Academic Profiles: Current Position: Evidence-Based Medicine CEEBM

Transcription

1 CURRICULUM VITAE Academic Profiles: Medical Doctor FMUI, 1986 Internist FMUI, 1996 Post Graduate Education in Geriatric Medicine Dept. of Geriatric & Rehab Medicine Royal Adelaide Hospital, Australia, 1997 Consultant (Subspecialist) in Geriatric Medicine FMUI, 2000 Master of Clinical Epidemiology Universitas Indonesia, 2003 Doctor of Philosophy (PhD) Universitas Indonesia, 2006 Professor of Medicine - Universitas Indonesia, 2013 Current Position: Chair Indonesian Geriatrics Society (PERGEMI) Chair Clinical Epidemiology and Evidence-Based Medicine (CEEBM) Unit, Cipto Mangunkusumo Hosp-FMUI. Vice Chair The Indonesian Journal of Internal Medicine (Acta Medica) Senior staff in Geriatric Medicine Division Internal Medicine Department, FMUI-RSCM

2 Evidence-based Medicine in The Very Old Patients Siti Setiati

3 What is Evidence-based Medicine? The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients Pemanfaatan bukti mutakhir yang terbaik, terkini, dalam tatalaksana pasien Best research evidence Patients preferences EBM Clinical expertise

4 An expert opinion Statement in textbook What the latest paper in a prestigious journal says Traditional approach It s the way we ve always done it Continuing Medical Education course Choosing the most expensive treatment that patient can afford Those are not EBM

5 WHY EBM? 1. Information overload 2. Keeping current with literature 3. Our clinical performance deteriorates with time ( the slippery slope ) 4. Traditional CME does not improve clinical performance 5. EBM encourages self directed learning process which should overcome the above shortages Our textbooks are out-of-date Fail to recommend Rx up to ten years after it s been shown to be efficacious. Continue to recommend therapy up to ten years after it s been shown to be useless. On average, the clinically-important knowledge of physicians deteriorates rapidly after we complete our training.

6 Diagnosis Area of EBM (Determination of disease or problem) Treatment (Intervention to help the patient) Prognosis (Prediction of outcome of disease) Etiology (Cause of an outcome or disease) Systematic Reviews Meta-analysis Clinical guidelines Economic analysis Clinical decision making Cost-effectiveness analysis Qualitative research

7 Interpreting the Evidence Frame Patient Scenario into a Clinical Question Systematically retrieve best evidence available CRITICAL APPRAISE EVIDENCE Patient Intervention Comparison Outcome Electronic searching Database Keywords & combination of search term(s): AND, OR, bracket Hand searching Type of articles: inclusion & exclusion criteria Apply results to patient Is this study valid? Are the result important? Can the result help you? Evaluate decision making Validity Importance Applicability

8 Characteristics of Very Old Patient Multimorbidity Decreased organ function Polypharmacy Reduced Functional Status Poor Nutritional Status Geriatric Syndrome Halter, JB et al. Hazzard s Geriatric s_setiati@yahoo.com Medicine and Gerontology. Edisi 8 7. McGraw Hill Education. 2017

9 Improving EBM in Elderly: Generating More Scientific Evidence Using a multimorbidity approach guidelines for elderly difficult to manage their treatments or day-to-day activities have frailty or frequent falls frequently seek unplanned or emergency care prescribed multiple regular medicines Multimorbidity refers to the presence of 2 or more long-term health conditions, which can include: Defined physical and mental health conditions such as diabetes or schizophrenia Ongoing conditions such as learning disability Symptom complexes such as frailty or chronic pain Sensory impairment such as sight or hearing loss

10 Multiple chronic diseases (multimorbidity) Consequences of Aging: Tidak aman Increased Disease Prevalence Ageing Research Reviews 10 (2011) Multiple clinical practice guidelines (multiple PPK) Polypharmacy, multiple appointment, unplanned care Prevalence of multimorbidity (defined as 2+ concurrent diseases) widely varied across studies, around 20 30% whole population; 55 to 98% in older persons

