David M. Wiseman PhD, MRPharmS

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• David M. Wiseman PhD, MRPharmS
• International Adhesions Society,
• Synechion, Inc., Dallas, TX, USA
• www.adhesions.org

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• What is ARD?
• IAS
• Accomplishments
• Future

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ARD Adhesions Related Disorder

• Adhesions related to severe problems
• Infertility
• Bowel Obstruction
• Chronic Pain
• Complications in subsequent surgery
• Caused by any trauma within the body as a
  consequence of normal healing (surgery,
  endometriosis, infection, radiation)

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What are Adhesions?

• A scar that forms an abnormal connection between
  two parts of the body

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Bowel Adhesions
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Background

• Adhesion-related disease (ARD) is underestimated
  and unappreciated
• Recent studies show that ARD admissions rival
  those for CABG, appendix, etc.
• Much ignorance prevails

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How big a problem?

• 34.5 of women undergoing open GYN surgery
• will be admitted an average of 1.9 times
• in the next ten years
• for a problem directly related to adhesions
• or for a procedure that could be complicated by
  adhesions
• Lower et al., Br J Ob Gyn 2000

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Intestinal Adhesions with Obstruction 560.81

• 67884 Discharges
• 9.8 days Length of stay
• 32,054 Cost per stay total 2.15 billion.
  2/3 cost borne by Medicare/Medicaid
• 2219 deaths, 63 of these female (as discharge)
• 3.3 of diagnosis result in death
• Healthcare Cost and Utilization Project (HCUP)
• http//www.ahrq.gov/data/hcup/hcupnet.htm

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Unmet Needs

• Physician awareness of the extent of problem
• Physician awareness of options for treatment
  /prevention
• Patient frustration for treatment and access to
  treatment
• Health provider appreciation for the
  pharmacoeconomics of ARD

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Patient Frustration

• "For the suicidal thoughts I have thought of them
  but have come to realize that suicide is not the
  escape"

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"Subj Scar tissue and adhesions Date 97-04-07

• I have been suffering from this for 10 years now
  and I am happy that I am not alone (well not
  happy but you know!) I have been put through the
  mill with the testing and dr's and all the famous
  diagnosis' and I still have not found a solution.
  Why is this? They can put an artificial heart
  into a human but they can't get rid of ADHESIONS!
  Pain meds are taking there toll on me and I still
  have not found any relief.

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Multiple Surgery

• have had 9 surgeries for adhesion repair
• Beginning 12 surgeries - 5 for adhesions alone
• 'I have had 5 surgeries for very dense adhesions

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IAS Mission

• To provide information on ARD, its treatment and
  prevention to patients, doctors, and other
  professionals.
• To support patients suffering from ARD.
• To promote research in the prevention and
  treatment of ARD.
• To promote awareness of ARD, its prevention and
  treatment

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Medical Advisory Board

• Dr. Michael Diamond, Detroit, MI
• Professor Harold Ellis, London, UK
• Dr. Lena Holmdahl, Göteberg, Sweden
• Dr. Matthias Korell, Duisburg, Germany
• Mr. Donald Menzies. Colchester, UK
• Dr. Harry Reich, New York, NY
• Dr. Steven Schwaitzberg, Boston, MA
• Dr. Togas Tulandi, Montreal, Canada

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Main Activities

• Providing and gathering information on ARD
• Internet Chats - OBGYN.net, WebMD
• Message forum
• Questions from patients and doctors
• Referring patients to adhesion-aware doctors
• Conducting research

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Achievements

• gt 100,000 Visitors/ month
• 1 Google and Yahoo site under adhesions
• Pivotal role in ICD 9 code 99.77
• Citations in legislatures (NY, WI, LA, MA, MN)
• Presentations at 2 FDA meetings
• NIH requested assistance for patient recruitment
• Major Contributions to Understanding ARD
• Pivotal role in ARD clinic

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ICD 9 Code

• 99.77
• Application or administration of an adhesion
  barrier
• IAS instrumental in the creation of this code

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Awareness is everything!!
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New York Daily News Crazy glue By RANIT
MISHORI, M.D. Tuesday, June 28th, 2005
Post-surgical adhesions required Maria de los
Reyes to seek pain relief through 14 followup
surgeries and other palliatives.
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NIH Recognition
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Major Contributions to Understanding ARD

