1. Symposium #: 445 THE WAR AGAINST POLYPHARMACY - RETHINKING AND RE-EVALUTION NEEDED FOR EACH AND EVERY DRUG IN THE ELDERLY Symposium #: 445 THE WAR AGAINST POLYPHARMACY - RETHINKING AND RE-EVALUTION NEEDED FOR EACH AND EVERY DRUG IN THE ELDERLY SPEAKERS: JOHN ELLERSHAW, LIVERPOOL, UK THIERRY CHRISTEANCE, GHENT, BELGIUM DEE MANGIN, CHRISTCHURCH, NEW ZEALAND DORON GARFINKEL, PARDES-HANA, ISRAEL CHAIR: DORON GARFINKEL, ISRAEL

2. INTRODUCTION DORON GARFINKEL, M.D. HEAD, GERIATRIC PALIATIVE DEPARTMENT DORON GARFINKEL, M.D. HEAD, GERIATRIC PALIATIVE DEPARTMENT SHOHAM GERIATRIC MEDICAL CENTER PARDES – HANA, I S R A E L SHOHAM GERIATRIC MEDICAL CENTER PARDES – HANA, I S R A E L Symposium #: 445 THE WAR AGAINST POLYPHARMACY - RETHINKING AND RE-EVALUTION NEEDED FOR EACH AND EVERY DRUG IN THE ELDERLY Symposium #: 445 THE WAR AGAINST POLYPHARMACY - RETHINKING AND RE-EVALUTION NEEDED FOR EACH AND EVERY DRUG IN THE ELDERLY

3. THE “BAD SIDE” OF AGING: AGE-RELATED DISEASES & DISFUNCTIONS ATHEROSCLEROSIS – IHD. & CHF, CVA, PVD & RENAL C A N C E R - MOST TYPES D E M E N T I A ( ALZHEIMER’S DIS.) D E P R E S S I O N ATHEROSCLEROSIS – IHD. & CHF, CVA, PVD & RENAL C A N C E R - MOST TYPES D E M E N T I A ( ALZHEIMER’S DIS.) D E P R E S S I O N IMPAIRED IMMUNITY -> INFECTIONS OSTEOPOROSIS & OSTEOARTHROSIS, F A L L S IMPAIRED IMMUNITY -> INFECTIONS OSTEOPOROSIS & OSTEOARTHROSIS, F A L L S DIABETES MELLITUS, PARKINSON’S DISEASE CATARACT, GLAUCOMA, AMD, HEARING LOSS, PROSTATIC HYPERTROPHY, INCONTINENCE, PRESSURE SORES... BED RIDDEN DIABETES MELLITUS, PARKINSON’S DISEASE CATARACT, GLAUCOMA, AMD, HEARING LOSS, PROSTATIC HYPERTROPHY, INCONTINENCE, PRESSURE SORES... BED RIDDEN D R U G S THE BAD SIDE OF D R U G S

5. POLYPHARMACYPOLYPHARMACY...preferably defined as : “The administration of more medications than are clinically indicated” medications than are clinically indicated” Hanlon et al. Suboptimal prescribing in older inpatients & outpatients. J Am Geriatr Soc 2001; 49: 200-9. J Am Geriatr Soc 2001; 49: 200-9. “Inappropriate Medication Use” (IMU) - medication use that has more potential risk for harming than potential benefit, is less effective or most costly than alternatives available... or does not agree with accepted medical standards.

6. Inappropriate Medication Use (IMU) Extent of the Problem 44000 - 98000 Americans Die Each Year Secondary to Medical Mistakes.. Vehicle Accidents 43460 Breast Cancer 42300 Deaths/year 44000 - 98000 Americans Die Each Year Secondary to Medical Mistakes.. Vehicle Accidents 43460 Breast Cancer 42300 Deaths/year Institute of Medicine (IOM) Report, 1999: To Err Is Human: Building a Safer Health Care System Institute of Medicine (IOM) Report, 1999: To Err Is Human: Building a Safer Health Care System

7. EXTENT OF THE PROBLEM IN THE ELDERLY...Use 3 TIMES the number of medications......Consume OVER ONE THIRD of the prescription & nonprescription medications used in the US The RISK OF HOSPITALIZATION secondary to IMU outcomes in elderly patients is estimated at 17% Almost 6 TIMES GREATER than that for the general population The RISK OF HOSPITALIZATION secondary to IMU outcomes in elderly patients is estimated at 17% Almost 6 TIMES GREATER than that for the general population Lombardi & Kennicutt. Medscape Pharmacists 2 (1), 2001 Nananda C et al, Arch Int Med 1990; 150: 841-6.

