Learning Objectives. Why Target Rehospitalization in COPD? Agenda. Case: 78-year-old Smoker with Progressive SOB and Cough, Sputum for One Week

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Learning Objectives Utilize guideline-concordant maintenance pharmacotherapy, along with appropriate nonpharmacologic strategies, to reduce exacerbation risk and improve quality of life in patients with COPD Educate patients regarding appropriate self-management techniques to reduce COPD exacerbations, utilizing an interprofessional care team to optimize patient engagement Why Target Rehospitalization in COPD? Agenda Case: 78-year-old Smoker with Progressive SOB and Cough, Sputum for One Week Impact of Hospitalization for COPD Exacerbation on Patients Impact of Rehospitalization on Healthcare Systems Treatment and Prevention of COPD Exacerbations During admission Stable state Pharmacological Non-pharmacological Risk Factors for Rehospitalization Approach to Minimizing Rehospitalization HPI COPD (FEV1 35%) No LTOT Two bronchitis episodes last year one treated with antibiotics the other antibiotics/medrol dosepak CAP 3 years ago on ICS PMH Hypertension OSA Depression Heart failure with preserved EF SH 1 pack/day for 5 years DC ed 15 years ago Home meds Tiotropium/olodaterol qd Albuterol prn Beclomethasone HCTZ Diltiazem Lisinopril PE 14/82, 9, 24, 99.8, 88% RA HEENT negative No JVD Chest decreased BS, B wheezes/no rales CV S4, no m Ext no clubbing, cyanosis, trace edema Consequences of COPD Exacerbations Negative impact on quality of life Impact on symptoms and lung function Recovery of Lung Function and Symptoms Following an Exacerbation Is Often Prolonged and Sometimes Incomplete PEF Symptoms Time to Recovery*, median days (IQR) 6 (1-14) 7 (4-14) Exacerbations Recovering within 35 days 75.2% 86.1% Exacerbations Recovering within 91 days 8.2% 9.9% Exacerbations that Did Not Recover within 91 days 7.1% 4.6% Accelerated lung function decline EXACERBATIONS Increased economic costs * Recovery time was defined as the time for the parameter (PEF or Symptoms) to return to baseline from the onset of the exacerbation. Baseline was defined as the 8-14 period preceding the exacerbation. Increased mortality Data are not shown for the percentage of exacerbations where recovery time could not be determined and where the next exacerbation occurred before complete recovery. IQR=Interquartile Range 215 Global Initiative for Chronic Obstructive Lung Disease. Seemungal T et al. Am J Respir Crit Care Med. 2;161:168-1613. 1

55% of Patients Died Five Years After Hospitalization for COPD Mortality 6% 5% 4% 3% 2% 1% % Mortality Among Patients Who Were Admitted to the Hospital in the First Year of the Study (n=89) 12% Soler-Cataluna JJ et al. Thorax. 25;6:925-931. 26% 4% 47% 55% 1 2 3 4 5 Year COPD Patients with a Greater Frequency of Severe Exacerbations* Per Year Have Higher Risk of All-Cause Mortality Probability of Surviving 1..8.6.4.2. 1 2 3 4 5 6 Time (months) Soler-Cataluna JJ et al. Thorax. 25;6:925-931. A P<.2 B P=.69 C P<.1 No exacerbations 1-2 exacerbations 3 exacerbations *Severe exacerbations = exacerbation required emergency visits or hospital admissions. Why Target Rehospitalization in COPD? Agenda Economics of COPD: Patient Perspective Impact of Hospitalization for COPD Exacerbation on Patients Impact of Rehospitalization on Healthcare Systems Treatment and Prevention of COPD Exacerbations During admission Stable state Pharmacological Non-pharmacological Risk Factors for Rehospitalization Approach to Minimizing Rehospitalization Out-of-pocket expenses 11.5% of total COPD expenditures Increases as the number of chronic conditions increase Among adults who spent more than 1% of their income on out-of-pocket costs, prescription drug spending accounted for more than 5% of spending, totaling on average $2,5/year. Mean Annual Costs Per Person $14, $12, $1, $8, $6, $4, $2, $ Outpatient Inpatient Emergency Provider stays Room visits visits Prescription Medications Cunningham PJ. Issue Brief Commonwealth Fund. 29;63:1-14. Hospital Readmission Reduction Program (HRRP) $13 billion cost for COPD admissions each year In 214, readmissions for any reason within 3 days after hospital admission for COPD counts towards penalty No one-size-fits-all solution Possible solutions Inpatient and transition care teams Pulmonary rehabilitation In the UK, COPD is second most common cause of emergency admissions Multiple proposed projects to reduce ED admissions for COPD Many of these projects focused on care integration Shah T et al. Chest. 216;15:916-926. 2

