9/27/2015

1

2015 Year in Review

Barbara Messinger-Rapport, MD, PHD, FACP, CMD

Associate Professor, Cleveland Clinic Lerner College of Medicine

Disclosures

Off-label and clinical trial pipeline drugs for Alzheimer’s disease to be discussed and identified as non-FDA

Learning Objectives

By the end of the session, participants will be able to:

• Consider practice changes based on recent publications

• Identify controversial that may affect the direction of research or practice

• Incorporate techniques of critiquing publications that emphasize geriatric outcomes

SELECTION CRITERIA

• Goal: improving care frail elders • Focus: Continuum of care

• Focus: reducing morbidity and/or improving function

• Themes

Outline

• Multiple Chronic Conditions

• Deprescription

• Cognitive impairment & dementia

• Care coordination- 2 geriatric models

• Delirium

MCC in the literature!

7 4 14

32

49

116

169

2002 2004 2006 2008 2010 2012 2014

Number of articles indexed in PubMed each year (Multimorbidity OR multi-morbidity OR “multiple chronic

conditions” OR “multiple chronic medical conditions”) AND Human, Aged 65+, English

9/27/2015

2

27.0%

40.3%

68.0%

90.7%

6.7%

16.8%

42.8%

73.1%

0%

20%

40%

60%

80%

100%

Ages 0–19 Ages 20–44 Ages 45–64 Ages 65+

One or more

chronicconditions

Two or more

chronicconditions

Source: Medical Expenditure Panel Survey, 2006

Healthcare Transformation

Prevalence of multiple chronic conditions in the aging population

Source: CMS. Chronic Conditions among Medicare Beneficiaries, Chart book. 2011.

0

10

20

30

40

50

60

<= 55 55 - 59.9 60 - 64.9 65 - 69.9 70 - 74.9 > 75

Pe

rce

nt

RC

T st

ud

ies

Mean age range (years)

Percent RCT with mean age as represented below

AF

HF

ACS

Systematic review of RCT incorporated into 3 AHA/ACC guidelines. Sardar. JAMA. Nov 2014

Few studies with mean Subject age 70 yr

Every chronic condition guidelines requires at least one pill

• DM

– 2-3 hypoglycemic agents A1c < 7.5, 8

– Statin; ACE-I; ASA

– Hypertension control

• Osteoporosis

– Ca++, Vit D

– Bisphosphonate

• Afib

– βblocker or?

– Anticoagulation

• CAD

– Beta blocker

– Statin; ACE-I; ASA

– Clopidogrel if stent

HFrEF: • βB, ASA, ACE/ARB, aldactone antagonist

Individual management of each of the MCC’s?

• Following concomitant clinical guidelines: – Polypharmacy! – Confusing, expensive, and potentially dangerous

• Also- generalization to old-old is questionable – Mean age subjects in clinical trials which are

incorporated into the guidelines < 70 years (see upcoming slide)

– Trial enrollment criteria exclude • Specific geriatric conditions e.g. cognitive impairment • NH residents ; multiple chronic conditions, etc.

• Better approach: ascertain patient care goals!

MCC: there’s an app for that in 2015! Start with patient’s primary concern and consider patient preferences….

How to utilize a patient centered approach to chronic disease

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3

Multiple Chronic Conditions results in: The Prescription Cascade

Provided by the owner of a Parma, Ohio nursing facility

Deprescription theme in the literature!

0

3

7

10

22

28

2010 2011 2012 2013 2014 2015

Number of articles indexed in PubMed each year (“Deprescribe” OR “deprescription” OR “deprescribing”)

Canada statistics

• In 2008 2/3 older adults: 5 drugs

– 21% took at least 10

– Canadian institute for Health Information

• 2013 CIHI study: Prevalence adverse drug events requiring medical attention

– 6% among those with 1-2 drugs

– 13% among those with 5+ drugs

Medications dominate New Zealand Injury compensation claims data set

• Primary care treatment injury claims July 1, 2005 through June 30, 2009

• Include: primary care, therapy, lab, radiology, dental, nursing facility

• Exclude: hospital, specialty & maternity care

• There were 3,844 treatment injuries

– 861 injuries (22%) were in persons 65+ years

– About 1/3 of total injuries were medication

Wallis. Ann Fam Med. 2015

Number of injuries by medications > # of failure to diagnose or treat!