• Informed consent and adhesions
• The role of iron-regulating genes in
  suspectibility to adhesions
• Describing ARD from the patients point of view
• Formulating integrated approach
• Development of worlds first dedicated ARD clinic

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Informed Consent and Adhesions
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possible Intergel Reaction Syndrome (pIRS) and
Iron Overload

• 3/7 (43) had a HFE mutation (cf 25)
• 5/7 (71) Irish/Scottish ancestry (cf 1/7)
• Three women (HFE normal) had had prior
  hysterectomies
• Animal findings and clinical disturbances in
  calcium and leukocyte levels suggest pIRS risk
  factors are
• Extensive surgery (a mediator of iron imbalance)
• HFE mutations, ethnic propensity for iron
  overload, prior hysterectomy, male gender
• Possibility of long term effects of Intergel
  exposure
• Intercontinental differences in adverse event
  rates to Intergel explainbale by genetic
  differences

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Implications for HFE Heterozygotes

• Iron perturbation and accumulation leads to redox
  reactions, tissue damage, cancer.
• HFE heterozygotes have propensity to iron
  overload. May be at greater risk of adhesions.
• Antioxidant prophylaxis may be appropriate in HFE
  heterzygotes undergoing surgery
• Patent application filed POLYMERS FOR MEDICAL
  AND BIOLOGICAL USE AND USE OF IRON MODIFIERS

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What does an adhesions patient look like?What
can we learn about other CPP-related conditions?
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Adhesions and Bowel Survey

• Patients reporting a diagnosis of adhesions were
  asked to complete an Internet survey regarding
• Time since diagnosis Bowel obstruction
• GI disturbances Nutritonal status
• Ability to work Ability to receive
  disability benefits
• Social support structure

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ARD Survey
Patients 466
Years since Dx with adhesions 7.0 0.3
Years between obstructions 0.9 (n270)
Number of obstructions 9.1 0.7 (n270)
Pts. w/ obstruction 317
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Severe ARD Summary

• Significant history of bowel obstruction
• 71 gastrointestinal disturbance
• 81 chronic pain, 46 take pain medications that
  worsen condition
• 29 of those who tried PT, obtained benefit
• 42 could not work
• 74 reported had problems with family or friends
• 42 reported that their physican wanted to help
  but couldnt.

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Its not just...

• Adhesions
• Chronic Pain
• Endometriosis
• Irritable bowel syndrome
• Interstitial cystitis
• Fibromyalgia.............

Its C.A.P.P.S. Complex Abdomino-Pelvic
and Pain Syndrome
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My journey
NEW Individual disorders merge to a Common
Disorder ????

• OLD
• Individual disorders
• stay
• as
• Individual disorders
• ADHESIONS

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Traditional View of Adhesion - Related Pain

• Single monolithic condition
• Largely treated surgically
• Other conditions are also viewed as monolithic
• Same issues about the way adhesions are viewed
  apply to other CPP-related conditions

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High coprevalance of other conditions
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Disease Progression
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The Problem

• CPP - variety of coalescing and overlapping
  conditions
• (Pelvic Pain, Adhesions, Endometriosis, IBS,
  Interstitial Cystitis etc.)
• Treated as individual entities by different
  specialists
• Often without regard to the other conditions
• Are these different conditions or are they
  manifestations of a common underlying disorder?

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Typical Scenario

• CPP patient likely to display most of these
  symptoms, the most dominant of which will
  determine the specialty to which the patient is
  referred.

Symptom Specialty Diagnosis
Dysmenorrhea, dyspareunia, CPP Gynaecology PID, adhesions, endo
Bowel Gastro-Intestinal IBS
Urinary Urology Interstitial Cystitis
Neurology Pudendal neuralgia
Once locked into a diagnostic paradigm, the
patient will be treated according to its specific
rules. Treat what you findnot what you are
looking for! (Fred L. Mitchell, D.O, F.A.A.O.)

