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“Setting up a New-fill® clinic”
Sharron Brown, Gillian Dean, Odile Brennan, Louise Kerr
Objectives
• To know / understand:
– background of facial lipoatrophy in context HIV
– what products are available / mode of action / adverse events
– the practicalities of setting up a Newfill® clinic
– overview of current services
– if you can’t set up a Newfill® clinic….
– how service requirements have changed over last 8 years
– understand the patients’ experience
– Q & A session
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Pathogenesis & incidence of lipoatrophy
• Multi-factorial
• Host, viral & therapeutic elements
• Lipoatrophy exists in HIV infection &
increases with HAART
• 30-40% of cohorts with clinically
significantchanges
• HAART selection strategy to minimise
risk of lipoatrophy0
5
10
15
20
25
30
35
40
45
HIV neg HIV + (noHAART)
HIV + (HAART)
arms legs face
%
Palella FJ et al. Clin Infect Dis. 2004;38:903–907
Lipoatrophy in HIV
• No standard definition
• Subcutaneous fat loss
– limbs, face, buttocks
• 40-50% fat loss by the time
clinically apparent (limbs)
• Facial area maybe more sensitive
• Difficult to diagnose – often
triggered by patient concerns
• Once present – difficult to reverse
© elementshiv.org
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Pathophysiologic mechanisms
X 400Increased number ofmacrophages
Control x 400↑↑↑↑ no. of smalleradipocytes x 200
• Mitochondrial dysfunction
– inhibition of mitochondrial DNA polymerase → mitochondrial injury
• Pro-inflammatory mediators
– increased IL-6 / TNF-α expression
– macrophage infiltration
• Compromised adipocyte life cycle
– adipocytes replaced by fibrous tissue
– ↓ adipocyte size, ↑ apoptosis
© elementshiv.org
Implications of lipoatrophy
• Psychological effects / quality of life1
– ↓ self-confidence, self-esteem
– anxiety / depression2
• Social effects3,4
– social alienation
– difficulty finding clothing
– impaired quality social relationships (OR 0.38)
• Sexual dysfunction5
• Decreased adherence6-7
• Physical effects (e.g. discomfort while sitting)
1. Rajagopalan R et al, Antiviral Therapy 2007;12Suppl 2:L322. Marin A et al. Qual Life Res. 2006;15:767–775
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Implications of lipoatrophy
• Psychological effects / quality of life1
– ↓ self-confidence, self-esteem
– anxiety / depression2
• Social effects3,4
– social alienation
– difficulty finding clothing
– impaired quality social relationships (OR 0.38)
• Sexual dysfunction5
• Decreased adherence6-7
• Physical effects (e.g. discomfort while sitting)
3. Santos CP et al. AIDS. 2005;19(suppl 4):S14–S214. Collins E et al. AIDS Read. 2000;10:546–551
Implications of lipoatrophy
• Psychological effects / quality of life1
– ↓ self-confidence, self-esteem
– anxiety / depression2
• Social effects3,4
– social alienation
– difficulty finding clothing
– impaired quality social relationships (OR 0.38)
• Sexual dysfunction5
• Decreased adherence6-7
• Physical effects (e.g. discomfort while sitting)
5. Guaraldi G et al. Antivir Ther. 2007;12:1059–1065
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Implications of lipoatrophy
• Psychological effects / quality of life1
– ↓ self-confidence, self-esteem
– anxiety / depression2
• Social effects3,4
– social alienation
– difficulty finding clothing
– impaired quality social relationships (OR 0.38)
• Sexual dysfunction5
• Decreased adherence6-7
• Physical effects (e.g. discomfort while sitting)
6. Duran S et al. AIDS. 2001;15:2441–24447. Ammassari A et al. J Acquir Immune Defic Syndr. 2002;31(suppl 3):S140–S144
Treatment options for facial lipoatrophy
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Treatment options for facial lipoatrophy
• Bioabsorbable fillers - effective, temporary intervention– Collagen – bovine – 3-6 months