8. EXTENT OF IMU IN NURSING HOMES Patients receive an average of 6 Over 20% receiving > 10 medications daily 2 Patients receive an average of 6 Over 20% receiving > 10 medications daily 2 1). Liu GG & Dale BC. J Am Pharm Assoc 2002; 42 (6): 847-57. The total number of prescriptions correlates with the increase number of IMU 1 The total number of prescriptions correlates with the increase number of IMU 1 1). Liu GG & Dale BC. J Am Pharm Assoc 2002; 42 (6): 847-57. 2). Bernabei R, et al. J Gerontol Series A 1999; 54: M 25-33. 1). Liu GG & Dale BC. J Am Pharm Assoc 2002; 42 (6): 847-57. 2). Bernabei R, et al. J Gerontol Series A 1999; 54: M 25-33.

9. DRUG DISTRIBUTION

10. PALLIATIVE CARE - WHEN TO START? D I S E A S E Relieve suffering (Palliative, Hospice) QUALITY OF LIFE >>> PRESENTATION CURATIVE & LIFE PROLONGING THERAPY DEATH

11. CURATIVE & PREVENTIVE THERAPY D I S E A S E PALLIATIVE – QOL & RELIEVING SUFFER D I S E A S E ONLYPALLIATIVE PALLIATIVE PERCEPTION – WHEN TO APPLY? HEALTH DEATH BIRTH THE SUGGESTED MODEL THE CURRENT MODEL HEALTH PRESENTATION

12. D I S E A S E 2 D I S E A S E 4 HEALTH D I S E A S E 1 DISEASE 3 HEALTH HEALTH HEALTH DEATH ONLYPALLIATIVE ONLYPALLIATIVE ONLYPALLIATIVE THE COMPLEX IMPACT OF CO-MORBIDITY ONLYPALLIATIVE THE “REAL-LIFE” MODEL IN MOST ELDERLY PEOPLE QUALITY OF LIFE > > > > > > > > >.... QUALITY OF LIFE > > > > > > > > >....

13. THE “BAD SIDE” OF AGING: AGE-RELATED DISEASES & DISFUNCTIONS ATHEROSCLEROSIS – IHD. & CHF, CVA, PVD & RENAL CANCER - MOST TYPES DEMENTIA ( ALZHEIMER’S DIS.) DEPRESSION ATHEROSCLEROSIS – IHD. & CHF, CVA, PVD & RENAL CANCER - MOST TYPES DEMENTIA ( ALZHEIMER’S DIS.) DEPRESSION IMPAIRED IMMUNITY -> INFECTIONS OSTEOPOROSIS & OSTEOARTHROSIS, FALLS IMPAIRED IMMUNITY -> INFECTIONS OSTEOPOROSIS & OSTEOARTHROSIS, FALLS DIABETES MELLITUS, PARKINSON’S DISEASE CATARACT, GLAUCOMA, AMD, HEARING LOSS, PROSTATIC HYPERTROPHY, INCONTINENCE, PRESSURE SORES... BED RIDDEN DIABETES MELLITUS, PARKINSON’S DISEASE CATARACT, GLAUCOMA, AMD, HEARING LOSS, PROSTATIC HYPERTROPHY, INCONTINENCE, PRESSURE SORES... BED RIDDEN PREVENTIVE & CURATIVE MEANS IN MOST AGE RELATED DISORDERS EXCEPT ~10% WHO EXPERIENCE SUDDEN DEATH- PALLIATIVE THERAPY IN ALL ! T H E B A D S I D E O F D R U G S

14. William Shakespeare, As You Like It, 2.7 VIGELAND GARDENS, OSLO GUSTAV VIGELAND GARDENS, OSLO “And so from hour to hour we ripe and ripe, and then from hour to hour we rot and rot; “And so from hour to hour we ripe and ripe, and then from hour to hour we rot and rot; and thereby hangs a tale.“ and thereby hangs a tale.“ We Can Improve the tale

15. HOW DO WE DIE ??? Nowadays, very few adults / elders die suddenly while apparently healthy; most experience time-related increased number of incurable co-morbidities, disability and suffering for increasingly prolonged periods of time before death.