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• Traditional View/ Acute Pain
• Damage in organ leads to generation of pain
  impulses
• Impulses pass through various plexi
• Impulses reach spinal chord
• Impulses transmitted to brain
• Pain is perceived

Wesselmann et al. The urogenital and rectal pain
syndromes. Pain 199773269
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Problems with Traditional Viewof Adhesions or
Other Conditions

• Some patients with CPP have no obvious pathology
• 33 No visible pathology
• 24 Endometriosis
• 33 Adhesions
• Not all adhesions cause pain, not all pain is
  caused by adhesions
• Different patterns of overlapping symptoms
• No consideration of disease progression
• Chronic pain is only viewed as a direct result of
  the condition
• Fails to consider role of neural pathways in
  development of disease

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Emerging View

• Pain may, at one time, have been due to the
  condition,
• BUT
• Once chronic, pain itself becomes an independent
  disease
• Emerging view considers pathology within neural
  pathways

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Emerging View
Retrograde impulses from cross-talk or spinal
chord causes actual inflammation eg bowel to
bladder bladder to bowel uterus to bladder etc.
Continuous barrage of pain impulses causes
changes within spinal chord which sends
unsolicited inappropriate impulses to
brain Phantom pain
Common pathways through plexi allow for
cross-talk. Pain is perceived from normal
neighboring organs.
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CPP an emerging view

• Explains
• Surgical removal of pelvic pathology may not
  reduce long-standing pain
• Phantom pain syndrome
• Surgical intervention or diagnostic laparoscopy
  may be effective for some period
• Aberrant impulses have long dormancy after
  anesthesia
• High co-prevalance of various conditions
• Disparate conditions coalesce into one
• Mis-diagnosis or inability to get diagnosis
• Progression of single symptom to a multi-symptom
  condition

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Treatment Consequences of Emerging View

• Prevent and treat initial condition where
  possibleBUT KEEP on the LOOK OUT
• Integrated and multidisciplinary approach to
  diagnosis and treatment
• Treatment not to rely solely on one type of
  intervention
• Neuromodulation, psychotherapy, physical therapy,
  surgery, analgesia, other modalities.etc..

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Integrated Approach

• Pain mapping
• Complete team evaluation GYN, URO, GI,
  psychologist, dietitian, PT
• Set realistic goals
• Surgery may not be the answer
• Integrated approach
• Neurostimulation
• Use adhesion barriers as appropriate

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It takes a nurturing interdisciplinary team to
practice the nature of palliative care
Core Team Comprehensive
Assessment Coordinate Interventions Discharge
Planning
Thanatology Grief Counseling Family
Support, End-of-Life Issues Community
Transition
Recreational Therapy Relaxation Stress
Management Pet, Music, Art Therapy
Co-morbidity Concomitant Disorder
Treatment Regimen
Rehabilitation Functional
Interventions Assistive Devices Energy
Conservation
Complementary Acupuncture/
Acupressure Tai Chi Trigger Point Release
Symptoms
Clinical Trials Protocol
Disease Process
Individuals Quality of Life
Social Work Socioeconomic Support
Community Resources Coping Skills
SpiritualMinistry Pastoral Presence Prayer
Hope Peace
Psychological Predisposition
Spirituality
Suffering
Roles and Relationships Isolation
Level of Function
Nutrition Satiety, Dysphagia
Nausea Intake Modification, TPN/Tube
Feedings
Pharmacy Pharmacological
Counseling Equianalgesia Adjuvant Agents
Economic Burden
Emotional State
Grief
From NIH Courtesy Dr. Ann Berger
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Integrated CentersEstablished or Developing

• United Kingdom
• Southampton, UK - Mr. R.W. Stones
• Leicester, UK Dr. B. Collett
• USA
• Rochester, NY Dr. F. Howard (Pelvic Pain)
• Birmingham, AL Dr. C.P. Perry (Pelvic Pain)
• Chapel Hill, NC Dr. J. Steege (Pevic Pain)
• Celebration, FL Dr. J. Redan (Adhesions and
  Related Disorders)

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CAPPS - SIZE

• Chronic Pelvic Pain
• Interstitial cystitis
• Endometriosis
• PID
• IBS

• Voiding disorders
• Urge frequency
• Urge Incontinence
• Mixed Incontinence
• Stress Incontinence
• Urinary retention

• Large overlap of conditions

• Diagnosis
• Drug therapy
• Surgery options

• CAPS target population

Refractory patients

• 23,000-150,000 new cases/year

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CAPS POPULATION THROUGH CONTINIUUM OF CARE

• Refractory Refractory to surgical interventions
• Severe Surgical intervention and probably
  refractory cases
• Moderate Patients still undergoing first or
  second line treatments

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CAPPS - Breakdown
Refractory Severe Moderate
Index procedure       
In patient discharges for PCS (all) 3783
PID - CPP /year 11000
In patient female laparoscopies for CPP 164220
Failed laparoscopies for CPP 14000
LUNA performed by AAGL 22000
Failed LUNA 1980 3960
Hysterectomies for CPP 60000 60000
Failed hysterectomies for CPP 3000
In patient female adhesiolysis 13780 16,000
Refractory adhesiolysis 2756
Dyspareunia 1842
In patient vulvectomies 5987
IC - In patient discharges with Dx 1241 6700
IC - Outpatient hydrodistensions for IC 28609
IBS - Discharges in patient with Dx/year 11200
Ilioinguinal, iliohypogastric nerve block 4494.5
Pudendal nerve block 3058
23312 150744 269003
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Now that we are beginning understand this
condition, we can start to figure how to prevent
and treat it.
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What Next?

