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Physician Folder Information

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P HY SIC IA N INFO RMAT ION

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PH YSICIAN INF OR MAT IO N FO LDER

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P H Y S I CIA N IN FOR MATION Please find enclosed your Ananda Professional physician information folders Please take some time to thoroughly review the information If you have questions please contact Dr Alex Capano Medical Director for Ananda Professional prior to meeting with a physician Alex Capano DNP holds the first doctorate in Cannabinoid Therapy She is a faculty member of The Lambert Center for the study of Medicinal Cannabis Hemp at Thomas Jefferson University Dr Capano can be reached at clinical AnandaProfessional com

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ONCE Y OU F E E L CO N F ID E N T WI TH TH E M AT E R I A L P RO V I D E D WE S U G G E S T 1 The pharmacy identify their top prescribers for pain sleep and anxiety medications These should be pain specialists psychiatrists sleep specialists pulmonologists rheumatologists neurologists and family practitioners 2 Consider using the letter provided to introduce the Ananda Professional product line to the physicians on your list The physicians that respond to the letter should be receptive to having a discussion with you about CBD These physicians will be the most likely to send patients to your pharmacy They often have patients that are buying it elsewhere and are looking to give guidance on a trusted place to purchase CBD products 3 When you meet with these physicians provide them with the Ananda Professional presentation and review it with them Their questions will primarily be related to a They quality of the product you have chosen to sell in your pharmacy b The types of patients for which it is appropriate c The outcomes they might expect to see d Dosing and delivery e Drug drug interactions f Patient cost 4 If the physician has specific clinical questions that you are not comfortable answering you can provide them the contact information for Dr Alex Capano They will be able to contact her directly to get their questions answered

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TA BL E O F CO N TE N TS 1 Sample Introductory Letter to Physicians 2 Letter of Introduction Dr Alex Capano Medical Director for Ananda Professional 3 Ananda Professional physician presentation 4 Clinical information a Cannabinoids Pain b The Health Effects of Cannabis and Cannabinoids 5 How Ananda Professional products can positively impact opioid use a CBD and Opioid Reduction b Neurotherapeutics Early Phase in the Development of Cannabidiolas Treatment for Addictions Opioid Relapse Takes Initial Center Stage c Trends in Neuroscience Cannabidiol Swinging the Marijuana Pendulum from Weed to Medication to Treat the Opioid Epidemic d American Pain Society Medical Cannabis Use is Associated with Decreased Opiate Medication Use in a Retrospective Cross Sectional Survey of Patients with Chronic Pain e Cannabis and Cannabinoid Research Cannabis as a Substitute for Opioid Based Pain Medication Patient Self Report 6 Ananda Professional Product Sheet a Tinctures b Soft gels 7 Dosing card 8 Patient Brochure 9 Prescription pads

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SAM P LE IN T RO D UC TO RY L E T T E R T O P H Y S I CI ANS Click to download 

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LETTER OF INTRODUCTION DR ALEX CAPANO MEDICAL DIRECTOR FOR ANANDA PROFESSIONAL Click to download 

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ANANDA P ROFESSIO NA L P H Y S I CI A N P R E S E NTATI O N

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Click Play button to start video

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CLI NICAL IN FORMATI O N THE NATIONAL ACADEMIES OF SCIENCES ENGINEERING MEDICINE 1 Click to download Click to download