– Poly-L-lactic acid injections1-5 (New-Fill)
– Hyaluronic acid filler6 (Restylane, Hylaform, Juvederm)
– Calcium hydroxylapatite (Radiesse)
• Permanent fillers– Used with caution in HIV/AIDS patients due to continuing body changes
– Risk of migration, foreign body reactions, late stage infections
– Bio-Alcamid7
• Autologous fat transplant 3,8-10
– Surgical procedure, temporary, costly, low availability fat for harvest, lipohypertrophy
1. Barton SE et al. Int J STD AIDS. 2006;17:429–4352. Cattelan AM et al. Arch Dermatol. 2006;142:329–3343. Guaraldi G et al. Antivir Ther. 2005;10:753–7594. Kates LC et al. Aesthet Surg J 2008;28:397-403 5. Moyle GJ et al. HIV Med 2006;7:181-56. Skeie L et al. HIV Med 2010;11: 170-77
Treatment options for facial lipoatrophy
• Bioabsorbable fillers - effective, temporary intervention– Collagen – bovine – 3-6 months
– Poly-L-lactic acid injections1-5 (New-Fill)
– Hyaluronic acid filler6 (Restylane, Hylaform, Juvederm)
– Calcium hydroxylapatite (Radiesse)
• Permanent fillers– Used with caution in HIV/AIDS patients due to continuing body changes
– Risk of migration, foreign body reactions, late stageinfections
– Bio-Alcamid7
• Autologous fat transplant 3,8-10
– Surgical procedure, temporary, costly, low availability fat for harvest, lipohypertrophy
7. Loutfy MR et al. AIDS. 2007;21:1147–1155
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Treatment options for facial lipoatrophy
• Bioabsorbable fillers - effective, temporary intervention– Collagen – bovine – 3-6 months
– Poly-L-lactic acid injections1-5 (New-Fill)
– Hyaluronic acid filler6 (Restylane, Hylaform, Juvederm)
– Calcium hydroxylapatite (Radiesse)
• Permanent fillers– Used with caution in HIV/AIDS patients due to continuing body changes
– Risk of migration, foreign body reactions, late stage infections
– Bio-Alcamid7
• Autologous fat transplant 3,8-10
– Surgical procedure, temporary, costly, low availability fat for harvest, lipohypertrophy
3. Guaraldi G et al. Antivir Ther. 2005;10:753–759 8. Guaraldi G et al Ann Intern Med. 2009 ;150:61-3. 9. Levan P et al. AIDS. 2002; 16:1985-8710. Cohen et al. J Drugs Dermatol. 2009; 8:486-9
Ideal injectable
• Safe & effective
• Approved (CE mark, FDA)
• Biodegradable/ bioresorbable
• Longer-lasting result
• Non animal origin
• No skin test required
• Cost effective
• Easy to use / store
• Widely available
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New-fill®
• Class III medical device (PLA)
• Highly bio-compatible
• Safety profile well documented
• Used for ∼30 years in medicine
– skull & facial reconstructive surgery
– tissue regeneration
– resorbable implants, screws - orthopaedics
– resorbable sutures - ophthalmics, neurosurgery
– carrier for slow release medication (prostate cancer)
– encapsulation of vaccines
Mechanisms of action
Dual Mechanism:
– immediate mechanical action - related to volume
– delayed reaction - formation of new collagen, persists despite
resorption of P.L.A. particles
– micro particles (diameter 40µ-63µ), held in gel suspension
– <10µ phagocytosis, <30µ dispersed into capillaries, >100µ
difficult to inject
Duration of Stimulus– biodegradation (approx. 24 months, based on clinical response)
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Complications of New-fill ® - rare
Early• Swelling, erythema, bruising
• Blanching / vasoconstriction
– related to lignocaine?
– generally transient, painless
• Infection
– no cases infection identified by
C&W, Brighton, St Thomas’s &
Harley Street practices
Late• Nodules
– incorrect technique– less common with more dilute
suspension– initially 3mls; now up to 8mls– 31% cases in early studies,
now <1%
• Late stage granulomas– non-allergic immunological
phenomenon– intra-lesional steroid injection
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Practicalities of setting up a New-fill® Clinic
What’s involved?
