ from one country to the other country.  These variables are risk factors for chronic heart disease or cancer.

Other sources have also not found consistent evidence to recommend minerals and dietary supplements for the primary prevention of cardiovascular disease and cancer.  An article titled “Nutrient supplements and cardiovascular disease” discussed associations between carotenoids, folic acid, and vitamin E with CVD risk.5 As the article illustrated, previous researchers thought that vitamin E, due to its antioxidant effect, may reduce CVD. However, the article also noted more recent randomized placebo-controlled interventional trials do not support the original assumption regarding vitamin E.5 The article also pointed out that “With few exceptions, a large series of primary and secondary prevention trials have reported no significant benefit of moderate-to high-dose vitamin E supplementation of cardiovascular outcomes”.5

In addition, the use of dietary supplement folate and its association with cardiovascular health benefit was discussed in another review article by Ulrich and Potter et al. This article also is consistent with the previous reviews and studies mentioned above. “The prevention of cardiovascular disease was assumed to be another health benefit of increased folate intake; unfortunately, the results from randomized controlled trials with actual disease outcomes provide no evidence for such an effect.”6 Therefore, there is currently a lack of evidence to suggest that folate prevents cardiovascular disease or cancer.

In conclusion, after reading these reviews and studies, I agree with Mr. Todd Neale, that there is no clear answer for the following question: Is there clear evidence to recommend minerals and dietary supplements for the primary prevention of cardiovascular disease?  I would like to get your professional opinion on this matter. Please participate if you have found studies that do have a better explanation as to whether to recommend or to not recommend dietary supplements for the primary prevention of cardiovascular disease or cancer.


  1. Harvey R, Ferrier D. Lippincott’s illustrated Reviews. 6th ed. Wolters Kluwer Health, Philadelphia, PA/Lipincott Williams & Wilkins; 2011.
  2. Neale T. USPSTF: Evidence for Supplement Use Lacking. Medpage Today. Published: Nov 11, 2013 Retrieved from
  3. Fortmann S, Burda B, Senger C, Lin J, Whitlock E. Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2013; published on-line doi:10.7326/0003-4819-159-12-201312170-00729. 
  4. Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164(21):2335-42. [PMID: 15557412]
  5. Lichtenstein A. Nutrient supplements and cardiovascular disease: a heartbreaking story. J. Lipid Res. 200; 50:(S429-S433).Available from:
  6. Ulrich M, Potter J. Folate Supplementation: Too Much of a Good Thing? Cancer Epidemiology Biomakers & Prevention Feb 2006;15:189. Retrieved from

Are e-cigarettes a good option for smoking cessation?

Monday, December 2nd, 2013

by Tiffany Zehel, PharmD student

In 2011, an estimated 43.8 million U.S. adults were current cigarette smokers,[i] and currently, estimates of over one billion people worldwide are smokers.[ii] Cigarette smoking is a global epidemic that can give rise to several serious diseases with nearly 6 million deaths annually.[iii] The risk of serious diseases is significantly reduced after one quits smoking and maintains life-long abstinence. Unfortunately many nicotine replacement therapies (NRT’s), such as the patch or gum, have a low efficacy rate in real life practice.[iv] Many studies evaluating the use of nicotine replacement therapies find that while traditional NRT’s provided the chemical need for the individual, the behavioral and psychological needs of the individual were not being met.[v],[vi],[vii]

 The electronic cigarette (e-cigarette) was introduced to the U.S. market in 2007 to provide smokers with more freedom to smoke as well as a safer alternative compared to tobacco cigarettes.[viii] The standard e-cigarette is a battery powered electronic nicotine delivery device (ENDD) that resembles a cigarette, and delivers nicotine in a vaporized solution. The acceptance of the e-cigarette is attributed to the similarities of smoking, including the hand-to-mouth repetitive motion and the visual cue of the vapor, addressing the psychological and behavioral aspects of the addiction.[ix]

According to an article published in The Lancet, E-cigarettes were not shown to have a statistically significant difference in individuals that quit. However, they significantly reduced the amount of traditional cigarettes an individual used in a given day compared to the patch.[x] In this news article e-cigarettes are celebrated based on the fact that they show promise to eliminate tobacco smoking completely in the future, but not so much for the promise of helping people break their addiction. Smoking tobacco is very harmful and traditional cigarettes contain toxins that are carcinogenic. In that respect, e-cigarettes should be admired for their ability to replace cigarettes. The issue is that e-cigarettes are not regulated by the FDA like other NRT’s, and their safety has not been extensively researched, due to the recent emergence of the product.

