wally r. smith, md professor, division of general internal medicine principal investigator vcu basic...

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Wally R. Smith, MD Wally R. Smith, MD Professor, Division of General Internal Medicine Professor, Division of General Internal Medicine Principal Investigator Principal Investigator VCU Basic and Translational Research Program in Sickle Cell Disease VCU Basic and Translational Research Program in Sickle Cell Disease VCU Sickle Cell Disease Outcomes Research Center, SCD Clinical VCU Sickle Cell Disease Outcomes Research Center, SCD Clinical Research Network Research Network Scientific Director Scientific Director VCU Center on Health Disparities VCU Center on Health Disparities Sickle Cell and Pain Sickle Cell and Pain Management: A New Era Management: A New Era

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Wally R. Smith, MDWally R. Smith, MDProfessor, Division of General Internal MedicineProfessor, Division of General Internal Medicine

Principal Investigator Principal Investigator VCU Basic and Translational Research Program in Sickle Cell VCU Basic and Translational Research Program in Sickle Cell

DiseaseDiseaseVCU Sickle Cell Disease Outcomes Research Center, SCD VCU Sickle Cell Disease Outcomes Research Center, SCD

Clinical Research NetworkClinical Research NetworkScientific DirectorScientific Director

VCU Center on Health Disparities VCU Center on Health Disparities

Sickle Cell and Pain Sickle Cell and Pain Management: A New EraManagement: A New Era

Chronic Chronic Palliative/Symptomatic Palliative/Symptomatic

TherapyTherapy• FolateFolate• Opioids--Short and long-actingOpioids--Short and long-acting• Non-steroidals, other analgesicsNon-steroidals, other analgesics• Local therapyLocal therapy

– HeatHeat– MassageMassage– TENSTENS

• Coping, psychosocial, holistic Coping, psychosocial, holistic interventionsinterventions

• Case managementCase management

SmithSmith’’s Hypothesess Hypotheses• Pain phenotype transformation to mixed phenotype Pain phenotype transformation to mixed phenotype

– in some patients in some patients – From acute-on-chronic, multi-local inflammatory pain From acute-on-chronic, multi-local inflammatory pain – to also central and/or peripheral neuropathic pain to also central and/or peripheral neuropathic pain – due to acute-on-chronic vaso-occlusion, inflammation, and ischemia, resulting in central or local due to acute-on-chronic vaso-occlusion, inflammation, and ischemia, resulting in central or local

neuronal damageneuronal damage– A threshold of ischemic necrosis of neurons, before phenotype transformationA threshold of ischemic necrosis of neurons, before phenotype transformation

• SCD ischemic neuropathy may share common SCD ischemic neuropathy may share common mechanisms with other neuropathic pain mechanisms with other neuropathic pain syndromessyndromes

• Opioid, non-opioid chemical, and other approaches Opioid, non-opioid chemical, and other approaches may improve pain in SCDmay improve pain in SCD

• By far, the best approach to SCD pain is By far, the best approach to SCD pain is interruption of sickle cell vasculopathy in childhoodinterruption of sickle cell vasculopathy in childhood

Nociceptive PainNociceptive Pain

• a noxious stimulus-detecting sensory system. …an alarm mediated by high-threshold …primary sensory neurons that feed into nociceptive pathways of the central nervous system …. tuned to respond to intense thermal or mechanical stimuli as well as exogenous and endogenous chemical mediators

– Costigan M, Scholz J, Woolf CJ. Neuropathic pain: Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1-32. damage. Annu Rev Neurosci. 2009;32:1-32. Review. PubMed PMID: 19400724; PubMed Review. PubMed PMID: 19400724; PubMed Central PMCID: PMC2768555.Central PMCID: PMC2768555.

Inflammatory PainInflammatory Pain• This pain occurs in response to

tissue injury and the subsequent inflammatory response. Here the imperative shifts from protecting the body against a potentially damaging noxious stimulus to addressing the consequences of damage. To aid healing and repair of the injured body part, the sensory nervous system undergoes a profound change in its responsiveness; normally innocuous stimuli now produce pain and responses to noxious stimuli are both exaggerated and prolonged.

– Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1-32. Review. damage. Annu Rev Neurosci. 2009;32:1-32. Review. PubMed PMID: 19400724; PubMed Central PMCID: PubMed PMID: 19400724; PubMed Central PMCID: PMC2768555.PMC2768555.

The Neuropathic Pain The Neuropathic Pain PhenotypePhenotype

• After nerve injury maladaptive changes After nerve injury maladaptive changes can occur in can occur in injured sensory neurons and along the entire nociceptive injured sensory neurons and along the entire nociceptive pathway within the CNS, which may lead pathway within the CNS, which may lead to spontaneous to spontaneous pain or pain hypersensitivitypain or pain hypersensitivity. The resulting neuropathic . The resulting neuropathic pain syndromes present as a complex combination of negative pain syndromes present as a complex combination of negative and positive symptoms, which vary enormously from and positive symptoms, which vary enormously from individual to individual. This variation depends on a diversity individual to individual. This variation depends on a diversity of underlying pathophysiological changes resulting from the of underlying pathophysiological changes resulting from the convergence of etiological, genotypic, and environmental convergence of etiological, genotypic, and environmental factors. factors.

• The pain phenotype can serve therefore, as a window The pain phenotype can serve therefore, as a window on underlying pathophysiological neural mechanisms on underlying pathophysiological neural mechanisms and as a guide for developing personalized pain and as a guide for developing personalized pain medicine.medicine.

– 1: von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012 Feb 1: von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012 Feb 23;73(4):638-52. Review. PubMed PMID: 22365541; PubMed Central PMCID: PMC3319438.23;73(4):638-52. Review. PubMed PMID: 22365541; PubMed Central PMCID: PMC3319438.

Pain Phenotype Transition in Pain Phenotype Transition in SCDSCD

SmithSmith’’s Hypotheses—Level of s Hypotheses—Level of SupportSupport1.1. Sickle cell pain may in some patients transform from purely Sickle cell pain may in some patients transform from purely

acute-on-chronic, multi-local inflammatory pain to also acute-on-chronic, multi-local inflammatory pain to also central and/or peripheral neuropathic pain (phenotype central and/or peripheral neuropathic pain (phenotype transformation)transformation)

2.2. The phenotype transformation occurs due to acute-on-The phenotype transformation occurs due to acute-on-chronic vaso-occlusion, inflammation, and ischemia, chronic vaso-occlusion, inflammation, and ischemia, resulting in central or local neuronal damageresulting in central or local neuronal damage

3.3. A threshold of ischemic necrosis of neurons must be A threshold of ischemic necrosis of neurons must be reached, likely during late childhood, before phenotype reached, likely during late childhood, before phenotype transformation in SCDtransformation in SCD

4.4. Sickle cell disease ischemic neuropathy may share common Sickle cell disease ischemic neuropathy may share common mechanisms with other neuropathic pain syndromesmechanisms with other neuropathic pain syndromes

5.5. Phenotype transformation manifests as both inflammatory Phenotype transformation manifests as both inflammatory pain and neuropathic pain—a mixed phenotypepain and neuropathic pain—a mixed phenotype

6.6. Thus, opioid, non-opioid chemical, and other approaches Thus, opioid, non-opioid chemical, and other approaches may improve pain in SCDmay improve pain in SCD

7.7. Opioid-induced hyperalgesia is a minor component of pain in Opioid-induced hyperalgesia is a minor component of pain in SCDSCD

8.8. By far, the best approach to SCD pain is interruption of sickle By far, the best approach to SCD pain is interruption of sickle cell vasculopathy in childhoodcell vasculopathy in childhood

• 1 Pain chronicity manifests over time 1 Pain chronicity manifests over time • 1 Etiology of chronic pain not 1 Etiology of chronic pain not

etiologically distinguishable using current etiologically distinguishable using current data (1 study) data (1 study)

• 1, 2,3 Acute pain fluctuations continue 1, 2,3 Acute pain fluctuations continue throughout life, supporting.throughout life, supporting.

