Assessment of Painful Diabetic Peripheral Neuropathy (pdpn):

Assessment of Painful Diabetic Peripheral Neuropathy (pdpn): An Essential Part of the Diabetic Foot Exam Pfizer Medical Affairs

Objectives Review the epidemiology, burden, pathophysiology, and clinical features of DPN and pdpn Review components of the comprehensive foot examination for patients with diabetes Review risk classification based on the comprehensive foot examination Review current guidelines for the screening, diagnosis, and management of DPN and pdpn Provide patient education for appropriate diabetic foot care 2

Prevalence of Diabetes in the United States Diabetes affects 30.3 million people in the US (9.4% of the population) 1 Prevalence of diabetes by age group 1 : 18-44 years: 4.6 million (4.0%) 45-64 years: 14.3 million (17.0%) 65 years: 12.0 million (25.2%) Diabetes was the 7 th leading cause of death in the US in 2015 1 Diabetes is the leading cause of kidney failure, lower-limb amputations, and adult-onset blindness in the US 2 A major cause of heart disease and stroke 2 23.8% (7.2 million) 76.2% (23.1 million) Diagnosed Undiagnosed 1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; 2017. 2. Centers for Disease Control and Prevention. At A Glance 2016 Diabetes: Working to Reverse the US Epidemic. https://www.cdc.gov/chronicdisease/resources/publications/aag/diabetes.htm. Accessed August 10, 2018. 3

Diabetes and Associated pdpn Are Prevalent 1,2 ~30.3 million Americans have diabetes 1 DPN = diabetic peripheral neuropathy pdpn = painful diabetic peripheral neuropathy Up to 15.2 million of these have DPN 2 ~6.1 million of these have pdpn 2 Up to 50% of patients with diabetes have DPN 2 ~20% of patients with diabetes have pdpn 2 1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; 2017. 2. Singh R, et al. Pharmacol Res. 2014;80:21-35. 4

Scope of the Problem

The Diabetic Foot Foot ulceration is the most frequently recognized lower extremity complication of diabetes 1 15 to 25% of people with diabetes will develop a lower extremity ulcer during the course of their disease 1 Foot ulceration is the precursor to approximately 85% of lower extremity amputations (LEAs) in people with diabetes 2 7% to 20% of patients with foot ulcers will subsequently require amputation 3 Diabetes is the main initiating factor for foot ulceration and the most common cause of nontraumatic LEA in the Western world 3 Approximately 45% to 60% of all diabetic ulcerations are purely neuropathic 1. Armstrong DG, et al. N Engl J Med. 2017;376:2367-2375. 2. Zhang P, et al. Ann Med. 2017;49:106 116 3. Clinical Practice Guideline Diabetes Panel of the American College of Foot and Ankle Surgeons. J Foot Ankle Surg. 2006;45(suppl 5):S1-S66. 6

The Diabetic Foot Patients who have chronic neuropathic pain associated with DPN are also at risk for foot ulcers and subsequent infections 1 Ritzwoller and colleagues demonstrated a higher prevalence of limb complications in pdpn patients compared to matched diabetes controls 2 : >2 times as many limb infections (P<.001) A nearly 10-fold increase in limb amputations (P<.001) Mean diabetic foot ulcer-related annual medical costs were $5,285 and $9,590 in Medicare and privately insured patients, respectively. 3 Total annual medical cost of diabetic foot ulcers ranges from $9-13 billion in addition to the costs associated with diabetes Direct and indirect costs of LEA range from $20,000 to $40,000 per event 4 1. Hartsfield CL, et al. Popul Health Manag. 2008;11(6):317-328. 2. Ritzwoller DP, et al. Curr Med Res Opin. 2009;25(6):1319-1328. 3. Rice JB, et al. Diabetes Care. 2014;37:651-658. 4. Clinical Practice Guideline Diabetes Panel of the American College of Foot and Ankle Surgeons. J Foot Ankle Surg. 2006;45(suppl 5):S1-S66. 7

pdpn Impacts Physical and Mental Health Status 1 SF-12v2 Scores for Study Subjects and Normative Groups (N=255) 60 General US Population Patients with Diabetes pdpn Patients 50 40 Mean Score 30 20 10 0 Physical Functioning Role Physical Bodily Pain General Health Vitality Social Functioning Role Emotional Mental Health SF-12v2 = Short Form Version 2 health form. Higher scores correlate to better health status. 1. Gore M, et al. J Pain Symptom Manage. 2005;30(4):374-385. 8

