Integrative Pain and Symptom
Management
William Zempsky, MD, FAAP
Timothy Culbert, MD, FAAP
Sessions S131 and S169
Faculty Disclosures
In the past 12 months, we have not had a significant
financial interest or other relationship with the
manufacturer(s) of the product(s) or provider(s) of the
service(s) that will be discussed in my presentation.
This presentation will include discussion of
pharmaceuticals or devices that have not been approved
by the FDA or if you will be discussing unapproved or
“off-label” uses of pharmaceuticals or devices.
Overview of Presentation





Introduction: Integrative Pediatrics
Introduction: Pain and Symptom Management
Description of Programs
CAM Therapies in Pediatric Pain
Clinical Applications




Headache
Insomnia
Experiential
Audience Q and A
Integrative Medicine Vs. CAM

1
CAM-complementary and alternative medicine




Specific therapies/modalities
Not typically taught, used or reimbursed in USA
hospitals
A group of diverse practices not presently considered
part of conventional medicine
5 domains defined by NIH-NCCAM





Mind/Body
Biological
Manipulative/Body- based
Alternative Systems
Energetic
Integrative Medicine Vs. CAM

Integrative Medicine-A system of care that
emphasizes wellness and healing

Principles









2
Mind/body/spirit
Patient –provider as collaborative partners
Natural, less invasive approaches when possible
Facilitating the body’s natural healing capacities
Need for provider self-care
Conventional and CAM in balance
Customized to patient need and preference
Balance of evidence and safety considerations
Note-over 20 Pediatric CAM Programs in USA
Kids and CAM



2%-30% in primary care settings
30%-70 % of kids with chronic illness
1999-2000 Children’s Hospitals and
Clinics of Minnesota Data





Simpson, 1998 Ambul Child Health
Ernst, 1999 Eur J Pediatrics
Davis, 2003 Arch Peds Adol Med
Grootenhuis, 1998, Cancer Nurs
Stern, 1992, J Adol Health
CAM Use at Children’s
Minnesota-52% Overall





59% of Oncology Patients
51% Pulmonary Patients
32% General Pediatrics
62% Pediatric Epilepsy
47% Pediatric Sickle Cell
Types of CAM Used
45
40
35
Oncology
Pulmonary
Gen Peds
30
25
20
15
10
5
0
Prayer
Massage
Chiropractic
Vitamins
Relaxation
Herbals
AromaRx
Doctors and CAM

Pediatricians in Michigan


>50% would refer for CAM
>50% used CAM themselves


Pediatricians National Survey

66% believed CAM could be helpful


Kemper & O’connor, 2004, Ambul Peds
Pediatricians in Ohio and Minnesota


97% would refer kids with chronic pain for CAM if more was
known about efficacy
73% of female peds and 58% of male peds surveyed classified
themselves as “believers”


Sikand, 1998, Arch Ped Adol Med
Charmond, Banez, Culbert, 2006 Submission in process
**All-expressed need for more CAM education
CAM and Pain Management




Most common reason for CAM usage in adults
surveys is chronic pain –particularly
musculoskeletal pain
For many children with chronic painconventional options –psychotropic meds and
PT-are not working
Increasing evidence that CAM is quite useful
and also safe (particularly non-drug options)
Personal use of Cam by physicians pedicts
likelihood of patient referral for CAM
CAM & Kids:Legal & Ethical Aspects

Complex issues at boundary of medicine, law
and public policy


Cohen et al, 2005, Pediatrics
Clinical Risks






Parents abandon effective care in life-threatening situation?
Does CAM divert from or delay necessary treatment?
Evidence for CAM treatment –known to unsafe or ineffective?
Consent of proper parties?
Is risk/benefit ratio acceptable?
Your knowledge of CAM provider you are referring the patient to
 Cohen and Kemper, 2005, Pediatrics
Evidence: Safety vs. Efficacy
effectiveYes
effective
No
SafeYes
Safe No
Recommend
Monitor closely
Tolerate
Advise against
Weiger et al, 2002, Annals Int Med
Cohen, Pediatrics, 2005
Chronic Pain: Diagnosis





Study of general academic pediatriciansinvestigated opinions of children presenting with
unexplained chronic pain
134 patients, 8-18 y.o.-chart review –3 M.D.’s
60% had psychiatric co-morbidity (kids not docs)
Did not agree on cause of pain for 57% of pts
Did not agree on appropriate diagnostic workup
for 37% of patients

