References for CME Article "Mirror Therapy for Phantom Limb Pain and Stroke" References [1] Chan Pl et al. Mirror Therapy for Phantom Limb Pain. N Engl J Med. 357:2206-2207. November 22, 2007. Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJMc071927 [2] Ramachandran VJ & Rogers-Ramachandran D.  Synaesthesia in phantom limbs induced with mirrors. Proceedings: Biological Sciences, Vol. 263, No. 1369 (Apr. 22, 1996), pp. 377-386. Retrieved from: https://journalpsyche.org/articles/0xc11c.pdf [3] Ramachandran VS, Altschuler EL, The use of visual feedback, in particular mirror visual feedback, in restoring brain function, Brain, Volume 132, Issue 7, July 2009, Pages 1693–1710. Retrieved from: https://academic.oup.com/brain/article-abstract/132/7/1693/328686?redirectedFrom=fulltext&login=false [4] Twombly R. Neuroscientists Explore Science of Music and Movement in the Blind. Georgetown University Medical Center. February 4, 2015. Retrieved from: https://gumc.georgetown.edu/gumc-stories/neuroscientists-explore-music-movement-in-blind/# [5] Ramadugu S et al. Intervention for phantom limb pain: A randomized single crossover study of mirror therapy. Indian Journal of Psychiatry 59(4):p 457-464, Oct–Dec 2017. | DOI: 10.4103/psychiatry.IndianJPsychiatry_259_16. Retrieved from: https://journals.lww.com/indianjpsychiatry/fulltext/2017/59040/intervention_for_phantom_limb_pain__a_randomized.9.aspx [6] Finn et al. A Randomized, Controlled Trial of Mirror Therapy for Upper Extremity Phantom Limb Pain in Male Amputees. Front. Neurol., 06 July 2017.  Volume 8. Retrieved from:  https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00267/full [7] Yildirim M & Kanan N. The effect of mirror therapy on the management of phantom limb pain. Agri.  2016;28(3):127–134. https://jag.journalagent.com/agri/pdfs/AGRI-48343-EXPERIMENTAL_AND_CLINICAL_STUDIES-YILDIRIM.pdf   [8] Xie H-M et al. Effectiveness of Mirror Therapy for Phantom Limb Pain: A Systematic Review and Meta-analysis. Archives of Physical Medicine and Rehabilitation. Volume 103, Issue 5, 2022, Pages 988-997. Retrieved from: https://www.sciencedirect.com/science/article/abs/pii/S0003999321013794 [9] Herrador Colmenero L et al. Effectiveness of mirror therapy, motor imagery, and virtual feedback on phantom limb pain following amputation: A systematic review. Prosthetics and Orthotics International . 2017;42(3):288-298. https://journals.sagepub.com/doi/full/10.1177/0309364617740230 [10] Barbin J et al. The effects of mirror therapy on pain and motor control of phantom limb in amputees: A systematic review. Annals of Physical and Rehabilitation Medicine. Volume 59, Issue 4, 2016, Pages 270-275. Retrieved from: https://www.sciencedirect.com/science/article/pii/S1877065716300318 [11] Altschuler EL. Rehabilitation of hemiparesis after stroke with a mirror. The Lancet • Vol 353 • June 12, 1999, 2035-2036.  Retrieved from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)00920-4/fulltext [12] Thieme H et al. Mirror therapy for improving motor function after stroke. Cochrane Database Syst Rev. 2018;7(7):CD008449. Published 2018 Jul 11. Retrieved from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6513639/ [13] Hussain MA et al. Virtual reality as a non-conventional rehabilitation for stroke: A comprehensive review. Journal of Neurorestoratology. Volume 12, Issue 3, 2024. Retrieved from: https://www.sciencedirect.com/science/article/pii/S2324242624000421 LINK CME article: " "Mirror Therapy for Phantom Limb Pain and Stroke"

Chronic Disease Rates in American Children also Increasing In a study published in July 2025, the authors examined mortality trends in U.S. children.  They compared mortality data from the U.S. to 18 high-income countries: Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Ireland, Italy, Japan, the Netherlands, New Zealand, Norway, Spain, Sweden, Switzerland, and the United Kingdom. Between the years 2007 and 2022, U.S. infants less than one year of age had a 78% increased risk of dying compared to infants from the other 18 countries.  American 1- to 19-year-olds had an 80% higher risk of dying compared to the other countries.  During the study period, it was calculated that there were 315,795 excess deaths in the U.S. compared with the other 18 countries, which equals 54 excess American infant/child/teenage deaths per day.  Infants in the U.S. were 2.22 times more likely to be born premature, 48% more likely to have congenital abnormalities, 69% more likely to have a respiratory infection, and 2.39 times more likely to suffer a sudden unexpected infant death than in the other countries. U.S. infants did have a 22% lower risk of dying from birth related respiratory problems or trauma.   In the 1- to 19-year-old age group, there was a 15.43 times greater risk of dying from firearms in the U.S. compared to other countries.  American children and teenagers were 2.45 times more likely to die from motor vehicle accidents, 5.25 times more likely to die from substance abuse, and 5.32 times more likely to die from homicide than in the other 18 countries.  Suicide rates and cancer deaths were approximately equal for the U.S. and the other countries.  The authors also compared chronic medical conditions of U.S. children/teenagers ages 3 to 17 from the years 2011 to 2023. They reported that American children/teenagers had 15% to 20% more chronic condition diagnoses in 2023 compared to 2011. The eight conditions with the greatest increase, in 2023 compared to 2011 were: a 3.3 times higher risk of major depression, a 3.22 times higher risk of sleep apnea, a 3.2 times higher risk of eating disorder, a 3.06 times higher risk of anxiety, a 2.62 times higher risk of autism spectrum disorder, a 2.37 times higher risk of obesity, a 2.06 times higher risk of a lipid metabolism disorder, and a 2.05 times higher risk of a developmental disorder. The authors concluded that their study indicated that the health of U.S. children had steadily declined from 2007 to 2023. Weaknesses of the study include that the authors did not compare the subjects’ socioeconomic status to the risk of mortality or chronic condition. There may be significant differences in children’s health outcomes depending on their family’s socioeconomic status.  They did not delve into the root causes of their findings.  The data was based on retrospective databases, which are dependent on the level of documentation by practitioners.  There was also some mortality data missing from some of the countries during the COVID epidemic years.  Comments:  This is a sobering report that, if true, indicates U.S. children are dying from various causes at a higher rate than children in the other 18 income-rich nations they were compared to.  In addition, the overall health of American children appears to have worsened over a 12-year period, with an increased rate of both chronic medical and psychological disease diagnoses.   This report should be a wake-up call for the U.S. to re-evaluate what can be done to improve the overall health of American children/teenagers.  According to the data, in the 1- to 19-year-old age group, there are 54 excess deaths in the U.S. every day compared to other countries.  There has been a 15% to 20% increase in the rate of chronic disease diagnoses in U.S. 3- to 17-year-olds from 2011 to 2023.   Hopefully, steps will be taken to alter what the data in this study reveals: that growing up in America appears to increase the chances of a premature death, compared to other income-rich countries in the world, and the risk of U.S. children/teenagers developing a chronic medical or psychological condition has increased over time. References Forrest CB, Koenigsberg LJ, Eddy Harvey F, Maltenfort MG, Halfon N. Trends in US Children’s Mortality, Chronic Conditions, Obesity, Functional Status, and Symptoms. JAMA.  Published online July 07, 2025. Retrieved from: https://jamanetwork.com/journals/jama/article-abstract/2836060?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jama.2025.9855