16. AFTER AGING......”GET SICK AND DIE”, which once covered no more than a few weeks, Now often goes on for YEARS Lynn J & Cretin S. Editorial, J Am Ger Soc 2000; 48: 1017- 8. The USUAL “ END “ END OF OF LIFE ” LIFE ” has has come to be LIFE WITH SERIOUS CHRONIC ILLNESS FOR A LONG TIME........

17. TIME IN LIFE 100 % HEALTH – DISEASE PERCEPTION IN THE 21 TH CENTURY HEALTH – DISEASE PERCEPTION IN THE 21 TH CENTURY GOOD HEALTH & LIFE QUALITY GOOD HEALTH & LIFE QUALITY BAD QUALITY OF LIFE BAD Q O L. BAD Q O L DEATH D E A T H WHICH ONE IS WORSE? D Y I N G...

18. DRUG THERAPY – THE HISTORIC 20 TH CENTURY CHANGE DRUG THERAPY – THE HISTORIC 20 TH CENTURY CHANGE EBM MEANS OF PREVENTION (DRUGS & OTHER) EBM MEANS OF PREVENTION (DRUGS & OTHER) REPRESENT THE MOST COST EFFECTIVE INTERVENTIONS TO PROMOTE HEALTH & Q O L, INTERVENTIONS TO PROMOTE HEALTH & Q O L, DELAY DISEASES & COMPLICATIONS, DELAY DISEASES & COMPLICATIONS, DELAY & COMPRESS SUFFERING & DISABILITY, INTO A SHORTER END OF LIFE PERIOD INTO A SHORTER END OF LIFE PERIOD BEFORE DEATH. BEFORE DEATH. DO WE ACTUALLY ACHIEVE THIS GOAL IN MOST PEOPLE? DO WE ACTUALLY ACHIEVE THIS GOAL IN MOST PEOPLE?

19. MEDICATION GUIDELINES – WE KNOW WHEN TO START DRUGS WHY DO PHYSICIANS CONTINUE TO GIVE PREVENTIVE & CURATIVE MEDICATIONS OCCASIONALLY UNTILL DEATH ? WHY ARE PHYSICIANS, BEING AWARE OF POLYPHARMACY / IMU RELUCTANT TO DISCONTINUE MANY DRUGS ? DO WE KNOW WHEN TO STOP ?

20. WHY DON’T WE STOP DRUGS ??? Drugs are often given to elders based on Clinical Practice Guidelines (CPGs) that extrapolate evidence of benefit in younger adults without significant co-morbidity, who have a life expectancy of several decades. Drugs are often given to elders based on Clinical Practice Guidelines (CPGs) that extrapolate evidence of benefit in younger adults without significant co-morbidity, who have a life expectancy of several decades. Physicians usually EXTRAPOLATE from these CPGs to include all elders, Even Those with MULTIPLE CO-MORBIDITIES, SEVERE DISABILITY, DEMENTIA & even “TERMINAL” PATIENTS Physicians usually EXTRAPOLATE from these CPGs to include all elders, Even Those with MULTIPLE CO-MORBIDITIES, SEVERE DISABILITY, DEMENTIA & even “TERMINAL” PATIENTS

21. Adhering to current CPGs in elders with several co-morbidities may have undesirable effects; basing standards for quality of care and pay-for-performance on existing CPGs could lead to inappropriate judgment of the care provided, Create perverse incentives that emphasize the wrong aspects of care for this population and diminish the quality of their care Boyd CM, Darer J, Boult C, et al. J Am Med Ass 2008;294: 716 – 24. Clinical practice guidelines (CPGs) and quality of care for older patients with multiple comorbide diseases. P R I M U M N O N N O C E R E !