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CLI NICAL IN FORMATI O N CBD and Opioid Reduction CBD and Opioid Reduction Neurotherapeutics Trends in Neuroscience American Pain Society Cannabis and Cannabinoid Research Neurotherapeutics 2015 12 807 815 DOI 10 1007 s13311 015 0373 7 REVIEW Preclinical and pilot studies have shown CBD may reduce opioid cravings and alleviate opioid withdrawal symptoms Hurd et al s study published in Neurotherapuetics and a follow up published in Trends in Neurosciences expresses that CBD does not pose a risk for addiction or dependence Animal studies reveal that CBD is not hedonistic not rewarding and does not induce drug seeking behavior Hurd et al 2015 Hurd 2017 Animal studies also showed reduced heroin seeking behavior after CBD exposure Ren et al 2009 What is most impressive is that the results lasted weeks after last administration Hurd et al 2015 Additionally animal studies revealed that CBD exposure reduced morphine withdrawal symptoms The Journal of Pain Vol No 2016 pp 1 6 Available online at www jpain orgCannabis and www sciencedirect com and Cannabinoid Research Volume 2 1 2017 DOI 10 1089 can 2017 0012 Early Phase in the Development of Cannabidiol as a Treatment Outstanding Questions for Addiction Opioid Relapse Takes Initial Center Stage How can authors and journals more clearly detail the contribution of all team members and how far should lists of contributors reach e g lab technicians Yasmin L Hurd 1 Michelle Yoon 1 Alex F Manini 2 Stephanie Hernandez 2 Researchers then evaluated the effects of CBD and opioid cravings in humans Research supported that CBD Ruben Olmedo 2 Maria Ostman 3 Didier Jutras Aswad 4 was safe when used in conjunction with opioids A double blind placebo controlled crossover study found that CBD did not exacerbate adverse effects of opioids such as respiratory depression and cardiovascular complications A second pilot study evaluated heroin cravings in human subjects Similar to the results in animal studies the human study revealed that the effects of CBD were long lasting Specifically those who received one dose of CBD reported fewer cravings at 1 hour 24 hours and even 7 days post exposure than those who received placebo Additionally the authors note that CBD reduced anxiety in the patients who received it Hurd et al 2015 Also of note is that one study revealedPublished CBD decreased cigarette online 13 August 2015 use among The American Society for Experimental NeuroTherapeutics Inc 2015 dependent participants Multiple cannabinoids from the marijuana In response to the opioid epidemic researchers evaluated whether orAbstract not medical cannabis accessderived reduced opioid related deaths An analysis of public health records revealed that medical cannabis lawsbut hadmost have not plantstates have with potential therapeutic benefits a 24 8 lower mean annual opioid overdose mortality rate compared been to states medical cannabis well without investigated despite the widespread legalization access Bachhuber et al 2014 Another study revealed that Medicare prescriptions for in drugs to treat of medical marijuana the USA and pain other countries Theradepression anxiety nausea psychoses seizures and sleep reduced peutic bin states with cannabinoids as to which indications will depend on Bradford determinations Bradford 2016 In Michigan a retrospective survey revealed a 64 of decrease in opioid use a decrease the multiple cannabinoids and otherinbiologically active side effects and an overall improved quality of life in those who used cannabinoids Boehnke Litinas Clauw chemicals that are present in the marijuana plant can be de2016 In California a survey of 2 897 revealed that 97 of opioid users reported that they strongly veloped to treat specific symptoms and or diseases Such inagreed agreed that cannabinoids reduced their opioid use Reiman Welty Solomon 2017 sights are particularly critical for addiction disorders where different phytocannabinoids appear to induce opposing acAdditionally new research from Maine Medical Center evaluated the effect of cannabinoids in over 1 500 tions that can confound development patients who used opioids for chronic pain Piper et al 2017 Over three quarters 76 7 the of the patients of treatment interventions Whereas reductions 9 tetracannabinol has as been well docureported opioid reduction after initiation of medical cannabis Additional polypharmacy occurred mented sleep to be 65 2 rewardingand andmigraine to enhance sensitivity to other patients reduced use of medications for anxiety 71 8 depression 37 66 7 Medical cannabinoids also reduced alcohol consumption in 42 of participants drugs cannabidiol CBD in contrast appears to have low reinforcing properties with limited abuse potential and to inI d also like to link you to this article in Medscape While it is not a study shows one physician s success in hibititdrug seeking behavior Other considerations such as reducing opioids with CBD He shares a few case studies and also gives some guidance on pediatric dosing CBD s anxiolytic properties and minimal adverse side effects https www medscape com viewarticle 893684 also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction However significant research is still needed as CBD investigations References published to date primarily relate to its effects on opioid drugs Bachhuber M A Saloner B Cunningham C O Barry C L 2014 Medical cannabis laws and opioid analgesic overdose mortality