The article also had several limitations. First, the study was underpowered, meaning any effect could have gone undetected, so the results may not be reliable. Another limitation is that there was a high drop out rate in the group given the nicotine patch; this is speculated to be due to the participants wanting to try e-cigarettes but instead where randomly assigned to receive the patch. A third limitation is that the e-cigarette, that this particular study group used, contained less than optimal amounts of nicotine and delivered nicotine inefficiently. As technology advances and e-cigarettes become more efficient in nicotine delivery, e-cigarettes may be proven more effective. The final limitation is that this study was over six months while the amount of time to quit cigarettes can be much longer depending on the individual.x The short amount of time also provided little ability to evaluate adverse effects that the e-cigarette may cause. Due to these obstacles, it is difficult to say whether e-cigarettes would or would not be better than the nicotine patch.

In an article published in the journal of Addiction Science and Clinical Practice (ASCP), a group of people that regularly used e-cigarettes were followed through a forum and interviewed regularly. One repetitive theme in the article was that the subjects, who identified themselves as “vapers,” drew a line between smoking cessation and nicotine cessation. They claimed that they wished to stop smoking because of the health ramifications, but because of the convenience and perceived safety of the e-cigarettes, they had no desire to quit their nicotine addiction.[xi] Up to this point, smoking cessation and nicotine cessation went hand-in-hand. NRT’s were prescribed to step the patient down from their nicotine addiction; currently e-cigarettes are not set up in this way. So now that we have this unique delivery system on our hands, we need to decide if nicotine cessation is as important as smoking cessation. We also need to do further studies on the long-term effects of e-cigarettes to evaluate their benefits over the alternative.

I do not think that replacing one addiction with a modified version of it is the best idea. While it does reduce the health risk, it does not solve the issue of nicotine addiction, the possible long-term effects, and the cost of feeding the addiction. However, I think that e-cigarettes can be beneficial for smoking cessation and nicotine cessation with proper monitoring from healthcare professionals and social support.

 Do you think that smoking cessation is more important than nicotine cessation? Do you think e-cigarettes should be utilized for nicotine-cessation?


[i] Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults—United States, 2011. Morbidity and Mortality Weekly Report 2012;61(44):889–94 [accessed 2013 Nov 29]

[ii] Available at: Accessed November 29, 2013.

[iii] Polosa R. Rodu B, Caponnetto P, Maglia M, Raciti C. A fresh look at tobacco harm reduction: the case for the electronic cigarette. Harm Reduction Journal 2013;10(19)1-11 [accessed 2013 Nov 29].

[iv] Casella G, Caponnetto P, Polosa R: Therapeutic advances in the treatment of nicotine addiction: Present and Future. Ther Adv Chronic Dis 2010, 1(3):95-106 (accessed Nov 29).

[v] Bullen C, Howe C, Laugesen M, McRobbie H, Parag V, William J, Walker N. Electronic cigarettes for smoking cessation: a randomized controlled trial. The Lancet. 2013;382(9905)1629-1637 [accessed Nov 29).

[vi] Barbeau A, Burda J, Siegel M.  Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach. ASCP Journal 2013;8(5):1-7 (accessed 2013 Nov 29).

[vii] Cahn Z and Siegal M. Electronic cigarettes as a harm reduction strategy for tobacco control: a step forward or a repeat of past mistakes? Journal of Public Health Policy 2011;32(1)16-31 (accessed 2013 Nov 29)

[viii] Pozin I. Electronic cigarettes : booming industry or health fiasco?;;; (accessed 2013 Nov 29)

[ix] Polosa R. Rodu B, Caponnetto P, Maglia M, Raciti C. A fresh look at tobacco harm reduction: the case for the electronic cigarette. Harm Reduction Journal 2013;10(19)1-11 [accessed 2013 Nov 29].

[x] Kelland K. E-cigarettes as good as nicotine patches in helping smokers quit. (accessed 2013 Nov 29)

[xi] Barbeau A, Burda J, Siegel M.  Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach. ASCP Journal 2013;8(5):1-7 (accessed 2013 Nov 29).

