This document discusses varicella zoster virus (VZV) which causes chickenpox and shingles. It provides statistics on the incidence of chickenpox pre- and post-vaccine era in the US. It also discusses risk factors for shingles and strategies to reduce its incidence including exposure to children with chickenpox and the shingles vaccine.

1. Evidence-Based Geriatric Pharmacotherapy: 2010 H. Edward Davidson, PharmD, MPH Eastern Virginia Medical School Insight Therapeutics, LLC

2. Vaccines

3. Varicella Zoster Infection Primary Infection (Chickenpox) Latency Reactivation (Shingles) Varicella Zoster Dorsal Ganglion

4. Varicella Zoster In US (Pre-Vaccine Era) Primary Infection in the U.S. 4 million cases annually 95% of persons infected by age 15 145 deaths annually; adult rate higher 12,000 hospitalizations annually

5. Varicella Zoster In US (Post-Vaccine Era) Primary Infection in the U.S. ~ 800,000 cases annually 81% of persons vaccinated ~ 1500 hospitalizations annually 66 deaths annually

6. Risk Factors for “Shingles” Stressful events trauma, surgical procedures, X-ray, other physical, emotional stress Immune system alteration HIV, malignancy drugs - cytotoxic, corticosteroids Age age-related decline in cell mediated immunity

7. Reducing Incidence of “Shingles” Exposure to children with primary varicella infection (“Chickenpox”) Pediatricians have a reduced rate of zoster Household exposure enhances cell mediated immunity Varicella vaccination of adults Several small studies and one large study (38, 500 patients) have shown reduced incidence of zoster Vaccine (Zostavax) approved by FDA in 2006

8. Number of Herpes Zoster Cases Observed in MSGP4 Age Zoster cases Data – Children < 16 years Data – No Children Model – Children < 16 years Model – No Children Brisson, M et al. Vaccine. 2002 MSGP4 = National Survey of Morbidity in General Practice 4

9. Prediction of Post-Vaccination Incidence of Herpes-Zoster No Vaccination Best Fit, 20yrs immunity 95% CI, 7-41yrs immunity Zoster incidence rate (per 100,000 per year) Year after start of vaccination Brisson, M et al. Vaccine. 2002

10. Herpes Zoster Related Hospitalizations and Expenditures Before and After Introduction of the Varicella Vaccine in the United States Patel MS et al. Infect Control Hosp Epidemiol 2008;29:1157-63

11. Herpes-Zoster Related Hospitalizations Retrospective analysis of a deidentified dataset, Nationwide Inpatient Sample (NIS) (AHRQ) Nationally representative sample Study period 1993 – 2004 Herpes zoster-related hospital discharges (HZHDs) and varicella-related hospital discharges (VRHDs) identified (ICD-9) Resource utilization and clinical data analyzed

12. HZHDs and VRHDs by Year Universal Vaccination in U.S.

13. HZHDs by Year and Age Universal Vaccination in U.S.

14. Cost of HZHD and VRHD by Year Universal Vaccination in U.S.

15. Barriers to Use of Herpes Zoster Vaccine Hurley LP et al. Ann Intern Med 2010;152;555-60. Mail + internet-based survey of general internists and family medicine physicians, July-Sept 2008 Funded by CDC Measured survey responses on: Current vaccination practices Knowledge and practice regarding reimbursement Barriers to vaccination

16. Perceived Barriers to Administering HZ Vaccine in the Office 56 19 13 12 Difficulty in obtaining vaccine 35 30 23 12 More pressing medical issues 42 22 20 16 Need to store in freezer 34 18 25 23 Patient pick-up at pharmacy 19 17 21 43 Up-front costs for practice 13 10 25 52 Reimbursement issues 7 10 30 53 Cost for patient Not at all Minor Somewhat Major Responses, % Barrier

17. Provider strength of recommendation for herpes zoster vaccine compared with other vaccines Hurley L P et al. Ann Intern Med 2010;152:555-560 ©2010 by American College of Physicians

18. Take away … Less than 7% of target population (> 59 yrs, no recent hx) for HZ vaccine have received it 1 Epidemiologic evidences suggest a “rash” of new cases in the elderly are coming Barriers exist to HZ vaccine administration Storage – refrigerator stable formulation licensed in EU Cost – covered by Medicare (under Part D); need to streamline reimbursement process Lack of awareness of epidemiology trend 1. Schiller JS, Euler GL. CDC, 2010.

19. Psychopharmacology

20. Snitz BE, O'Meara ES, Carlson MC, et al. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA 2009;302:2663–2670. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia. JAMA 2008; 300: 2253–2262.