• 4-Pain Locations multiple, somewhat 4-Pain Locations multiple, somewhat bilateral, pain descriptors often bilateral, pain descriptors often neuropathicneuropathic

• 5-No data5-No data

• 6-Weak, correlational support for 6a6-Weak, correlational support for 6a

• 7-Data not conclusive-correlational7-Data not conclusive-correlational• 8-Rel8-Rel’’.of sev. of SCD pain to sev. of .of sev. of SCD pain to sev. of

vasculopathy (response to HU, vasculopathy (response to HU, transplantation, geography of residence, transplantation, geography of residence, and seasonal temperature/climate and seasonal temperature/climate changes).changes).

Above water

Submerged

Pain Intensity On Crisis Vs Non-Pain Intensity On Crisis Vs Non-crisis Vs. Utilization Dayscrisis Vs. Utilization Days

*Percentage of days. Utilization= utilization with or without crisis or pain; Crisis= crisis without utilization; Pain= pain without crisis or utilization

Adapted from Smith WR, et. al. Ann Intern Med 2008 Jan 15, 148(2):94-101

39.3%

44.1%

13.1%

3.5%

Intensity Mean Std Dev

Utilization

6.5 2.3

Crisis w/o utilization 5.5 2.1

Pain w/o crisis, util. 4.2 2

No Pain 0 0

Acute Nociceptive, Inflammatory Pain Likely Hierarchy of Sub Acute Nociceptive, Inflammatory Pain Likely Hierarchy of Sub BiologiesBiologies

Acute Acute sicklingsickling

Acute Acute deoxygenationdeoxygenation

Acute Temperature Acute Temperature change (cold climate, change (cold climate, wind speed)wind speed)Barometric pressure Barometric pressure changechangeOxygen delivery Oxygen delivery change (infection, change (infection, other)other)

Acute Acute Hemolysis, Hemolysis, free Hb, NO free Hb, NO depletiondepletion

Acute Vaso-Acute Vaso-occlusion, occlusion, ischemiaischemia

CHRONIC CHRONIC PAINPAIN

Acute Vaso-Acute Vaso-constrictionconstriction

Acute inflammation, Acute inflammation, Fig. (1). Probable hierarchy of the major sub-biologies participating in development of sickle vasculopathy. Modified from Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT; Vasculopathy in Sickle Cell Disease: Biology, pathophysiology, genetics, translational medicine and newresearch directions. [Meeting Report] Am. J. Hematol., 2009.

Reperfusion Reperfusion Injury Injury PhysiologyPhysiology

InflammationInflammation

Macrophage & Macrophage & immune Activationimmune Activation

Oxidant generationOxidant generation

NO depletionNO depletion

Coagulation Coagulation activationactivation

Endothelial activationEndothelial activation

Vascular Vascular stasis stasis

RBC RBC sicklingsickling

Hemolysis, Hemolysis,

Chronic Nociceptive, Inflammatory Pain Likely Hierarchy of Sub Chronic Nociceptive, Inflammatory Pain Likely Hierarchy of Sub BiologiesBiologies

ENVIRONMENTALENVIRONMENTAL SYSTEMS BIOLOGYSYSTEMS BIOLOGY

ACUTE ACUTE PAINPAIN

Acute Acute sicklingsickling

SYSTEMS BIOLOGYSYSTEMS BIOLOGY

Contributors to Inflammation of Contributors to Inflammation of SCDSCD

• ↑ ↑ number of granulocytes & monocytes in bloodnumber of granulocytes & monocytes in blood• ↑ ↑ activation of granulocytes and monocytesactivation of granulocytes and monocytes• activated phenotype of circulating endothelial cells (pro-adhesive, activated phenotype of circulating endothelial cells (pro-adhesive,

procoagulant, pro-oxidative)procoagulant, pro-oxidative)• ↑ ↑ soluble VCAM and P-selectinsoluble VCAM and P-selectin• activation of the coagulation systemactivation of the coagulation system• ↑ ↑ levels of inflammatory mediators (e.g., IL6, CRP, TNFα, IL1β)levels of inflammatory mediators (e.g., IL6, CRP, TNFα, IL1β)• ↑ ↑ levels of acute phase reactants (e.g., CRP, phospholipase-A2, ferritin)levels of acute phase reactants (e.g., CRP, phospholipase-A2, ferritin)• ↑ ↑ levels of endothelial cell perturbants *levels of endothelial cell perturbants *• ↑ ↑ microparticles from monocytes, platelets, endothelial cells, red cells. microparticles from monocytes, platelets, endothelial cells, red cells.