Herbal Supplements: The Whole Truth

Monday, December 2nd, 2013

by Olumami Amaye, PharmD student

Herbal supplements come in all forms. They may be taken internally as pills or powders, dissolved into tinctures or syrups, or brewed in teas. Ointments, shampoos, or poultices may be applied to the skin, scalp, or mucous membranes. What puzzles me, however,  are the unlisted ingredients in the supplements. In fact, an article published by Live-Science on October 11th, 2013 discusses a new study which found that herbal supplements contain unlisted ingredients and may pose a health hazard to consumers.1

In the United States, herbal and other dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as foods. This means that they do not have to meet the same standards as drugs and over-the-counter medications for proof of safety, effectiveness, and what the FDA calls Good Manufacturing Practices. The active ingredient(s) in many herbs and herbal supplements are not known. There may be dozens, even hundreds, of such compounds in an herbal supplement. In 2011, some researchers conducted a study to verify the contents of 5 known herbal products: St John’s wort, Asian ginseng, echinacea, garlic and ginkgo.2  What they found was so alarming that it forced the European Union (EU) to change some legislation on herbal supplement products.3 Some herbal supplements have been found to be contaminated with metals, unlabeled prescription drugs, microorganisms, or other substances, the researchers said.3

However, in a recent article in the Archives of Internal Medicine, DM Marcus and AP Grollman stated that “Even when the Food and Drug Administration (FDA)” identifies an unsafe product, it lacks authority to mandate its removal from the market because it must meet the very high legal requirement to demonstrate a ‘significant or unreasonable’ risk.3 According to the article published by Live-Science on October 11th, 2013 BMC medicine studied a very new technique “ called DNA  barcoding test” where they analyzed 12 companies herbal products. However, out of the 12 companies that manufacture herbal supplements only 2 products were found to have no substitution, contaminants or fillers.4 The Newmaster et al. study also found that one product labeled as St.John’s wort was substituted with senna alexandrina. It contained only senna barcodes and no St. John’s wort barcoding.1  From my understanding of senna, it’s a stimulant laxative agent which if not properly used can cause  adverse effects such as diarrhea, abdominal pain, skin disorders and blistering.5 Several herbal products contained Parthenium hysterophorus (feverfew), which can cause swelling and numbness in the mouth, oral ulcers and nausea. It also reacts with medications metabolized by the liver and may increase the risk of bleeding, especially if taken with blood-thinning medications, the researchers said.1

The findings of the study are also consistent with earlier studies. For examples, one study shows   51 (75%) of 68 products contained none of the key safety messages, while other studies also share similar results.6   In light of these and other studies conducted in North American and European countries, I believe there should be some regulations in place for testing and approval of herbal products.  Personally, after reading this article I felt that using supplements can be dangerous to a person’s health. I would be very cautious before putting one of these into my body for any reason. I have learned that the improper use of supplements might lead to some health issues.

The limitations to this study are the use of new DNA barcoding methods, lack of barcode library, and not listing the names of herbal supplement manufacturers. The DNA barcoding is not generally accepted by herbal product manufacturers and no set standards are in place for industries to follow. The study also failed to list the herbal products that were tested and the brands or companies that are following unethical activities and false advertising. By not listing the companies involve, the study might mislead other consumers to think that all herbal supplements are totally bad.

Would you take herbal supplements? Do you think they are beneficial to your health?,



  1. Newmaster S, Grguric M, Shanmughanandhan D, Ramalingam S, Ragupathy S. DNA barcoding detects contamination and substitution in North American herbal products. BMC Medicine [serial online]. November 2013;11(1):18-35. Available from: Academic Search Complete, Ipswich, MA. Accessed November 12, 2013.
  2. Marcus DM, Grollman AP. The consequences of ineffective regulation of dietary supplements. Arch Intern Med. 2012 Jul 9;172(13):1035-6. PubMed PMID: 22777632.
  3. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448.
  4. Rettner, Rachael. Herbal Supplements Often Contain Unlisted Ingredients. LiveScience, October 11th, 2013. Available at   Accessed November 12, 2013.
  5. Krinsky, D. L., Berardi, R. R., & Ferreri, S. P. (2011). Handbook of nonprescription drugs: An interactive approach to self-care (17th ed.). Washington, D.C: American Pharmacists Association.
  6. Raynor D, Dickinson R, Knapp P, Long A, Nicolson D. Buyer beware? Does the information provided with herbal products available over the counter enable safe use?. BMC Medicine [serial online]. August 9, 2011;9:94. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed November 12, 2013.