21. Overview of GEMS Primary outcome : Determine whether occurrence of dementia (any type) and Alzheimer’s disease specifically is lower for older people with normal memory treated with Ginkgo biloba compared with a placebo Design: Randomized, double-blind, multi-center clinical trial 3,069 persons ≥ 75 years old with normal memory or very mild cognitive impairment (MCI = 10%)

22. Secondary Outcomes All-cause mortality Combined CHD – nonfatal MI, CHD death, coronary revascularization, hospitalized angina Combined CVD – combined CHD, stroke, lower extremity revascularization, treated angina, fatal/ hospitalized/treated CHF, hospitalized or outpatient PAD General cognitive function (change over time) Physical function

23. Sites in GEMS 5 clinical sites in the United States, all Academic Medical Centers: Johns Hopkins (Hagerstown, MD) University of California, Davis (Sacramento, CA) University of Pittsburgh, (Pittsburgh, PA) Wake Forest University Winston-Salem, NC Greensboro, NC

24. Randomized Design of GEMS Persons with Normal Memory Function or Mild Cognitive Impairment (MCI) Consent / Randomize (3,069) Ginkgo biloba or Placebo Test every 6 months for: New onset dementia of any type and Alzheimer’s disease specifically, and Other outcomes until death or end of study (up to 6.5 years).

25. GEMS Results: Baseline Characteristics

26. GEMS Results: Baseline Characteristics

27. GEMS Results: Cumulative Dementia Rates by Treatment

28. GEMS Results Hazard Ratios for Cox Regression Analyses All Dementia and Subtypes of Dementia comparing Ginkgo to placebo

29. GEMS Results Adverse Events

30. Overall Conclusion Ginkgo biloba at 120 mg twice a day is not effective in reducing the overall incidence of dementia or Alzheimer’s disease in older adults. Neither is Ginkgo biloba effective in preventing dementia in persons with mild cognitive impairment.

31. GEMS Memory Study

35. A Case Study of Herbal Remedy Polypharmacy 77 yo wm referred to geriatric assessment clinic in CA spring 2009 Progressive problems with word finding, disorientation, agitation, and irritability Sister with dementia History of smoking (quit 30 yrs ago), ethanol abuse, illicit drug use Problem list (PCP); Alzheimer’s dementia (MMSE 15/30, could not draw clock), CAD with history of MI, bradycardia, hypertension, dyslipidemia, gait and balance problems, hx falls, incontinence, depression

36. Prescription Medications Pravastatin Lisinopril Aspirin Niacin Triamterene/hydrochlorothiazide Sertraline Donepezil Memantine

37. Dietary and Herbal Supplements B-100 complex Coenzyme Q-10 Omega-3 fatty acids Core complex (quercetin) CardioHealth B-12 Folic Acid Vitamin C Vitamin E Beta carotene Valerian root complex Vitamin D3 Calcium complex Triple berry complex Schizandra plus Mega garlic plus Garden 7 phytonutrients Rose OX Joint support Generic multivitamin Cell activator NiteWorks (amino acids)

38. Strategies to Address this Issue Include discussion of supplements/herbal remedies with each medication reconciliation Natural Medicines Comprehensive Database (available from Prescriber’s Letter, www.naturaldatabase.com ) On-line version also available Research is limited on these products May be a waste of limited resources

39. Preferred Medications in the Elderly Historically, medication use in the elderly has evolved around avoiding “potentially inappropriate medications” (e.g., Beers criteria) Medicare Part D and PDPs have developed formularies based primarily on cost/rebates Need for “geriatrics-focused expert review”

40. “Positive” Beers Criteria First article published August 2009 Consult Pharm 2009;24:601-10. http:// www.ascp.com/resources/clinical/upload/BeersCriteria.pdf Focus on CNS medications Consensus panel of geriatricians, other providers Literature review using AHRQ criteria for comparative effectiveness Delphi consensus process on final selection

41. Definition: IOM Comparative effectiveness research (CER) is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers and policy makers to make informed decisions that will improve health care at both the individual and population levels. National Priorities for Comparative Effectiveness Research Institute of Medicine Report Brief June 2009

42. AHRQ’s Role in Comparative Effectiveness Using Information to Drive Improvement: Scientific Infrastructure to Support Reform Lead federal funding Engage private sector Aggregate best evidence to inform complex learning and implementation challenges Increase knowledge base to spur high-value care 21 st Century Health Care

43. Comparative Effectiveness and the Recovery Act The American Recovery and Reinvestment Act of 2009 includes $1.1 billion for comparative effectiveness research: AHRQ: $300 million NIH: $400 million (appropriated to AHRQ and transferred to NIH) Office of the Secretary: $400 million (allocated at the Secretary’s discretion) Federal Coordinating Council appointed to coordinate comparative effectiveness research across the federal government

