HOT TOPICS IN INTEGRATIVE MEDICINE Pediatric Residency Coaching Program Ann Ming Yeh, MD Integrative Medicine Potpourri •What is Integrative Medicine? •Introduction to IM Modalities: •Mind – Body Exercise •Top 3 Herbs and Supplements •Probiotics •TCM/ Acupuncture/ Acupressure Demo •3 minute Ted Talk on Gratitude Integrative Medicine is… … healing oriented medicine that takes account of the whole patient, including all elements of lifestyle and family health. It emphasizes the powerful triad of patient-family-practitioner, is informed by evidence, and makes use of all appropriate therapies. Good Medicine! My journey/ My approach •Intake – 90 min •Standard H and P •Deeper dive into sleep, psychosocial, nutrition •Traditional Chinese Medicine Eval - if time allows PIMR http://integrativemedicine.arizona.ed u/program/Pediatric_IMR_2017/mind _body_medicine_in_practice/modalit ies_overview/9.html MIND BODY MEDICINE http://integrativemedicine.arizona.ed u/program/Pediatric_IMR_2017/mind _body_medicine_in_practice/modalit ies_overview/9.html LET’S PRACTICE HERBS AND SUPPLEMENTS FOR URI Elderberry Umckaloabo Zinc Case While rotating in Urgent Care: 4 year old and 6 year old non vaccinated sibs with myalgia, runny nose, cough, fever x 2 days. Mom wants to know what she can do for the kids? Elderberry Sambucus nigra Elderberry – Mechanism of action • BioFlavonoids • Anthocyanins – water soluble pigments that appear red, purple or blue depending on the pH • Cyanidin-3-sambubiocide – • Shown to bind influenza neuramidase (similar mechanism as oseltamivir/ Tamiflu) • Antiviral, anti influenza effects • Seen 2-4 days after starting therapy Swaminathan. Anal Bioanal Chem 2013 Elderberry – The Evidence • Three RCT’s in humans • Zakay-Rones (n=40) adults and children (>2yo) of Influenza B outbreak (1993) • Placebo controlled RCT of Sambucol® • Included patients (not vaccinated) with sx of myalgia, fever, nasal discharge, cough of <24hrs • Symptoms recorded x 6 days: • Significant symptom improvement • Control group – 92% improved in 6 days, • Elderberry – 93% improved in 2 days • Higher Influenza B titers in treatment group • Limited by small n, high drop out (13/40) and no intention to treat analysis Zakay-Rones: J Altern Complement Med 1995 Elderberry – The Evidence • Zakay-Rones – RCT of n= 60 non-vaccinated adults with flu A or B • 15mL elderberry syrup QID during first 24 hours of influenza symptoms • Symptoms relieved 4 days earlier in treatment group • Use of rescue medication significantly less Zakay-Rones. Journal of Intern Med Res, 2004 Elderberry - Dose • Sambucol – extract • Adults: 15mL QID x 3-5 days • Children: 15mL BID x 3 days • Syrup – 38% of standardized elderberry extract Elderberry - Safety • COOKED / Ripe fruit is safe • NO adverse effects reported in clinical trials (adults and children, age 2+) • Uncooked leaves and other plant parts and Unripened, uncooked green berries – NOT SAFE • Contains cyanide-producing chemical - sambunigrin • Causes nausea, vomiting, diarrhea • Large volume ingestion toxicity. • COOKING eliminates toxicity • Side effects: mild laxative, GI upset Holst 2015; Zakey Rones 2004, 1995; Kong 2009 Contraindications • Avoid in patients with known allergy or hypersensitivity to elder or honeysuckle plants • Use cautiously in patients with arrhythmias and on diuretics and on immunosuppressive medications • NO safety data in pregnancy (not recommended) Case At PAMF continuity clinic – Mom comes in saying that she heard Umckaloabo was good for URI’s. Her daughter gets frequent URI’s and she wants to know if she can give it to her 12 y/o daughter who you are seeing for a WCC. Umcka-wah? Lane.stanford.edu peds portal Natural Medicines Database Pelargonium sidoides- Umckaloabo Umckaloabo – mechanism of action • Pelargonium sidoides root – • African geranium • Historical uses for sinusitis, bronchitis, pharyngitis • In vitro: • Release of antibacterial cytokines (TNF-alpha, interferon-beta) • Enhances phagocytosis and NK cell activity Evidence • Cochrane Database Review 2012 for acute bronchitis • 12 clinical trials, 10 included for analysis • Placebo controlled RCT’s • In children – 2 RCT’s (n= 200, n=220), using liquid extract on treating acute bronchitis • Decreased bronchitis specific symptoms (BSS) from day 0 to Day 7 • RCT (n-143) children >6y/o with non-strep pharyngitis: • Reduced severity and duration of symptoms by 2 days compared to placebo Timmer. Cochrane Database Sys Rev. 2012 Berenznoy 2003 • Relative effect (RR = 0.82) for failure to recover by day 7 Timmer. Cochrane Database Sys Rev. 2012 Safety/ Contraindications • No published adverse effects except for rare hypersensitivity/ allergy reactions • Some GI upset side effects: • nausea, vomiting, diarrhea • CAUTION with: • Antiplatelet medications • Coumarin - May have mild anti platelet aggregation effect • No effect on platelet aggregation in animal models • Immunosuppressive medications • Allergy to pelargonium or ethanol Dosing • Dosing: (extraction 1:8-10; ethanol solvent) 100g of finished product = 80 g pelargonium extract corresponding to 8 gram of dry material + 20g glycerol (85%) bronchitis • 1-6 y/o: • 6-12y/o • 12-18 y/o 10 drops TID 20 drops TID 30 drops TID pharyngitis 3mL TID 3mL TID on bottle 5ml TID 7.5ml TID Zinc (Zn) Ods.od.nih.gov Zn – Mechanism of action • Important for immune cell function • Deficiency causes imbalance between TH1 and TH2 functions • Decreased production of TNF-alpha, IFN-g, IL-2 • Zinc may help regenerate new CD4+ T cells • Intestinal barrier function • Improves duration, severity and volume of diarrhea in acute gastroenteritis (Developing countries) • Human rhinoviruses attach to nasal epithelium via intracellular adhesion molecule 1 (ICAM-1). • Zn ion blocks ICAM-1 receptor, exerting an antiviral effect Zn – Evidence • Randomized, double-blind, placebocontrolled trials on Zn in common cold • for at least 5 days to treat or • for at least 5 months to prevent • 16 therapeutic trials (n=1387) • 2 preventive trials (n=394) • Both in children Cochrane Review 2013 Zn –Evidence for Common Cold Treatment • If administered within 24 hours of symptoms Zn: • Lower duration of sick days (P=0.003) • Does not reduce severity of symptoms (P= 0.11) • Less of those symptomatic after 7 days of treatment (P=0.05) Prevention (x 5 mo) • Lower Incidence Rate Ratio (IRR) of developing a cold (IRR 0.64, 95% CI 0.47-0.88) • School absence less in Zn group (P = 0.0003) • Prescription of antibiotics lower in Zn group (P < 0.00001) Adverse effects higher in Zn group • Bad taste (OR 2.31, 95% CI 1.71 to 3.11) (P < 0.00001) • Nausea (OR 2.15, 95% CI 1.44 to 3.23) (P = 0.002) Cochrane Review 2013 Zn –Evidence JAMA 2014 Zn – Dose • RDA • ~2mg infants, ~5mg children, ~10mg adults • In studies: • 10-15mg in children • ~75mg in adults Zn - Safety • Oral generally safe if don’t exceed tolerable upper limit • 4mg/d (<6 mos) to 34mg/d (14-18 yrs) • Side effects: • Bad taste • Nausea • Long-term high dose (450-1600mg/d) may lead to copper deficiency • Intranasal Zn may cause irreversible loss of sense of smell and should not be used. NCCIH 2015 Cochrane 2013 JAMA 2014 BUGS AND GUTS AND PROBIOTICS Intestinal Gut Microbiota • 100 trillion bacterial cells, most are anaerobes • GI tract sterile at birth • In infancy, gut flora varies greatly • Vaginal vs. C Section • More bacteroides and bifidobacterium in vaginal birth • Premature birth – more staph species • Formula fed vs. breastfed • Breastfed – more bifidobacterium, more diverse microbiome • Neonatal antibiotic use Impact of Diet on Gut Microbiome Worldatlas.com Fecal Microbiota Transplantation •Stool from donor transplanted into recipient •Routes: • From below (via colonoscopy or enema) • Or Above (via NG-tube) • Capsules PO •Only indication currently IN ADULTS: • recalcitrant C. difficile infection • failed standard antimicrobial therapy •Research underway • recurrent Cdiff, for IBD, diabetes, etc … … Probiotics - “the good bacteria” “Live microorganisms, which, when administered in adequate amounts, confer health benefits to the host.” <nourishedkitchen.com> Functional Food •a modified food or food ingredient that has potential benefits on the health beyond basic nutrition •Examples: •Baby formula with probiotics •Yogurt with probiotic cultures •Kefir Probiotics in foods <theguardian.com> <theguardian.com> <realsimple.com> <simple.wikipedia.org> <allrecipes.com> <en.wikipedia.org> ... Not to be confused with Prebiotics Prebiotics – nondigestible ingredients stimulate growth of beneficial microorganisms – ferment in the colon. •Inulins (bananas, agave, wild yams, jerusalem artichokes, jicama) •Fructooligosaccharides (FOS) •Galactooligosaccharides (GOS) – human milk <en.wikipedia.org> … not to be confused with Synbiotics • Nutritional supplements that combine both probiotics and prebiotics. • Ex: Lactobaccillus acidophilus and inulins Quality Control • http://Consumerlabs.com • May not contain viable organisms • Microbial contamination • Potential for transmission of antibacterial resistant plasmids • Effectiveness of different formulations • Actual amount advertised is present • “active cultures” • Ability to survive gastric acid Side Effects and Contraindications • Abdominal discomfort and allergic reactions • diarrhea, nausea, vomiting, gassiness, bloating • Invasive