Treatment injuries age 65+ All

(n=861) Serious or Sentinel (n=78)

Med 34% 72%

Minor surg 15% 0%

Injection 4% 9%

Vaccination 4% 4%

Failure to diagnose or treat

3% 12%

Other Rest each < 6%

Medication injuries in 65+ All

(n=294) Serious or Sentinel (n=56)

Antibiotic 51% 39%

NSAID 9% 5%

ACE 9% 2%

Warfarin 4% 14%

Steroid 3% 7%

Opiate 3% 5%

Other Rest each < 6%

Wallis. Ann Fam Med. 2015

Specific injuries + payouts NOT detailed in the article. Some likely allergy. Some may be due to interaction with chronic medication.

Nested case control, Ontario residents Sudden death in elders on spironolactone with

newly prescribed antibiotics

Antoniou. CMAJ. 2015

* * *

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Maximize benefit, minimize harm: Careful prescription & deprescription

• Each drug should have a reason

• Consider patient-centered goals

– current/ future benefit, harm, burden

• Periodic reassessment for discontinuation

– CrCl should be considered

• Deprescription is not a one-time action

– Pt needs to be monitored for improvement

– or for onset adverse effects

Scott. JAMA Int Med. 2015

Available tools

• STOPP/START criteria for PIMs (potentially inappropriate medications)

– Updated 2015 Age & Ageing

• Beers List for PIMs

– Updated Fall 2015 (pending)

• Good palliative geriatric practice (GPGP)

– Algorithm for systematic deprescription

– Garfinkel 2007 (nursing home), 2010 (community)

Classic deprescription study of antipsychotics in dementia

Ballard. DART-AD. Lancet Neurol. 2009

Antipsychotic discontinued

Antipsychotic continued

Statin Deprescription

• 381 subjects, RCT w/ LE < 1 year.

– Intervention: d/c longstanding statin.

– Control: continue statin

– Outcome: mortality, QOL, CV events

• Results: Mean age 74.1(11.6) yrs

– 22% cog impaired, 49% cancer

Kutner. JAMA. 2015

Statin Deprescription Results, cont

• Mortality: discontinue v. continue

– 23.8% v. 20.3% (90%CI -3.5% to +10.5%)

• QOL: mean McGill QOL score

– 7.11 v. 6.85, p = .04

• CV events: 13 v. 11

McGill: mean of 16 QOL questions, range 0 (worst) – 10 (best)

Kutner. JAMA. 2015

“OncPal” deprescribing guideline

• Prospective non-interventional cohort study

• 4 stages

– Development evidence-based guideline

– Recruit onc-pal patients < 6 month prognosis

– Assess meds by both:

• Panel medical experts

• Clinical pharmacist w/Oncpal deprescribing guideline

– Evaluate guideline by testing concordance

Lindsay. Support care cancer. 2015

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Onc-Pal Deprescribing Guideline (Lindsay. Support Care Cancer 2015)

Med Class Medication Considerations for limited benefit

Explanation

Blood & blood-forming organs

Aspirin Primary prevention Little short or intermediate risk of stopping. Time-to-benefit > LE

Cardiovascular system

Lipid meds & antihypertensives

Primary & secondary prevention – consider deprescription. Continue if used for tachy-cardia or heart failure symptoms

Statins: little short or intermediate risk of stopping. Antihypertensives: unnecessary in very short LE

Osteoporosis Bisphosphonates, Raloxifene, Strontium,

Denosumab

Only if bisphosphonates treating hypercalcemia due to bone mets

Little short or intermediate risk of stopping.

GI tract PPI, H2 blockers If no h/o GIB, PUD, gastritis, GERD, NSAID use

Ongoing therapy unnecessary in most shortened LE

Oral hypoglycemics

Metformin, GLP-1, sulfonylureas, DPP-4, glitazones, acarbose

If sole use to reduce mild hyperglycemia

Potential ST complications > benefit

Vitamins, CAMs, Minerals,

All If not indicated to treat a low blood concentration

No evidence for effectiveness

Lindsay. Support care cancer. 2015

“OncPal” deprescribing: Results:

• 61 pts, 44% female, median age 66 (23 – 93)

• Median meds per patient: 10 (range 4 – 21) – Total 617 medicines

• Median karnofsky score 50 (range 20 – 80 )