44. Preferred CNS Medications for the Elderly Entacapone (add-on only) Ropinirole Carbidopa/Levodopa Parkinson’s Disease Citalopram Duloxetine Escitalopram Bupropion Mirtazapine Depression Donepezil Galantamine (ER only) Memantine (add-on only) Dementia Medication Therapeutic Area

45. Take Away … Comparative effectiveness is coming Research funded by American Recovery and Reinvestment Act of 2009 will begin soon This is an example of how criteria might be applied and the results NICE (National Institute for Clinical Evidence), the European Union equivalent to proposed comparative effectiveness, provides an example of what we might expect in the future http://www.nice.org.uk/

46. Chronic Kidney Disease

47. Creatinine Excretion and Serum Creatinine by Age Creatinine Excretion, mg/day Serum Creatinine Conc., mg % Average Age, years 20 40 60 80 10 73 122 152 94 68 29

48. Equations for Estimating GFR Abbreviated MDRD Study Equation GFR (mL/min/1.73 m 2 ) = 186.3  SCr -1.154  Age -0.203  0.742 (if female)  1.210 (if African American) MDRD = Modification of Diet in Renal Disease; CrCl = creatinine clearance; SCr=serum creatinine in mg/dL Levey AS, et al. Ann Intern Med. 2003;139:137-47. Cockcroft-Gault Equation CrCl = (mL/min) (140 – Age)  Weight in kg 72  SCr  0.85 if female

49. Prevalence of Low GFR in Nursing Home Elderly – Cockcroft-Gault Age (years) Percent of Patients Garg AX, et al. Kid Int 2004;65:649-53.

50. Prevalence of Low GFR in Nursing Home Elderly – MDRD Age (years) Percent of Patients Garg AX, et al. Kid Inter 2004;65:649-53.

51. Cockcroft-Gault (CG) or MDRD? Recent Study in JAGS 2009;57:1638-43 Measured CrCl based on 24-hour urine collection Comparison to measured value: CG slightly underestimates CrCl MDRD strongly overestimates CrCl KDOQI guidelines recommend MDRD for diagnosing and staging of CKD CG should be used for dosing medications KDOQI = Kidney Disease Outcomes Quality Initiative

52. Drugs That Need Special Attention in CKD Warfarin Warfarin metabolism not significantly altered Hemorrhage more likely - probably due to platelet dysfunction/drug-interactions Low-molecular-weight heparins Cleared primarily by the kidneys Risk of hemorrhage more likely with CKD Dose reduction required for most (usual cut-off 30 ml/min) Direct thrombin inhibitors Reduce dose for most – Hirudin, lepirudin Fondaparinux – avoid when CrCl less than 30 ml/min Gabardi S, Abramson S. Med Clin N Am 2005;89:649-87.

53. Drugs That Need Special Attention in CKD (2) ACE inhibitors As a class, generally cleared by the kidney (exception is fosinopril – hepatobiliary excretion) Reduce dose, however use not contraindicated ACEs beneficial in many with CKD (diabetes, CHF) NSAIDs should be avoided with ACEs in CKD ARBs Metabolized by liver – no adjustment needed Similar risk for ARF to ACE – monitor appropriately Combination of ACE + ARB seems to be safe in CKD Gabardi S, Abramson S. Med Clin N Am 2005;89:649-87.

54. Drugs That Need Special Attention in CKD (3) Antihypertensive agents Alpha-blockers – increased risk of orthostasis/hypotension Beta-blockers – increased risk of bradycardia: reduce dose of acebutolol, atenolol, nadolol, and sotalol Diuretics Spironolactone + ACE in HF ( ↑ K + ) ; careful in advanced CKD (SCr ≥ 2.5; GFR <15 mL/min) Thiazides have little effect if used alone in CKD – trouble reaching the nephron Loops have similar problems, but dose increases or the addition of a thiazide may overcome resistance Ototoxicity is more common in CKD due to impaired clearance and higher doses of loops used Gabardi S, Abramson S. Med Clin N Am 2005;89:649-87.

55. Drugs That Need Special Attention in CKD (4) NSAIDs; problems in CKD include hyperkalemia, hyponatremia, fluid retention, acute renal failure Narcotics Meperidine metabolism altered in CKD, resulting in accumulation of normeperidine (metabolite); may cause seizures Morphine metabolites (morphine-3 and morphine-6-glucuronide) can accumulate in CKD causing prolonged sedation and respiratory depression Oxycodone concentrations about 50% higher in CKD Gabardi S, Abramson S. Med Clin N Am 2005;89:649-87.