Konijnenberg et al, 2004, Pediatrics
Chronic Pain: Treatment




Feasiblity and acceptability of integrative
treatment package for pediatric chronic
pain (hypnosis and acupuncture)
33 kids chronic pain clinic, 6-18 years
6 weekly sessions
Highly acceptable >90% completed
treatment, no adverse effects

Zeltzer et al, 2002, J Pain Symptom Manage
Chronic Pain Book

Conquering Your Child’s Chronic Pain

Lonnie Zeltzer, MD
Children in Pain

Long history of undertreatment of pain in
children




Perioperative pain
Newborn pain
Pain of Chronic Disease
Problems persist



Emergency department
Common pain problems
Sickle Cell pain
Do children feel pain?




Pain fibers present at end of 2nd trimester
Increased heel sensitivity post heel sticks
Crying increases for days post
circumcision
6 month olds-anticipate and avoid pain
Pain Memory

3 groups





Uncircumcised
Circumcised with EMLA
Circumcised with placebo
Pain scores at 4 and 6 mos shots
Circumcised infants had higher pain
response
Taddio et al. Lancet, 1997




Children involved in a placebo trial of
transmucosal fentanyl
Subsequent study all children received opiates
Patients in original placebo group had higher
pain scores with subsequent procedures
Inadequate analgesia effects future pain
response
Weisman et al, Arch Pediatr Adol Med, 1998.
What symptoms do we need to
consider?





Pain
Nausea
Insomnia
Anxiety
Depression
Acute Symptoms

Pain





Acupuncture
Massage
Relaxation
Herbal Remedies

Arnica
Nausea




Acupuncture
Aromatherapy
Herbal Remedies
Anxiety


Acupuncture
Relaxation
Chronic Symptom Management



Patients and families often looking for
something else
Change the paradigm from a treatment of
last resort
Make integrative approach the norm
Chronic Pain Management






Behavioral Therapy
Herbal therapy
Biofeedback
Physical Therapy
Osteopathic
Manipulation
Craniosacral Therapy




Acupuncture
Massage
Yoga
Reiki
16 yo with CRPS



Sprained ankle 2
months ago
Placed in a boot
PE





Pain
Allodynia
Cool
Swoolen
Blue

Visit 1

PT program


Behavioral Therapy






Subsequent visits
Tens Unit
Aquatic Therapy
Desensitization



Coping
Meditation
Melatonin for sleep
Acupuncture


Anxiety
Pain
Yoga
Massage area with
arnica gel
Children’s Minnesota Integrative
Medicine Program: Overview





Clinical, Research and Educational
Activities
Inpatient and Outpatient Services
Collaborative Model with other disciplines
System-Wide activities
Are integrating services with new Pain and
Palliative Care Team
Children’s Minnesota Integrative
Medicine Program: Staffing






MD-trained as developmental/behavioral
pediatrician (1.0 FTE)
PhD-Pediatric Psychologist (2.0 FTE)
APRN-research and education
background (1-2 FTE)
Massage therapists (2-3 FTE)
MD acupuncturist (0.2 FTE)
Support Staff (3.0 FTE)
Integrative Medicine Clinical
Services

Inpatient

Volumes


Massage 2005 –1,453
IM Consults 2005-378


Massage Up 69%
2006-2,460
2006-536
IM Consults Up 41.7%
Outpatient

Volumes

Massage 2005-93 2006-303


Medical 2005- 1063 2006-1188


Massage Up 212%
Medical Visits Up 11.7%
Psychology 2005-506 2006-749

Psychology Visits Up 48%
Children’s Minnesota Integrative
Medicine Program: Therapies

Mind/Body Skills








Hypnosis, biofeedback, relaxation, groups
Massage and Bodywork
Energy Therapies
Acupuncture/Acupressure
Clinical Aromatherapy
Exercise Physiology and Nutrition
Herbals and supplements
Conventional (psychopharm and psychotherapy)
Children’s Minnesota Integrative
Medicine Program: Diagnoses

Chronic Pain




Holistic Mental Health


Depression, anxiety, adhd, autism
BioBehavioral Problems


Functional GI Disorders
Headaches (TT, Migraine, Chronic Daily)
CRPS, Myofascial pain, somatoform
Enuresis, encopresis, sleep disorders, habits
Chronic Illness Related Problems