Lou Kerr
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Approximate size of required cohort
Estimated incidence of facial lipoatrophy – 30-40% with >50% fat loss i.e. clinically significant
How many likely to need New-fill®? 10% looking at bigger cohorts
Estimated need to do 6 treatments / month to maintain competencies(average number treatments per patient = 4)
Equivalent of ~ 20 individual patient referrals each year
Individual cohort Part of network
Royal College of Nursing Competencies
• An integrated career and
competence framework for
nurses working with HIV-
associated facial lipoatrophy in
adults
• Minimum number of patients to
be treated per month to
maintain skills = 6
http://www.rcn.org.uk/__data/assets/pdf_file/0019/255322/003537.pdf
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Approximate size of required cohort
Estimated incidence of facial lipoatrophy – 30-40% with >50% fat loss i.e. clinically significant
How many likely to need New-fill®? 10% looking at bigger cohorts
Estimated need to do 6 treatments / month to maintain competencies(average number treatments per patient = 4)
Equivalent of ~ 20 individual patient referrals each year
Individual cohort Part of network
Approximate size of required cohort
Incidence lipodystrophy 30-40% 1,000 patients
5-10% take up New-fill® for facial lipoatrophy15-30 patients
300 patients
Average 4 treatments each60-120 treatments per year
5-10 per month
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Clinic referrals
• Important to have clear referral pathway
• Patients registered at clinic for >6
months – prevent clinic hopping to
access treatment
• Be on or has been on HAART
• Referred by clinic doctors / clinician
• Importance of having ‘gate keepers’
Patient referral criteria
• Moderate to severe atrophy – physical / psychological
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Patient referral criteria
• Very few contra-indications
– pregnancy, lidocaine allergy
• Cautions
– haemophilia – ensure good control (extra factor VIII), more dilute
product (less traumatic / less viscous)
– individuals prone to keloid scarring
– on high dose steroids / other medical immunosuppression
– acute skin conditions
• Agree to photos
Who’s going to deliver the service
• Some degree of dexterity /
good aesthetic eye
• Aesthetics practitioner / HIV /
dermatology / plastic surgeon
• Need for an assistant?
• Doctor vs registered nurse
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Registered Nurses
• Lidocaine - prescription only medn
– prescribers course for nurses
– formatted prescription
– Patient Group Directions (PGDs)
• Band 6 or above
– extended scope of practice
– Trust policy & role definition
– vicarious liability / private insurance
– 5hs/fortnight - £3220 (incl. on-costs)
• Sanofi–Aventis approval
• Assistant – HCA?
Doctors
• All can prescribe
• No differences in adverse events vs nurses4
• Insurance – need to inform defence union but covered by Trust indemnity for NHS work
• Sanofi – Aventis approval
• Work with an assistant – HCA/RN?
4. Enrique Castro Sanchez, 2007, Mortimer Market Centre, London
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Training process
Advance practitioner/ trainer status
Observation of practice of advanced practitioner & theoretical training
Supervised practice – 4-6 sessions, mixture of new patients / top-ups
Competency based practice assessment by advanced practitioner -endorsed by Sanofi-Aventis
Independent practiceSkills maintenance (6 treatments / month)
Peer & network support
Training process
Advance practitioner/ trainer status
Observation of practice of advanced practitioner & theoretical training
Supervised practice – 4-6 sessions, mixture of new patients / top-ups
Competency based practice assessment by advanced practitioner -endorsed by Sanofi-Aventis
Independent practiceSkills maintenance (6 treatments / month)
Peer & network support
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Training process
Advance practitioner/ trainer status
Observation of practice of advanced practitioner & theoretical training
Supervised practice – 4-6 sessions, mixture of new patients / top-ups
Competency based practice assessment by advanced practitioner -endorsed by Sanofi-Aventis
Independent practiceSkills maintenance (6 treatments / month)
Peer & network support
Training process
Advance practitioner/ trainer status
Observation of practice of advanced practitioner & theoretical training
Supervised practice – 4-6 sessions, mixture of new patients / top-ups
Competency based practice assessment by advanced practitioner -endorsed by Sanofi-Aventis
Independent practiceSkills maintenance (6 treatments / month)
Peer & network support
18
Training process
Advance practitioner/ trainer status
Observation of practice of advanced practitioner & theoretical training
Supervised practice – 4-6 sessions, mixture of new patients / top-ups
Competency based practice assessment by advanced practitioner -endorsed by Sanofi-Aventis
Independent practiceSkills maintenance (6 treatments / month)
Peer & network support
Training process
Advance practitioner/ trainer status
Observation of practice of advanced practitioner & theoretical training
Supervised practice – 4-6 sessions, mixture of new patients / top-ups
Competency based practice assessment by advanced practitioner -endorsed by Sanofi-Aventis
Independent practiceSkills maintenance (6 treatments / month)
Peer & network support
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Competency documents for nurses
Sanofi-Aventis support
• Comprehensive training manual
• DVD
• Patient information leaflets & after care
• Support from local representatives
• Theoretical training
• Updates (but often aimed at aesthetic nurses)
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Administrative issues
• Secretarial – system for sending
appointments
• Finance– invoicing
– chasing up unpaid bills
• Database– often maintained by clinician
Audit
• Total referral – new vs top-up
• Adverse events
– asymmetry
– bruising
– nodules / granulomas,
– infection
• Pre & post photos
• Waiting times
• Patient satisfaction survey – provides evidence of service value
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Odile Brennan
• Where existing NewFill services are-map
• Models for service delivery – e-questionnaire
• Changing patient profile - how service requirements
have changed over last 8 yrs
• Funding of service - capping/rationing
• Standard costs
• Contact details and USB sticks
Map of existing UK services
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• E- questionnaire – (75%) return.