56. Drugs That Need Special Attention in CKD (5) Oral Hypoglycemics Acetohexamide, chlorpropamide, glyburide, and tolazamide; all have active metabolites that may accumulate causing prolonged hypoglycemia Metformin: increased risk of lactic acidosis in CKD Antimicrobials Aminoglycosides/vancomycin: use with caution and if using, monitor serum concentrations closely Cephalosporins/penicillins; most are renally eliminated: in most cases, dose is reduced in lieu of interval; Efficacy in UTI may be reduced Fluoroquinolones; most are renally eliminated. Better in UTI than cephs/pens in CKD Gabardi S, Abramson S. Med Clin N Am 2005;89:649-87.

57. Transitions of Care

58. Transition of Care vs Transitional Care The movement of patients from one practitioner or setting to another Multiple levels Within Settings Primary care  Specialty care Between Settings Hospital  Home Across health states Curative care  Palliative care/Hospice A set of actions ensuring the coordination and continuity of care as patients transfer between locations or levels of care Includes: Logistical arrangements Education of the patient and family Coordination among the health professionals involved in the transition Coleman E, et al. J Am Geriatr Soc 2003;51:556-7.

59. Ineffective Transitions Lead to Poor Outcomes Wrong treatment Delay in diagnosis Severe adverse events Patient complaints Increased healthcare costs Increased length of stay Australian Council for Safety and Quality in Health Care. Clinical hand-over and Patient Safety literature Review Report. March 2005. Available www.safetyandquality.org/internet/safety/publishing.nsf/Content/ AA1369AD4AC5FC2ACA2571BF0081CD95/$File/clinhovrlitrev.pdf

60. Care Transitions 30 Days Following Acute Care Hospital Home 64% 77% 13% 11% Nursing Facility Hospital or TCU 16% 10% 74% TCU = Transitional Care Unit Coleman EA et al. Health Svcs Research 2004;37:1423-40

61. Predictors of Complicated Care Transitions Heart disease Diabetes # of prior hospitalizations Visual impairment Medicaid recipient Prior stroke Coleman EA et al. Health Svcs Research 2004;37:1423-40. Increasing Risk

62. Medication Discrepancies: Hospital to SNFs Transitions Tija et al. J Gen Intern Medicine 2009. Cross-sectional study of patients admitted to SNF for subacute care (N=199, 2319 meds) Results: 21.3% of medication orders had a discrepancy At least one discrepancy in 71.4% of patients CV agents, opioid analgesics, neuropsychiatric agents, hypoglycemics, antibiotics, and anticoagulants accounted for > 50% of all discrepancies SNF=Skilled nursing facility

63. Models of Care Guided Care http://www.guidedcare.org/ The Transitional Care Model (TCM) http://www.transitionalcare.info/ The Care Transitions Intervention (CTI) http://www.caretransitions.org/ Project RED http://www.bu.edu/fammed/projectred/

64. Project RED http:// www.bu.edu/fammed/projectred/index.html http://relationalagents.com/red_demo_4545.wmv

65. CTM-3 The hospital staff took my preferences and those of my family or caregiver into account in deciding what my health care needs would be when I left the hospital. When I left the hospital, I had a good understanding of the things I was responsible for in managing my health. When I left the hospital, I clearly understood the purpose for taking each of my medications. http://www.caretransitions.org/documents/CTM3Specs0807.pdf

66. “ Ideal Transition Record” (ACP, SGIM, SHM, AGS, ACEP, and SAEM) Primary, secondary diagnoses and problems list Medication list (reconciliation) including OTC/other Treatment and diagnostic plan Clearly identifiable medical home/coordinating and transferring MD/institution and contact information Prognosis and outcome goals Test results (available and pending) Patient cognitive status Advance directives, power of attorney, consent Planned interventions, med equipment, wound care Emergency plan, contact information Assessment of caregiver status Snow V et al. J Gen Intern Med 2009;24:971-6.

67. Medication List Toolkit www.patientsafety.org/page/109587/

68. H.R. 3590 and H.R. 4872 Community-based Care Transitions Program Demonstration project to evaluate integrated care around hospitalization Independence at home demonstration program State option to provide health homes to Medicaid enrollees with chronic conditions Community Health Teams to support the Patient-Centered Medical Home CMS Innovation Center to test models of care

69. Working to Address the Issues www.ntocc.org

70. Recent Practice Guidelines American Geriatrics Society - Pharmacological Management of Persistent Pain in Older Persons Infectious Disease Society of America/ Society for Healthcare Epidemiology of America – Clostridium difficile infection in adults: 2010 update American Medical Directors Association – Transitions of Care in the Long-Term Care Continuum

71. Questions?