Adjustment issues, fatigue, other symptom
management
Children’s Minnesota Integrative
Medicine -Other Activities

Inpatient Consultation Services



Integrative Nurse Training




Massage
Non-drug symptom management
 Nausea, pain, insomnia, anxiety
3 full cohorts of day surgery nurses
3 more to come
8 hour basic curriculum expanding to 40 hr AHNA model
Research




Mind/body interventions for pediatric pain
CAM and pediatric oncology
Clinical Aromatherapy
Massage, stress and cancer
Children’s Minnesota Integrative
Medicine: What Works?






We complement and work closely with all subspecialties-value
added
Work with difficult cases that are “stuck” –conventional approaches
not getting it done
Psychologist and MD work very closely-assessment and treatment
More willingness from patients and families to consider mind/body
approaches without “stigma” associated with “mental health”
Carefully considered therapy mix and political milieux
Great support from leadership team –we bring in philanthropic
dollars, great PR and academic notice (talks and publications)-even
though we don’t make big $$-we have controlled revenue and
expenses very well
Value of Pain Service*




23 hospitals, 5837 patients
half anesthesia pain service, half control
Decreased pain intensity, decreased
nausea, decreased itching, decreased
sedation in pain service group
Less pain than patient expected; more
likely to receive education; quicker
discharge
*Miaskowski, Pain 199:80:23-29
Surveys of Adequacy of Pain
Relief

Cummings et al. 1996





Survey of all children in children’s hospital
Clinically significant pain was present in 21%
of population
Pain intensity not related to age, diagnosis
Children offered less meds than prescribed
“No one” identified as helping with pain
For nearly thirty years I have studied the
reasons for inadequate management of
pain, and they remain the
same….inadequate or improper
application of available information and
therapies is certainly the most important
reason for inadequate postoperative pain
relief
John Bonica, 1990
We realized a traditional Pain Service only
helps those patients with whom it interacts


Action plan which emphasizes CCMC’s
fundamental commitment to pain control
which suffuses through all disciplines and
departments
Basic premise is that pain control and
comfort measures will be a part of all
patient encounters and that barriers to pain
relief will be identified and removed.
Affects the quality of life of all children in
hospital and its community; not select few
with complex pain
Mission

Provision of high quality clinical care in the area
of pain control




Direct care to inpatients and outpatients with pain
Helping other disciplines treat pain problems more
effectively
Creating an atmosphere throughout CCMC
where pain treatment is viewed as important
Establishing a tradition of education and
scholarship in the area of pain management
Pain Relief Program at CCMC

Specific Aspects of Pain Program



Acute Pain Consultation Service
Chronic Pain Program
Comfort Central
Patient Population
(Acute)

Chronic Medical Illness




Complicated postoperative pain care
Weaning and dose escalation
Alternative medications




Heme/Onc, Developmental Disabilities
Sleep, anxiety
Pain out of proportion to illness
NICU pain problems
Sedation questions
Inpatient Complementary
Programs




Acupuncture
Hypnosis
Biofeedback
Yoga
Chronic Pain Clinic

Multidisciplinary Approach


MD, Psychologist, PT, Nursing, MDAcupuncturist, Biofeedbacker, Yoga Therapist,
Meditator
Focus on function

Emphasize behavioral cognitive and physical
and complementary therapies
Patient Population
(Chronic)


Referrals primarily from Rheumatology,
Neurology, GI, Orthopedics, private practice
Frequently referred problems:







CRPS
Widespread pain and fatigue (fibromyalgia, CFS)
Headache
Abdominal pain
Pain associated with genetic disorders (Stickler’s
syndrome, Ehlers-Danlos)
Pain associated disability syndrome
Prolonged postoperative pain
Complementary Programs





Acupuncture
Biofeedback
Meditation
Yoga
Massage
Comfort Central




Protocol Development
Phlebotomy Lab Project
Topical Anesthetic Trials
Injection Protection Project
Mind-Body Skills Training:
Applied Psychophysiology




Biofeedback
Hypnosis
Meditation
Relaxation Training



Breathing
PMR
Autogenics

Sussman and Culbert, 1996, Developmental-Behavioral
Pediatrics
Mind/Body Skills Indications