sickle mice have an inflammatory statesickle mice have an inflammatory state– * which include, but are not limited to: hypoxia, thrombin, IL2, IL4, IL8, endotoxin,TGF* which include, but are not limited to: hypoxia, thrombin, IL2, IL4, IL8, endotoxin,TGFβ, β,

thrombospondin, G-CSF, GM-CSF,endothelin-1, 12-HETE, peroxynitrite, serum amyloid a, PGE2, thrombospondin, G-CSF, GM-CSF,endothelin-1, 12-HETE, peroxynitrite, serum amyloid a, PGE2, fibrinogen, leukotriene B4, homocysteine, CD40 Ligandfibrinogen, leukotriene B4, homocysteine, CD40 Ligand

• Robert P. Hebbel, Greg M. Vercellotti and Karl A. Nath. A Systems Biology Consideration of the Vasculopathy of Sickle Cell Anemia: Robert P. Hebbel, Greg M. Vercellotti and Karl A. Nath. A Systems Biology Consideration of the Vasculopathy of Sickle Cell Anemia: The Need for Multi-Modality Chemo-Prophylaxis. Cardiovascular & Haematological Disorders-Drug Targets, 2009, 9, 271-292 The Need for Multi-Modality Chemo-Prophylaxis. Cardiovascular & Haematological Disorders-Drug Targets, 2009, 9, 271-292

Replacement By Donor Derived Replacement By Donor Derived Red Cells Allows Tapering Of Red Cells Allows Tapering Of OpioidsOpioids

• Takes weeksTakes weeks– Data, courtesy Tisdale, et al. Data, courtesy Tisdale, et al.

Pain Locations in PiSCESPain Locations in PiSCES

• 201 subjects had:201 subjects had:– more than 5 days with pain >0more than 5 days with pain >0– body locator boxes endorsed body locator boxes endorsed

• 15,563 patient-days of body locator 15,563 patient-days of body locator chart information analyzedchart information analyzed

• On these days:On these days:– an average of 11.3% of boxes were checked an average of 11.3% of boxes were checked

• (analyses of % boxes checked not shown)(analyses of % boxes checked not shown)

– an average of 3.3 of 16 sites (21%) were an average of 3.3 of 16 sites (21%) were painfulpainful

No Association of No Association of Predominant Bilaterality Predominant Bilaterality

With:With:• GenderGender• AgeAge• GenotypeGenotype

– SS vs SCSS vs SC

• Calendar Seasons Calendar Seasons – Warm (April-Sept) vs Cold Warm (April-Sept) vs Cold

(Oct-March) seasons (Oct-March) seasons • Although intensity of pain and frequency of Although intensity of pain and frequency of

pain higher in colder monthspain higher in colder months

Mean Pain Intensity on Pain Days (SD)*

Percent Pain Days (SD)+

4.8 (1.5) 81.9 (25.4)

4.1 (1.4) 51.9 (35.3)

3.0 (1.2) 16.8 (23.3)

2.8 (2.0) 12.3 (30.9)

LA=long-acting, SA=Short-acting.*Mean pain on pain days, overall ANOVA p<0.0001. All paired comparisons statistically significant except none vs non-opioid and none vs SA opioid. + Percent pain days, overall ANOVA p<0.0001. All paired comparisons statistically significant except none vs. non-opioid

Relationship of Pain to Opioid Relationship of Pain to Opioid UseUse

• Fewer (38.8%) used LA opioids (w or w/o other analgFewer (38.8%) used LA opioids (w or w/o other analg’’s) s) than used SA (47.0% w or w/o non-opioids)than used SA (47.0% w or w/o non-opioids)

• 9.6% only non-opioid, 4.6% none analgesics 9.6% only non-opioid, 4.6% none analgesics • Pain intens, freq higher with LA or higher total opioidPain intens, freq higher with LA or higher total opioid

Opioid Use and SCD Lab, Pain Opioid Use and SCD Lab, Pain ComplicationsComplications

N Number (%) of subjects who use opioids (n=188)