in the United States 1999 2010 JAMA internal medicine 174 10 Yasmin L Hurd 1668 1673 yasmin hurd mssm edu Boehnke K F Litinas E Clauw D J 2016 Medical cannabis use is associated with decreased opiate medication use in a retrospective cross sectional survey of 1patients withofchronic pain The Journal Departments Psychiatry Neuroscience and Pharmacology and Systems Therapeutics Icahn School of Medicine at Mount Sinai of Pain 17 6 739 744 New York NY USA Bradford A C Bradford W D 2016 Medical marijuana laws 2reduce prescription medication useofinEmergency Division of Medical Toxicology Department Medicine Icahn School of Medicine at Mount Sinai New York NY Medicare Part D Health Affairs 35 7 1230 1236 USA 3 Department of Psychiatry Karolinska Institutet Stockholm Sweden Research Center Centre Hospitalier de Hurd Y L Yoon M Manini A F Hernandez S Olmedo R Ostman M Jutras Aswad D l Universit 2015 de Montr al Department of Psychiatry Universit Montr al Montreal Canada Early phase in the development of cannabidiol as a treatment for addiction opioid relapse takesdeinitial center stage Neurotherapeutics 12 4 807 815 4 Can laboratories and institutions facilitate skill specialization and team science approaches organically that is without the encouragement of funding agencies 14 Koch C and Jones A 2016 Big science team science and open science for neuroscience Neuron 92 612 616 15 Abbott B P et al 2016 Observation of gravitational waves from a binary black hole merger Phys Rev Lett 116 61102 Science Society Cannabidiol Swinging the Marijuana Pendulum From Weed to Medication to Treat and CBD s efficacy at different phases of the abuse cycle for different classes ofopportunity addictiveto substances remain largely the Opioid Epidemic do justice to the complexity If neuroscience is to become increasingly collaborative should this be re ected in increasingly standardized procedures and formats for data acquisition preservation and sharing of future scienti c understudied Our paper provides anquestions overview of preclinical Yasmin L Hurd1 animal and human clinical investigations and presents prelimiInstitute for Brain and Behaviour nary clinical data thatDonders collectively setsCognition a strong foundation in Epidemics require a paradigm shift Radboud University and Radboud University Medical support of the furtherCentre exploration of Netherlands CBD as a therapeutic interNijmegen The in thinking about all possible soluvention against opioid relapse As the legal landscape for medical tions The rapidly changing socio Correspondence marijuana unfolds it g fernandez donders ru nl is important to distinguish it from Bmedical G Fern ndez political marijuana landscape http dx doi org 10 1016 j tins 2016 12 005 CBD and other specific cannabinoids that can more appropriprovides a foundation for the therately be used to maximize the medicinal potential of the apeutic development of medicinal References 1 Larsen P O and von Ins M 2010 The rate of growth in cannabidiol to address the current marijuana plant 1 scienti c publication and the decline in coverage provided by Science Citation Index Scientometrics 84 575 603 opioid abuse crisis Human Rat Craving 2 The Royal Society The Scienti c Century Securing Our Keywords THC Cannabis Heroin Future Prosperity The Royal Society 3 Kinman G and Wray S 2013 Higher Stress a Survey of Stress and Well Being among Staff in Higher Education University and College Union Curbing an Epidemic In an unprecedented report the US Surgeon General recently released their rst state of the science on substance use addiction and health to fully recognize Larivi re V 2009 The declinemarijuana in the concentration With debates about5 so called medical andof the substance use and addiction as signi cant citations 1900 2007 J Am Soc Inf Sci Technol 60 widespread media coverage 858 862 on the subject the call for the and substantial public health challenges 6 Vieira Cannabis E S and Gomes J A N F 2010 Citations to scienlegalization of marijuana sativa both for recrea 1 As emphasized in the report a major ti c articles its distribution and dependence on the article component of the current substance use tional and medical purposes has gained considerable momenfeatures J Informetr 4 1 13 Della Briotta Parolo P 2015 Attention decay in science J crisis is the misuse and abuse of opioid tum in recent years 7 While much attention has been given to Informetr 9 734 745 drugs The numbers are alarming In the the medicinal promises that theLibrary marijuana might possess 8 U S National of Medicineplant 2015 Number of authors per MEDLINE PubMed citation Published online July 2 United States approximately 2 5 million the spotlight on marijuana has also raised awareness about the 2002 https www nlm nih gov bsd authors1 html people have been diagnosed with an opiChen S et al studies 2015 Are top cited papersbeen more interdisciremarkable dearth of9 scientific that have conductoid use disorder OUD Over 80 people plinary J Informetr 9 1034 1046 ed on this plant s therapeutic potential As shown in Fig 1 the 10 The Academy of Medical Sciences 2016 Improving rec die each day from opioid overdose that ognition of team scienceon contributions in biomedical number of research studies published cannabis has coinnumber was even higher the past few research careers Published online March 2016 https years before many lives were saved due cided temporally with major changes in the social and political