Insomnia: Not just about sleep

Monday, December 2nd, 2013

by Chelsae Ward, PharmD student

Insomnia is one of the most common patient complaints for Americans, third only to headache and the common cold. It is estimated that 33 percent of the United States population experiences insomnia.1 As defined by the CDC, insomnia “is an inability to initiate or maintain sleep.” 2 While the symptoms of insomnia are similar and easily identifiable, the causes can be vast and often hard to determine. Many times insomnia is not the primary condition but the effect of an underlying problem. One of the major causes of insomnia is emotional unrest due to either excitement or stress/worry. Therefore, insomnia is often a tell sign of depression or other emotional disorder. Pain or physical disturbances are also a common cause of insomnia. Other times, sleep disorders, such as sleep apnea cause insomnia.3, a pharmacy news website, reviewed a study on the effects of insomnia in the article, It’s More Than Beauty Sleep.”4 The study was conducted by the CDC and looked at the correlation between insomnia causing diabetes and/or heart disease. Specifically, they focused on insomnia caused by mental distress and obesity. The study used over 50,000 participants who were 45 years and older. It concluded that a majority of people (64.8 percent) were optimal sleepers in terms of amount of time spent sleeping each night. Those who were short sleepers (31.1 percent) were more likely to develop heart disease, stroke, mental disorders, obesity, and diabetes. The authors of the study point out limitations in that it is difficult to determine which of the factors are the cause and which are the effect. For example, does insomnia cause diabetes or does diabetes cause insomnia? Sleep expert, Robert S. Rosenberg, states that the former has been most evidenced in recent studies.4 Another limitation was that the study was open to recall bias because the participants gave their own opinions on their sleep habits. The Rxdaily article concludes that medical professionals need to be more attentive to patients sleep patterns and habits.4

I agree with the Rxdaily article that health care professionals, including pharmacists, need to be attentive to a patient’s sleeping habits. Recognizing insomnia in patients can help identify a possible disease state since insomnia can be either a cause or effect of many disorders.5 Based on this knowledge it would make sense that Health Care Professionals would be attentive to a patient’s insomnia. One way in which this process can be easily implemented is to begin asking patients with a known medical history of heart disease, diabetes, obesity, or stroke of their sleeping habits. Along with this step, health care professionals can stress the importance of quality sleep to all patients, and thus the patient can address insomnia if/when it becomes a problem for them.

Not only is it important to pinpoint insomnia in patients due to its ability to cause medical issues, but many patients attempt to self-treat insomnia with over-the-counter medication (9 percent) or alcohol (11 percent).1 Pharmacists, being the best patient contact for over-the-counter medication, need to be aware of their patient’s insomnia. The pharmacist can then appropriately guide the patient on the best way to treat their insomnia. Benadryl, the most common over-the-counter sleep aid, may be used beneficially in short-term insomnia; but its use is not recommended long term.1 Many patients believe that alcohol will help to solve their sleep insomnia. It is important that alcohol users are aware that while alcohol may initially cause drowsiness and help one get to sleep, it will be more difficult to stay asleep. Many people will wake up more frequently throughout a night with alcohol use.6

The best way that has been found to treat chronic insomnia is through sleep training (also known as sleep hygiene), in which the patient trains themselves in proper sleeping habits.7 Sleep training are basic steps to take in order for one’s body to be in a suitable sleeping environment. It is important to keep a steady sleep schedule in which the patient will go to bed at the same time every night and wake at the same time every morning. The bedroom should be quiet, dark, and a place where the patient feels they can relax. The temperature of the room should not be too hot or too cold. The bed should be comfortable to the patient, neither too soft nor too firm. The bed should only be used for sleeping, making sure activities like reading, watching TV, or completing work, are done outside the bedroom. It would also be helpful to avoid large meals two hours before bedtime. Avoid taking naps throughout the day. If still unable to fall asleep, it is recommended to, instead of trying to force sleep, carry out a relaxing activity away from the bedroom.1,2

With the new evidence linking chronic illness and insomnia as found in the research study reviewed by, and the high rate of self-treatment for insomnia, it would seem, not only important, but also necessary for health care professionals to be aware of patients sleeping difficulties. Do you think the health benefits of sleep are being under-rated in today’s health system?



1) Melton, C. K. Insomnia, Drowsiness, and Fatigue. In: R. R. Daniel L. Krinsky, Handbook of Nonprescription Drugs An Interactive Approach to Self-Care. Washington, DC: American Pharmacists Association; 2012: 867-876.

2) Sleep and Sleep Disorders. Centers for Disease Control and Prevention. May, 2012.

3) Staff, M. C. Insomnia. Mayo Clinic. Janurary, 2011.

4) Robert S. Rosenberg, D. F. It’s More Than Beauty Sleep. October, 2013.

5) Lawrence Robinson, G. K. Sleeping Pills & Natural Sleep Aids. May, 2013.