Primary





Headache (TT and Migraine)
FAP and IBS
Acute Procedural Pain and Distress
Somatoform Disorders
Adjunctive






Cancer –associated symptoms
Insomnia
Anxiety, stress, panic
Chronic Pain
Burns
Nausea
Biofeedback

The use of electronic or electromechanical
equipment to measure and then feedback
information about physiologic process
which can then be controlled in desirable
directions



Video games for your body
Peripheral-emg, temp, eda, hrv, png
EEG

Culbert, 1996 , J Dev Behav Peds
Hypnosis

An altered state of awareness within which
persons experience heightened
suggestibility (and other phenomena)



Mental imagery
Self-hypnosis
Visualization

Culbert, 1994, Internat J Clin Exp Hypnosis
Hypnosis Reduces Distress and
Duration of VCUG I



Kids who had experienced previously
distressing VCUG
Routine care group as controls
N = 44
Hypnosis Reduces Distress and
Duration of VCUG II

Results




Parents rating of Child’s distress decreased
Observations support less distress
Improved compliance
Duration of procedure shortened on average
by almost 14 minutes

Butler et al, 2005, Pediatrics
Hypnosis versus Midazolam as
Premedication





50 children ages 2-11 years randomized
One group-midazolam preop
Other group-hypnosis training preop
Less children anxious in hypnosis with induction
of anesthesia
Post-op-hypnosis group had less behavioral
distress by approximately 50% on both day 1
and day 7

Calipel et al, 2005, Pediatric Anesthesia
Comfort Kit for Kids & Families






Best of currently available
psychological/behavioral strategies
Self-care design
Booklet for kids with “exercises”
Booklet for parents to be good coach
Items to make it fun
Trial of 100 kids (day surgery)
Pilot Study





132 kits out, 63 to kids, 56 parent
responses (89% response rate)
Inpatient and Outpatient
Mailed for day surgery kids 2 weeks prior
to procedure
Diabetes and Heme/Onc clinic just given
out with planned follow-up
Brief telephone survey
Day Surgery




Tonsillectomy
Adenoidectomy
Hernia Repair
Orchiopexy
Pilot Study Preliminary Results

How Helpful was the Kit in Helping you/your child cope
with pain and distress?
 Parents: n=56




Very Helpful: 31%
Somewhat Helpful: 59%
Not at all: 5%
Kids: n=12 mean age 9.9 years



Very Helpful: 0 %
Somewhat: 50%
Not all: 25%
Pilot Study Preliminary Results II

Would you Recommend this Kit to Another
Family?

Parents:


Yes: 89%
Kids:

Yes: 67%
Pilot Study Preliminary Results III

Were the Booklets Easy to Understand?

Parents:
Yes: 86%
 No: 2%


Kids:
Yes: 67%
 No: 8%

Pilot Study Preliminary Results IV

What Items did You use?








Squeeze Ball: 80%
Massage Pen: 73%
Stress Card: 61%
Comfort Ruler: 57%
Essential Oil: 45%
Bubbles: 43%
Pinwheel: 43%
Stickers: 30%
Pilot Study Preliminary Results V

What Skills did you try?




Breathing: 38%
Muscle Relaxation: 30 %
Imagery: 29%
Self-Talk: 29%
Audience Experiential: Thermal
Biofeedback





Peripheral temperature monitoring-indirect
reflection of sympathetic nervous system
arousal
Typical 75-85 degrees
With relaxation training-looking for increaseideal if 90-95 degrees
Many ways to facilitate temp warming-imagery,
breathing, autogenics
Particularly relevant for Migraine and Raynaud’s
Anxious Parents


2 Studies
Effectiveness of auricular
accupressure/acupuncture for anxious parents
of children having surgery



Wang et al, 2004, Anesthesiology
Wang et al, 2005, Anesth Analges
Note: children of mothers also less anxious
upon entry to operating room and during
anesthesia induction
Acupuncture
AJ





14 year old
Rhabdomyosarcoma
Leg and back pain
On narcotics and
other pain meds
Needle Phobia




Immediate relief from
pain
Lasts 2-4 days
“Better than
morphine”
Weaned self off of
narcotics
Acupuncture-Classical Concepts