11 How the Aging Process Affects EBM Elements Characteristics of very old: Multimorbidity Polypharmacy Decreased physical, psychological and social function Increased rehospitalization, adverse events, mortality Every elderly is very heterogenic due to those characteristics However, studies need to make their subjects as homogen as possible We need to critically appraise those studies before applying them to our elderly patients. to prevent OVERTREATMENT of vulnerable patients and UNDERTREATMENT of fit older patients

12 Scientific Evidence in Old Patients Multimorbidity Polypharmacy Multidomain functioning Different requirements for clinical studies Inclusion of representative older patients Reporting and weighing of all four geriatric axes Inclusions of study endpoints that are relevant for elderly Age-related physiological changes, multimorbidity, polypharmacy Cognitive, functional, psychosocial, diseases Physical, psychosocial, or social functioning; quality of life Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

13 Scientific Evidence in Old Patients: Randomized Control Trials To study the effects of a drug that is cleared by the kidney, a patient population may be required that does not include patients with renal failure. Whereas the renal function of an elderly is commonly reduced, especially in the very old

14 Scientific Evidence in Old Patients: Randomized Control Trials Explicit exclusion criteria: An upper age limit Exclusion of diseases that are almost only seen in older adults (eg. Dementia) Exclusion of elderly with mobility problems in a trial protocol that requires participants to visit study center multiple times Elderly will be underrepresented in RCTs Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

15 Scientific Evidence in Old Patients: Randomized Control Trials Endpoints in RCTs are often related to the incidence of disease and mortality, whereas for elderly patients the physical, psychological and social functioning may be considered more important!!!. Psychological function Somatic diseases Older adult Social function Physical function Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

16 Scientific Evidence in Old Patients: Etiological Studies Observational studies if performed in representative older patients, may provide useful evidence for the treatment. Essential to understand how health and disease work in aging body Risk factors for aspiration pneumonia: sputum suctioning (OR = 3.276, 95% CI: ) deterioration of swallowing function in the past : Manabe T, Teramoto S, Tamiya N, Okochi J, Hizawa N (2015) Risk Factors for Aspiration Pneumonia in Older Adults. PLoS ONE 10(10): e doi: /journal.pone months (OR = 3.584, 95% CI: ) dehydration (OR = 8.019, 95% CI: ) dementia (OR = 1.618, 95% CI: ) Method: observational study of 9930 patients (median age 86 y.o, women : 76%) who were divided into 2 groups : those who had experienced and episode of aspiration pneumonia in the previous 3 months and those who had not. Data on demographics, clinical status, activities of daily living (ADL), and major illnesses were compared between subjects with and without aspiration pneumonia These results could help improve clinical management for preventing repetitive aspiration pneumonia

17 30 days mortality rate (%) Absolute Risk Reduction (ARR) Study are often conveyed in terms of relative risk reduction (RRR) rather than ARR, which often suggest impressive outcomes (eg. a 25% RRR) But, RRR is uninterpretable if the baseline risk is not reported. ARR is based on the baseline risk minus the risk of the outcome with treatment may reflect the difference between two comparator treatments Trial 1 ARR = 40%-30% =10% RRR = 1- RR = 1- (0.3/0.4) = =0.25 (25%) Trial 2 ARR = 10%-7.5% =2.5% RRR = 1- RR = 1- (0.075/0.1) = =0.25 (25%)

18 Time Horizon to Benefit Studies often reports results in terms of number needed to treat/harm without cosideration of time period to outcome Time horizon to benefit is the length of time needed to receive and observable, clinically meaningful risk reduction for a specific outcome. For some chronic conditions, certain interventions are beneficial only after longer durations of treatment. the NNT to prevent one death was 50 patients over 5 years of treatment Example: The time horizon to benefit of tight glycemic control in DM is believed to be at least 5-7 years For the very old elderly, do the anticipated benefits outweigh the long-term burden and potential harms of treatment for the patients?