Number (%) of subjects who do not use opioids (n=31)

p-value comparing opioid users and non-users

Hydroxyurea user 0.0013 Yes 59 58 (98.3) 1 (1.7) No 160 130 (81.2) 30 (18.8) Ankle Ulcers 0.3385 Yes 26 24 (92.3) 2 ( 7.7) No 192 164 (85.4) 28 (14.6) Avascular Necrosis

0.0871

Yes 48 45 (93.7) 3 ( 6.3) No 170 143 (84.1) 27 (15.9)Priapism (males only)

0.8912

Yes 15 13 (86.7) 2 (13.3) No 68 58 (85.3) 10 (14.7)Lab values (means)

N Mean (SD) for opioid user

Mean (SD) for those not using opioid

P value comparing opioid users and non-users

%Fetal Hemoglobin

180 3.9 (7.2) 4.1 (7.3) 0.8955

White Blood Count

158 11.2 (4.5) 10.5 (4.3) 0.4913

Pain Management in Pain Management in SCD: The New EraSCD: The New Era

•HydroxyureaHydroxyurea•Non-opioid neuropathic agentsNon-opioid neuropathic agents•Anti-sickling medicationsAnti-sickling medications

– Anti-inflammatories/Selectin InhibitorsAnti-inflammatories/Selectin Inhibitors– Amino AcidsAmino Acids– Platelet inhibitorsPlatelet inhibitors– Hb-O2 Covalent BindersHb-O2 Covalent Binders

HydroxyureaHydroxyurea• Only FDA approved anti-sickling medicationOnly FDA approved anti-sickling medication• It helps make fetal hemoglobin (Hb F, baby’s It helps make fetal hemoglobin (Hb F, baby’s

hemoglobin) within the red cellshemoglobin) within the red cells• This stops abnormal hemoglobin strands, This stops abnormal hemoglobin strands,

decreases sicklingdecreases sickling• Hydroxyurea makes the red cells healthierHydroxyurea makes the red cells healthier• 50% reduction in hospitalization50% reduction in hospitalization• 40% improved mortality40% improved mortality• Also drops the white blood cell countAlso drops the white blood cell count

– Major side effectMajor side effect– Sometimes too lowSometimes too low

Hydroxyurea –approved Hydroxyurea –approved for SCD 1996for SCD 1996

• Ribonucleotide reductase inhibitor Ribonucleotide reductase inhibitor • Reduces cell division during S-Reduces cell division during S-

phasephase• Inhibits RNA and protein synthesis Inhibits RNA and protein synthesis • Metabolized to genotoxic products Metabolized to genotoxic products

– Potential for adverse effectsPotential for adverse effects• Timson J. Hydroxyurea. Timson J. Hydroxyurea. Mutat ResMutat Res 1975; 1975;

32(2):115-132.32(2):115-132.

Hydroxyurea-- Reduction Hydroxyurea-- Reduction in:in:

– Acute painful episodesAcute painful episodes– Acute chest syndrome eventsAcute chest syndrome events– Hospitalizations Hospitalizations – Blood transfusionsBlood transfusions

• Charache S, Terrin ML, Moore RD, Dover GJ, McMahon RP, Charache S, Terrin ML, Moore RD, Dover GJ, McMahon RP, Barton FB et al. Design of the multicenter study of hydroxyurea Barton FB et al. Design of the multicenter study of hydroxyurea in sickle cell anemia. in sickle cell anemia. Controlled Clin TrialsControlled Clin Trials 1995; 16:432-446. 1995; 16:432-446.

• Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV et al. Effect of hydroxyurea on the frequency of painful SV et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. crises in sickle cell anemia. N Engl J MedN Engl J Med 1995; 332:1317-1322. 1995; 332:1317-1322.

– Costs of careCosts of care• Moore RD, Charache S, Terrin ML, Barton FB, Ballas SK, Moore RD, Charache S, Terrin ML, Barton FB, Ballas SK,

Investigators of the MUlticenter Study of Hydroxyurea in Sickle Investigators of the MUlticenter Study of Hydroxyurea in Sickle cell Anemia. Cost-effectiveness of hydroxyurea in sickle cell cell Anemia. Cost-effectiveness of hydroxyurea in sickle cell anemia. anemia. Am J HematolAm J Hematol 2000; 64:26-31. 2000; 64:26-31.