Relationship Between Pain Severity and Impact of pdpn on Daily Function 1 100 Mild Pain (n = 50) Moderate Pain (n = 149) Severe Pain (n = 194) Percent A Lot or Somewhat Affected 90 80 70 60 50 40 30 20 10 57% 84% 82% 42% 26% * 50% 12% * 28% 49% 34% 52% 79% * 70% 69% * * 42% 42% 20% 16% 0 1. Sadosky A, et al. Patient. 2014;7:107-114. Sleep Walk Drive Exercise Work Perform Daily Activities *P 0.05 versus mild; P 0.05 versus mild and moderate. 9

Impact of pdpn on Annual Health Care Costs 1 Excess Health Care Costs Attributable to pdpn $ 10000 $ 9000 $ 8000 $ 7000 $ 6000 $ 5000 $ 4000 $ 3000 $ 2000 $ 1000 Annual health care costs for patients with pdpn were up to $7200 higher when compared to patients with diabetes but no pdpn +$7238 +$6246 $ 0 Medstat Data IMS Data Patients with pdpn were selected from 2 different administrative databases of health care claims and matched to control subjects with a diagnosis of diabetes but no pdpn. Multivariate regression analyses were used to estimate the differences in health care costs between cases and control subjects. 1. Dworkin RH, et al. J Pain. 2010;11(4)360-368. 10

Economic Burden of pdpn Increases With Greater Pain Severity 1 $25,000 $20,000 Total Direct Costs* Total Indirect Costs** Total Cost $21,083 $16,196 $15,000 $10,000 Total Cost $14,571 $9,730 Total Cost $8,037 Total Cost $13,769 $8,916 $5,000 $0 $3,077 $4,841 $4,960 $4,853 $4,887 Overall Mild Moderate Severe * Average annualized total direct cost per pdpn subject was significantly different by pain severity (P <0.0001). Direct costs include physician visits, other healthcare provider visits, prescription medications, TENS device, outpatient tests/procedures, emergency room visits, hospital outpatient visits, hospitalizations, direct medical costs to subjects, and direct non-medical (child care, help with house and/or yard work, and help with activities of daily living) due to pdpn ** Average annualized total indirect cost per pdpn subject was significantly different by pain severity (P = 0.0003). Total indirect costs include overall work impairment, activity impairment, disability, unemployment, early retirement, and reduced work schedule due to pdpn Scores on the BPI Pain Severity Index were used to classify average pain severity as mild, moderate, or severe. 1. Sadosky A, et al. Diabetes Metab Syndr Obes. 2013; 6:79-92. 11

Health Care Costs in Patients with pdpn 1 $35,000 $30,000 ER Visits Hospitalizations $27,931 $30,755 $25,000 Office Visits Mean Cost $20,000 $15,000 Other Outpatient Prescriptions $12,492 $10,000 $6,632 $5,000 $0 Mean direct medical costs for the 12-month period after diagnosis for the subset of patients with claims data in the Optum DataMart database. Dollar values represent charges rather than actual costs to patients. Patients with DPN had a pain score of 1 for current pain that was obtained within 15 days (before or after) the DPN diagnosis; patients with severe DPN had pain scores of 7 to 10. DPN, painful DPN, and severe DPN cohorts were compared against diabetes-only cohort all comparisons were statistically significant. 1. Sadosky A, et al. J Diabetes Complicat. 2015;29:212-217. Diabetes Only DPN Painful DPN Severe Painful DPN n = 41,928 n = 5,686 n = 466 n = 260 12

Overview of pdpn

Diabetic Peripheral Neuropathy A symmetrical, length-dependent sensorimotor polyneuropathy attributable to metabolic and microvessel alterations as a result of chronic hyperglycemia exposure and cardiovascular risk covariates 1 The most common presentation of neuropathy in diabetes 2 Insidious in onset. May be present in at least 10-15% of newly diagnosed patients with type 2 diabetes. 2,3 Up to half of patients may be asymptomatic, with the diagnosis made during a routine neurological exam or when the patient presents with a painless foot ulcer 2 1. Tesfaye S, et al. Diabetes Care. 2010;33(10):2285-2293. 2. Pop-Busui R, et al. Diabetes Care. 2017;40:136-154. 3. Vinik AI, et al. Endocrinol Metab Clin N Am. 2013;42:747 787. 14