• 25 existing services • All services 4-5 yrs old• Average clinic No – 1 x wk • 2-4 patient appointments per week• Practitioners – doing 8-16 treatments per month• Ratio of new to top-up patient – 1:3
Models for service delivery
Changing patient profile
• New patients are decreasing and are mild to moderate in severity
• Increasing numbers of repeats or top-ups
• Extreme variation in the duration of patient perceived result (12-36 months!) – some don’t need it ever again...
• Some patients have had treatment privately before with a variable or unknown protocol or had other types of facial fillers or permanent implants
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Funding of services
• Own in-house service
• Regional Networks - feeding to main trust clinics,
• Individual case funding - reimbursement from PCT
• Private treatment – paid for by patient (more expensive!)
• Capping/rationing – for sustainability
Approximate cost of standard 4 treatments within NHS
• Newfill - £282 per box inc VAT
• Equipment £4• Staff cost £50• Admin. Charge
• TOTAL
• £1128
• £16• £200• £50
• £1394
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Sharron Brown
Treatment Challenges
• Nodules and their management
• Presence of permanent implants
• Presence of facial hypertrophy
• Lipoatrophy and ageing
• Female sex
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Management of nodules
• Best way to avoid nodules
• Dilution 7-8mls
• Reconstitution 24-72hrs
• Injection Technique
• Time between treatment sessions
1. Fitzgerald R. Advanced Techniques for Sculptra J Drugs Dermatol. 2009;8(4);S17-S202. Vleggaar D. Facial Volumetric Correction with poly-L-lactic Acid. Dermatol Surg. 2005;31(11Pt 2 ) 1511-15173. Sculptra poly-L-lactic acid. Physician Introductory Training Workbook UK 7/2008
Management of nodules
• Most nodules are non- visible & may resolve spontaneously 1,2
• Published advise from Dr D Veglaar states if nodule is visible to subcise the nodule using a 26G needle then inject with sterile saline to break it down then massage area 2
• ASDS Guidelines of care for Injectable Fillers recommends if nodules or less commonly, foreign body granulomas, are present these may be broken down injecting sterile saline with a 26G needle and intralesional steroids 3
1. Fitzgerald R. Advanced Techniques for Sculptra J Drugs Dermatol. 2009;8(4);S17-S202. Vleggaar D. Facial Volumetric Correction with poly-L-lactic Acid. Dermatol Surg. 2005;31(11Pt 2 ) 1511-15173. Sculptra poly-L-lactic acid. Physician Introductory Training Workbook UK 7/2008
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MORE COMPLICATIONS
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Autologus Fat Transfer
Facial lipohypertrophy
• Body disfigurement
• Limited range of upper
extremity and neck motion
• Neck & back discomfort
• Difficulty with sleep
including sleep-study-
confirmed obstructive sleep
apnoea
• Excess subcutaneous
and / or visceral fat,
lipomas
• Dorsocervical (buffalo
hump)
• Submental, lateral and
anterior neck, pre
parotid
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Lipohypertrophy: remove extra volume!
• Ultrasonic assisted liposelection with Vaser• Lipectomy• Facelift, necklift
(N=135) (N=64)(N=138)
% o
f pat
ient
s
0
4
8
12
16
20
<40 yr 40–49 yr >50 yr
HIV-positive patients with moderate to severe lipoa trophy (N=337) at a median of 20 months of follow-up
Lichtenstein KA et al. J Acquir Immune Defic Syndr. 2003;32:48–56
Age
Lipoatrophy prevalence increases with age
10.1
13.3
18.8
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Brown T. Approach to the Human Immunodeficiency Virus-Infected Patient with Lipodystrophy.. The Journal of Clinical Endocrinology and Metabolism,Aug 200893 (8):2937=2945
LIPOATROHPY• Multiple facial shadows sometimes with accentuated facial folds• Sunken temples and cheeks• Protruding facial musculature and bony landmarks
PreDuring Post
3D Surface Imaging
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Question & answer session
Question & answer session
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Learning points
• ↓ incidence drug-induced facial lipoatrophy
• ↑ incidence age related changes
• Following thorough training - Newfill® excellent treatment for facial
lipoatrophy
• Maintenance of competence essential
• Most cases straight forward – minority are complex
• 3 models of service - need to decide which suits your cohort
– set-up own clinic
– work as part of regional HIV network
– feed into national expertise with PCT approval (NHS / private sector)