22.  DO WE HAVE TO CONTINUE ALL CURATIVE AND PREVENTIVE MEDICATIONS UNTILL DEATH? PREVENTIVE MEDICATIONS UNTILL DEATH?  ARE THEY STILL COST EFFECTIVE, HAVING POSITIVE BENEFIT / RISK RATIO : POSITIVE BENEFIT / RISK RATIO : IN A VERY ADVANCED AGE ? IN A VERY ADVANCED AGE ?  IN THE PRESENCE OF SEVERE CO-MORBIDITY? DISABILITY? DEMENTIA ? DISABILITY? DEMENTIA ?  IN THE PRESENCE OF SIGNIFICANT SUFFERING ?  IN THE PRESENCE OF LIMITED LIFE EXPECTANCY ? THERE ARE NO GOOD EVIDENCE BASED ANSWERS ! PRINCIPLES OF DRUG THERAPY – THE 21 TH CENTURY ENLIGHTMENT

23. DISEASES DEATHDEATH PALLIATIVE PERCEPTION – WHETHER / WHEN TO STOP DRUGS?? HEALTH ASPIRIN, WARFARIN, DIPIRIDAMOLE, STATINES, β BLOCKERS, ACE / ARI, CALCIUM CHANNEL BLOCKERS, NITRATES, DIURETICS, OMEPRAZOLE, H 2 BLOCKERS, BENZODIAZEPINES, TCI & OTHER ANTIDEPRESSENTS, IRON, SALTS AND VITAMIN SUPPLEMENTATIONS... ASPIRIN, WARFARIN, DIPIRIDAMOLE, STATINES, β BLOCKERS, ACE / ARI, CALCIUM CHANNEL BLOCKERS, NITRATES, DIURETICS, OMEPRAZOLE, H 2 BLOCKERS, BENZODIAZEPINES, TCI & OTHER ANTIDEPRESSENTS, IRON, SALTS AND VITAMIN SUPPLEMENTATIONS... CURATIVE, LIFE EXTENDING DRUGS PREVENTIVE MEDICATIONS PREVENTIVE MEDICATIONS BIRTH PRESENTATION TILL WHEN?? PALLIATIVEONLY TILL WHEN??

24. ... NO ONE WOULD SUGGEST CONTINUATION OF PREVENTIVE & CURATIVE GUIDELINES

25. DISEASES DEATHDEATH PALLIATIVE PERCEPTION – WHETHER / WHEN TO STOP DRUGS?? HEALTH ASPIRIN, WARFARIN, DIPIRIDAMOLE, STATINES, β BLOCKERS, ACE / ARI, CALCIUM CHANNEL BLOCKERS, NITRATES, DIURETICS, OMEPRAZOLE, H 2 BLOCKERS, BENZODIAZEPINES, TCI & OTHER ANTIDEPRESSENTS, IRON, SALTS AND VITAMIN SUPPLEMENTATIONS... ASPIRIN, WARFARIN, DIPIRIDAMOLE, STATINES, β BLOCKERS, ACE / ARI, CALCIUM CHANNEL BLOCKERS, NITRATES, DIURETICS, OMEPRAZOLE, H 2 BLOCKERS, BENZODIAZEPINES, TCI & OTHER ANTIDEPRESSENTS, IRON, SALTS AND VITAMIN SUPPLEMENTATIONS... CURATIVE, LIFE EXTENDING THERAPY PREVENTIVE THERAPY PREVENTIVE THERAPY BIRTH PRESENTATION PALLIATIVEONLY PALLIATIVEONLY TILL WHEN?? GERIATRIC-PALLIATIVE PERCEPTION THE “REVERSED EXTRAPOLATION” METHOD

26. SUMMARIZING THE PROBLEM FOR MOST CURATIVE / PREVENTIVE MEDICATIONS 1). The Positive Benefit / Risk Ratio is. Decreasing or Non - Exsistant Decreasing or Non - Exsistant In Correlation to Age, Multiple Co-Morbidities, Disability, Dementia & Quality of Life 2). The extent of Drug Related Problems and IMU is Increasing In Correlation to Age, Co-Morbidities, Disability, Dementia and the Number of Drugs Consumed (Polypharmacy) being particularly disturbing in LTC departments

27. PREVENTIVE THERAPY ??? PREVENTIVE THERAPY ??? CURATIVE, LIFE EXTENDING ??? CO-MORBIDITIES PALLIATIVEONLY HEALTH? DEATH TO GIVE ? OR NOT TO GIVE? REVERSED EXTRAPOLATION (TIME BEFORE DEATH...) TIME BEFORE DEATH HOURS... D D D DAYS...>> W W W WEEKS << M M M MONTHS > >< << Y YEARS REVERSED EXTRAPOLATION - TYPE OF PATIENTS INDEPENDENT ELDERS << COMMUNITY FRAIL ELDERS << DISABILITY / DEMETIA REVERSED EXTRAPOLATION - TYPE OF PATIENTS INDEPENDENT ELDERS << COMMUNITY FRAIL ELDERS << DISABILITY / DEMETIA THE WAR AGAINST POLYPHARMACY THE “REVERSED EXTRAPOLATION” METHOD