19 Improving EBM in Elderly: Generating More Scientific Evidence For specific diseases and guidelines, existing evidence can be assessed for validity for elderly in general and individual patients specifically More representative elderly patients should be included in clinical studies Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

20 Questions to Ask Regarding the Medical Literature To what extent were older adults with multimorbidity included in the trials? Is there evidence of effect modification? What is the quality of the evidence, using accepted EBM methodologies? What are the hoped- for outcomes of the treatment or intervention? Are these outcomes important to patients? Is there meaningful variation in baseline risk for outcomes that the treatment or intervention is designed to affect? Are the risks and side effects of the treatments and interventions in older patients with multimorbidity clearly known, so that a decision can be made whether the treatment for one condition will exacerbate another? What are the comparator treatments or management strategies? Is it known how long it takes to accrue the benefit or harms of the treatment or intervention? Does the document give absolute risk reductions or merely relative risk reduction? Is it possible to estimate absolute risk reduction? How precise are the findings? What are the confidence limits?

21 Assessment of Patient s Medical Conditions Cognitive performance Apathy and depression Psychological function Somatic diseases Older adult Physical function Level of physical activity Ability to perform ADL Those four axes may serve as determinants of disease and also an endpoints Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015 Social function Presence of a spouse Outdoor social activities with friends Level of support provided by children

22 Improving EBM in Elderly: Systematic Acknowledgement of the Patient Situation Somatic diseases Psychological function Older adult Physical function Patient s preference of treatment goals!!!... Frailty Assessment Social function Comprehensive Geriatric Assessment (CGA) Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

23 Patient Preferences Older people with multimorbidity are able to evaluate choices and the prioritize their preferences for care, considering relevant personal and cultural contexts about health and health care. Process of eliciting patient preferences: Recognize when the older adult with multimorbidity is facing a preference sensitive decision. Example: Therapy that may results in long-term benefits but may cause short term harm (statin may reduce CVD risk but also may cause cognitive impairment or muscle weakness) Ensure that elderly with multimorbidity are adequately informed about the expected benefits and harms of different treatment options.

24 Patient Preferences Process of eliciting patient preferences: Elicit patient preferences only after the elderly with multimorbidity is sufficiently informed Typical outcomes: living as long as possible, maintaining function, alleviating pain and other symptoms Let the patients speak their mind Ask the patients if they want their family/caregiver to be involved in decision making Re-examined those preferences, those may change overtime This whole process doesn t mean that patients has the right to demand any options without reasonable expectation of some benefits.

25 Assess Treatment Costs and Benefits Slow recovery from an intervention Inactivation and immobilization Symptoms Lifespan Cure Complication Side effect Burden Loss of muscle mass Risk for falls Functional decline Postoperative delirium Drug interaction Older Patients Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015 Higher dose more side effects Lower dose undertreatment

26 Assess Treatment Costs and Benefits Shorter remaining life expectancy Smaller restoration of physical function Large heterogenicity same calendar age, different in biological age Symptoms Lifespan Cure Complication Side effect Burden Overtreatment of the frail Undertreatment of the fit Older Patients Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

27 Other things to consider Prognosis: Remaining life expectancy Functional status Quality of life Clinical Feasibility: The more complex a treatment regimen, the higher risk of non-adherence, adverse reactions, poor quality of life and economic burden, greater depression in caregivers Treatment complexity and feasibility Number of medications Dosage Frequency of dosing Administration instruction

28 Improving EBM in Elderly: Increasing Doctor s Experience and Expertise Knowledge of the pathophysiology of the ageing process and its implications for treatment effects The lack of evidence should be discussed with the patient in the light of individual patient situation and preferences. There is no one single best treatment option shared decision making Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The Netherlands Journal of Medicine. Vol 73. No June 2015

29 Careful and Kind Care Sensible Resolution Clear Situation Unhurried Conversation Situation alone never tells us what to do, but trustworthy and useful evidence may help