www acmedsci ac uk viewFile 56defebabba91 pdf 11 MacCoun R and Perlmutter S 2015 Hide results to seek to the recent availability of the overdoseclimates of the time such as in the early 2000s after states such the truth Nature 526 187 189 reversing agent naloxone Disconcertas California legalized marijuana Unfortunately scien12 Freedman L P et al 2015 The economicsmany of reproducingly four in ve new heroin users started ibility in preclinical research PLoS Biol 13 e1002165 tific and medical questions remain with respect to the potential 13 Bergin S et al 2016 Bratislava declaration of young out misusing opioid prescription painPublished online August http or actual benefits andresearchers risks of medicinal and1 2016 recreational killers This has signi cant implications www eu2016 sk data documents marijuana use Although the public and the media use the term bratislava declaration of young researchers nal pdf for the current course of the opioid Introduction 4 Button K S et al 2013 Power failure why small sample size undermines the reliability of neuroscience Nat Rev Neurosci 14 365 376 Bmedical marijuana liberally few acknowledge or are even aware of the complex nature of the plant which consists 124 Trends in Neurosciences March 2017 Vol 40 No 3 Cannabis and Cannabinoid Research epidemic because over 200 million opioid painkiller prescriptions are still written ORIGINAL RESEARCH Open Access each year a number closely approximating the entire adult population in the United States While the burden of OUDs for the individual their families and communities is enormous so are the economic costs currently estimated at US 78 billion yearly Amanda Reiman 1 Mark Welty 2 and Perry Solomon3 The currentF opioid epidemic has gripped Kevin Boehnke Evangelos Litinas y and Daniel J Clauwz x every community in the United States and Department of Environmental Health Sciences School of Public Health University of Michigan Ann Arbor Michigan crossed political party lines such that there Abstract y Om of Medicine Ann Arbor Michigan isz for the rst time complete agreement Introduction Prescription drug overdoses are the leading cause of accidental death in the United States AlterDepartments of Anesthesiology Medicine Rheumatology and Psychiatry Medical School University of Michigan about the critical need to limit production natives to opioids for the treatment of pain are necessary to address this issue Cannabis can be an effective treatAnn Arbor Michigan and x consumption of opioid medications It for pain greatly reduces the chance of dependence and eliminates the risk of fatal overdose compared to Chronic Pain and Fatigue Research Center Medical School University of Michigan Ann Arbor ment Michigan is my opinion that bold steps are also opioid based medications Medical cannabis patients report that cannabis is just as effective if not more than required to escalate the pipeline in developioid based medications for pain oping creative and innovative Abstract Opioidstreatments are commonly used to treat patients with chronic pain CP thoughMaterials there is little and Methods The current study examined the use of cannabis as a substitute for opioid based pain to help curb this epidemic evidence that they are effective for long term CP treatment Previous studies reported strong associmedication by collecting survey data from 2897 medical cannabis patients ations between passage of medical cannabis laws and decrease in opioid overdose statewide Discussion Our Thirty four percent of the sample reported using opioid based pain medication in the past 6 The Changing Sociopolitical aim was to examine whether using medical cannabis for CP changed individual patterns of opioid months Respondents overwhelmingly reported that cannabis provided relief on par with their other medicaPendulum Medicinal Marijuana use ofUsing an online questionnaire we conducted a cross sectional retrospective surveytions of 244 butmedwithout the unwanted side effects Ninety seven percent of the sample strongly agreed agreed The predominant pharmacological treat CP who patronized a medical cannabis dispensary in Michigan ical cannabis patients with between that they are able to decrease the amount of opiates they consume when they also use cannabis and 81 ments currently prescribed OUDs are November 2013 for and February 2015 Data collected included demographic information changes in strongly agreed agreed that taking cannabis by itself was more effective at treating their condition than taking methadone buprenorphine and opioid use quality of naltrexlife medication classes used and medication side effects before and afterwith initi opioids Results were similar for those using cannabis with nonopioid based pain medications cannabis one which directly target the usage opioid sysation of cannabis Among study participants medical cannabis use was associated with a 64 Conclusion Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain tem These medications haveuse been decrease in opioid n of118 decreased number and side effects of medications andtreatment an improved and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence signi cantquality clinical value but 45 also have their of life This study suggests that many CP patients are essentially substituting medical Keywords opiates pain harm reduction substitution opioids cannabis own challenges often associated cannabis for opioids andwith other medications for CP treatment and finding