• 70%: lung, ENT, gyn, colorectal. 30% other

• Concordance of guideline w/ expert panel: – 580/617 (94%). Kappa 0.83 (95% CI 0.76 – 0.89)

• Least concordance (< 50% in class of meds) – antiarrhythmics, neoplastics/ immunomodulators

Lindsay. Support care cancer. 2015

Summary of OncPal

• Practical methodology

• May be generalizeable to others with serious illness & shortened LE

• Actionable guideline

• Limitations – single center (prescribing habits)

– Small “n”

– Doesn’t cover prescribing practices for patients with cognitive impairment who also have cancer

Lindsay. Support care cancer. 2015

Cognition

• More than memory

• Mental abilities, processes – Memory; decision making

– Attention; problem solving

• Cognition critical to – Follow recipes, drive, manage doctor appts

– Take medications, be safe in home

– Maintain financial independence, avoid elder abuse

Conceptual Model of Cognitive Impairment, Older Adults

Lifestyle (diet, physical activity,

socialization)

Genetics; in utero;

childhood

Events (infection, fall,

brain injury, delirium)

Management of chronic (vascular) conditions

Cognitive aging

Mild cognitive

impairment

Vascular dementia

Alzheimer disease

Other dementia

M

i

x

e

d

Genetics; events

Lifestyle; vascular disease

Based on Cognitive Aging. Progress in Understanding & Opportunities for Action. IOM. 2015

Mild Cognitive Impairment (MCI)

• How do we find? (screening)

• Should we look? (probably!)

0

10

20

30

40

50

71 - 79 80 - 89 90+

Pe

rce

nt

Age (years)

Prevalence of cognitive impairment without dementia (i.e. MCI)

Plassman et al 2006

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Screening for cognitive impairment

• USPSTF 2013: insufficient evidence

• CMS: Yes: annual wellness visit since 2013

– Seldom done/tracked

• Consensus conference of the IAGG (International Association of Gerontology & Geriatrics) : Yes. Morley. JAMDA. 2015

– Frame issue positively:

– Opportunity to reverse / reduce further decline

Interventions

• Physical activity

• Cognitive stimulation

• Socialization

• Diet (heart healthy; Mediterranean type)

• Cardiovascular health

• Avoiding trauma

• Anticipating/ avoiding financial exploitation

• (no pharmacological interventions)

Quality of lifestyle research?

• Systematic review of 3 types of RCT’s – Physical activity, cognitive , socialization

– Subjects with MCI (mild cognitive impairment)

– Studies of progression cognitive impairment

– Outcome: # criteria 37-item CONSORT checklist

• Results: – 23 studies:

• 8 physical activity, 14 cognitive intervention

• 1 socialization

Horr. JNHA. 2014

Quality of methodology Lifestyle interventions on MCI

Horr. JNHA. 2014

Exuberant publication of lifestyle interventions despite historical

methodological challenges! • LIFE: RCT Physical activity v. education x 2 years. Negative. KM Sink.

JAMA. 2015

• AREDS2: RCT LCPUFAs +/- Lutein/zeaxantin v. placebo x 5 years. Negative. Chew. JAMA. 2015

• FINGER: RCT diet, exercise, cognitive training, vascular risk monitoring v. genl health advice x 2 yrs. Positive. Ngandu. Lancet. 2015

• SMART: RCT Resistance training v. calisthenics + active v. sham cog training x 6 mo. w/18 mo. f/u. Positive. Fiatarone. JAMDA. 2014

• SAIDO: RCT Japanese learning therapy (math, reading, writing) v. usual care x 6 months. Positive. Kawashima. JAMDA. 2015

• Kyoto: 12 weeks multi-modal physical & cognitive exercise v. control. Positive. Nishiguchi. JAGS. 2015

AND MORE!! LCPUFAs: long-chain polyunsaturated fatty acids

Summary: delaying progression cognitive impairment?

• Physical & cognitive activity (types?)

• Heart-healthy diet (specifics?)

• Management of cardiovascular risk (targets?)

• Caution re: nutraceuticals and commercial brain games – May be low risk

– However, may detract from attention to cardiovascular risk management

• Drugs?