6) Szalavitz, Maia. Sleeping It Off: How Alcohol Affects Sleep Quality. Time: Health and Family. February 8, 2013.

7) Reinberg, S. Prescription Sleep Aids Common Choice for Insomnia. WebMD. August 29, 2013.

Exercise to Save Your Knees

Monday, December 2nd, 2013

by Jeniffer George, PharmD student

An estimated 27 million adults in the United States suffer from osteoarthritis of the knee or hip which is commonly seen in patients 65 and older.1 Osteoarthritis is the breakdown in cartilage that covers the ends of the bone to where they meet and form a joint to allow movement.1 As of today, researchers have not found a set cure for arthritis, however, mild pain relief can be found from the use of NSAIDS, acetaminophen and combination products such as glucosamine and chondroitin. In addition, with the increase in obesity in the United States, exercise can relieve stress that is placed on the knees for patients with osteoarthritis. A survey conducted by the Centers for Disease Control and Prevention showed 53% of patients with arthritis didn’t walk at all for exercise, and 23% meet the current recommendation for activity—walking for at least 150 minutes a week.2 So the question I pose is: as future pharmacists, should we recommend glucosamine and chondroitin or exercise to patients with osteoarthritis?

For almost 20 years, the nutritional supplement glucosamine and chondroitin has been marketed to the public for joint health. Glucosamine is an amino sugar that can help renew cartilage while chondroitin is thought to be a complex carbohydrate that helps cartilage retain water.3 Glucosamine and chondroitin are found as natural substances in and around the cells of cartilage.3

NPR recently released an article that presented a study published by the New England Journal of Medicine (NEJM) and another study by the Journal of American Medical Association (JAMA). The study found in NEJM, involved 1,583 randomly selected patients receiving glucosamine and chondroitin with placebo.4 They found that glucosamine/chondroitin, in comparison with placebo seemed to show no effect on patients with osteoarthritis, however, a smaller subgroup characterized with moderate to severe pain showed a significant reduction of knee pain after the use of glucosamine. The study was conducted well, however, patients measured at baseline reported having mild knee pain, as compared with that in classic studies of osteoarthritis, in which a criterion for entry was a disease flare after the discontinuation of NSAIDs.4 In general, the evidence on glucosamine/chondroitin is varied, leaving it difficult to answer if the use of supplements are proven to be effective.

The second study presented in JAMA, included 399 participants that are overweight and presented with knee osteoarthritis. Participants in the study endured 18 months of combined intense diet and exercise modifications to see if there would be an increase in knee function and reduction in pain. Participants in the diet and exercise and diet groups had greater reductions in Interleukin 6 (used to measure inflammation) levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group.5 The article does a great job on emphasizing the importance of exercise, however, patients with moderate to severe osteoarthritis, who may have difficulty exercising were excluded from the study.

I agree with most of the content in the article and seem to agree with the studies associated with the material. As a future pharmacist, I would recommend using glucosamine and chondroitin in conjunction with exercise while living a healthy dietary lifestyle to help patients with osteoarthritis. It is human nature to avoid doing things when you are in pain. Patients with osteoarthritis may avoid exercise when a hip, knee, or other joints hurt. As shown in the NEJM study, patients with moderate-to-severe pain saw a reduction in pain after using glucosamine and chondroitin. Recommending glucosamine and chondroitin can help patients have temporary relief in pain, which can enable them to engage in low impact activities, get the heart rate up and burn calories. If exercise is not an option for the patient, guiding the patient in dietary modifications can help in weight reduction. Other treatment options include: rest which helps reduce stress and tension that is put on the knees, hot and cold therapy to help increase blood flow and reduce inflammation near the joint area, and to avoid standing in one position for an extended time.

With studies like these, would you suggest glucosamine and chondroitin as a form of therapy? How can you advise a patient that is adamant on not losing weight due to the pain they are experiencing?




  1. National Center for Complementary and Alternative Medicine. Published May 2002. Updated October 2008. Accessed November 1, 2013.
  2. Skerrett PJ. Exercise is good, not bad, for arthritis. Harvard Health Publication Web site. Published May 8,2013. Accessed November 21, 2013.
  3. Patti Neighmond. National Public Radio. National Public Radio Website. Published October 14, 2013. Accessed November 1, 2013
  4. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis. N Engl J Med. 2006;354(8):795-808.
  5. Messier SP, Mihalko SL, Legault C, et al. Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis: The IDEA Randomized Clinical Trial. JAMA. 2013;310(12):1263-1273. doi:10.1001/jama.2013.277669.Accessed November 1, 2013.