Pathophysiology of DPN DPN involves both small and large nerve fibers. Symptoms vary according to the class of sensory fibers involved. 1 Large fibers (Aα/β) 2,3 Small fibers (Aδ and C) 2-4 Results in loss of: Light touch Pressure sensation Vibration sensation Proprioception Abnormal deep tendon reflexes Gnawing or aching pain Wasting of small muscles in feet/hands Neuropathic pain Burning, shooting, electric shock-like, stabbing, prickling Allodynia Hyperalgesia Loss of pain and temperature sensation Impaired autonomic function Decreased sweating, dry skin, poor blood flow, cold feet 1. Pop-Busui R, et al. Diabetes Care. 2017;40:136-154. 2. Vinik A, et al. Endocrinol Metab Clin N Am. 2013;42:747-787. 3. Viinik A. N Engl J Med. 2016;374:1455-1464. 4. Sene D. Joint Bone Spine (2017), https://doi.org/10.1016/j.jbspin.2017.11.002. 15

Pathophysiology of DPN DPN involves both small and large nerve fibers. Symptoms vary according to the class of sensory fibers involved. 1,2 Large fibers (Aα/β) 2,3 Small fibers (Aδ and C) 2,3 Diabetic peripheral neuropathy can Neuropathic present pain as either painful, Light touch with or without sensory deficit, or pain-free and mainly characterized by sensory loss. 5 Results in loss of: Pressure sensation Vibration sensation Proprioception Abnormal deep tendon reflexes Gnawing or aching pain Wasting of small muscles in feet/hands Burning, shooting, electric shock-like, stabbing, prickling Allodynia Hyperalgesia Loss of pain and temperature sensation Impaired autonomic function Decreased sweating, dry skin, poor blood flow, cold feet 1. Pop-Busui R, et al. Diabetes Care. 2017;40:136-154. 2. Vinik A, et al. Endocrinol Metab Clin N Am. 2013;42:747-787. 3. Viinik A. N Engl J Med. 2016;374:1455-1464. 4. Sene D. Joint Bone Spine (2017), https://doi.org/10.1016/j.jbspin.2017.11.002. 5. Guastella V, et al. Diabetes Metab. 2009;35(1):12-19. 16

Duration of Diabetes and Poor Glycemic Control Increase Risk for DPN Severity of DPN correlates with duration of diabetes 1 Prevalence of DPN is related to glycemic control 2 Duration of Diabetes (Years ± SD) 26 24 22 20 18 16 14 12 10 8 6 4 2 0 10.3 (±7.7) 10.1 (±8.1) 12.4 (±8.4) 13.3 (±8.2) 0 B 1 2 3 15.6 (±9.7) Prevalence of DPN (%) 50 40 30 20 10 0 17% 24% 29% 41% < 7 7-8 8.1-9.5 >9.6 SD = standard deviation Severity of Diabetic Neuropathy A1C (%) (Adjusted for Duration of Diabetes) 1. Fedele D, et al. Diabetes Care. 1997;20(5):836-843. 2. Tesfaye S, et al. Curr Diab Rep. 2009;9(6):432-434. 17

Duration of Diabetes and Poor Glycemic Control Increase Risk for DPN Severity of DPN correlates with duration of diabetes 1 Prevalence of DPN is related to glycemic control 2 Duration of Diabetes (Years ± SD) 26 24 22 20 18 16 14 12 10 8 6 4 2 0 SD = standard deviation Although poor glycemic control is a risk factor for 40 pdpn, patients who have good glycemic control 10.3 (±7.7) 15.6 13.3 (±9.7) 30 are still 12.4 at risk for developing pdpn 2 (±8.2) 24% 10.1 (±8.4) (±8.1) 20 17% 0 B 1 2 3 Severity of Diabetic Neuropathy Prevalence of DPN (%) 50 10 0 29% 41% < 7 7-8 8.1-9.5 >9.6 A1C (%) (Adjusted for Duration of Diabetes) 1. Fedele D, et al. Diabetes Care. 1997;20(5):836-843. 2. Tesfaye S, et al. Curr Diab Rep. 2009;9(6):432-434. 18