28. DORON GARFINKEL, M.D. THE WAR AGAINST POLYPHARMACY A NEW GERIATRIC-PALLIATIVE APPROACH THE WAR AGAINST POLYPHARMACY A NEW GERIATRIC-PALLIATIVE APPROACH SHOHAM GERIATRIC MEDICAL CENTER PARDES – HANA, ISRAEL SHOHAM GERIATRIC MEDICAL CENTER PARDES – HANA, ISRAEL IN THE COMMUNITY AND IN LONG TERM CARE FACILITIES HEAD, GERIATRIC PALIATIVE DEPARTMENT

29. PREVENTIVE THERAPY ??? PREVENTIVE THERAPY ??? CURATIVE, LIFE EXTENDING ??? CO-MORBIDITIES PALLIATIVEONLY HEALTH? DEATH TO GIVE ? OR NOT TO GIVE? REVERSED EXTRAPOLATION (TIME BEFORE DEATH...) TIME BEFORE DEATH HOURS... DAYS...>> WEEKS > < << YEARS REVERSED EXTRAPOLATION - TYPE OF PATIENTS INDEPENDENT ELDERS << COMMUNITY FRAIL ELDERS << DISABILITY / DEMENTIA REVERSED EXTRAPOLATION - TYPE OF PATIENTS INDEPENDENT ELDERS << COMMUNITY FRAIL ELDERS << DISABILITY / DEMENTIA IN LONG TERM CARE FACILITIES THE WAR AGAINST POLYPHARMACY THE “REVERSED EXTRAPOLATION” METHOD IN LONG TERM CARE FACILITIES

30. METHODS & PATIENTS Individualization of drug therapy was started in 180 elderly patients who were hospitalized in 6, out of the 10 nursing departments at the Shoham Geriatric Center METHODS & PATIENTS Individualization of drug therapy was started in 180 elderly patients who were hospitalized in 6, out of the 10 nursing departments at the Shoham Geriatric Center In each patient, an attempt was made TO STOP ALL DRUGS for which THERE WAS NO CLEAR CUT INDICATION, and / or REDUCE THE DOSAGE of drugs for which the indication was still relevant In each patient, an attempt was made TO STOP ALL DRUGS for which THERE WAS NO CLEAR CUT INDICATION, and / or REDUCE THE DOSAGE of drugs for which the indication was still relevant THE WAR AGAINST POLYPHARMACY A NEW GERIATRIC-PALLIATIVE APPROACH THE WAR AGAINST POLYPHARMACY A NEW GERIATRIC-PALLIATIVE APPROACH IN LONG TERM CARE FACILITIES IN LONG TERM CARE FACILITIES THE WAR AGAINST APPROACH THE WAR AGAINST POLYPHARMACY A NEW GERIATRIC-PALLIATIVE APPROACH IN LONG TERM CARE FACILITIES

31. METHODS & PATIENTS ATTEMPTS TO STOP/REDUCE DOSE WERE MADE FOR: METHODS & PATIENTS ATTEMPTS TO STOP/REDUCE DOSE WERE MADE FOR: NITRATES IN ALL ASYMPTOMATIC PATIENTS DRUGS FOR HTn GRADUALLY WITH STRICT MONITORING DIURETICS NO CLEAR SYMPTOMS/SIGNS OF CHF EXIST ANTIACIDS & H 2 BLOCKERS IN ALL ASYMPTOMATIC PATIENTS SEDATIVES & TRANQUILIZERS ANTI DEPRESSANTS, PSYCHOTROPIC DRUGS PENTOXIFYLLINE, DIPYRIDAMOLE, NSAIDs, MISCELLANEOUS: SLOW K, SLOW FE, ORAL HYPOGLYCEMICS CHOLESTEROL LOWERING, ASPIRIN, CHOLESTEROL LOWERING, ASPIRIN, ANTI EPILEPTICS, MINERALS, VITAMINS.. ANTI EPILEPTICS, MINERALS, VITAMINS.. THE WAR AGAINST POLYPHARMACY A NEW THE WAR AGAINST POLYPHARMACY A NEW GERIATRIC-PALLIATIVE APPROACH IN LONG TERM CARE FACILITIES