• 11 years of significant achievements
• Internet presence
• Government recognition
• Development of first ARD clinic (with IP)
• Contributions to understanding of ARD
• Some revenue generated
• THOUSANDS of patients helped
• Unique access to reach thousands of CAPS patients

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Needs

• Expansion of ability to service ARD patients
• Establishment of sustainable revenue model
• Flexibility to engage in novel projects that will
  serve patients and generate revenue

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Solution
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501c3 Well established method Poor revenue for .org and Synechion
For profit entity Tighter fidiciary control. Ability to leverage research Revenue non-recurring
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Chronic Disease Fund CDF Chronic Disease Management Group CDMG
Provide assistance to under-insured patients with chronic or life altering diseases requiring expensive, specialty therapeutics. Cost effective benefits to patients with chronic or life-altering disease. Performance-based solutions to manufacturers, managed care organizations, employers etc. DiseaseTrak provides HIPAA compliant data based on drug utilization, therapy management, and our compliance and persistence programs. Useful for drug research, evaluation of drug programs, effectiveness of coupon, copay, or marketing programs, and pharmacoeconomic studies.
www.cdfund.org www.diseasetrak.com
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Brand -advantaged marketing, coupon programs etc.
Pharma
Diary, therapy management
Copay
Software
Pharmacy dispenses all Rx in class
Need data
Enroll pts. to reduce cost
Patient
Improved compliance utilisation, reduce costs
Data on usage, compliance, disease condition,
efficacy
Need data
Managed Care
CD- Drug Model
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CAPPS ARD Patients

• Significant medication burden
• Analgesics, anti-depressants, hypnotics,
  disease-specific drugs (Zelnorm, Elmiron etc.)

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• Can drug model be applied to procedures?
• Is model particularly useful where procedures are
  linked to long term medication needs?

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Adhesions, Inc. CD Manage
Adhesions. ORG CD FUND
Center -advantaged marketing,
Referrals
CAPS Cent.
Diary, therapy management
Deductible
Enroll pts. to reduce cost
Patient
Best practices
Integrate center non-center data
Improved compliance utilisation, reduce costs
Data on disease condition, efficacy of therapy
Need data
Managed Care
Procedure Model
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Adhesions, Inc. CD Manage
Adhesions. ORG CD FUND
Brand -advantaged marketing, coupon programs etc.
Pharma
Copay/ deduct
Referrals
CAPS Cent.
Diary, therapy management
Software
Pharmacy dispenses all Rx in class
Need data
Enroll pts. to reduce cost
Patient
Best practices
Integrate center non-center data
Improved compliance utilisation, reduce costs
Data on usage, compliance, disease condition,
efficacy
Need data
Managed Care
Drug and Procedure Model
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Iscapps, Inc. CD Manage
iscapps.org CD FUND
Brand -advantaged marketing, coupon programs etc.
Pharma
Copay/ deduct
Referrals
CAPS Cent.
Diary, therapy management
Software
Pharmacy dispenses all Rx in class
Need data
Enroll pts. to reduce cost
Patient
Best practices
Integrate center non-center data
Improved compliance utilisation, reduce costs
Data on usage, compliance, disease condition,
efficacy
Need data
Managed Care
Drug and Procedure Model
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Drug- Procedure Model

• Builds and synergises with drug-only model
• Provides base for building a franchise/network of
  CAPS-Centers
• Can be applied to franchise or non-franchise
  situation
• Can be replicated for other conditions involving
  procedure-based therapy
• Solves dilemma of non- and for- profit

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Next Steps

• Incorporate CAPS into CD-Drug Model
• Incorporate other GYN in CD-Drug Model

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Investment Needed

• Programming
• Marketing
• Agreements
• Database
• 0.5-1MM

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Revenue Model