Odds Ratios for Key Risk Factors for Development of DPN 1 3.0 2.5 1.57 2.0 1.5 1.21 1.27 1.38 1.4 1.48 1.0 0.5 0.0 Triglycerides BMI History of Smoking Duration Hemoglobin A1C Hypertension 1. Tesfaye S, et al. N Engl J Med. 2005;352(4):341-350. 19

Clinical Presentation pdpn Up to 50% of patients with DPN experience painful symptoms 1-3 Burning Sharp pain Electric shocks Shooting Stabbing Deep aching Prickling Tingling Pins and needles Dysesthesias Discomfort on walking Sensations of heat/cold in feet Allodynia Hyperalgesia 1. Pop-Busui R, et al. Diabetes Care. 2017;40:136-154. 2. Tesfaye S, et al. Diabetes Metab Res Rev. 2011;27:629-638. 3. Tesfaye S. Medicine. 2015;43:26-32. 20

Clinical Presentation of pdpn First affects the feet and lower limbs, with the hands affected later 1,2 Symptoms occur symmetrically in a stocking and glove pattern 1,2 Symptoms tend to be worse at night and often result in sleep disturbance 2,3 Pain may be constant or intermittent 4 Patients often find it difficult to describe the symptoms, which may differ from the pain they've previously experienced 3 1. Tesfaye S. Medicine. 2015;43:26-32. 2. Tesfaye S, et al. Diabetes Metab Res Rev. 2012;28(suppl1):8-14. 3. Tesfaye S, et al. Diabetes Metab Res Rev. 2011;27:629-638. 4. Javed S, et al. Ther Adv Chronic Dis. 2015;6:15-28. 21

Clinical Presentation of pdpn The majority of patients report their pain as moderate or severe 1-3 Limited data on the natural history of pdpn 4 Some studies report no appreciable occurrence of remission or improvement in pain severity over time Other studies suggest painful symptoms may improve with the worsening of sensory loss There is no correlation between the intensity of pain symptoms and the severity of sensory loss 5 1. Sadosky A, et al. Diabetes Metab Syndr Obes. 2013; 6:79-92. 2. Sadosky A, et al. Patient. 2014;7:107-114. 3. DiBonaventura, et al. Pain Med. 2011;12(5):799-807. 4. Tesfaye S, et al. Diabetes Metab Res Rev. 2011;27:629-638. 5. Guastella V, et al. Diabetes Metab. 2009;35(1):12-19. 22

The Comprehensive Foot Exam

ADA Standards of Medical Care in Diabetes: Foot Evaluation and Screening for DPN 1 All patients should be assessed annually for DPN using medical history and simple clinical tests: Patients with type 1 diabetes for five or more years All patients with type 2 diabetes Perform a comprehensive foot evaluation at least annually to identify risk factors for ulcers and amputations Consider more frequent foot assessments in patients with histories of ulcers or amputations, foot deformities, insensate feet, and peripheral arterial disease All patients with diabetes should have their feet inspected at every visit 1. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 24

Key Components of the Foot Exam 1,2 Patient History Includes assessment for neuropathic pain symptoms General Inspection Dermatologic Musculoskeletal Vascular Assessment Neurological Assessment 1. Boulton AJ, et al. Diabetes Care. 2008;31(8):1679-1685. 2. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 25

Patient History 1,2 Ulceration Amputation Charcot foot Past History Angioplasty or Vascular surgery Cigarette smoking Foot care practices Neuropathic symptoms Positive (e.g., burning or shooting pain, electrical or sharp sensations etc.) Negative (e.g., numbness, feet feel dead) Vascular Symptoms Claudication Leg fatigue Rest pain Decreased walking speed Nonhealing ulcer Other Diabetic Complications Renal disease Retinopathy (visual impairment) 1. Boulton AJ, et al. Diabetes Care. 2008;31(8):1679-1685. 2. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 26