Why Target Rehospitalization in COPD? Agenda Systemic Corticosteroids for Acute Exacerbations of COPD Impact of Hospitalization for COPD Exacerbation on Patients Impact of Rehospitalization on Healthcare Systems Treatment and Prevention of COPD Exacerbations During admission Stable state Pharmacological Non-pharmacological Risk Factors for Rehospitalization Approach to Minimizing Rehospitalization Cochrane Database of Systematic Reviews 1 SEP 214 DOI: 1.12/14651858.CD1288.pub4. http://onlinelibrary.wiley.com/doi/1.12/14651858.cd1288.pub4/full#cd1288-fig-12. 5-day Course of Oral CS May Be Appropriate for COPD Exacerbations Re-exacerbations in the REDUCE Trial Early Antibiotics Reduces Treatment Failure In Patients Hospitalized for Acute Exacerbations of COPD Proportion of patients without re-exacerbation ITT analysis HR,.95 (9% CI,.7-1.29) P for non-inferiority =.6 Proportion of patients without re-exacerbation Per-protocol analysis HR,.93 (9% CI,.68-1.26) P for non-inferiority =.5 P<.1 P<.1 Patients (%) ITT = intention to treat; REDUCE = Reduction in the Use of Corticosteroids in Exacerbated COPD Lueppi JD et al. JAMA. 213;39:2223-2231. Ref: Ram FSF, antibiotics for exacerbations of COPD Cochrane 26 issue 3. Adapted from Rothberg MB et al. JAMA. 21;33:235-242. ACCP Evidence-based Guidelines Recommend Various Pharmacotherapies to Prevent Moderate/Severe Exacerbations of COPD Inhaled Therapy LABA LAMA LAMA/LABA SAMA/SABA ICS/LABA Evidence Grade 1b 1A 1C 2b 1B/1C Oral Therapy Macrolide Roflumilast Theophylline N-acetylcysteine Carbocysteine Evidence Grade 2A 2A 2B 2B Consensus Although no drugs have been specifically examined in the post-hospitalization ecopd* setting there are hints. Criner GJ et al. Chest. 215;147:894-942. ecopd = exacerbation of COPD 3