Man functions harmoniously
with the universe
Illness described in terms of

Disharmony between Yin and
Yang






Interior vs. Exterior
Cold vs. Hot
Dark vs. Light
Passivity vs. Activity
Deficiency vs. Excess
Balance maintained by flow of
Qi
Elements

Wood


Fire


Stability, grounded, balanced,
nurturing
Metal


Sun, heat, vitality, excitement
Earth


Tree, firm but flexible
Cool, brittle, inflexible, durable
Water

Movement, adaptable,
evolution
Organs




Functional
Energetic
Metaphorical
Kidney



Bones, marrow, joints, hearing and hair
Will and motivation
Spleen


Digestion, blood production, menstruation
Nuturing, introspection
Organs


Yin
Solid, Energy
Producing






Kidney
Liver
Lung
Spleen
Heart
Master of the Heart


Yang
Hollow, transport






Bladder
Small Intestine
Large Intestine
Gall Bladder
Stomach
Triple Heater
Energy pathways-Meridians

Tendinomuscular



Most superficial
First defense
Principal



Through muscular layer
Provide nourishment and
vitality
Connected with zone of
organ influuence

Distinct



Go deep to the organs
Allow organ energy to
circulate
Curious

Connections between
meridians
Patient Evaluation



Both western medical eval and eastern
approach
Explore the characteristics and behaviors
of the problem
Identify organ and energy circulation
divisions involved in the problem
Biostructural psychotype


Takes into account
traditional history
Also includes




Personality traits
Seasonal affinities
Color and taste
affinities
Elemental qualities
Patient Evaluation




Determine areas of deficiency or excess
Discover underlying biostructural
psychotype
Uncover obstructions to flow
Insert needles along channels that
influence energy flow to restore balance
Physical Exam


Standard attention to muscular bands and
trigger points
Inspect for tender spots (ashi points)
which may indicate underlying organ
problem
Somatotopic Systems

Evaluate somatotopic
systems

Tongue

Ear

Pulse
How does it work?

Corrects imbalance of
energy



Movement of energy
through bioelectric
channels
Activation of
endogenous opioid
system
Direct impact on brain

FMRI data
Acupuncture analgesia (AA) –
Opioid involvement




Naloxone blocks AA
Those with less opioid receptors less AA
Endorphins increase in CSF
Can provide AA with cross circulation
Functional MRI


Different acupuncture sites activate
different portions of the brain
Strong pain points


activate structures of descending
antinociceptive pathway
deactivate limbic areas involved in pain
association
Cool Stuff
Compared
fMRI of 3 groups
Stimulation of visual
acupoint


Stimulation of non-acupoint
Grad student looking at
flashlight

Outcome Trials

Strong evidence



Moderate evidence



PONV-Acupuncture equivalent to antiemetics in adult
and pediatric trials
Not a traditional use of acupuncture
Headache
Back Pain
Weak or no evidence

Almost everything else
J.M.






13 yo with dermoid cell
tumor
Severe nausea and
vomiting s/p
chemotherapy
Rx with benadryl, zofran
without relief
Stimulation of points in
wrist and feet
Decreasing symptoms
during procedure
N/V resolved l hour post
procedure
Why are clinical trials difficult?


Evaluate eastern medicine with western
techniques
Treatment is patient specific not drug specific


Treatments vary with practitioners





Personality traits
Underlying philosophy
Needle placement
Duration of needle placement
Type of needle stimulation
CAM defined disorders do not equal
biomedically defined disorders


Difficult to get adequate sample sizes
Placebo difficult to accomplish

Needles placed at non acupoints have intermediate
effect



Requires increased sample size to show differences
Patients can differentiate between real and sham
needle
Results of studies may not be generalizable
Making clinical trials better


Improving placebo
Manualizing treatment





Study particular acupuncture style
Allowing flexibility within a framework
Develop protocols through consensus
Standardized point selection and outcome variables
Study both individual and standardized
approaches
STRICTA







Designed to be analogous to CONSORT
Acupuncture Rationale
Needling Details
Treatment Regimen
Co-interventions
Practitioner Background
Control Interventions
Side effects





Needle Shock
Bleeding
Infection
Pain
Rare


Pneumothorax
Cardiac tamponade
What about children?

Aren’t they afraid of needles?




67% rate it as pleasant
Relaxing
Many patients sleep
Don’t the needles hurt?

Not really
J.M.