General Inspection 1 Careful inspection of skin integrity and musculoskeletal deformities performed in a well-lit room with shoes and socks removed Inappropriate footwear and foot deformities are common contributory factors in the development of foot ulceration Inspect the shoes. Are these shoes appropriate for these feet? Dermatologic Skin status: color, thickness, dryness, cracking Sweating Infection: check between toes for fungal infection Ulceration Calluses (particularly with hemorrhage), blistering, abnormal erythema Musculoskeletal Deformity (e.g., claw toes, prominent metatarsal heads, Charcot foot) Muscle wasting (guttering between metatarsals) 1. Boulton AJ, et al. Diabetes Care. 2008;31(8):1679-1685. 2. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 27

Vascular Assessment 1,2 Peripheral arterial disease (PAD) is a component cause in approximately 1/3 of foot ulcers and is often a significant risk factor associated with recurrent wounds Assessment of PAD is important in defining overall lower extremity risk status Assess for symptoms of vascular disease: claudication, rest pain, leg fatigue, decreased walking speed, nonhealing ulcers Vascular examination should include: Palpation of the posterior tibial and dorsalis pedis pulses Ankle-brachial index testing in patients with signs or symptoms of PAD 1. Boulton AJ, et al. Diabetes Care. 2008;31(8):1679-1685. 2. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 28

Neurological Assessment 1,2 Loss of Protective Sensation Simple clinical tests available At least two of these should be regularly performed during the exam Ideally the 10-g monofilament and at least one other test One or more abnormal tests would suggest LOPS At least 2 normal tests (and no abnormal test) rules out LOPS LOPS = Loss of Protective Sensation Clinical Tests 10-g monofilament * Pinprick sensation Temperature sensation Ankle reflexes * Vibration sensation * 128-Hz tuning fork Vibration Perception Threshold (VPT) testing with a biothesiometer * Large-fiber function 3 Small-fiber function 3 1. Boulton AJ, et al. Diabetes Care. 2008;31(8):1679-1685. 2. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 3. Pop-Busui R, et al. Diabetes Care. 2017;40:136-154. 29

ADA Risk Classification Based on the Comprehensive Foot Exam 1 Risk Category Definition Treatment Recommendations Suggested Follow-up 0 No LOPS, no PAD, no deformity 1 LOPS deformity 2 PAD LOPS 3 History of ulcer or amputation Patient education including advice on appropriate footwear Consider prescriptive or accommodative footwear Consider prophylactic surgery if deformity is not able to be safely accommodated in shoes. Continue patient education Consider prescriptive or accommodative footwear Consider vascular consultation for combined follow-up Same as category 1 Consider vascular consultation for combined follow-up if PAD present Annually (by generalist and/or specialist) Every 3 6 months (by generalist or specialist) Every 2 3 months (by specialist) Every 1 2 months (by specialist) LOPS = Loss of Protective Sensation 1. Boulton AJ, et al. Diabetes Care. 2008;31(8):1679-1685. 30

American Society of Pain Educators Consensus Guidelines: Key Elements in the Diagnosis of pdpn 1 Establish presence of neuropathy Use validated questionnaires to identify painful symptoms Perform neurological assessment (10-g monofilament, 128-Hz tuning fork) Assess pain characteristics Distal, symmetrical Numbness, tingling vs. burning, aching, throbbing pain Spontaneous pain (continuous or intermittent) vs stimulusevoked pain Rule out nondiabetic causes for neuropathy and/or pain 1. Argoff CE, et al. Mayo Clin Proc. 2006;81(suppl 4):S3-S11. 31

American Society of Pain Educators Consensus Guidelines: Key Elements in the Diagnosis of pdpn 1 Establish presence of neuropathy Use validated questionnaires to identify painful symptoms Perform neurological assessment (10-g monofilament, 128-Hz tuning fork) There is no correlation between the intensity of pain Assess symptoms pain characteristics and the severity of sensory deficit 1 Distal, symmetrical Numbness, tingling vs. burning, aching, throbbing pain Spontaneous pain (continuous or intermittent) vs stimulusevoked pain Rule out nondiabetic causes for neuropathy and/or pain 1. Argoff CE, et al. Mayo Clin Proc. 2006;81(suppl 4):S3-S11. 32