Savor summer's joy with watermelon! This hydrating fruit, rich in nutrients, offers a sweet escape and numerous health benefits. Culinary Medicine by Lori A Smolin, PhD    and Mary B Grosvenor, MS, RD You cannot dry it, can it, or freeze it, so watermelon is truly a seasonal fruit for the long, lazy, hot days of summer. An essential at picnics and barbeques, it is the most popular type of melon in the US. Mark Twain once said of watermelon “ When one has tasted it, he knows what the angels eat.”   Origins Watermelon, along with cucumbers, pumpkins, cantaloupe, and squash, is a member of the Cucurbitaceae family of plants. It has been part of the human diet for thousands of years. Five thousand-year-old seeds were found in northeastern Africa and watermelon images appear in a 4000-year-old Egyptian tomb.[1]  These early watermelons were a bitter, drought-tolerant ancestor of today’s melons and were likely used by ancients as natural canteens.[2] Sweet watermelons, more similar to what we enjoy today, emerged in the Mediterranean about 2000 years ago.[1]  Today there are more than 300 types of watermelon cultivated in the US, including seeded, seedless, mini, and yellow and orange varieties. The color of the watermelon flesh depends on the mix of carotenoids in the melon. Traditional vibrant pink watermelons are high in lycopene, the carotenoid that gives tomatoes their red color. Orange watermelons have more ß-carotene and less lycopene, and yellow watermelons get their color from the carotenoid pigment neoxanthin.[3]  Nutrition and Health Benefits Did you know that eating an average-sized watermelon wedge is the equivalent of drinking a cup of water? Watermelon is more than 90% water; this high water content makes it low in calories, about 45 calories per cup. It provides a small amount of protein and is very low in fat. Although watermelon tastes sweet, a cup has less sugar than a cup of grapes.[4] Because the total amount of carbohydrate in a serving of watermelon is relatively small, it can be eaten in moderation by people with diabetes without significantly affecting their blood glucose control.[5] Eating watermelon can benefit weight management by boosting satiety. In a study of overweight and obese adults, consuming 2 cups of watermelon per day for four weeks resulted in reductions in body weight, body mass index (BMI), and blood pressure.[6] The connection between watermelon consumption and blood pressure may be related to its citrulline content. Citrulline is an amino acid that can be converted into arginine, another amino acid.  Arginine is needed to synthesize nitric oxide, a signaling molecule that can relax artery walls and lower blood pressure.[7]  Watermelon also contains vitamins and phytochemicals that provide health-promoting antioxidant, anti-inflammatory, and anti-cancer properties.[8,9] One slice has a third of the daily requirement for vitamin C, an antioxidant that is essential for connective tissue health.  Watermelon is also a reliable source of ß-carotene, which can be converted into vitamin A in the body and also provides antioxidant protection. The lycopene in watermelon is another antioxidant. It may protect against heart disease and cancer, but is particularly important for eye health, reducing the risk of cataracts and macular degeneration.[10]  Picking the Sweetest Melon   Unlike peaches and pears that ripen and sweeten after picking, watermelons do not get sweeter after harvest, they will only soften and begin to spoil. To select a sweet watermelon, whether you are picking it from the field or the grocery store, focus on color and tone.[11] The green color of watermelon lightens when it is ripe, so look for paler ones. Also, look at the spot where the melon rested on the soil. It starts out white and turns creamy yellow once the fruit has matured. To assess the tone of your watermelon you may need to be musically inclined. If you slap it the sound should bounce back like a drum. If the sound is absorbed, it indicates that the flesh is mealy. The best melons have a tone that is not too high pitched but also not too low a bass note.  Including Melon in Your Meals You may think that the only way to enjoy a watermelon is as a cool treat at your summer picnic, but it is a great addition to salads and can be made into a salsa to serve alongside a hot meal. If sweet is not enough for you, you can spice it up by sprinkling on some chili powder and cumin. You can blenderize it for your breakfast smoothie or to make a frozen sorbet.[12] You can make it part of a main course by tossing it into a stir fry or curry recipe or using chunks to make a vegan sushi. Do not forget about the rind, you can pickle it or fry it.  Whether you choose the classic option or a more exotic presentation, enjoy the taste and health benefits of some watermelon whenever they are available. Check out this Watermelon Sashimi Poke Bowl Recipe References [1] Paris HS. Origin and emergence of the sweet dessert watermelon, Citrullus lanatus. Annals of Botany. 2015;116(2):133-148. doi: https://doi.org/10.1093/aob/mcv077 [2] Trinklein D. Watermelon: A Brief History (David Trinklein). ipm.missouri.edu . Published July 17, 2020. https://ipm.missouri.edu/MEG/2020/7/watermelon-DT/ ‌ [3] Zhao W, Pin Lv, Gu H. Studies on carotenoids in watermelon flesh. Agricultural Sciences. 2013;04(07):13-20. doi: https://doi.org/10.4236/as.2013.47a003  [4] Hopkins, C. How Healthy is Watermelon. New York Times. July 1, 2024https:// www.nytimes.com/2024/07/01/well/eat/watermelon-health-benefits-recipes.html [5] Gordon JP. Can I Eat Watermelon If I Have Diabetes? Healthline. Published September 27, 2016. https://www.healthline.com/health/diabetes/watermelon-and-diabetes#other-fruits ‌   [6] Lum T, Connolly M, Marx A, et al. Effects of Fresh Watermelon Consumption on the Acute Satiety Response and Cardiometabolic Risk Factors in Overweight and Obese Adults. Nutrients. 2019;11(3). doi: https://doi.org/10.3390/nu11030595 ‌ [7]Volino-Souza M, Oliveira GV de, Conte-Junior CA, Figueroa A, Alvares TS. Current Evidence of Watermelon (Citrullus lanatus) Ingestion on Vascular Health: A Food Science and Technology Perspective. Nutrients. 2022;14(14):2913. doi: https://doi.org/10.3390/nu14142913 ‌ [8] Manivannan A, Lee ES, Han K, Lee HE, Kim DS. Versatile Nutraceutical Potentials of Watermelon—A Modest Fruit Loaded with Pharmaceutically Valuable Phytochemicals. Molecules. 2020;25(22):5258. doi: https://doi.org/10.3390/molecules25225258 [9] Maoto MM, Beswa D, Jideani AIO. Watermelon as a potential fruit snack. International Journal of Food Properties. 2019;22(1):355-370. doi: https://doi.org/10.1080/10942912.2019.1584212 ‌ [10] Petre A. Lycopene: Health Benefits and Top Food Sources. Healthline. Published October 3, 2018. https://www.healthline.com/nutrition/lycopene#other-benefits [11] 1.Ko G. How to Pick a Watermelon. The New York Times. https://www.nytimes.com/2024/07/26/dining/how-to-pick-a-watermelon.html . Published July 26, 2024. [12] Groskreutz R. 13 Ways to Have Watermelon on a Hot Summer Day. FunCity Stuff DFW. Published July 28, 2018. https://funcitystuff.com/watermelon-recipes/

The Vegan "Tuna" Poke Bowl That Will Fool Your Taste Buds Marinated and baked to perfection, the watermelon takes on the texture and appearance of tuna, creating a delicious and healthy plant-based poke bowl. Recipe A traditional poke (pronounced POH-kay) bowl consists of raw fish served over rice with a variety of toppings such as raw and pickled vegetables, nuts, mango, avocado, edamame, and sesame seeds, flavored with a sweet or spicy sauce. This vegan version replaces the fish with marinated, baked watermelon that will have you thinking you are eating tuna sashimi. Enjoy it exactly as described below or get creative and add a different variety of toppings. Ingredients   Watermelon Sashimi ½ small seedless watermelon 3 Tbsp tamari or low sodium soy sauce  1 Tbsp mirin 1 tsp toasted sesame oil 2 tsp honey 1 Tbsp rice vinegar 2 Tbsp Nori flakes or 1 crumbled nori sheet Poke Bowls  1½ cups cooked short grain (sushi) rice 16 slices of watermelon sashimi ½ cup sliced cucumbers ½ cup julienned or shredded carrots ½ cup sliced pickled beets 1 small avocado, sliced ½ cup water chestnuts 1 tsp sesame seeds Instructions  Prepare Watermelon Sashimi Wash watermelon. Slice 2 1-inch-thick rounds from wide part of the melon, remove the rind. Mix tamari, mirin, sesame oil, honey, rice vinegar, and nori flakes in a small bowl. Place watermelon and the tamari mixture in a large resealable bag and marinate for 30-60 minutes at room temperature. Preheat oven to 350 degrees. Line rimmed baking sheet with parchment paper. Place watermelon steaks in a single layer on the baking sheet, pour on remaining marinade. Bake for 45-50 minutes flipping every 15 minutes. Melon should be red and edges may be charred. Cool watermelon slightly and then cut it into thin slices, holding the knife at 45 degrees to the watermelon steak. Each steak should make 8-10 slices. Assemble 2 Poke Bowls Place ½ of cooled rice in each bowl. Divide the sashimi, cucumbers, beets, avocado, water chestnuts, and carrots and arrange over the two bowls of rice. Sprinkle with sesame seeds. Add additional toppings and dressing of your choice such as scallions, fried onions, sea salt, Asian salad dressing or Sriracha mayonnaise. Nutrition information per serving Makes 2 poke bowls Calories 370, Fat 8g, Saturated fat 1.2, Cholesterol 0mg, Carbohydrate 70g, Fiber 5g, Protein 6.5g, Sodium 490mg, Potassium 570mg Nutrition Chef Authors: Mary B Grosvenor, MS, RD Lori A Smolin, PhD Medically Reviewed by FibonacciMD editors. Authors’ Notes:  You can make the watermelon sashimi ahead of time and keep it refrigerated for up to 3 days. Brown rice and quinoa can also be used instead of white rice. Include tofu or edamame in your toppings to boost the protein in this vegan bowl Editor’s note:   Appropriate for a low-cholesterol, low-fat, vegan dietary regimen. Also an excellent source of fiber. Learn more about Watermelon in this Culinary Medicine article