32. METHODS & PATIENTS The control group was composed of patients of the same 6 departments in whom discontinuation of drugs (DD) have not been performed. The study & control groups were treated by the same interdisciplinary teams who regarded DD in some patients as part of an overall clinical policy attempting to improve drug therapy. None of the team members was aware of our intention to evaluate the long term outcomes of patients in whom DD have/have not been performed. THE WAR AGAINST POLYPHARMACY THE WAR AGAINST POLYPHARMACY IN LONG TERM CARE FACILITIES

33. DEMOGRAPHY and CO-MORBIDITIES P - Value Control Group Control Group Study Group Study GroupParameter -71119 Total Number NS @ 44/2732/87Female/Male NS + 82 ± 8.7 81.2 ± 8.3 A G E (Mean ±S.D) NS 66 (93%) 112 (94%) Dementia * NS 66 (92%) 111 (93%) Double Incontinence NS 10 (14%) 21 (18%) Indwelling Urinary Catheter NS 29 (41%) 55 (46%) Hypertension NS 5 (7%) 12 (10%) Congestive Heart Failure NS 9 (13%) 6 (5%) Previous Myocardial Infarction NS 14 (20%) 16 (13%) Chronic Atrial Fibrillation NS 17 (24%) 36 (30%) Diabetes Mellitus NS 9 (13%) 6 (5%) C O P D NS 28 (39%) 45 (38%) Previous Stroke - CVA NS 18 (25%) 29 (24%) Hypo Albuminemia ** NS 13 (18%) 35 (29%) Recurrent Infections # @ Not significant. All parameters except Age, were analyzed employing the Chi square test + t - test * Mini Mental State Examination (MMSE) 14/30 or less ** Serum albumin < 3.0 g/dl # At least two proven infections in one year (UTI, Pneumonia, skin infections etc.) @ Not significant. All parameters except Age, were analyzed employing the Chi square test + t - test * Mini Mental State Examination (MMSE) 14/30 or less ** Serum albumin < 3.0 g/dl # At least two proven infections in one year (UTI, Pneumonia, skin infections etc.)

34. Annual Success Rate According to the No. Drugs Discontinued In Nursing Departments Annual Success Rate According to the No. Drugs Discontinued In Nursing Departments Rate of Failure - Re administration No. No.Patients No. Drugs Discontinued No. of No. ofDrugs No. of Patients 3/142/227 5/242/446 13/655/13135 5/605/15154 5/874/29293 1/521/26262 2/302/30301 33/33221/119119TOTAL 1018100PERCENT

35. No. Pts. Reccurence of % of. DRUG Stopped Symptoms/Signs Success. NITRATES 22 0 100 NITRATES 22 0 100 H 2 BLOCKERS 35 2 94 H 2 BLOCKERS 35 2 94 ANTI HTn 51 9 82 ANTI HTn 51 9 82 DIURETICS (fusid) 27 (25) 4 ( 4) 85 DIURETICS (fusid) 27 (25) 4 ( 4) 85 No. Pts. Reccurence of % of. DRUG Stopped Symptoms/Signs Success. NITRATES 22 0 100 NITRATES 22 0 100 H 2 BLOCKERS 35 2 94 H 2 BLOCKERS 35 2 94 ANTI HTn 51 9 82 ANTI HTn 51 9 82 DIURETICS (fusid) 27 (25) 4 ( 4) 85 DIURETICS (fusid) 27 (25) 4 ( 4) 85 Annual Success Rate According to Types of Drugs Discontinued Annual Success Rate According to Types of Drugs Discontinued PENTOXIFYLLINE 15 0 100 PENTOXIFYLLINE 15 0 100 SLOW K 20 0 100 SLOW K 20 0 100 SLOW FE 19 1 95 SLOW FE 19 1 95 SEDAT & TRANQUIL 16 2 88 SEDAT & TRANQUIL 16 2 88 ANTIDEPRESSANTS 19 5 74 ANTIDEPRESSANTS 19 5 74 ANTIPSYCHOTICS 13 4 69 ANTIPSYCHOTICS 13 4 69 PENTOXIFYLLINE 15 0 100 PENTOXIFYLLINE 15 0 100 SLOW K 20 0 100 SLOW K 20 0 100 SLOW FE 19 1 95 SLOW FE 19 1 95 SEDAT & TRANQUIL 16 2 88 SEDAT & TRANQUIL 16 2 88 ANTIDEPRESSANTS 19 5 74 ANTIDEPRESSANTS 19 5 74 ANTIPSYCHOTICS 13 4 69 ANTIPSYCHOTICS 13 4 69