Validated Questionnaires to Identify Neuropathic Pain The diagnosis of pdpn in practice is a clinical one, relying on the patient s description of pain 1 Patients often find it difficult to describe the symptoms of pdpn as they are different than the pain they have previously experienced 1,2 Use of validated questionnaires that can distinguish neuropathic from non-neuropathic pain is recommended in routine clinical practice 1-3 Examples of validated questionnaires: 4 ID Pain Leeds Assessment of Neuropathic Symptoms and Signs (LANSS and S- LANSS) Neuropathic Pain Questionnaire (NPQ and NPQ-SF) Neuropathic Pain Diagnostic Questionnaire (DN4 and DN4-Interview) 1. Tesfaye S, et al. Diabetes Metab Res Rev. 2011;27:629-638 3. Hartemann A, et al. Diabetes Metab. 2011;37:377-388. 2. Argoff CE, et al. Mayo Clin Proc.2006;81(suppl 4):S3-S11. 4. Bennett MI, et al. Pain. 2007;127:199-203. 33

ID Pain: Patient-Reported Screener 1 A 6-item validated screening tool that accurately indicates the presence of a neuropathic component of pain Validated using data from 2 independent multicenter study samples and a statistical and psychometric methodology informed by expert clinician review Self-administered or administered by staff Scores range from -1 to 5 with a higher score indicative of pain that contains a neuropathic component 1. Portenoy. Curr Med Res Opin. 2006;22(8):1555 1565. 34

ID Pain: Patient-Reported Screener Neuropathic vs Nociceptive Pain 1 Mark Yes to the following items that describe your pain over the past week and No to the ones that do not. Question Yes Score No 1. Did the pain feel like pins and needles? 1 0 2. Did the pain feel hot/burning? 1 0 3. Did the pain feel numb? 1 0 4. Did the pain feel like electrical shocks? 1 0 5. Is the pain made worse with the touch of clothing or bed sheets? 1 0 6. Is the pain limited to your joints? -1 0 A score of 3, 4, or 5 (indicating the likely presence of a neuropathic component) may justify a more detailed evaluation 1. Portenoy. Curr Med Res Opin. 2006;22(8):1555 1565. 35

Electronic Chronic Pain Questions (ecpq)* CHRONIC PAIN? PAIN INTENSITY & LOCATION Have you had pain most days in the past 3 months? Yes What was your average pain over the last week? (Y/N) No = Exit (0 10 NRS Scale) IMPACT ON FUNCTION, SLEEP, & MOOD Where is your pain? Thinking of the past week How much did pain interfere with your usual activities? How much did pain interfere with your sleep? How much did pain interfere with your mood? (Diagram) (0 10 NRS Scale for each item) PAIN QUALITY & TYPE Sensory Hypersensitivity or Fibromyalgia-like Pain ID PAIN Screener Did the pain feel like pins and needles? Did the pain feel hot/burning? Did the pain feel numb? Did the pain feel like electrical shocks? Is the pain made worse with the touch of clothing or bed sheets? Is the pain limited to your joints? Score: < 3 Consider Nociceptive Pain (Y/N) (Y/N) (Y/N) (Y/N) (Y/N) (Y/N) Score: 3 Consider Neuropathic Pain *For the purposes of this presentation, the ecpq questions have been paraphrased. Did you have trouble thinking or remembering in the past week? Were you sensitive to bright lights, loud noises, or smells in the past week? (0 10 NRS Scale for each item) Other information to help diagnose sensory hypersensitivity can be derived from medical history and other ecpq questions. It includes: Widespread pain from body map image / locations? (Y/N) Marked impairment of mood, sleep, and function? (Y/N) Medical history of 1 other sensory hypersensitivity condition? (Y/N) Consider Sensory Hypersensitivity Mostly Yes NRS = numeric rating scale 36