Curious about artificial food dyes? Explore recent insights into their presence in our food supply and potential implications for health, especially for children. The Department of Health and Human Services has recently indicated that by 2026, it wants to phase out eight commonly used artificial food dyes from food products.  There is some evidence that artificial dyes may be linked to hyperactivity and neurobehavioral problems in children.  Most artificial food colors are derived from petroleum products.  But how much of our food supply contains these dyes?  A recent study answered that question.  It was published in June 2025, and looked at the amount of artificial dye in food products for the year 2020.  Red Dye #3 was banned in 2023 in California and nationally last year.  Other commonly used dyes include Red No. 40, Blue No. 1, Blue No. 2, Yellow No. 5, Yellow No. 6, and Green No. 3. The authors reported that 19% of products produced by the top 25 food companies contained artificial dyes.  Red No. 40 was the most common, found in 14% of products reviewed.  A significant number of foods contained more than one dye, with 9% containing three or more.  Products containing dyes had, on average, 141% higher levels of sugar than those without dyes. The products containing the largest percentage of artificial dyes were: Sport drinks -79%, Beverage concentrates - 71%, confectionaries - 54%, both energy drinks and carbonated beverages - 39%, baked goods - 22%, and breakfast cereals - 20%.  They reported that 28% of the top five product lines marketed to children contained artificial dyes. Comment: Eliminating petroleum-based dyes from the food supply may be a positive step to improve health outcomes, especially in children.  However, the larger issue of exposure to petroleum-based plastics in the modern diet still remains problematic.  To learn more about this issue, read the FibonacciMedicine articles on The Effects of Plastics on Human Health , and   How to Reduce Exposure to Microplastics and Chemicals Leaching from Plastics.   References:  Dunford EK et al. All the Colors of the Rainbow: Synthetic Dyes in US Packaged Foods and Beverages in 2020. Journal of the Academy of Nutrition and Dietetics. Published online, June 24, 2025. Retrieved from: https://www.jandonline.org/article/S2212-2672(25)00166-2/fulltext Seversen K. Kennedy Plans to Phase Out 8 Commonly Used Food Dyes. The New York Times. April 21, 2025. Retrieved from: https://www.nytimes.com/2025/04/21/dining/rfk-jr-food-dyes.html Report Links Synthetic Food Dyes to Hyperactivity and other Neurobehavioral Effects in Children. State of California Office of Environmental Health Hazard Assessment. April 16, 2021. Retrieved from: https://oehha.ca.gov/risk-assessment/press-release/report-links-synthetic-food-dyes-hyperactivity-and-other-neurobehavioral-effects-children

A Crispy, Guilt-Free Twist on a Southern Fried Chicken Looking for a crispy, flavorful chicken dinner without the grease? This oven-fried chicken recipe delivers all the crunch and comfort with fewer calories and carbs. Creative Cooking for the Health-Conscious Gourmet FibonacciRECIPES  | Culinary Medicine   Recipe Craving fried chicken without the fryer guilt? This oven-fried chicken recipe gives you all the crispy, juicy goodness of traditional fried chicken—without the excess grease or carbs. Coated in crushed corn flakes and seasoned to perfection, these chicken legs or thighs bake up golden and flavorful. With just 398 calories and 28.7g of carbs per serving, this low-calorie, low-carb entrée is perfect for anyone looking to enjoy comfort food in a healthier way. Ingredients: 2 cups corn flakes, crushed 0.5 tsp garlic powder 0.5 tsp onion powder 0.5 tsp paprika 1 tbsp kosher salt 0.5 tbsp freshly ground black pepper 3 large eggs 1 cup buttermilk 6 bone-in, skin-on chicken legs or thighs Instructions Preheat oven to 425°F. Line a baking sheet with aluminum foil. In a medium bowl, mix together corn flakes and dry herbs. Season generously with salt and pepper. In another medium bowl, whisk together eggs and buttermilk. Pat chicken pieces dry, then dip into egg mixture. Next, dredge in cereal, making sure all sides are coated. Place on baking sheet, and bake until golden and crispy and a thermometer inserted in the center reads 165°F (about 1 hour). Makes 18 skewers or 6 servings Nutrition information per 6 serving Calories: 398, Total fat: 21.7 g, Cholesterol: 193 mg, Sodium: 1,524 mg, Total carbohydrate: 28.7 g, Dietary fiber: 1.1 g, Total sugars: 5 g, Protein: 23.2 g Vitamin D: 9 ug Nutrition Chef Authors: Justin Gillette, Certified Executive Chef, Chef Author Medically Reviewed by FibonacciMD editors. Editor’s Note: Low-calorie entrée and low-carb recipe. more health-conscious recipes

AKA Texting Thumb or DeQuervain’s Syndrome Explore De Quervain's tenosynovitis, or "Texting Thumb." Understand symptoms, causes, the Finkelstein test, and treatment options for effective relief from thumb and wrist pain. texting thumb   by Allan Strongwater, M.D. De Quervain syndrome is an inflammatory disorder affecting the tendons of the first dorsal extensor compartment of the hand. Upon physical examination, there is tenderness along the abductor pollicis longus and the extensor pollicis brevis tendons in the compartment. Swelling of the compartment is often present. Resisted thumb extension elicits pain as seen in the Finkelstein test (holding the wrist in radial deviation, flexing the thumb metacarpophalangeal [MCP] joint and interphalangeal [IP] joint into the palm, and closing the fist over the flexed thumb). The wrist is then deviated ulnarly. The test is positive if ulnar deviation causes pain. There is a high degree of correlation between a positive Finkelstein test and de Quervain syndrome. Signs and Symptoms Patients often complain of pain in the thumb with motion of the MCP and/or interphalangeal IP joints of the thumb. The pain may radiate proximally to the wrist, and ulnar deviation of the wrist may exacerbate the pain. Patients may also complain of swelling at the base of the thumb and along the course of the two extensor tendons. Tenderness is apparent along the abductor pollicis longus and the extensor pollicis brevis tendons in the compartment. Swelling of the compartment is often present. Resisted thumb extension elicits pain as seen in the Finkelstein test. Causes and Risk Factors De Quervain syndrome may result from a number of etiologies. Women are affected more often than men. There is a higher observed incidence during and immediately after pregnancy. Tenosynovitis has been reported following trauma to the region of the dorsum of the first metacarpal, injuring the two tendons (the abductor pollicis longus and the extensor pollicis brevis) in the first extensor compartment of the hand. Mechanical overload, most commonly due to repetitive activities, may induce the tenosynovitis as is seen in "texting thumb." Systemic inflammatory diseases (eg, rheumatoid arthritis) may trigger tenosynovitis of the first extensor compartment, resulting in de Quervain syndrome. Diagnostic Evaluation The Finkelstein test is used during physical examination to elicit the diagnosis. The test is positive if ulnar deviation causes pain. Radiographs of the hand should be obtained to rule out other pathology, including stress fracture. Treatment Options De Quevain syndrome may be treated like other inflammatory tenosynovitis. Some cases of de Quervain syndrome spontaneously heal and become asymptomatic. Initial treatment should include avoidance of activities that exacerbate the pain. Splinting of the thumb and wrist has been used, but its efficacy is questionable. Additional studies are needed. Medications, including anti-inflammatory medications and acetaminophen, are useful to control pain and reduce inflammation. More resistant cases may be relieved with steroid injection into the tendon sheaths. In resistant, severe, disabling, de Quervain syndrome unresponsive to the above measures, surgical decompression of the compartment and tendons may be necessary.