30 Trustworthy Evidence Independently produced Error-proofed Spin-free Fully reported de Vries YA, Roest AM, de Jonge P, Cuijpers P, Munafò MR, Bastiaansen JA (2018). The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression. Psychological Medicine /S

31 Conclusions Before applying the evidence to help us treating elderly patients, we need to understand about the consequences of ageing and consider the cost and benefit of applying the evidence in elderly patients, especially in the very old. We must fully aware that there are many trials (studies) which didn t include the very old group as participant; some prognostic tools and guidelines are also not validated in the very old group. To improve EBM in elderly, we need to fully assessed our patients (by doing CGA, frailty assessment, and discuss about patient s preferences); use only trustworthy and useful evidence; and provide careful and kind care.

32 Thank You

33 Case Example Current Concerns and Objectives for This Visit Mr. X 87 y.o man accompanied by his son and daughter to your clinic They are concerned that Mr. X is excessively fatigued and is taking too many medicines They need to make sure that their father is safe and will be able to stay alone in his own home He has an health insurance to cover some of his prescribed medications, but the expense of other medicines is a financial burden.

34 Review of the Overall Clinical Management Plan What are the current medical conditions and interventions? Current medical conditions Current medical data Medications and Interventions Probable Alzheimer s disease CHF OA Osteoporosis Insomnia Type 2 DM BPH MMSE score today 23/30; 6 months ago 25/30 BP sitting 110/70, standing 100/60; pulse sitting 54 bpm, standing 56 bpm HbA1c today 6.8%; 3 months ago 7% Echocardiogram: 1 year ago EF 30% Total Chol 180 mg/dl; LDL 70 mg/dl; HDL 50 mg/dl; TG 300 mg/dl BUN 40 mg/dl; Cr 1.7 mg/dl; Glucose 100 mg/dl 1. Metformin 2x500mg 2. Glyburide 1x10 mg 3. Enteric coated aspirin 1x325 mg 4. Donepezil 1X10 mg bedtime 5. Memantine 2x10 mg 6. Furosemide 2x40 mg 7. Metoprolol 2x100mg 8. Lisinopril 2x20 mg 9. Tamsulosin 1x0.4 mg evening 10. PCT 2x650 mg 11. Tramadol 2x50 mg prn severe pain 12. Calcium/vit D3 600mg/500IU 2x1 tab 13. Alendronate 70 mg/weekly 14. Zolpidem 1x10 mg bedtime 15. Simvastatin 1x40 mg evening 16. Blood sugar checked 3x/week 17. Exercise 1-2 mile walk/day

35 Is the patient comfortable with, and adherent to, the clinical management plan? Tn X. admits that He often forgets his evening medications because he is tired He doesn t check his blood sugar regularly because the fingerstick hurts

36 What are the preferences of the individual and his family? Mr. X and his children express the following priorities: To stay alive To optimize quality of life To reduce out-of-pocket expenses since the patient lives on a fixed income To remain safely in his home despite the mild Alzheimer s disease (first noted 3 years ago)

37 What evidences are available regarding intervention effects? Cholinesterase inhibitor, donepezil, has had only modest success in delaying institutionalization and in maintaining functional status, and results are mixed. Memantine has shown no benefit alone or in combination therapy for mild Alzheimer s disease Data from the Fracture Intervention Trial Long-term Extension (FLEX) study of women with osteoporosis taking alendronate for longer than 5 years suggest that fracture protection exists for up to 5 more years after stopping it. Tight glycemic control may result in more harm than benefit, and the appropriate HbA1c target may be 8-9%.

38 What is the prognosis? Given this individual s age and multimorbidity, life expectancy is estimated to be 2-3 years. Ongoing cognitive decline is likely, with average loss on the MMSE of 2-3 points/year He will probably experience progressive dependence in his IADL

39 Are there interactions with medications and medical conditions? Fatigue: Mr. X enjoy exercise but has been feeling more fatigued lately. increased dose of metoprolol + donepezil slow heart rate Glyburide should be avoided in elderly because of the greater risk of hypoglycemia May be an adverse effect of statin statin therapy for dyslipidemia need to be reevaluated.