Diabetic Foot-Related Quality Measures in the Quality Payment Program Quality Measure Name (Quality ID #) Diabetes Mellitus: Diabetic Foot and Ankle Care, Peripheral Neuropathy Neurological Evaluation (#126) 1 Percentage of patients aged 18 years and older with a diagnosis of diabetes mellitus who had a neurological examination of their lower extremities within 12 months 10-g monofilament plus testing any one of the following: vibration using 128-Hz tuning fork, pinprick sensation, ankle reflexes, or vibration perception threshold Diabetes Mellitus: Diabetic Foot and Ankle Care, Ulcer Prevention Evaluation of Footwear (#127) 1 Percentage of patients aged 18 years and older with a diagnosis of diabetes mellitus who were evaluated for proper footwear and sizing Includes a foot examination documenting the vascular, neurological, dermatological, and structural/biomechanical findings. The foot should be measured using a standard measuring device, and counseling on appropriate footwear should be based on risk categorization. Diabetes: Foot Exam (#163) 2 The percentage of patients 18-75 years of age with diabetes (type 1 and type 2) who received a foot exam (visual inspection and sensory exam with monofilament and a pulse exam) during the measurement year Measure Type Process Process Process Submission Methods Registry Registry EHR 1. Centers for Medicare and Medicaid Services. Claims Registry Measures 101-150. https://www.cms.gov/medicare/quality-payment-program/resource-library/2018-resources.html. Accessed August 10, 2018. 2. Centers for Medicare and Medicaid Services. Quality Measure Specifications Supporting Documents 2/28/2018-2018 Quality Payment Program Measures List. https://www.cms.gov/medicare/quality-payment-program/resource-library/2018-resources.html. Accessed August 10, 2018. 37

Management of pdpn

ADA Standards of Medical Care in Diabetes: Foot Care and Treatment for DPN 1 Optimize glucose control to prevent or delay neuropathy in type 1 diabetes and to slow neuropathy progression in type 2 diabetes Therapeutic strategies for the relief of pdpn can potentially reduce pain and improve quality of life Assess and treat patients with a tailored and stepwise pharmacologic strategy with careful attention to symptom improvement, medication adherence, and side effects Provide general foot self-care education to all patients with diabetes Refer patients who smoke, have prior lowerextremity complications, loss of protective sensation, structural abnormalities, or PAD to foot care specialists for ongoing preventive care and life-long surveillance Multidisciplinary approach recommended for those with foot ulcers and high-risk feet 1. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 39

American Society of Pain Educators Consensus Guidelines: pdpn Treatment Goals 1 Goal Primary: Zero pain Secondary: Restoration or improvement in functional measures and quality of life Recommendation Be realistic Many patients only achieve 30% to 50% pain reduction Aggressive pursuit of maximum relief is recommended Pain relief may translate to an ability to return to work or social activities and improved quality of life and mood Hopefully, improved function will follow pain relief If improved function does not follow, take measures to help patients optimize function in the presence of residual pain 1. Argoff CE, et al. Mayo Clin Proc. 2006;81(suppl 4):S12-S25. 40

Management of Pain Associated with pdpn Pharmacotherapy 1 Neurostimulatory 1 Interventional Regional Anesthesia 1 Treatment Approaches Physical Rehabilitation 1 Complementary/ Alternative 1 Psychologic 1 Lifestyle 2 1. Chen H, et al. Mayo Clin Proc. 2004;79(12):1533-1545. 2. Jensen TS, et al. Diabetes Vasc Dis Res. 2006;3(2):108-119. 41

Commonly Prescribed Classes of Medications for the Management of pdpn 1,2 Anticonvulsants* Serotonin-norepinephrine reuptake inhibitors* Tricyclic antidepressants Opioid analgesics* Dermal and topical treatments *FDA-approved treatment available within these classes. 1. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 2. Pop-Busui R, et al. Diabetes Care. 2017;40:136-154. 42

ADA Guidelines: Pharmacologic Management of pdpn 1 Treatment recommendations for painful DPN Recommended for first- or second-line use*, Anticonvulsants Recommended with caution Tricyclic antidepressants Not recommended for first- or second-line use Opioids Antidepressants *Ratings vary dependent of anticonvulsants/antidepressant agent. Rating level A; based on large, well-designed clinical trials or well-done meta-analyses. 2 Rating level B; based on supportive evidence from well-conducted cohort studies or well-conducted case-control study. 2 Opioid use is associated with high risk of addiction, abuse, sedation, and other complications and psychosocial issues. The ADA does not recommend opioids for the treatment of painful DPN before a trial of other agents that do not have these associated conditions. Rating level E; based on expert consensus or clinical experience. 2 1. Pop-Busui R, et al. Diabetes Care.. 2017;40:136-154. 43