References for CME Article "The Placebo Effect; Nuisance or Medical Treatment?" References [1] Colagiuri B. The placebo effect: From concepts to genes. Neuroscience . 2015;307:171-190. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367890/#R103 [2] Beecher HK. The powerful placebo. Journal of the American Medical Association. 1955;159:1602–1606. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/13271123/ [3] Levine JD, Gordon NC. Influence of the method of drug administration on analgesic response. Nature. 1984;312:755–756. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/6514008/ [4]Benedetti F. Open versus hidden medical treatments: The patient's knowledge about a therapy affects the therapy outcome. Prevention & Treatment. 2003, Volume 6, Issue 1 (Jun). Retrieved from: https://doi.org/10.1037/1522-3736.6.1.61a [5] Amanzio M. Response variability to analgesics: A role for non-specific activation of endogenous opioids. Pain. 90, 2001, 205–215. 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Retrieved from: file:///C:/Users/stuar/Downloads/s41598-021-83148-6.pdf [10] Colloca L et al. How the number of learning trials affects placebo and nocebo responses. Pain. 2010;151(2):430-439. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955814/ [11] Hunter T, Siess F, Colloca L. Socially induced placebo analgesia: a comparison of a pre-recorded versus live face-to-face observation. Eur J Pain. 2014;18(7):914-922. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061280/ [12] Vögtle E, Barke A, Kröner-Herwig B. Nocebo hyperalgesia induced by social observational learning. Pain. 2013 Aug;154(8):1427-33. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/23707275/ [13] Elliott, DB. The placebo effect: is it unethical to use it or unethical not to? Ophthalmic Physiol Opt 2016; 36: 513– 518. Retrieved from: https://onlinelibrary.wiley.com/doi/full/10.1111/opo.12315 [14] Holtedahl R, Brox JI, Tjomsland O. Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis. BMJ Open. 2015 Jan 30;5(1):e007331. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316431/ [15] Weimer, K., Gulewitsch, M., Schlarb, A. et al. Placebo effects in children: a review. Pediatr Res 74, 96–102 (2013). Retrieved from: https://www.nature.com/articles/pr201366#citeas [16] Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, Kosslyn SM, Rose RM, Cohen JD. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science. 2004;303:1162–1167. Retrieved from: https://www.science.org/doi/abs/10.1126/science.1093065 [17] Hashmi JA, Baria AT, Baliki MN, Huang L, Schnitzer TJ, Apkarian VA. Brain networks predicting placebo analgesia in a clinical trial for chronic back pain. Pain. 2012 Dec;153(12):2393-2402. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494789/ [18] Hall KT et al. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome. PLoS One. 2012;7(10):e48135. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479140/ [19] Leuchter A et al. Monoamine Oxidase A and Catechol-O-Methyltransferase Functional Polymorphisms and the Placebo Response in Major Depressive Disorder. Journal of Clinical Psychopharmacology: August 2009 - Volume 29 - Issue 4 - p 372-377. Retrieved from: https://journals.lww.com/psychopharmacology/Abstract/2009/08000/Monoamine_Oxidase_A_and.12.aspx [20] Peciña M et al. FAAH selectively influences placebo effects. Mol Psychiatry. 2014 Mar;19(3):385-91. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222079/ [21] Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Library. 20 January 2010. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/20091554/ [22] Tilburt Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ 2008;337:a1938. Retrieved from: https://www.bmj.com/content/337/bmj.a1938 [23] Aujla RS, Agarwal R, Sinha S, Kumar A. Perception and practice of placebo use among physicians in Mangalore. J Family Med Prim Care. 2020 Mar 26;9(3):1424-1430. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266198/ [24] Homeopathy-Delusion through Dilution. McGill University Office for Science and Society. 20 Mar 2017. Retrieved from: https://www.mcgill.ca/oss/article/homeopathy/homeopathy-delusion-through-dilution [25] Loudon I. A brief history of homeopathy. J R Soc Med. 2006 Dec;99(12):607-10. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1676328/ . [26] Global Homeopathy Products Market Will Reach USD 15.98 Billion by 2024: Zion Market Research. October 29, 2018. Retrieved from: https://www.globenewswire.com/news-release/2018/10/29/1638266/0/en/Global-Homeopathy-Products-Market-Will-Reach-USD-15-98-Billion-by-2024-Zion-Market-Research.html [25] Ernst E. A systematic review of systematic reviews of homeopathy. British Journal of Clinical Pharmacology. 17 December 2002. Retrieved from: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2125.2002.01699.x [27] Shang A et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 2005 Aug 27-Sep 2;366(9487):726-32. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/16125589/ CME Article: "The Placebo Effect; Nuisance or Medical Treatment?" For additional 3-minute read: The Curious Case of Dr. Mesmer's Mesmerism and How Benjamin Franklin Helped Introduce the Placebo Effect

General Medicine ✅ Earn Free CME Credit for Reading This Article Eligible for 0.5 PRA Category 1 Credit Click the button below to take a short quiz. A valid email is required to send your certificate. We’ll send you occasional updates. Your email stays private—never sold or shared.  😇 By Stuart M. Caplen, MD History One of the first documented uses of placebos as controls was by a French royal commission created by Louis XVI in 1784 and led by Benjamin Franklin. Franz Mesmer claimed to have uncovered “animal magnetism” that he believed contained healing properties. Franklin’s commission tested Mesmer’s theory by exposing patients to “mesmerised” objects or to placebos, without telling the subjects which ones they were being exposed to. They found that patients’ responses were unrelated to whether or not the object had been mesmerised and concluded that “animal magnetism” had no scientific basis.[1] As double-blind placebo-controlled trials came into more frequent use, the placebo effect was considered a nuisance variable that needed to be controlled for. However, in 1955 Beecher reviewed just the placebo group results of 15 studies and found a 35% improvement in symptoms from placebo treatment.[1,2] Experiments on the Placebo Effect In the 1980s, a trial of pain relief after dental surgery compared open administration of either placebos or analgesics, given by a nurse in the room in view of the subject compared to hidden administration (the patients were unaware when the dose was given) via an automated intravenous (IV) pump. It was found that the open administration of a placebo had equivalent pain relief to hidden IV administration of 8mg of morphine. They also found that naloxone blunted some of the open administration placebo’s pain reduction indicating a naloxone-antagonizable component of placebo-induced analgesia. The authors felt that a substantial component of treatment response to open treatments could be attributed to the placebo effect.[1,3] One trial compared open to hidden administration of pain and anti-anxiety medication. In one arm, post-operative patients were told they were getting IV pain medication with the doctor present in the room. The other group received the pain meds without being told when they were being administered. In other experimental arms, diazepam was administered IV in either an open or hidden manner. There was significantly more relief of pain and reduction of anxiety in the open treatment groups than in the hidden groups and in fact diazepam was found to have no effect in the hidden administration group. This provided some evidence that the placebo effect did not only occur with placebo use, but that active treatments may also involve a placebo component that contributes to the treatment response.[1,4] In another trial, open ketorolac dosing was found to be more effective than hidden administration. However, when naloxone was added to ketorolac in the open treatment group, pain relief dropped to similar levels as the hidden group. As this effect was not from blocking the effects of the ketorolac, it was suggested that part of the placebo effect in the open administration group may be from endogenous activation of opioid pain receptors which were blocked with the naloxone.[4,5] In a different trial, subjects were given repeated doses of IV ketorolac for pain relief as conditioning, with one group receiving only ketorolac with no statement that it would relieve their pain. The other group receiving ketorolac plus a verbal suggestion that the injection would relieve their pain. After the conditioning phase, when given a placebo injection that included naloxone, the ketorolac only conditioned group still had similar levels of pain relief, while in the placebo plus verbal expectation group there was partial blocking of pain responses by naloxone. One of the main findings emerging from this study is that cognitive factors such as the expectation of pain relief activated endogenous opioid systems which was blocked by the naloxone.