Tiotropium Prolongs Time to First Severe Exacerbation Compared with Salmeterol ICS/LABA Decreases Severe Acute Exacerbations of COPD in Comparison to Placebo FP/SM SCO 154 TORCH Subtotal.1.2.5 2 5 1 Odds Ratio (95% CI).77 (.31, 1.92).83 (.7,.97).83 (.7,.97) BDF Calverley 23 Szafranski 23. (.,.) -.45 (-.73, -.17) Abbreviations: FP/SM fluticasone propionate/salmeterol; BDF budesonide/formoterol -1-5 1 5 1 Favors ICS/LABA Favors placebo Vogelmeier C et al. N Engl J Med. 211;364:193-113. Nannini et al. Cochrane Database Syst Rev. 213;(8):CD6826. ICS/LABA + Tiotropium Decreases Exacerbation Rate in At-risk COPD Patients LABA/LAMA Superior to ICS/LABA in Exacerbation Reduction Severe AE COPD Hosp/ER.2.4.6.8 1 1.2 1.4 1.6 1.8 2. Favor BDF + tio Favor placebo + tio Abbreviations: AE = Acute exacerbations of COPD; BDF = budesonide/formoterol Welte T et al. Am J Respir Crit Care Med. 29;18:741-75. Wedzicha JA et al. N Engl J Med. 216;374:2222-2234. LABA/LAMA/ICS Reduces Severe Exacerbations Compared with Individual Dual Combinations in Same Device Annual rate of severe (hospitalised) exacerbations (95% CI).25.2.15.1.5 13% (95% CI: 1, 24) P=.64 (NS).15.13 (95% CI:.13,.16) (95% CI:.12,.14) 34% (95% CI: 22, 44) P<.1.13 (95% CI:.12,.14).19 (95% CI:.17,.22) FF/UMEC/VI FF/VI UMEC/VI n=4,145 n=4,133 n=2,69 Note: The n reflects the number of patients included in each analysis from the ITT population. Patients were excluded if they had predefined data missing; this varied according to the analysis. The ITT population comprised: 4,151 patients treated with FF/UMEC/VI, 4,134 patients treated with FF/VI and 2,7 patients treated with UMEC/VI. NS = Not Statistically Significant Lipson DA et al. ATS 218 (oral presentation) #A114. Roflumilast Response is Particularly Evident in COPD Patients with Prior Hospitalizations Mean rate of COPD severe exacerbations per patient per year 1 RR=.65 (95% CI.48,.89).7 P<.1.6.5.4.3.2.1 34.9% reduction RR=.92 (95% CI.67, 1.28), ns.39.6.17.18 ROF Placebo (n=322) (n=319) History of hospitalization 7.6% reduction ROF Placebo (n=647) (n=647) No prior history of hospitalization The primary endpoint was the annual rate of moderate (requiring treatment with SCS and/or antibiotics) and severe (necessitating hospitalization or leading to death) exacerbations. ROF = roflumilast 5 μg q.d; RR = rate ratio 1. Rabe KF et al. Eur Respir J. 217;5:pii-17158. 2. Martinez FJ et al. Am J Resp Crit Car Med. 216;194:559-567. Rate of moderate and severe exacerbations 2 3 2.5 2 1.5 1.5 Number of participants Number of severe at risk exacerbations/ hospitalizations in 12 months prior to Roflumilast Placebo Rate ratio randomization (n=1178) (n=1174) (95% Cl) P value 789 85 1.1.879 (.8, 1.18) 1 381 364.75.1 (.6,.93) 25% reduction 1.14 1.13 1.23 1.63 ROF Placebo ROF Placebo 1 1 Number of severe exacerbations/hospitalizations in 12 months prior to randomization 4

GOLD 217 Therapeutic Recommendations COPD Foundation Guide for COPD Treatment Group C Further exacerbation(s) Group A LAMA + LABA LAMA Continue, stop or try alternative class of bronchodilator Evaluate effect A bronchodilator LABA + ICS Group D Consider roflumilast if FEV1 <5% pred and patient has chronic bronchitis Further Exacerbation(s) LAMA + LABA + ICS Further Exacerbation(s) LAMA Group B LAMA + LABA LAMA + LABA Persistent symptoms Consider macrolide A long-acting bronchodilator (LABA or LAMA) Persistent symptoms/further exacerbations LABA + ICS Spirometry grade SG 1 SG 2/3 Short-acting Bronchodilator First line as needed LAMA or LABA or LAMA+ LABA Possibly First line ICS/LABA Roflumilast Oxygen Yes Yes * * Indicated if chronic bronchitis, high exacerbation risk, and spirometry grades 2/3 present. All potential options depending upon frequency of exacerbations and severity of COPD. Exercise/ Pulmonary Rehab First line as Regular symptoms First line Yes First line needed Exacerbation risk high First line First line Yes * Oxygenation Severe hypoxemia Episodic hypoxemia Emphysema Chronic bronchitis Yes * Comorbidities Yes Possibly Evaluate and treat identified comorbid conditions Lung Volume Reduction Surgery Select cases Vogelmeier CF et al. AJRCCM. 217;195:557-582. COPD Pocket Card. www.copdfoundation.org/resources/educationalmaterials.aspx. Accessed May 3, 213. Prevention of Respiratory Infections Influenza Vaccination Prevention of Hospitalizations Pneumococcal and Influenza Vaccination 16 12 Respiratory Hospitalizations/1 Patient-Years Unvaccinated Pneumococcal vaccination COPD hospitalization All cause mortality 8 4 Vaccinated Influenza 1 Interim 1 Influenza 2 Interim 2 Influenza 3 Pneumococcal + Influenza vaccination COPD hospitalization All cause mortality..2.4.6.8 1. 1.2 1.4 1.6 1.8 2. Relative Risk (95% CI) Nichol KL et al. Ann Intern Med. 1999;13:397-43. Wongsurakiat P et al. Chest. 24;125:211-22. Nichol KL et al. Arch Intern Med. 1999;159:2437-2442. Pulmonary Rehabilitation Following Exacerbations of COPD Self Management Interventions Including Action Plans for Exacerbations vs Usual Care in Patients with COPD Cochrane Database of Systematic Reviews, 8 DEC 216 DOI: 1.12/14651858.CD535.pub4. http://onlinelibrary.wiley.com/doi/1.12/14651858.cd535.pub4/full#cd535-fig-4. Cochrane Database of Systematic Reviews 4 AUG 217 DOI: 1.12/14651858.CD11682.pub2. http://onlinelibrary.wiley.com/doi/1.12/14651858.cd11682.pub2/full#cd11682-fig-14. 5