40 Are there interactions with medications and medical conditions? Insomnia: Donepezil may cause nightmares, especially when taken bedtime Zolpidem helpful for falling asleep, but may not keeping him asleep for the night, cause excessive somnolence during the day +hallucinations

41 Are there interactions with medications and medical conditions? CHF: Metformin : should be avoided in CHF and CKD because of the risk of lactic acidosis Alzheimer s disease: Zolpidem may worsen dementia, increase risk of falls primary safety concern for elderly with osteoporosis living alone Osetoporosis: Cr 1.7 BUN 40 bisphosphonate administration needs to be reevaluated

42 Benefits and Harms of the Intervention Reevaluation in treatment of: Type II DM Insomnia Dyslipidemia CHF Cognitive decline Osteoporosis Treatment complexity Medication burden Feasibility Adherence Quality of life

43 Communicate and discuss decisions about clinical management with the patient and family Consider: Feasibility of the approach Patient s and family s preferences Outcome priorities Make sure the patient understands and agree with clinician s recommendations We understand that you: Prefer to remain at home and in your community and avoid hospitalization Are not concerned about outcomes 5-10 years in the future Are at risk of low blood sugar and its consequences Would like to feel more energetic Would like to decrease expenses Therefore, we suggest that you reduce some of your medications and relax your effort to achieve tight control of your blood sugar levels

44 Possible revisions to the treatment plan, with consideration of the patient and family preferences Medications and Interventions Metformin 2x500mg Glyburide 1x10 mg Enteric coated aspirin 1x325 mg Donepezil 1X10 mg bedtime Memantine 2x10 mg Furosemide 2x40 mg Metoprolol 2x100mg Lisinopril 2x20 mg Tamsulosin 1x0.4 mg evening PCT 2x650 mg Tramadol 2x50 mg prn severe pain Calcium/vit D3 600mg/500IU 2x1 tab Alendronate 70 mg/weekly Zolpidem 1x10 mg bedtime Simvastatin 1x40 mg evening Blood sugar checked 3x/week Exercise 1-2 mile walk/day HbA1c target should be less restrictive 8-9%, so both drugs can be discontinued or changed to only one drug at lower dose to lower risk for hypoglycemia. To improve adherence, aspirin reduced to 81 mg/day To reduce insomnia, donepezil should be taken in the morning To improve adherence, furosemid reduced to 40 mg/day to minimize bradychardia metoprolol reduced to 50 mg in the morning only To improve adherence 1x20 mg in the morning Published evidence doesn t support the use of memantine in the mild stages of AD. But the family strongly believe that it will help him gaining independence, so memantine will be continued, but reduced to 10 mg/day in the morning. (considering the CrCl = 30 ml/min) Check vit D levels, to improve adherence take medicine once daily in the morning + greater dietary intake of calcium and vitamin D Stop alendronate because it may still give fracture protection for 5 years (beyond Tn. X s life expectancy) To reduce insomnia, zolpidem will be reduce to 5 mg at bedtime prn the goal is complete discontinuation Weighing prognosis, uncertain benefit, unreliable adherence, complains of fatigue discontinue simvastatin Patient has been avoiding fingerstick glucose monitoring 3x/wks changed to monitor only when symptomatic

45 Possible revisions to the treatment plan, with consideration of the patient and family preferences Medication management: Choose 1 of the children to have responsibility for filling pillboxes each week Give written instructions detailing new regimen Except for zolpidem, medications should be stored in family member s house, rather than with the patient.

46 Translating Evidence into Practice Clinical studies Systematic reviews Clinical quality improvement aware accepted applicable able acted on agreed to adhered to Glasziou and Haynes EBN 2005; 8:36-38 Evidence-based medicine Clinical decision making

47 Trustworthy Evidence Independently produced Error-proofed Spin-free Fully reported de Vries YA, Roest AM, de Jonge P, Cuijpers P, Munafò MR, Bastiaansen JA (2018). The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression. Psychological Medicine /S