[1,6] Placebo analgesic effects are not only modulated by the opioid system but other systems such as the dopamine, cannabinoid, and cholecystokinin systems appear to be involved. When placebo analgesia was given after previous ketorolac conditioning for pain in a 2011 trial, administering rimonabant (a CB1 cannabinoid receptor antagonist that was later removed from the market due to adverse effects) blocked the conditioned analgesic effects of the placebo. This was felt to indicate involvement of the endogenous cannabinoid system in some placebo effects.[1,7] One trial compared standard care for irritable bowel syndrome (IBS) with another group of patients getting standard care plus placebo treatment. The authors found that despite the fact that the patients in one group had been told that their additional treatment was a placebo, the placebo significantly improved IBS symptoms. The authors concluded that the benefit was attributable to the placebo effect and challenged the concept that deception is necessary to elicit a placebo effect.[1,8] A systematic review and metanalysis also found a significant effect from open label placebos, where the patients were aware the treatment was a placebo.[9] A number of studies have found a nocebo effect where placebos cause adverse effects. In Beecher’s 1955 study, placebo patients complained of headaches (25%), fatigue (18%), and nausea (10%) from the placebos.[1,2] What Causes the Placebo effect?[1] One theory is that the placebo effect is a learned response, where verbal, conditioned, and social cues form expectations that trigger the central nervous system and can generate placebo effects. Cues that initiate placebo effects do not need to be identical to those that have previously been experienced, but only share some features. A placebo response does not necessarily rely on conscious awareness, and in fact may be largely subconscious. Classical conditioning is frequently used to explain the placebo effect. Pavlov paired the ringing of a bell with the administration of morphine, which causes restlessness in dogs. Eventually the dogs became restless on hearing the bell alone, providing some evidence that drug-like placebo effects can be conditioned. The placebo effect may be created and conditioned with stimuli such as syringes, pills or medical personnel that when paired with an active treatment such as a narcotic, may produce a conditioned placebo effect resulting in better pain relief. Trials with long and short training intervals prior to placebo use found that a higher number of conditioning sessions caused an increase in placebo or nocebo effects. This was felt to indicate that the level of prior experience may be an important determinant of the strength of both placebo and nocebo effects.[10] Intermittent reinforcement during training was found to produce weaker placebo analgesia than continuous reinforcement, but the placebo effect of intermittent reinforcement was more resistant to extinction.[1] Verbal suggestions have been shown to be strong cues that can produce a placebo effect consistent with the direction of the verbal suggestion. It has been found that viewing a video of a research confederate reporting less pain when a placebo is used can induce placebo analgesia in the observer.[11] Nocebo effects can also be conditioned by having subjects observe a sham treatment that appears to increase pain in a research confederate which then causes more pain when the treatment is done to the subject.[12] For the placebo effect to work, the patient has to believe it will work. In a number of studies, subjects who strongly believed in the treatment felt less pain with placebo than those who were less confident in it.[13] The placebo effect for sham surgical interventions tends to be large, with a systematic review of 21 randomized controlled trials (RCTs) concluding that the placebo effect has a significant influence on positive results of actual minimally-invasive surgery.[14] It has been reported that the placebo effect may be more pronounced in children and adolescents than adults.[15] Brain Changes With Placebos[1] Multiple studies using functional MRI (fMRI) have found that pain processing is associated with several brain regions. A meta-analysis of fMRI studies of placebo analgesia identified certain areas of the brain as consistently having less activity during placebo analgesia. Those areas are the insula, dorsal anterior cingulate cortex, thalamus, amygdala and right lateral prefrontal cortex. One study found increased activity of the dorsolateral prefrontal cortex (DLPFC) in anticipation of pain relief, and that the fMRI signal in the DLPFC during anticipation of analgesia correlates with the strength of the placebo effect.[16] It is felt that the DLPFC is crucial in the processing of placebo and nocebo effects. Activation of regions of the brain associated with emotions and not cognitive thought or pain processing, were most predictive of placebo analgesia. This suggests that differences in emotional neurological pathways may be factors in individual variation to placebo analgesia. In a trial of patients with chronic back pain, connectivity between left medial prefrontal cortex and bilateral insula accurately differentiated between placebo responders and non-responders in one trial, suggesting that an individual’s neurologic pathways can partially explain individual differences in placebo responses.[17] Genetic Differences There also appear to be genetic differences in the extent of the placebo effect in individuals. A number of genetic variants have been found to either increase or decrease the placebo effect. Individuals that have variants that increase dopamine activity will tend to have greater effects from placebos. One variant of the catechol-O-methyltransferase (COMT) gene has been found to have less enzymatic activity to break down dopamine, and has been associated with increased dopamine activity in the prefrontal cortex. A study of subjects with irritable bowel syndrome found that carriers of this variant of the COMT gene, which results in higher levels of dopamine, had stronger responses to placebos.[18] A study looking at the association of MAO-A genotypes with the placebo effect for clinical depression found that individuals with high-dopamine-activity genotypes had greater placebo-induced reduction in depressive symptoms.[1,19] Another study examined genetic variants in the gene coding fatty acid amide hydrolase (FAAH Pro129 allele), the major degrading enzyme of endocannabinoids. Using PET scanners, it was discovered that individuals with different variants of the gene responded to placebos differently. It was also found that opioid receptor neurotransmissions were different depending on the variant. The authors suggested that this potentially demonstrates that there are interactions between endocannabinoid and opioid receptor neurotransmission in placebo responses.[1,20] Issues With Using the Placebo Effect Clinically A Cochrane database review of the placebo effect found that placebo interventions generally do not have important clinical effects. However, in certain settings, particularly for pain and nausea, placebos can affect patient‐reported outcomes. It was difficult for the reviewers to distinguish patient‐reported effects of placebo from biased reporting. The effect of placebos on pain varied in different trials, from negligible to clinically important. They concluded that “Most clinical placebo prescriptions involve deceit and the effect of placebo has not been tested in trials after full disclosure that the patients receive placebo. Therefore, we suggest that placebo interventions are not used outside clinical trials.”[21] Conversely it appears placebos may have some effect, especially with pain therapy. Clinical issues with using placebos include ethical considerations, such as whether to inform the patient or not. There is variability of effect, and it would not be not known which specific patients would benefit from placebo therapy. There could be medical legal issues if a serious illness is treated with a placebo rather than a standard treatment. Placebo therapy is currently prescribed by some physicians who recommend vitamins for disorders that are not vitamin deficiencies and antibiotics for non-bacterial diseases.[22,23] Dilute Homeopathic Medications – An example of Placebos in Actual Use? Although the effectiveness of homeopathic medications is hotly debated, they are diluted so many times that after 30 to 40 one to one-hundred dilutions, it is possible that there is not even one molecule of the original compound left, and some formulations use up to 200 dilutions.[24] Samuel Hahnemann, the inventor of homeopathy, felt that homeopathic medicines retained their therapeutic power when shaken violently during the process of dilution. According to Hahnemann this process, called “potentization”, left a “dematerialized spiritual force” in the solution. Hahnemann felt the more dilute the solution, the stronger the effect.[25] Thus, diluted homeopathic medications seem to meet all the criteria for an effective placebo. From a scientific pharmacological point of view, the diluted solution may contain no active chemical compounds. However, there is a theory that can inspire belief by the user that it is effective which may potentially trigger endogenous changes similar to those seen in the placebo effect. The placebo effect may therefore make these products effective for some conditions, and they may also be considered effective by patients when used for self-limited disease processes, which reinforces future use. Homeopathic medications are popular, with annual U.S. expenditures for homeopathic medications estimated to have been $6 billion in 2017 and to reach $16 billion by 2024.