Why Target Rehospitalization in COPD? Agenda Impact of Hospitalization for COPD Exacerbation on Patients Impact of Rehospitalization on Healthcare Systems Treatment and Prevention of COPD Exacerbations During admission Stable state Pharmacological Non-pharmacological Risk Factors for Rehospitalization Approach to Minimizing Rehospitalization Case: 78-year-old Smoker with Progressive SOB and Cough, Sputum for One Week He is treated with inhaled steroids, doxycycline, as well as IV and subsequently oral steroids His weight has risen by 6 kg since admission BNP measured at day 6 is 24 and he has been given one dose of IV furosemide He gradually improves and by day 7 is approaching his previous baseline He remains quite weak Factors Associated with Increased Risk of Early Readmission The Majority of Medicare Readmissions Occur in the First 15 days After ecopd Discharge Black race Comorbidities Congestive heart failure Frailty Other medical conditions Psychiatric disease Discharge to post-acute care Dual Medicare/Medicaid eligibility Elevated paco2 Low BMI Longer length of stay Male sex 6.6% of readmissions Shah T et al. Chest. 216;15:916-926. Abbreviations: ecopd = exacerbation of COPD Shah T et al. Chest. 215;147:1219-1226. Majority (5.6%) of Medicare Readmissions Related to Respiratory Disorders Numerous Factors Associated with Medicare Readmission Characteristic OR (95% CI) Age >8 yrs.97 (.96-.99) Female gender.89 (.88-.9) Black race 1.6 (1.4-1.8) Charlson sum of 2 (excluding COPD as a comorbidity) 1.43 (1.41-1.46) Dually eligible for Medicare and Medicaid 1.22 (1.2-1.24) Longer length of stay 1.3 (1.3-1.3) ICU use 1.3 (1.2-1.5) Discharge to skilled nursing facility 1.42 (1.4-1.45) Discharge home with home care 1.36 (1.34-1.38) Shah T et al. Chest. 215;147:1219-1226. Shah T et al. Chest. 215;147:1219-1226. 6

Multiple Factors are Associated with Readmission Among Managed Care COPD Enrollees Comorbid Conditions Are Frequently Seen in Hospitalized COPD Patients Longer length of stay Greater age Increasing comorbidity Chronic renal failure Non-lung cancer Pneumonia Severe COPD complexity Longer length of stay Greater age Increasing comorbidity Chronic renal failure Pneumonia Severe/moderate COPD complexity The size of the circle relates to the prevalence of the disease Candrilli SD et al. Hosp Prac. 215;43:199-27. Almagro P et al. Eur Respir J. 215;46:85-853. Composite Score Predicts 9-day Readmission From Patients Hospitalized for Exacerbations of COPD PEARL index Weighting Previous admissions (2+) 3 emrcd score 4 1 emrcd score 5a 2 emrcd score 5b 3 Age > 8 1 RV failure 1 LV failure 1 Max score 9 Psychological Disorders Are Associated with Increased 3-day Readmission Rates Following Hospitalization for Exacerbations of COPD Variable OR (95% CI) Depression 1.34 (1.29-1.39) Anxiety 1.43 (1.37-1.5) Psychosis 1.18 (1.1-1.27) Alcohol abuse 1.3 (1.15-1.47) Drug abuse 1.29 (1.11-15) Echevarria C et al. Thorax. 217;72:686-693. Singh G et al. Chest. 216;149:95-915. COPD Readmissions Higher as a Function of Hospital Type and HCAHPS Measures Why Target Rehospitalization in COPD? Agenda Hospital Level Factors COPD readmission correlated with: CHF readmissions MI readmissions Pneumonia readmissions Readmission levels higher for: Teaching hospitals Private for-profit hospitals Safety net hospitals Relation to HCAHPS Impact of Hospitalization for COPD Exacerbation on Patients Impact of Rehospitalization on Healthcare Systems Treatment and Prevention of COPD Exacerbations During admission Stable state Pharmacological Non-pharmacological Risk Factors for Rehospitalization Approach to Minimizing Rehospitalization Rinne ST et al. Am J Respir Crit Care Med. 217;196:47-56. 7