the benefit and side effect strict governmental governing profile ofregulations cannabis to be greater than these other classes of medications More research is needed to their use validate One emerging solution showing this finding potential therapeutic properties is cannaPerspective This article suggests that using medical cannabis for CP treatment may benefit some binoids States with legalized marijuana 1999 1 Interestingly Bachhuber et al found that states Introduction CP patients The reported improvement in quality of life better side effect profile and decreased laws have reported a reduction in opioid The Centers for Disease Control CDC and Preven with medical cannabis laws had signi cantly lower stateopioid use should be confirmed by rigorous longitudinal studies that also assess how CP patients use as evidenced by lower number of tion report that o pioids including prescription level opioid overdose mortality rates 2 Similarly Bradford use medical cannabis for pain management prescriptions for opioid painkillers opioid pain relievers and heroin killed more than and Bradford evaluated data on all prescriptions lled by 2016 by American Pain Society reduced number of the opioid overdoses 28 000 people in 2014 more than any year on record Medicare Part D patients from 2010 to 2013 and found words Medical and lowerKey opioid positive screenscannabis associ opioids chronic pain side effects Medical Cannabis Use Is Associated With Decreased Opiate Medication Use in a Retrospective Cross Sectional Survey of as a Substitute for Opioid Based Pain Medication Cannabis Patients With Chronic Pain Patient Self Report ated with car fatalities 2 The reasons for these associations have not been estabhronicspeculations pain CP isregarding among the the most common and lished despite affecting 100 potentialexpensive for medicinalmedical propertiesconditions of marijuana tomillion reduce Americans opioid use and with total direct and indi C The scienti c community has been largely Received December 4 2015 Revised and February missing from most conversations pol 23 2016 Accepted March 7 2016 icymaking regarding the legalization of Dr Clauw has performed consulting services for and or served on scientimarijuana medical purposes Indeed fic advisoryfor boards of Pfizer Lilly Forest Laboratories Johnson JohnPurdue Pharma Nuvo Cerephex Tonix Iroko Takaeda Cerephex it son is clear that the marijuana IMC Zynerba and legalization Samumed Heofhas received grant support from Pfizer Forest Merck Nuvo and Cerephex Litinas has outpaced the science this Dr is one ofis the Chief Medical Officer at Om of Medicine a medical cannabis dispensary in Ann Arbor Michithe rst times in US history that the quesgan Mr of Boehnke reports no conflicts interest tion whether a plant or any of drug is an Address reprint requests Daniel J Clauw at MD University of Michigan effective medicine has tobeen decided 24 Frank Lloyd Wright Dr PO Box 385 Ann Arbor MI 48106 E mail dclauw med umich edu 1526 5900 36 00 2016 by the American Pain Society http dx doi org 10 1016 j jpain 2016 03 002 Unfortunately this statistic has done little to curb the prescribing and consumption patterns for prescription opioids The CDC estimates that since 1999 the amount that the use of prescription drugs for which cannabis could serve as a clinical alternative fell signi cantly once a state medical cannabis law was implemented They rect costs of up to 635 billion per year 8 Despite their of prescription opioids sold in the United States nearly found that implementing an effective medical cannabis high prevalence treatment of CP conditions is difficult quadrupled yet there has not been an overall change in law led to a reduction of 1826 daily doses for opioid Treatments for CP conditions often require incremental the amount of pain that Americans report Deaths from pain relief lled per physician per year 3 lifestyle changes exercise sleep hygiene stress reducprescription opioids drugs Patients who suffer with pain continue to use opioids tion and repeated doctor visits to monitor changes like oxycodone hydrocodone and methadone have also quadrupled since for chronic pain conditions despite their limited longwhich is increasingly challenging in the current economic and medical climate 14 Furthermore other potentially 1 efficacious therapies eg cognitive therapy School of behavioral Social Welfare University of California Berkeley Berkeley California 2 School of Lifespan Development and Educational Services Kent State University Kent Ohio and complementary approaches are not often covered 3 Chief Medical Of cer HelloMD San Francisco California by insurance Finally opioids one of the most common Addressineffective correspondencefor to Amanda medication used to treat CP are manyReiman PhD MSW School of Social Welfare University of California Berkeley 120 Haviland Hall Berkeley CA 94720 E mail areiman berkeley edu types of CP as well as being addictive and associated 1 Amanda Reiman et al 2017 opiPublished by Mary Ann Liebert Inc This is an Open Access article distributed under the terms of the Creative Commons with significant morbidity and mortality Indeed Attribution License which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited oids are the most common prescription drug implicated in overdose deaths involved in up to 75 of overdoses 160 and estimated to be responsible for at least 17 000 deaths annually 10 1 Click icon above paper to download