[26] Do Homeopathic Medications Work? A review of systemic reviews of homeopathic medications found many methodological issues in some of the literature and concluded that there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo.[25] Another meta-analysis suggested that the clinical effects of homeopathic drugs were from a placebo effect.[27] Conclusions The placebo effect has some convincing experimental evidence that it is real, and that placebos can cause changes in brain activity and stimulate endogenous opioid and cannabinoid receptors. However, making use of placebos for clinical disease treatment is fraught with ethical and possible medical legal issues if a patient is not informed it is a placebo or if a serious disease is treated with a placebo rather than a proven medication. There also appear to be genetic and individual differences in the strength of positive placebo effects. It had been shown that subjects who do not know they are getting pain medication have less pain relief than those who are aware of the treatment. The positive effects of a placebo medication appear to stimulate internal receptors such as the opioid receptors improving pain relief both with placebos and standard medications. Practitioners can try to utilize the placebo effect by emphasizing how the medication they are prescribing typically does work well in most people with that patient’s particular condition. Dilute homeopathic medications seem to fulfill placebo criteria of lacking pharmacological potency, but still providing a belief system that the medication is effective. Their popularity might be partially due to their placebo-like effects. 🎓  Want Free CME Credit for This Article? Take the quiz now at www.FibonacciMD.app . It only takes a few minutes! Your certificate will be emailed to you after you pass the quiz and complete a short evaluation We’ll send you occasional updates. Your email stays private—never sold or shared.  😇 References For additional 3-minute read: The Curious Case of Dr. Mesmer's Mesmerism and How Benjamin Franklin Helped Introduce the Placebo Effect

The Curious Case of Dr. Mesmer's Mesmerism and How Benjamin Franklin Helped Introduce the Placebo Effect MEDICAL HISTORY by Stuart M. Caplen, MD   Patients in Paris receiving Mesmer's animal magnetism therapy. In the late 1700s, German-born Austrian physician Franz Anton Mesmer claimed to have a miracle cure using animal magnetism that eventually became known as mesmerism.  Treating patients with the armonica and magnetic water He was curing patients of various maladies using magnets.  He soon discovered the magnets were unnecessary, and he could magnetize water by placing his hands over it, and he then claimed cures for illnesses such as sleepwalking and throat spasms.  He initially had his patients swallow iron filings but soon stopped that.  After a failed attempt to cure blindness in a famous pianist, he fell out of favor in Vienna and moved to Paris.  He refined his technique and would “magnetize water” with his hands and place the bottle in a wooden tub (baquet) that patients would sit around.  Iron rods stuck out of the tub that patients could grab onto or touch to body parts. Coincidentally, Mesmer started using the armonica (or glass harmonica), which was invented by Benjamin Franklin, at his sessions. The armonica could produce eerie sounds similar to the sound that is made when rubbing the rim of a moist glass with a finger.  As word of cures spread, his practice became larger.  He started going to private parties where it was reported that his mostly upper-class women patients would frequently scream, faint, or convulse (also called crises) after being mesmerized.  Actual baquet (tub) used for mesmerism (from the Lyon Musée d’Histoire de la Médecine et de la Pharmacie) Benjamin Franklin, Antoine-Laurent Lavoisier, and Joseph-Ignace Guillotin Investigate Mesmerism Blinded Experiments Mesmer eventually came to the attention of King Louis XIV, who appointed two commissions to look into mesmerism.  One was led by Benjamin Franklin, who happened to be in Paris as the U.S. ambassador.  Antoine-Laurent Lavoisier, considered to be the father of modern chemistry, and Dr. Joseph-Ignace Guillotin, who invented the guillotine as a way to make the death penalty more humane, were also on the commission. They designed several “blinded” experiments where the subject did not know if they were truly being mesmerized or not. These experiments were designed to determine if mesmerism was real, and used placebos for the first time in scientific experimentation. In one case, they told a woman that the Mesmer practitioner was behind a closed-door directing animal magnetism to her, although he wasn’t.  The woman responded by going into convulsions.  Another woman was given water to drink she told had been magnetized, but wasn’t.  She fainted, and then without telling her, she was given water to drink to revive her that had been magnetized, with no effect.  A different woman was mesmerized by a practitioner behind a paper curtain without telling her, which had no effect.  However, later when the practitioner did the same moves with the woman aware, she collapsed within a few minutes.  They magnetized one tree in Franklin’s garden, and then had a 12-year-old boy, who hadn’t seen which tree was magnetized, hug trees that weren’t magnetized. The boy reportedly collapsed at the fourth unmagnetized tree. A mesmerist using animal magnetism on a woman who responds with convulsions. Wood Engraving, 1845. The Placebo Effect The commission came to the conclusion that the source of mesmerism cures was people’s belief that it would work, not due to the actual process of using animal magnetism.  They also noted that the male mesmerizer was frequently in very close physical contact with the mostly female patients, with knees and faces right up against each other, and there was also physical touching.  They thought this close contact could possibly impair the morals and health of susceptible women.  The commission recommended that the practice of mesmerism be banned. Comments:  Benjamin Franklin, who was considered one of the greatest scientists of his day, played a part in the creation of the placebo-controlled experimental model and the repudiation of a treatment that in itself relied on the placebo effect. If you enjoyed this article, click here to read The Placebo Effect; Nuisance or Medical Treatment? This article is associated with a free online CME. References  Dingfelder SF. The first modern psychology study, Or how Benjamin Franklin unmasked a fraud and demonstrated the power of the mind. American Psychological Association. July/August 2010, Vol 41, No. 7. Retrieved from: https://www.apa.org/monitor/2010/07-08/franklin Laukaityte U. Mesmerising Science The Franklin Commission and the Modern Clinical Trial. November 20, 2018. The Public Domain Review. Retrieved from: https://publicdomainreview.org/essay/mesmerising-science-the-franklin-commission-and-the-modern-clinical-trial/ Patients in Paris receiving Mesmer's animal magnetism therapy. Coloured etching after C-L. Desrais. Attribution 4.0 International (CC BY 4.0). Source: Wellcome Collection. Retrieved from: https://wellcomecollection.org/works/fthv79zp A mesmerist using animal magnetism on a woman who responds with convulsions. Wood engraving, 1845. Attribution 4.0 International (CC BY 4.0). Source: Wellcome Collection. Retrieved from: https://wellcomecollection.org/works/xesrp7eh Initially posted October 2024

Impress guests with this Patriotic Appetizer Platter—red, white & blue fruits, veggies, cheese & chicken arranged like the American flag! Creative Cooking for the Health-Conscious Gourmet FibonacciRECIPES  | Culinary Medicine   Recipe Celebrate the summer holidays, Memorial Day, Flag Day or Fourth of July with an American flag. This appetizer platter uses fruits, vegetables, cheese, and cooked chicken breast in its design. The only component you need to cook is the “Patriotic Potatoes” which are a great way to serve potatoes at room temperature. You can follow the recipe exactly or if you’re not a fan of one of the components, use your imagination to select your own red, white or blue substitution. Platter Ingredients: Rectangular platter or cutting board (approx. 