Case: 78-year-old Smoker with Progressive SOB and Cough, Sputum for One Week He is treated with inhaled steroids, doxycycline, as well as IV and subsequently oral steroids He gradually improves and by day 7 is approaching his previous baseline He remains quite weak His weight has risen by 6 kg since admission BNP measured at day 6 is 24 and he has been given one dose of IV furosemide His long acting bronchodilator is not available on your hospital formulary so he has been receiving short acting agents every six hours His discharge is processed with anticipate discharge at 3PM His PCP has an available appointment in one month Interventions That May Decrease Early Readmission Risk Patient self-management Inhaler device training Early outpatient follow-up within 3 days after discharge Pulmonary rehabilitation Receipt and filling of all respiratory medications at discharge Pharmacist-supervised medication reconciliation Medications (e.g. roflumilast) Shah T et al. Chest. 216;15:916-926. Lack of Continuity in Care Among Medicare Beneficiaries >65 Years Old is Associated with Greater Preventable Hospitalization Lack of Pulmonary Follow-Up Visit Associated with Readmission Characteristic HR (95% CI) Continuity of care.98 (.98-.99) Female 1.17 (1.16-1.18) Black 1.7 (1.6-1.8) Hispanic 1.7 (1.5-1.9) Medicaid dual eligibility 1.6 (1.5-1.7) Total preventable hospitalizations in the prior year 1.17 (1.17-1.18) Characteristic OR (95% CI) Distance residence 3. (1.24-7.28) Previous hospitalizations 1.34 (1.2-1.75) Previous pulmonary visit.82 (.73-.93) Nyweide DJ et al. JAMA Intern Med. 213;173:1879-1885. Gavish R et al. Chest. 215;148:375-381. Outpatient Follow-up Visits Are Associated with Decreased 3-day Readmission Rates Adherence to Inhaled Medications Is Poor Among COPD Patients Outcomes Rate, % Adjusted HR (95% CI) 3 DAY ER VISIT Patient with follow-up Patient without follow-up 3 DAY READMISSION Patient with follow-up Patient without follow-up 21.7% 26.3% 18.9% 21.4%.86 (.83-.9).91 (.87-.96) Prospective study of 244 COPD patients (16 post exacerbation) Electronic monitoring of compliance with diskus device: Mean adherence was 22.6% Adherence >8 in only 6% Sharma G et al. Arch Intern Med. 21;17:1664-167. Sulaiman I et al. Am J Respir Crit Care Med. 216;195:1333-1343. 8