Hydroxyurea: Increase Hydroxyurea: Increase in:in:

• Fetal hemoglobin (HbF)Fetal hemoglobin (HbF)– Steinberg MH, Lu Z-H, Barton FB, Terrin ML, Charache S, Dover GJ et al. Fetal Steinberg MH, Lu Z-H, Barton FB, Terrin ML, Charache S, Dover GJ et al. Fetal

hemoglobin in sickle cell anemia: Determinants of response to hydroxyurea. hemoglobin in sickle cell anemia: Determinants of response to hydroxyurea. BloodBlood 1997; 89:1078-1088. 1997; 89:1078-1088.

• Physical capacityPhysical capacity– Hackney AC, Hezier W, Gulledge TP, Jones S, Strayhorn D, Busby M et al. Effects Hackney AC, Hezier W, Gulledge TP, Jones S, Strayhorn D, Busby M et al. Effects

of hydroxyurea administration on the body weight, body composition and of hydroxyurea administration on the body weight, body composition and exercise performance of patients with sickle-cell anaemia. exercise performance of patients with sickle-cell anaemia. Clin SciClin Sci 1997; 1997; 92:481-486.92:481-486.

• Quality of lifeQuality of life– Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH et al. Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH et al.

Hydroxyurea and sickle cell anemia: effect on quality of life. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Health Qual Life OutcomesOutcomes 2006; 4:59. 2006; 4:59.

• Survival (40% reduction in mortality) Survival (40% reduction in mortality) – Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A et al. Effect Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A et al. Effect

of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. benefits up to 9 years of treatment. JamaJama 2003; 289(13):1645-1651. 2003; 289(13):1645-1651.

Ship HUShip HUEnhancing Use of Hydroxyurea in Enhancing Use of Hydroxyurea in Sickle Cell Disease Using Patient Sickle Cell Disease Using Patient

Navigators Navigators R18HL11273R18HL11273

77 Funded byFunded by

National Heart National Heart Lung and Lung and Blood Blood InstituteInstitute

Sept 2012-Sept 2012-June 2017June 2017

What does “Ship HU” What does “Ship HU” Mean?Mean?

Start healing in patients with Start healing in patients with hydroxyureahydroxyurea

Stop hemolysis in patients with Stop hemolysis in patients with hydroxyureahydroxyurea

Stop hurting in patients with Stop hurting in patients with hydroxyurea hydroxyurea 

SHIP HU: Specific Aim 1SHIP HU: Specific Aim 1

Demonstrate the feasibility of a Demonstrate the feasibility of a patient patient navigatornavigator-based program to -based program to improve the improve the percentage percentage of adult (age 15 and older) of adult (age 15 and older) patients with sickle cell disease (SCD) in the patients with sickle cell disease (SCD) in the Richmond and Tidewater regions of Virginia Richmond and Tidewater regions of Virginia who are in SCD specialty carewho are in SCD specialty care..

SHIP HU: Specific Aim 2SHIP HU: Specific Aim 2

Demonstrate the effectiveness of a patient Demonstrate the effectiveness of a patient navigator-based program to navigator-based program to improve improve hydroxyurea hydroxyurea (HU) (re-) (HU) (re-) initiation and initiation and adherence adherence among adult patients with SCD in among adult patients with SCD in the Richmond and Tidewater regions of Virginia the Richmond and Tidewater regions of Virginia who are eligible for HU.who are eligible for HU.

Overall Justification of Ship Overall Justification of Ship HUHU

• Hydroxyurea (HU) may be life-Hydroxyurea (HU) may be life-saving and should be given to saving and should be given to eligible SCD patients.eligible SCD patients.

• Specialists prescribe Specialists prescribe Hydroxyurea to SCD patients Hydroxyurea to SCD patients

• Large % SCD patients not in Large % SCD patients not in SCD specialty care, barriers to SCD specialty care, barriers to care. care.

What is a Patient What is a Patient Navigator?Navigator?

• Lay member of a community Lay member of a community – worksworks either for pay or as a volunteer in either for pay or as a volunteer in

association with the local health care association with the local health care system. system.