10”x14”) 8 oz cherry tomatoes 6 oz sliced cooked chicken breast 10-12 radishes 10 oz cherry-size mozzarella balls 6 oz grape tomatoes 1 batch patriotic potatoes (see below) ½ red bell pepper, sliced 1 cup blueberries 1 small pear, peeled and diced Patriotic Potato Ingredients Glass oven-proof baking pan* 2 Tbsp high-heat oil, such as avocado or grapeseed 12 oz small new potatoes ½ tsp sea salt ½ tsp onion powder ½ tsp garlic powder Instructions Cook the Patriotic Potatoes Add 1½ Tbsp oil to oven-proof baking pan, and place in oven Heat oven to 400 degrees While the oven heats, peel the potatoes, slice into 1-inch discs, and mix in remaining ½ Tbsp oil, salt, and onion and garlic powders Once the oven reaches temperature, carefully transfer the potato discs to the pan in a single layer After 15 minutes, check the potatoes and lightly stir in the pan, cook for another 15-20 minutes until they can be easily pierced with a fork. Remove from oven and cool slightly While potatoes cook and cool, prepare the flag Create your flag Make the corner of the flag with blueberries, add a few Tbsp of the pear cubes Make the top stripe with cherry tomatoes Place slices chicken breast for the next stripe Cut the ends off the radishes and make the next stripe Drian the mozzarella and place for the next stripe Make the next stripe with grape tomatoes Line up the cooled potatoes for the next stripe Add the last stripe using the sliced peppers *Note the glass pan helps keep the potatoes from browning significantly – for this recipe, they need to be a white stipe on the flag. Makes 6 appetizer-sized servings Nutrition information per serving (assuming each includes a portion of each component) Calories  230, Total Fat 9g, Saturated Fat 4 g, Cholesterol 70mg, Total Carbohydrate 16g, Dietary fiber 3.3g, Protein 20g, Potassium 530mg, Sodium 270mg Nutrition Chef Authors: Mary B Grosvenor, MS, RD Medically Reviewed by FibonacciMD editors. Editor’s Note- Appropriate for a low-calorie, low saturated fat, low-carb, high protein dietary regimen.  Also contains a good source of fiber. more health-conscious recipes

What Is SIBO, and How Is It Diagnosed and Treated? Read Article, Take Test , Get FREE 🎓 CME Certificate with Valid Email We’ll send you occasional updates. Your email stays private—never sold or shared.  😇 By Stuart M. Caplen, MD   This article will discuss small intestinal bacterial overgrowth, or SIBO, which can cause gastrointestinal disturbances due to pathological bacterial overgrowth. SIBO was first described in the medical literature in 1939 by Barber and Hummel.[1]  In 2000, Pimentel et al. published a report showing that SIBO was present in 78% of patients with irritable bowel syndrome (IBS), and antibiotic treatment led to resolution of IBS symptoms in almost half of those treated in the study.[2]  In another study, 33.8% of patients with symptomatic gastrointestinal issues were positive for SIBO.[3] What Is SIBO? [4] It is estimated that the human intestine contains 100 trillion bacteria which, along with viruses and fungi, make up the gastrointestinal microbiome.  There are approximately 500 to 1,000 different species of bacteria in the microbiome.  The numbers of bacteria increase progressively from the small intestine to the large intestine.  By the time digested food arrives at the small intestine, bile and stomach acid have helped eliminate  many bacterial organisms.  Rapid movement of ingested food through the small intestine also serves to reduce the number of bacteria.  The greater circumference and slower movement of partially digested food in the large intestine allows many more bacteria to survive there.  SIBO occurs when pathogenic bacteria replace normal flora which may result in abdominal distension, bloating, diarrhea, gas formation,[4] or constipation.  Pseudomonas aeruginosa , Escherichia coli , Acenetobacter lwoffii , Staphylococcus species , Klebsiella pneumoniae , Streptococcus species, Acinetobacter baumannii , Enterococcus faecalis , and Enterococcus faecium  were found to be the dominant bacteria in SIBO patients in one study.[5] The actual prevalence of SIBO in the general population has a wide variation in various studies, from 1% to 40%, which may be due to diagnostic test performance, age range of the subjects, dietary differences, and the ethnicity of the subjects tested.[5] Risk Factors Risk factors for SIBO include anatomical and motility disorders in the small intestine, diabetic enteropathy, underlying connective tissue disease, chronic opiate use, diverticula, small bowel adhesions, and blind loop syndromes.  These conditions may lead to intestinal stasis and can be caused by surgery, fistulas, diverticula, motility disorders, and inflammatory diseases, such as Crohn’s disease.  Cecal valve incompetence where large intestine contents reflux back into the ileum can also be a precipitating factor.  Drugs such as antidepressants and anticholinergics, which can impair intestinal motility, can increase the risk of SIBO.[6]  Impairments in normal bacteria reduction mechanisms such as reduced bile output in pancreatitis or hypochlorhydria with reduced stomach acid caused by chronic use of proton pump inhibitors (PPIs) can also increase the risk of SIBO.  Additionally, SIBO is more prevalent in elderly patients and women. In one study, small bowel dysmotility was shown to more than triple the risk of SIBO.  As previously mentioned, the first study to examine the relationship of SIBO and irritable bowel syndrome reported 78% of IBS patients also had SIBO.[2]  However, a later meta-analysis reported the SIBO incidence in irritable bowel patients to be a much lower 22.3%.[7]  Another meta-analysis reported that extended PPI use increased the risk of SIBO by 70%.[8] Testing The “gold standard” test for SIBO is a bacterial culture of small bowel aspirate.  A positive test consists of a bacterial count equal to or more than 1,000 colony-forming units per milliliter (CFU/mL).  However, the invasive nature of the test, which requires tube insertion into the small intestine, combined with possible contamination by oropharyngeal flora that can invalidate the test, has limited its use.  Instead, breath tests have emerged as the preferred diagnostic tests.[4] In patients with SIBO, small bowel pathogenic bacteria produce methane and hydrogen gases.  Most of the gas is rapidly eliminated with passing flatus.  However, approximately 20% of the gases are absorbed by the lung and then subsequently exhaled, allowing for measurement during breath testing. Methanobrevibacter smithii  is the predominant organism that produces methane.  These organisms are not considered true bacteria but are Archaea , a separate domain ( Archaea  are one-celled but have different RNA and lipids in their cell membrane than bacteria).  The American College of Gastroenterology guidelines suggest that a more proper nomenclature, when methane is the predominant gas, is intestinal methanogen overgrowth (IMO) as opposed to SIBO.[9]  (The use of IMO nomenclature is not uniform in the literature, and for the rest of this article, IMO will be called by the older term methane-positive SIBO.)   Methane-positive SIBO patients are five times more likely to suffer constipation than hydrogen-positive SIBO patients.[10] In standard breath tests the patient drinks either a glucose or lactulose solution.  Breath samples are then measured for hydrogen and methane, which were created by bacteria or Archaea  fermenting the compounds.  Glucose is superior for detecting bacterial overgrowth in the proximal part of the small intestine, while lactulose is thought to be better for detecting bacterial overgrowth in the distal part of the small intestine, as it is absorbed more slowly.  Guidelines state that a rise in breath hydrogen levels of ≥ 20 ppm (parts per million) 90 minutes after ingestion of glucose or lactulose should be considered a positive result.  A rise in exhaled breath methane levels by ≥ 10 ppm should be considered a methane-positive result.[4]  Spot testing of methane levels in fasting patients has also been found to be an accurate way of diagnosing and performing follow-up testing of methane-positive SIBO patients, instead of having to complete an entire breath testing protocol.[11]  For breath testing, patients should not be taking antibiotics, probiotics, antimotility agents, or antacids and should be fasting for the exam.[4]  Stopping PPIs is not necessary.[10]  A bland diet avoiding high fiber and complex carbohydrates for one to two days before the exam is also recommended.[4]  Smoking can increase hydrogen in the exhaled breath and increase intestinal transit time and should be stopped on the day of the exam.[10]  Deviating from the testing protocol can affect the accuracy of the test. There can be false positives and negatives in breath testing.  Hydrogen breath tests are dependent on the patient’s oro-cecal transit time.  If transit time is rapid, such as in those with previous upper abdominal surgery, the glucose breath test may lead to false positive results.  This would be due to the glucose or lactulose reaching the colon too rapidly and colonic bacteria fermenting the carbohydrates, producing hydrogen.  Some researchers have suggested use of gastrointestinal tract scintigraphy, which measures the rate of intestinal movement of food, during a breath test to help decrease the false positive rate in high-risk patients with rapid oro-cecal transit time.[12]  Conditions that slow intestinal transit time, such as achalasia and gastroparesis, may lead to false negative results due to delay of glucose or lactulose reaching the majority of small intestine in time to give a positive result.  Methane breath tests are generally less affected by intestinal transit times.[13] One meta-analysis reported that the sensitivities of the hydrogen lactulose and glucose breath tests were 42% and 54.5% with specificities of 70.6% and 83.2%, respectively.