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FDA approved drugs for dementia Medication Side effects

Acetylcholinesterase inhibitors: Donepezil (Aricept) Rivastigmine (Exelon) Galantamine (Razadyne)

Diarrhea Loss of appetite/weight loss Nausea Syncope Bradycardia Confusion Dizziness Insomnia or Hypersomnolence Fatigue Headache

Memantine (Namenda) Syncope Confusion Dizziness Headache Diarrhea or Constipation Vomiting Hypertension

Donepezil & Memantine (Namzaric) All of the above

Sheffrin. JAGS. 2015 Time to lost 10 # NNH 21 over 1 year (95% CI 12.5 – 71.4)

Drugs on the Horizon for Alzheimer’s Disease?

• Three categories of drugs 2002 - 2014 – Symptomatic (36.6%) – Disease modifying- small molecule (35.1%) – Disease modifying- immunotherapy (18%)

• Since 2002 – 413 AD trials with 244 drugs – 1 approved by FDA (memantine in 2004) – 99.6% approval failure rate

• As of 2/2014, only 22 drugs in Phase I • Desperate need to have more drugs in pipeline

Cummings. Alz Res & Therapy. 2014

Current direction of AD research

• Disease modifying:

– Target higher risk subjects

– Find subjects earlier in disease course

– Utilize

• Biomarkers

• Structural & functional brain imaging

• Treating symptoms (memory, agitation)

– Continue to seek new drugs

Gantenerumab Scarlet RoAD

• Fully human monoclonal antibody designed to decrease levels of β amyloid

• Monthly IV infusion x 104 weeks • Late onset “prodromal” AD

– MMSE > 24 – Clinical & biomarker evidence for AD

• Failed phase 3 (safety was ok) • DIAN-TU (dominantly inherited Alzheimer

Network- Trials Unit) continues trials of Gantenerumab & solanezumab

19 Dec 2014 Press release HoffmannLaRoche

Oligomannurate known as GV-971

• Targets multiple regions on Aβ – May inhibit Aβ aggregation better with lower

neurotoxicity

• Phase 1 did well • Phase 2 utilized 600 mg/d & 900 mg/d

– Mild-mod dementia – MMSE 10 to 24

• ADAS cog/12 was endpoint. – 900 mg/d at 6 months statistically sign cog

• Phase 3 to start (China)

Shifu Xiao. 7th Clinical Trials Conference on Alzheimer’s Disease. Nov 2014.

Aducanumab formerly B11B037

• Monoclonal antibody – Selectively binds aggregated forms of β-amyloid

• Prodromal (MCI) or mild disease, including – MMSE 24 to 30 – Amyloid in brain imaging

• Aducanumab reduced – Amyloid accumulation – Rate of decline in MMSE

• by 2 point difference over 1 year

• 78-week phase 3 (ENGAGE) started June 2015

Sevigny. Abstract 269 at AD/PD 2015. March 20, 2015

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Further analysis “delayed start”

• Combine certain trials

• Different statistical approach

– compare outcomes (clinical & biomarker)

– early drug v. delayed drug

• Finding: delayed starters do not catch up

– suggests potential benefit to disease progression

• May need to identify subjects even earlier in disease to modify course disease

AAIC 2015, Hong Liu-Seifert

Symptom Control Agitation in AD

• Common, distressing to caregiver – Aggressive physical (destroy, grab, fight), and/or – Aggressive verbal (scream, curse), and/or – Non-aggressive physical (pacing, fighting)

• No FDA approved treatment • Cit-AD 2014: 30 mg/d citalopram reduced agitation

– Prolonged QTc. MMSE 1 point lower in treated group

• Anecdotal benefit with agitation noted in the pseudo-bulbar affect trial

• Dextromethorphan: NMDA antagonist, SNRI, and other – Only FDA approved for PBA

Agitation in Alzheimer Disease Dementia

• Dextromethorphan-quinidine 30/10 bid • Phase 2 RCT, DB, placebo controlled. All settings • 220 pts, MMSE 8-28, at least moderate agitation

• Clinical Global Impression-Severity agitation score 4+

– Serial, parallel, comparative design – Two 5-week stages to manage placebo effect

• Stage 1: 93 to drug, 127 to placebo • Stage 2: placebo non-responders re-randomized drug v. PL

• Outcome: – change in NPI agitation/aggression domain – ADCS CGIC, PGIC, ADL, Cornell scale, MMSE, QTc

Cummings. JAMA. 2015

Results

• Mean age 77.8 yr, 56.5% W, 88% outpatient • More than 88% retention rate • Baseline