36. P - Value ControlGroupStudyGroup 71119 Total No. 0.001 (45%) 32 (45%) 32 25 (21%) Deaths Annual Rate of Deaths

37. P - Value ControlGroupStudyGroup 71119 Total No. 0.001 (45%) 32 (45%) 32 25 (21%) Deaths 0.002 (30%)21 14 (11.8%) Referrals to Acute Care Acute CareFacilities Annual Rate of Deaths and Referrals to Acute Care Facilities Annual Rate of Deaths and Referrals to Acute Care Facilities

38. 1 – 6 / 20031 – 6 / 2004 P Value Control group No 2 * (4 Wards) 1.65 1.39 0.07 ** Study Departments (6 Wards) 1.74 1.28 0.02 FOUR DEPARTMENTS (132 Patients) in which our new therapeutic approach was not applied. * FOUR DEPARTMENTS (132 Patients) in which our new therapeutic approach was not applied. SIX DEPARTMENTS (198 Patients) in which our new therapeutic approach was applied. ** SIX DEPARTMENTS (198 Patients) in which our new therapeutic approach was applied. The figure represents cost of drugs of 119 patients of the study group The figure represents cost of drugs of 119 patients of the study group that of patients in whom no change in drugs was made. + that of patients in whom no change in drugs was made. The Average Daily Cost of Drugs per Patient in US dollars

39. Application of the Good Palliative-Geriatric Practice (GPGP) methodology in disabled elders enables simultaneous discontinuation of several medications and yields several benefits: reduction in mortality rates & referrals to acute care facilities, lower costs and improved quality of living. Conclusions

41. POLYPHARMACY Inappropriate Medication Use (IMU) medication use that has more potential risk more potential risk for harming than potential benefit... than potential benefit...

42. At least in Nursing Departments, the Sum Total of Negative Impacts of MEDICATIONS, OUTWEIGHS the Sum Total of the Potential Beneficial Effects of all specific drugs. At least in Nursing Departments, the Sum Total of Negative Impacts of MEDICATIONS, OUTWEIGHS the Sum Total of the Potential Beneficial Effects of all specific drugs.

43. DORON GARFINKEL, SARAH ZUR-GIL, JOSHUA BEN-ISRAEL ISRAEL MEDICAL ASSOCIATION JOURNAL (IMAJ) 9: 430 - 4 (June 2007) THE WAR ON POLYPHARMACY : A New, Cost Effective, Geriatric - Palliative Approach for Improving Drug Therapy in Disabled Elderly People THE WAR ON POLYPHARMACY : A New, Cost Effective, Geriatric - Palliative Approach for Improving Drug Therapy in Disabled Elderly People

44. PREVENTIVE THERAPY ??? PREVENTIVE THERAPY ??? CURATIVE, LIFE EXTENDING ??? CO-MORBIDITIES PALLIATIVEONLY HEALTH? DEATH TO GIVE ? OR NOT TO GIVE? REVERSED EXTRAPOLATION (TIME BEFORE DEATH...) TIME BEFORE DEATH... DAYS...>> WEEKS > > WEEKS > < << YEARS REVERSED EXTRAPOLATION - TYPE OF PATIENTS INDEPENDENT ELDERS << COMMUNITY FRAIL ELDERS << DISABILITY / DEMETIA REVERSED EXTRAPOLATION - TYPE OF PATIENTS INDEPENDENT ELDERS << COMMUNITY FRAIL ELDERS << DISABILITY / DEMETIA IN LONG TERM CARE FACILITY THE WAR AGAINST POLYPHARMACY THE “REVERSED EXTRAPOLATION” METHOD IN LONG TERM CARE FACILITY