American Academy of Neurology Evidence-Based Guideline: Treatment of pdpn 1 Objective: To develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of pdpn Addresses the efficacy of pharmacologic and nonpharmacologic treatments to reduce pain and improve physical function and quality of life in patients with pdpn Classified studies according to the AAN classification of evidence scheme for a therapeutic article. Recommendations were linked to the strength of evidence 1. Bril V, et al. Neurology. 2011;76:1758-1765. 44

Impact of pdpn on Diabetes Care Regular exercise is an important part of the diabetes management plan 1,2 : Improves blood glucose control Reduces cardiovascular risk factors Contributes to weight loss Improves well-being The inclusion of an exercise program or other means of increasing overall physical activity is critical for optimal health in individuals with type 2 diabetes. 2 American College of Sports Medicine and American Diabetes Association 2010 Joint Position Statement on Exercise and Type 2 Diabetes pdpn negatively impacts exercise and walking ability 3 Guidelines recommend aerobic exercise (e.g., brisk walking) as part of the diabetes management plan 1,2 1. American Diabetes Association. Diabetes Care. 2018;41(Suppl.1):S38 S50. 2. American College of Sports Medicine and the American Diabetes Association. Diabetes Care. 2010;33:e147-e167. 3. Sadosky A, et al. Patient. 2014;7:107-114. 45

Painful DPN May Affect Treatment Goals Painful DPN Exercise 1,2 Glucose regulation 3,4 Sleep 5-7 Painful DPN may make it difficult to engage in appropriate exercise regimens, a critical component of diabetes management The risk of DPN increases with rising A1c levels and longer duration of diabetes Even patients with good glycemic control are at risk for developing DPN due to other risk factors such as smoking, hypertension, and cardiovascular disease Painful DPN may impact sleep, leading to sleep loss In a cross-sectional survey (N=255), sleep problems increased with the severity of painful DPN with 64% of patients reporting suboptimal sleep DPN pain may interrupt regular exercise routines, which have a beneficial effect on glucose levels Sleep loss has a negative impact on glucose homeostasis Poor sleep quality may lead to reduced levels of activity 1. Quattrini C, et al. Diabetes Metab Res Rev. 2003;19(suppl 1):S2-S8. 2. American College of Sports Medicine and the American Diabetes Association. Diabetes Care. 2010;33:e147- e167. 3. Fedele D, et al. Diabetes Care. 1997;20(5):836-843. 4. Tesfaye S, et al. Curr Diab Rep. 2009;9(6):432-434 5. Knutson KL. Sleep Med Clin. 2007;2(2):187-197. 6. Dzierzewski JM, et al. J Sleep Res. 2014;23(1):61-68. 7. Gore M, et al. J Pain Symptom Manage. 2005;30(4):374-385. 46

Patient Education

Management of the Diabetic Foot: Patient Education 1 Control your diabetes Check your feet every day Wash your feet every day Smooth corns and calluses gently Keep skin soft and smooth Trim your toenails straight across Wear shoes and socks at all times Protect your feet from hot and cold Keep blood flowing to your feet Get a foot check at every health care visit 1. National Diabetes Education Program. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/foot-problems. Accessed August 10, 2018. 48

Management of the Diabetic Foot: Footwear Assessment 1 Examine the inside of the shoes Look at the type of footwear Look at the fit of the footwear Avoid pointed-toe and open-toe shoes, high heels, thongs and sandals Shoes should accommodate any deformities Should corrective shoes or inserts be prescribed? 1. National Diabetes Education Program. Feet Can Last a Lifetime: A Health Care Provider's Guide to Preventing Diabetes Foot Problems. November 2000. 49

Summary pdpn is a prevalent chronic complication of diabetes that is associated with significant health and economic burden 1 According to the ADA, an annual comprehensive foot exam and assessment for DPN are standards of medical care for patients with diabetes 2 The American Society of Pain Educators recommends the use of validated questionnaires to identify and assess neuropathic pain in patients with diabetes 3 The ADA recommends both pharmacologic and non pharmacologic therapies to help patients manage and treat symptoms of pdpn 1,2 1. Pop-Busui R, et al. Diabetes Care.. 2017;40:136-154. 2. American Diabetes Association. Diabetes Care. 2018;41(Suppl 1):S105 S118. 3. Argoff CE, et al. Mayo Clin Proc. 2006;81(suppl 4):S3-S11. 50