infections of immunocompromised Host • Case Reports of Saccharomyces fungemia and death • >100 cases of fungemia in literature • Indwelling Catheters/ Central Lines • Lactobacillus line infections • Patients with short gut • Case report of lactobacillemia <surgery.med.umich.edu> Handout/ Reference from probiotic review In urgent care, you diagnose a 9 month old female with acute otitis media. You prescribe amoxicillin. The mom asks: “I heard antibiotics can give babies diarrhea. Can I do anything to prevent this?” On the ward, you admit a 2 year old previously healthy boy for dehydration. He was found to have norovirus on stool antigen. After giving hydration and supportive care… “What else do you want to do for this patient?” Your 6 y/o patient ex-premie with a history of short gut due to NEC and is TPN dependent. He just finished a course of antibiotics for line sepsis. He also has a history of recurrent clostridium difficile. The parents are asking about starting probiotics to prevent recurrent c. diff. What do you think? Take Home to your Practice… • Think Probiotic when prescribing antibiotic • Saccharomyces Boulardii • Lactobacillus rhamnosus GG • Baby with Colic/ Reflux • Lactobacillus Reuterii • Teen with Ulcerative Colitis • VSL#3 ** Encourage breastfeeding, plant based diet, fiber and fermented foods, yogurt, playing in the dirt, pets <cartoonstock.com> INTRO TO TCM CONCEPTS AND DEFINITIONS WHAT ARE ACUPUNCTURE POINTS? ACHIEVING BALANCE • Lifestyle/ Diet/ Psychology • Herbs • Acupuncture can balance Qi • Inserting thin sterile, stainless steel needles into the points on the meridian pathways • Needles are inserted to various depths but typically just beneath the skin • Needles are sometimes stimulated by manipulation, moxibustion (‘Arternisia Vulgaris’, also called mugwort), or with electrical stimulation 5 Elements Theory – BiopsychoTypes “Needlephobia in children before and after experience with acupuncture Acupuncture Analgesia Mechanism Spinal cord level – Gate theory of pain • Mechanisms in the spinal cord prevent pain fibers from transmitting in the presence of competing sensory information ACUPUNCTURE – Central modulation • Acupuncture modulates activities in the central nervous system (CNS) • Influences treatment areas via release of neurotransmitters/hormones • Normalize stress responses in the hypothalamicpituitary-adrenal (HPA) axis • Acupuncture blocks cold stress induced increases in HPA axis in rats • Eshkevari, et al. J endocrinology. March 2013 FMRI STUDIES ON PC6 – modulation of cerebellar activities Group activation map in cerebellar ROIs (region of interest) (A) real acupuncture > sham acupuncture condition (B) real acupuncture > tactile stimulation Yoo et.al - Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study. Neuroimage 2004 A B PC6 for Nausea/ Vomiting in Children • Chemo induced nausea and vomiting – • 3 small published clinical studies in Peds literature • Show improvement in N/V scores (n=10-30) • Post-operative N/V • 1 clinical study – (n=120) • Acupuncture improved incidence and timing of N/V significantly compared to sham acupuncture (63% vs 88%) Yeh, C.H. et al J. Altern. Complement. Med. 2012, 18, 334–340. Gottschling, et all Klin. Pädiatr. 2008, 220, 365–370. Reindl, et al. Support Care Cancer 2006, 14, 172–176. Rusy, L.M. et al. Anesthesiology 2002, 96, 300–305. GERD and Dyspepsia • Points PC6, ST36 and CV 12 have in vitro and invivo effects on improving gastric motility and decreasing basal acid production • Study: Acupuncture vs. Double Dose PPI • In 30 adults who failed standard PPI dosing (nl EGD) • Acupuncture more effective at improving sx scores than doubling PPI dose • Dickman et.al, Aliment Pharm Therapy, Nov 2007 LET’S LEARN SOME POINTS ACUPRESSURE PC 6 – NEI GUAN: INDICATIONS • Nausea/ vomiting • • • • Post operative N/V Chemotherapy induced N/V Pregnancy induced N/V Motion Sickness • Contraindicated if cardiac arrhythmia LI 4 – HE GU POINT • Headache • Sore throat • Toothache • Sinus Congestion • Contraindicated in pregnancy – increases uterine contractions LI-4: POINT LOCATION • On dorsum of first interosseus space of the hand • On the belly of the first interosseus dorsalis muscle • At the level of the midpoint of the shaft of the 2nd metacarpal bone BL 32 - LOCATION • One index finger length above the top of the buttock crease • Approximately one thumb width either side of the spine. • Over the second sacral foramen Dimple = posterior superior iliac spine BL32 - INDICATIONS • Relieve labor contraction pain • Use feedback from the laboring women – point may move downward as baby descends • Speeds up labor GRATITUDE “TED TALK” THANKYOU!