17 yo with sickle cell
disease
Severe chronic pain
especially in back and
hips
Opioid dependent
Treatments focused on
relaxation and
decreasing in back and
hip pain
Treatments separated
by 3 weeks
Children with Chronic Pain







Headache
Abdominal Pain
Arthritis
RSD
Sickle Cell
Cancer Pain
Fibromyalgia/Chronic Fatigue
O.J.



13 yo with Crohns
disease persistent
abdominal pain
Low energy and
mood
Treatment focused
on increasing
energy, decreasing
abdominal pain




Immediate feeling of
relaxation
Incidentally noted
decreased knee pain
after first visit
Persistent improvement
in energy, mood post 2nd
treatment
Abdominal pain resolved
post 5th treatment.
M.S.




16 yo with
incapacitating
migraine headaches
Likely stress induced
Misses 1-3 days per
week of school
Grades suffering




Hated it from the start
No improvement in
headache over 6
weeks
Last treatment
targeted relaxation
Patient fell asleep
during therapy
G.M.




9 yo neuropathic pain
both feet
Became anxious and
extremely tearful
Pain improved post
acupuncture
Returned for a 2nd try
but couldn’t tolerate it
B.Z.






Long distance runner
Chronic knee pain patellar tendinitis
Left >> Right
Took 2 mos off without
improvement in
symptoms
Treatment with 2 needle
technique on Left
Marked lasting
improvement on Left
Integrative Approach to Pediatric
Headache


Assess for psychiatric co-morbidity
Adjust all lifestyle factors


Review medications


analgesic rebound, polypharmacy
Primary CAM Therapies (safety and efficacy)


Sleep, diet, overscheduling, exercise
Mind/Body, Acupuncture, Psychotherapy
Adjunctive CAM Therapies (safety but unclear
efficacy)

Massage, Aromatherapy, Cranial Sacral Therapy
Mind/Body Skills and Headache

Hypnosis Vs Propanolol for Migraine


Prospective crossover-hypnosis,placebo and
propanolol
Significant decrease in frequency of HA with selfhypnosis group only


Olness & MacDonald, 1987, Pediatrics
Biofeedback for TT and Migraine HA




SEMG with bifrontal placement
Peripheral temperature biofeedback
Heart rate Variability Biofedback
Neurofeedback

Andrasik & Schwartz, 2006, Behavior Modification
Acupuncture and Headache





22 children with migraine
Randomized to either acupuncture or sham
acupuncture groups
10 healthy controls
Checked serum panopiod levels before and
after treatment on all groups
True acupuncture group only-significant
reduction in HA freq and severity and also
increase in panopiod levels back to normal
(control)levels

Pintov et al, 1997, Pediatric Neurology
Aromatherapy and Headache







The use of essential oils that are steam distilled
from plants
Inhalation, topical application, ingestion
Minimal published studies, but safe and kids
really enjoy it
Kids preferences different from adults-study
HA-inhalation-rosemary and chamomille
HA-topical-lemongrass, peppermint
Portable-bring to to school etc
Massage and Headache

Massage effects







Increased blood flow
ANS balancing
Decrease muscle spasm
Enhanced lymph drainage
Different Forms
6 sessions over 3-6 weeks
Limited study evidence in kids-some in adults

Field, 2002, Med Clin NA
Botanicals/Supplements and
Headache




Magnesium, B2 (riboflavin)
Feverfew
Anti-Inflammatory Diet and Omega 3 FA
Butterbur for Migraine



108 kids, 6-17 years, multicenter, prospective open
label trial
50-150 mg of butterbur for 4 months
77% of patients had decrease of at least 50% freq of
HA, few SE

Pothman and Danesch, 2004, Headache
Headache: Pediatric Case Study

Video-common CAM therapies for
pediatric HA
HA-Refractory to Conventional Rx






Tool Kit Approach
Can still use abortive or preventative
medications if necessary
Active versus passive strategies
“Portability” a consideration
DCG teaching model
Self-management
Integrative Approaches for
Insomnia






Aromatherapy
Audio Visual Entrainment
Relaxation Training
Music Therapy
Herbal Therapy-teas
Melatonin
Training and Information







www.pangea2006.org
www.childrensintegrativemed.org
www.holistickids.org
www.ahma.org
www.csh.umn.edu
www.integrativemedicine.arizona.edu
www.longwoodherbal.org