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ANANDA P ROFESSIO NA L P R O DU CT S H E E T Full Spectrum allows for the entourage effect in which cannabinoids work synergistically to promote the most therapeutic response Research supports that isolated CBD is not as effective or as well tolerated as full spectrum CBD products F UL L SPECTRU M HEMP EXTRACT F UL L SP E C T R UM HE MP E XT R AC T 3 00mg p e r B ottle 30ml 6 0 0 m g p e r Bot t l e 3 0 m l Each bottle contains 300mg of active cannabinoids The tincture contains a scored pipette for accurate dosing One 1 milliliter contains 10mg of active cannabinoids Sublingual tinctures bypass first pass metabolism which allows users to get the most out of their CBD oil This is our more concentrated tincture Each bottle contains 600mg of active cannabinoids The tincture contains a scored pipette for accurate dosing One 1 milliliter contains 20mg of active cannabinoids Sublingual tinctures bypass first pass metabolism which allows users to get the most out of their CBD oil 300mg of active cannabinoids 600mg of active cannabinoids 10mg active cannabinoids per ml 20mg active cannabinoids per ml Full spectrum of cannabinoids Full spectrum of cannabinoids Carried in organic cold pressed hemp seed oil Carried in organic cold pressed hemp seed oil Plant based ingredients Plant based ingredients Made in the USA Made in the USA INGREDIENTS INGREDIENTS Organic cold pressed hemp seed oil hemp flower extract natural botanically derived terpenes Click to download

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DOS ING C ARD Click to download

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PATI E NT BRO C HURE Click to download

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P HY SIC IA N INFO RMAT ION Click to download

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THANK YOU clinical anandaprofessional com