[14]  It is generally felt that testing for both methane and hydrogen increases testing accuracy.[15] In patients with SIBO, as there may be malabsorption, vitamin B12 and fat-soluble vitamins A, D, E, and K may also be decreased, and blood levels should be measured.[4] Researchers have attempted to examine SIBO metabonomics.  Metabonomics is the study of small metabolites in a biological system known as the metabolome.  Using proton nuclear magnetic resonance spectroscopy on body fluids allows identification of an individual’s “metabolic fingerprint”.  This may eventually allow for more specific diagnoses of different SIBO subtypes, but it is only experimental at the present time.[16,17] Treatment Antibiotics Antibiotics are considered the first-line treatment for SIBO to eradicate the pathogenic strains.  Rifaximin is typically the preferred medication and is a non-absorbable antibiotic which acts against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Rifaximin can also preserve normal colonic flora and may increase the relative abundance of SIBO-protective lactobacilli  and bifidobacteria  in the gut.[4]  There are a number of different dosage regimens, but 1200 mg to 1,650 mg per day for 14 days in adults is commonly recommended.[18]  There is some evidence that the higher doses are more effective than the lower dose regimen.[19]  Rifaximin is FDA-approved for IBS treatment, but not specifically approved for SIBO, and thus is considered an off-label use of the drug. Combination therapy of rifaximin and neomycin for patients with methane-positive breath tests may be more effective than rifaximin alone.  In one study, rifaximin and oral neomycin combination therapy led to 85% of the subjects having a clinical improvement and 87% having a negative repeat methane breath test.  Rifaximin solo therapy resulted in only 56% of subjects having clinical improvement and 28% converting to a negative methane breath test.  Neomycin therapy alone was also not as effective as combination therapy.[20] Other drugs that may be used to treat SIBO include metronidazole, tetracyclines, amoxicillin/clavulanate, and fluoroquinolones.[4] Probiotics Probiotics, by introducing healthy bacteria, have been recommended for treating SIBO.  A pro biotic is a food or supplement that contains live bacteria.  In contrast, a pre biotic is a non-absorbable high-fiber food that encourages the growth of probiotics. One meta-analysis reported that probiotics could not prevent SIBO but were helpful in eliminating harmful bacteria from the gut.[21]  However, another study found a correlation of brain fog, D-lactic acidosis, and SIBO with probiotic use and postulated that in certain cases, probiotics could make SIBO worse.[22]  Finally, one study, published only in abstract form as a scientific meeting presentation, reported that recent probiotic use in patients with suspected SIBO was associated with an increase in methane-positive lactulose breath tests.  This suggests that probiotic use may possibly predispose to overgrowth of methanogenic bacteria.[23] Dietary Therapy Dietary therapy may be helpful in the treatment of SIBO patients.  In SIBO, gut bacteria or Archaea  ferment carbohydrates, such as fructose, lactose, oligosaccharides, disaccharides, and monosaccharides, which may result in gas formation, bloating, flatulence, and abdominal pain.  The FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet is the most widely recommended as it reduces the amount of carbohydrates fermenting in the gut.  This decreases nutrients for the gut bacteria, which can limit their growth.  In the FODMAP diet plan, after initiation and improvement, there is a phase where foods are reintroduced slowly to see which, if any, worsen symptoms and can be avoided in the future.[4] For more information on the FODMAP diet, click here. [24] There are some data that the FODMAP diet can reduce some of the symptoms of IBS, but the data are of low quality, and better studies are needed.  The FODMAP diet is meant to be used as short-term therapy because there is the possibility of causing a nutritional imbalance with long-term use, and data is lacking on long-term efficacy.[25] In SIBO therapy, an elemental diet is sometimes recommended.  This consists of oral enteral liquids which contain proteins, fats, and carbohydrates in their basic forms of amino acids, short-chain triglycerides, and short-chain maltodextrins, with additional vitamins, minerals, and electrolytes.  An elemental diet allows easy absorption of nutrients and rests the gut.  Most absorption of this diet occurs in the proximal small intestine, which limits bacterial nutrients getting to more distal parts of the small bowel.[4]  In one study of elemental diets, 80% of subjects normalized their lactulose breath test within two weeks, and a total of 85% of the subjects’ breath tests were normalized by 3 weeks.  About 11% of the subjects dropped out of the study as they could not tolerate the diet.[26] Herbal Supplements Using herbs with known antimicrobial activity has also been trialed to treat SIBO.  In one experiment, subjects were either given rifaximin tablets or herbal supplements for four weeks.  In rifaximin non-responders, subjects were either given triple antibiotics (clindamycin, metronidazole, and neomycin) or herbal supplements for an additional four weeks.  There was no statistically significant difference in the response rate between herbal therapy and antibiotic therapy both at four and eight weeks.[4,27]  It should be noted that data on herbal supplements are extremely limited, and ingredients of various supplements may vary and are not FDA approved for treating SIBO. A study compared subjects with SIBO eating a FODMAP diet to another group where L-glutamine was added to the FODMAP diet.[27]  L-glutamine is an amino acid that can improve gut microbiota and intestinal barrier integrity through several mechanisms, including control of pathogen colonization and overgrowth, increased production of secretory immunoglobulin A, and formation of tight junctions between enterocytes (intestinal cells).[26]  It was reported that the methane-positive SIBO group had significant improvement in clinical symptoms with the addition of the L-glutamine, while the hydrogen-positive SIBO group did not.  However, there was no objective finding of improvement of breath test results.[28]  Another study compared antibiotic plus FODMAP diet to another group which also received herbal medications, L-glutamine, prebiotics, and probiotics.  It was reported that only the methane-positive group had a subjective improvement in clinical symptoms with the ingestion of the nutritional additives.[29] Fecal Microbiota Transplants In one study, 55 patients with SIBO were given either capsules containing normal donor fecal material or a placebo.  There were statistically significant symptom improvements in the patients given fecal transplant compared to those given placebo.  It was also reported that there was a significant drop in the hydrogen levels during a lactose breath test in the transplant group after therapy, not seen in the control group.[30] Another study looking at subjects with chronic constipation compared giving fecal microbiota transplants to patients both with SIBO and without SIBO.  They reported that the transplants worked better in patients with SIBO than those without SIBO.  56% of patients with SIBO were cured, and 81% had an improved clinical response.  There were significantly improved abdominal, rectal, and defecation symptoms in the SIBO group, and quality of life scores improved with significant decreases in abdominal discomfort, anxiety, and psychosocial discomfort.[31] Treatment Failure Up to 40% of patients with SIBO will not respond to antibiotic therapy, and in those cases, other causes of abdominal symptoms, such as lactose intolerance or other gastrointestinal disorders, should be considered.[4]  Repeat breath testing may be necessary to confirm resolution.  Additional treatments, such as dietary therapy, may be helpful to attempt to improve symptoms and prevent recurrences.[24,25] Summary SIBO is a relatively common disease leading to abdominal symptoms, especially in patients with risk factors such as IBS or PPI use.  Breath testing for hydrogen and methane has made diagnosis of this disorder much easier than obtaining a jejunal aspirate for culture. Antibiotics are the mainstay of treatment, but dietary therapy such as the FODMAP diet, elemental diet, or selected supplements have demonstrated some efficacy.  It is possible that fecal microbiota transplants may become a standard therapy in the future. Author’s note:  Thank you to Dr. Theodor Feigelman for editing this article. 🎓  Want Free CME Credit for This Article? Take the quiz now at www.FibonacciMD.app . It only takes a few minutes! Your certificate will be emailed to you after you pass the quiz and complete a short evaluation We’ll send you occasional updates. Your email stays private—never sold or shared.  😇 E arn CME Credit Now References ✅ Earn Free CME Credit for Reading This Article Eligible for 0.5 PRA Category 1 Credit Click the button below to take a short quiz. A valid email is required to send your certificate. We’ll send you occasional updates. Your email stays private—never sold or shared.  😇 Earn CME Credit Now