45. PREVENTIVE THERAPY PREVENTIVE THERAPY CURATIVE, LIFE EXTENDING T X. DISEASES PALLIATIVEONLY HEALTH? DEATH TO GIVE ? OR NOT TO GIVE? TIME BEFORE DEATH...) TIME BEFORE DEATH HOURS... DAYS.> WEEKS > < < YEARS MANY YEARS TYPE OF PATIENTS IN THE COMMUNITY INDEPENDENT ELDERS << FRAIL ELDERS << DISABILITY / DEMETIA TYPE OF PATIENTS IN THE COMMUNITY INDEPENDENT ELDERS << FRAIL ELDERS << DISABILITY / DEMETIA THE “REVERSED EXTRAPOLATION” METHOD IN COMMUNITY DWELLING ELDERS

46. THE WAR AGAINST POLYPHARMACY : IN COMMUNITY DWELLING ELDERLY PEOPLE PRELIMINARY RESULTS 70 elders, mean age 82.8 ± 7, 92% independent / frail. 94% suffered ≥ 3, 51% > 6 different health problems (co-morbidities). Mean Follow Up 19.2 ± 11 months. Elders used 7.73 ± 3.7 drugs (range 0-16). DD recommended for 57.5% (4.4 ± 2.5 drugs/elder) of all drugs 47% (3.7±2.5 drugs/elder) actually stopped. 47% (3.7±2.5 drugs/elder) actually stopped. Only 5/256 DD had to be readministered (failure 2%) successful DD eventually achieved in 80.7%. successful DD eventually achieved in 80.7%. No significant adverse effects 80% of Patients/Families reported medical - functional - mental - cognitive improvement, defined as significant in 37%, outstanding in 29%. 10 elders (14%) died, mean age at death 88 years, FU 13 ± 9 months.

47. Application of the GPGP methodology was executed in several dozens of community dwelling elders. DRUG DISCONTINUATION could be performed in almost all of them (1 – 9 drugs) with no significant adverse effects. In some, a remarkable improvement was noticed in the quality of life: improvement in mobility, alertness and cognitive status (e.g. an increase in mini mental state examination [MMSE] from 14/30 to 30/30 in two months) THE WAR AGAINST POLYPHARMACY : APPLYING THE GPGP APPROACH IN THE COMMUNITY THE WAR AGAINST POLYPHARMACY : APPLYING THE GPGP APPROACH IN THE COMMUNITY

48. THE GPGP APROACH – WHEN/IF TO STOP MEDICATIONS The decision is based on clinical common sense and should be taken together with the patient & family. An attempt should be made to be less aggressive in reaching rigid target goals (Blood Pressure, serum glucose & lipid levels), while giving more room to QUALITY of LIFE and PATIENT / FAMILY preferences. The decision is based on clinical common sense and should be taken together with the patient & family. An attempt should be made to be less aggressive in reaching rigid target goals (Blood Pressure, serum glucose & lipid levels), while giving more room to QUALITY of LIFE and PATIENT / FAMILY preferences.

49. uidelines The Sum Total of all potential beneficial effects of all specific drugs and Guidelines The Sum Total of all negative Impacts of Polypharmacy & combined Guidelines Primum non nocere Individualization Autonomy Advance Directives Patient / family preferences COMMONSENSE HUMANITY – EXPERIENCE - EBM KNOWLEDGE

50. “ I feel a lot better since I ran out of those pills you gave me.”

51. “ It is an art of no little importance to administer medicines properly: Philippe Pinel, 1745-1826 ( 18th. Century !!! ) but, it is an art of much greater and more difficult acquisition to know when to suspend or altogether to omit them."

52. Do the known adverse reactions of the drug outweigh possible benefit in old, disabled patients? Any adverse symptoms or signs that may be related to the drug that may be related to the drug ? Another drug that may be superior to the one in question Can the dosing rate be reduced with no significant risk? CONTINUE WITH THE SAME DOSING RATE REDUCE DOSE S H IFT TO A N O T H E R D R U G Improving Drug Therapy in Disabled / Frail Elderly Patients - An algorithm YES NO YES NO / NOT SURE S SSTOPTOP DRUG DRUGSSTOPTOP DRUG DRUG Indication seems valid and relevant in this patient’s age group and disability level NO YES An evidence-based consensus exists for using the drug for the indication given in its current dosing rate, in this patient’s age group and disability level, and in this patient’s age group and disability level, and the benefit outweigh all possible known adverse effects YES