– sharesshares ethnicity, language, socioeconomic ethnicity, language, socioeconomic status, and life experiences with community status, and life experiences with community members. members.

– links links community members to the medical community members to the medical care system, provide social networking, care system, provide social networking, social support, and personalized social support, and personalized interventionsinterventions

• Other termsOther terms– Community Health Advisor, Lay Health Community Health Advisor, Lay Health

Advocate, Promotor, Outreach Educator, Advocate, Promotor, Outreach Educator, Community Health Representative, Peer Community Health Representative, Peer Health Promoter, or Peer CounselorHealth Promoter, or Peer Counselor

Planned Journey of Ship Planned Journey of Ship HUHU

• Address barriers to care and to HU useAddress barriers to care and to HU use• Two-phase demonstrationTwo-phase demonstration

– Improvement in the % with SCD who are in SCD specialty Improvement in the % with SCD who are in SCD specialty care (Phase I)care (Phase I)

– Improvement in adherence to HU of eligible SCD adults Improvement in adherence to HU of eligible SCD adults (Phase II).(Phase II).

• Use existing health apparatusUse existing health apparatus– State of Virginia (VDH), two academic med. Ctr’sState of Virginia (VDH), two academic med. Ctr’s

• Use specially trained SCD patient navigators Use specially trained SCD patient navigators (PNs)(PNs)

Ship HU: Participating Ship HU: Participating ProvidersProviders

• Two adult, two pediatric Two adult, two pediatric specialty clinics specialty clinics – VCU VCU

• Pediatric clinic (15 and older)Pediatric clinic (15 and older)• Adult Clinic (17 and older)Adult Clinic (17 and older)

– EVMS/CHKDEVMS/CHKD• CHKD (15 and older, including Oyster Point CHKD (15 and older, including Oyster Point

clinic)clinic)• EVMS (17 and older)EVMS (17 and older)

Interventions to Alter Health BehaviorsInterventions to Alter Health Behaviors

Enviromental Setting

Macro-Level Sectors of Influence

Institutions

Patient-Clinician Relationship

Social Networks

Individual Factors

Biopyschosocial spriritual

Intervention Target

Law/Policy Change Environmental Setting

Advertising Macro-level Sectors of influence

Health Fair, Build Clinic, change clinic operations

Institutions

Hire Doctor or Navigator

Patient-Clinician Relationship

Family or church intervention, Facebook

Social Networks

One-to-one counseling (from Navigator, anyone), Rx

Individual Factors

Template for Regional Template for Regional Recruitment StrategyRecruitment Strategy

Intervention Target Expected Benefits Immediate Recruitment Results

Advertising (Radio, newspaper, fliers, etc.)

Macro-level influence • Awareness• Reach the “tipping point”• Find partners• Generate recruitment leads

Low

Health Fairs Institutions • Awareness• Reach the “tipping point”• Find partners• Generate recruitment leads

Low

Presentations, Events Institutions, patient social networks

• Awareness• Find partners• Generate recruitment leads• Recruit

Medium

Navigator calls, followup of leads

Social networks (of navigators)

• Find partners• Generate recruitment leads• Recruit

Medium

ED and Clinic Recruitment Social networks (of patients)

• Generate recruitment leads• Recruit

High

Church interventions Social Networks (of patients)

• Generate recruitment leads• Recruit

Medium to high

Electronic Pre-screening (Medicaid, Health Dept Records)

Individuals • Recruit High

Ways ODMS can help Ship Ways ODMS can help Ship HUHU

• Help identify clients and assist with recruitment into our Help identify clients and assist with recruitment into our

study. study. 800-828-6938800-828-6938– Send a letter to your patients on your letterhead with study Send a letter to your patients on your letterhead with study

details.details.

– Organize recruiting events at which Ship HU staff could speak .Organize recruiting events at which Ship HU staff could speak .

– Tips to Ship HU staff about how best to reach clients.Tips to Ship HU staff about how best to reach clients.

– Letters of support or other endorsements to organizations and Letters of support or other endorsements to organizations and media outlets who may advertise our study or refer clients.media outlets who may advertise our study or refer clients.