Patient Education on Inhaler Technique Associated with Decreased Acute Care Events Within 3 Days of Discharge for Asthma or COPD Exacerbation Pharmacist-facilitated Transition and Training on Inhaler Use Associated with Decreased 3-day Readmission Rates Variable OR (95% CI) Multidose medication dispensing on discharge program 2.5 (1.4-4.3) Male 1.1 (.7-1.7) Patient age 1. (.98-1.) Inhaler type.87 (.7-1.) Current smoker 1.3 (.8-2.1) Diabetes mellitus.7 (.4-1.1) Congestive heart failure.4 (.3-.6) Press VG et al. Ann Am Thorac Soc. 216;13:816-824. Blee J et al. Am J Health-Syst Pharm. 215;72:124-128. Comprehensive Discharge Bundle Decreases Readmission Health Coaching Intervention During Hospitalization for COPD Exacerbations Reduces COPD-related Hospitalization COPD-RELATED ALL CAUSE 6 * * * 5 4 3 2 1 * * 1 month 3 months 6 months 9 months 12 months * P<.5 Control Intervention Hopkinson NS et al. Thorax. 212;67:9-92. Benzo R et al. Am J Respir Crit Care Med. 216;194:672-68. Multidisciplinary Intervention DID NOT Reduce 3-day Readmission Rates Comprehensive Intervention Can Decrease Readmission Risk Intervention Standard hospital management Smoking cessation counseling Trend COPD to longer clinic time within to first 2 weeks readmission of discharge (239 vs 2.11 days, p=.1) Referral to pulmonary but rehabilitation No Periodic difference phone in 3 day calls readmission rates (15.4 vs 17.4%, p=.71) Results INTERVENTION Carolinas Health System Building IT in inpatient and outpatient settings Root cause analysis for COPD readmissions Early follow-up appointments (2-7 days) Case management/rt during hospital stay Assigning medical home Medication education Follow-up call at 48 hours PRE-POST RESULTS Decrease in 3-day readmission from 21.8% to 13% Bhatt SP IAnn Am Thorac Soc. 217;14:643-648. https://www.healthcaredive.com/news/hospitals-find-ways-to-reduce-copd-readmissions/4328. 9

Non-invasive Ventilation Plus Oxygen Reduces Readmission Randomized trial of patients (n=124) with persistent hypercapnia (Paco2 >53 mm Hg) 2-4 weeks after resolution of respiratory acidemia 59 patients received home oxygen alone (median oxygen flow rate, 1. L/min [interquartile range {IQR},.5-2. L/min]) 57 patients received home oxygen plus noninvasive ventilation (NIV) (median oxygen flow rate, 1. L/min [IQR,.5-1.5 L/min]) Results: 12-month risk of readmission or death; 63.4% in home oxygen plus NIV group vs 8.4% in the home oxygen alone group; absolute risk reduction, 17.% Conclusions: adding home noninvasive ventilation to oxygen therapy prolonged the time to readmission or death within 12 months in patients with persistent hypercapnia following an acute COPD exacerbation How to Minimize Rehospitalization in COPD Hospitalized exacerbations are major negative events to the patient and the healthcare system In-patient management can decrease risk of relapse (steroids and antimicrobial administration) Pharmacotherapy may decrease need for hospitalization, but not impact risk for early readmission Non-pharmacological therapies may decrease early relapse (pulmonary rehabilitation, self management) Approach to minimize rehospitalization needs to be comprehensive Murphy PB. JAMA. 217;6;317:2177-2186 Ideal COPD Treatment Team A Patient s Perspective Comprise a team to approach the proper care and treatment of the patient. The team should include the patient, support person (family member or caregiver), the primary care physician, and any specialists involved in the patient s care and treatment. This group will be called the treatment team. The treatment team will formulate an action plan to address specific issues that the patient may encounter. Specific instructions should accompany the action plan and be signed off on by all parties. Ideal COPD Treatment Team (2) Things To Avoid On a biannual basis, the treatment team should communicate with other members of the team and update the action plan. Each participant must understand their role in the implementation of the plan. This appears to be a huge task, but if properly carried out, it will save time and improve the outcome of the patient s treatment. Technology can play a huge role in reducing the workload of sharing and transmitting information. Avoid rushing or appearing to rush through a visit. Answer all of the questions that the patient has. Avoid over-estimating your ability if you are the primary care physician. Bring in a pulmonologist, even if only on a consulting basis. Avoid casting judgement about how the person got this disease and understand that the patient has a chronic illness. Avoid allowing the patient to become complacent in their treatment. Demand that they play an active role in care. 1

Positive Actions to Take Give the patient a folder with information and request that the patient read over the materials and make at least one contact. Provide phone numbers for the local support groups and the name of the main contact person. Impress upon the patient that prompt medical attention is necessary to avoid major problems. Make same-day appointments available for your COPD patients. CME Credit Post-activity Survey Now that the program has completed, please take a moment to answer the Post-activity Survey questions on your form Your answers are important and will help us identify remaining educational gaps and shape future CME activities CME Evaluation If you re seeking credit, ensure you ve filled in your name and demographic information on page 1 and complete the CME Evaluation on your form (after the Post-activity Survey) Return all forms to on-site CME staff Thank you for joining us today! 11