– MMSE 17.3 (of 30), Caregiver Strain Index 6.8 (of 26)

• Concomitant drugs: – 73% AChI; 49% memantine; – 56% anti-depressants; 20% antipsychotics

• Common adverse effects: – Falls (8.6 v 3.9%); diarrhea (5.9% v. 3.1%); – UTI (5.3% v. 3.9%); dizziness (4.6% v. 2.4%)

• Mean QTc during study: 5.3 ms – 10% on drug & 6.7% on placebo had 30 ms in QTc

Cummings. JAMA. 2015

RESULTS, cont

Statistically significant benefits Reduction in NPI-agitation More than 50% in 50% subjects; > 30% in 65% subjects Reduction in Caregiver strain index (CSI) for each 5-week stage -not the 10-week stage (?) Reduction in NPI caregiver distress agitation score in 1 5-week stage -not the other 5-week stage, and not the 10-week stage (?) No benefit to patient QOL

Cummings. JAMA. 2015

Comments

• Improvements in agitation & caregiver strain – May facilitate staying longer in community – May not apply to NH residents

• Need longer follow-up • Will likely see this novel study design in future • QTc small but may be important for some • More falls in treated group

– Baseline h/o falls unevenly distributed (17.2% v. 12.6%)

• Awaiting phase 3 trial

Cummings. JAMA. 2015

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Managing the cognitively impaired population: Start with the caregivers!

• 65% care needs met by family, friends • Women provide majority of care • 30% of eldercare given by caregiver 65+ • Most care is informal

– Unpaid, not associated with a healthcare system

• Lack of caregiver associated with institutionalization (& concomitant care costs)

• What kind of caregiver support and education – Will reduce institutionalization risk? – Cost of care?

Caring for Older Adults & Caregivers at Home COACH Program

• VAMC care coordination program – Different than PDC (partners in dementia care Bass.

JAGS. 2013) which focused on caregiver support

• 133 dyads (demented elder w/caregiver) c/w 29 dyads who met criteria but did not enroll

• Intervention: consultative home-based dementia care coordination for dyads. Emphasis on FUNCTION and SAFETY

• Outcome: placement & quality measures – Dementia Management Quality Measures (DMQMs) – Caregiver, Med assessment, delirium, sleep

D’Souza. JAGS. 2015

COACH intensity

• Experienced geriatric SW, RN full time

• Weekly IDT discuss the initial visit, formulate plan – Geriatrician, geri-psych, geri-pharmacist

– Plan communicated via E H R (PCP must sign)

• Support: – FU telephone or home at 1,3,6 months minimum

– Telephone visits q3 months thereafter

– Home visits annually and after change in condition

D’Souza. JAGS. 2015

COACH characteristics Patient COACH n=133 Control n=29

Age 82.5 81.3

F 1.5% 3.6%

B 36.4% 37.9%

Married 68% 69%

Income $27,500 $22,000

Chronic disease

3.8 4.1

Mean MMSE

16 16

Caregiver

Age 70+/- 13.3

Wives 60%

Dtrs 25%

mCSI 7+ 55%

D’Souza. JAGS. 2015

COACH- results

Home Died Placed Unk

COACH N=133

78 (58.6%)

27 (20.3%)

24 (18%)

4

Control N=29

16 (55.2%)

5 (17.2%)

5 (17.2%)

3

• Time to placement outside the home not statistically different • Unclear on total # interventions (safety, function) that the COACH subjects received • Study did not report quality measures or how many transitioned to hospice, ED visits or hospitalizations. Did not report if deaths were at home, hospital, or hospice

D’Souza. JAGS. 2015

Indiana University

• Aging Brain Care – Include: Dementia, depression, cognitive

impairment

– Focus on: dyad

– Based on their ABC clinic- • Co-management pilot program

• Preliminary results 2011

• Received CMMI funds in 2012

• 2015 reporting preliminary data

Lamantia. JAGS. 2015

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Outcomes of IU pilot program co-management

55 Boustani et al. 2011

ABC: Aging Brain Care PCC: Primary Care Clinic

ABC MedHome

• Unique team with trained nurse extenders • 1,500 dyads (refreshed continuously)

– 2 FTE RN each with 750 persons – Each RN (or CC care coordinator) has 5 FTE CC

assistants (CCA’s) with 150 persons each • A CCA is a HS grad w/ extra training in dementia care

– 1.0 FTE administrator – 1.5 FTE SW – 0.3 FTE medical director

• Many customized ABC tools • Inclusion via ICD 9 screening

LaMantia. JAGS. 2015

Enhanced Care Coordination Features

57

ABC MedHome intervention

• CCA: Initial assessment at home or any preferred location- complete measures

• CCA meets w/CC & SW to develop care plan – www.agingbraincare.com – Connection with community & in-home services

• FU home visit by CCA in 2-4 weeks – Then monthly x 3 month, then q3 months – w/in 72 hours of change in condition – PHQ-9, HABC-M each visit – Weekly IDT to adjust plan continuously

LaMantia. JAGS. 2015

Intense, coordinated Supportive technology

• CCAs and rest of team have:

– Smartphone, tablet computer, mobile internet

• Population health management software

• Enhanced medical record for aging brain care

– Track individual & population outcomes

– Provides alerts of admission to any hospital or ED in entire state of Indiana

LaMantia. JAGS. 2015

Process results at 18 months • 1,650 enrolled, 361 discharged

– 190 (11.5%) died, 27(1.6%) entered LTC

• Participants: mean of 13 visits • Dementia patients w/wo

depression: – 1.6 protocols of care triggered,

4.1 care handouts

• Depression w/o dementia: – mean 1.6 protocols, 3.5 handouts

• Reduction in PHQ-9 & HABC-M scores – i.e. sx of dementia & depression

ABC MedHome participants

Age (years) 74.6 +/- 8.3

F 77.5%

B 46.5%

# conditions 3.3 +/- 1.8

MMSE 21.2

LaMantia. JAGS. 2015

Quality & cost outcomes- pending

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Underappreciated risk of cognitive impairment: Delirium

• Most common surgical complication in older adults – up to 50% incidence

• Serious complication leading to – Falls, other medical/ surgical complications – Longer length of stay, higher cost – Higher risk institutionalization – Loss functional independence – Reduced cognition – Death

• Preventable in up to 40% of patients

NonPharmacological Multicomponent Interventions (NPMIs) in hospital

• Systematic review, studies w/ mean age 65+ • Interventions: cognition, mobility, hearing, sleep,

vision, hydration • Exclude: terminal illness • Outcomes: incidence, falls, LOS, d/c to institution,

change in function, change in cognition • 14 studies (n=4267, mean age 80y)

– 9/14 studies based NPMI on HELP – Range study duration 3-36 months – 4 RCT, 2 matched, 8 unmatched or historical controls

Hsieh. JAMA int med. 2015

0

1

2

3

4

5

6

1 2 3 4 5 6

Freq

uen

cy

Number of following interventions: cognition, mobility, hearing, sleep, vision, hydration

14 studies and their number of non-pharmacological interventions

Hsieh. JAMA int med. 2015

Nonpharmacologic multicomponent delirium interventions v. control in older hospital inpatients

Outcomes Studies

(pts) Falls/1000 patient-d At 3-36 months

Intervention Control RRR (95%CI) NNT (CI)

Falls 2 (485) 4.3 12.9 57% (32-72) 15 (12-20)

Weighted event rates

Incidence delirium

4 (1986) 8.1% 14% 40% (21-54) 20(13-34)

Hsieh. Odds ratios. JAMA Int Med. 2015 Hirsch. RRR & NNT. ACP journal club. 2015

The following outcomes were not significant: Length of stay (3358 patients) Institutionalization (1196 patients) Change in functional status ( 1068 patients) Change in cognitive status ( 1610 patients)

LOS, NPMI and delirium

Vidan. JAGS. 2009. 542 patients 6/6 NPMI delirium

Hsieh. Odds ratios. JAMA Int Med. 2015

Considering NPMI outcomes

• Delirium incidence

• falls should save hospitals money – Who pays for inpatient falls?!

• Length of stay not reduced?!! – Heterogeneity in

• Interventions used

• Diagnoses; Severity illness

• How well NPMI’s applied

• Delirium reduction is staff/time intensive – Challenge to maintain outside of a research study

Hsieh. JAMA Int Med. 2015

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Reducing delirium risk

• NPMI for all patients are – Time intensive re: staff – Difficult to maintain longterm (e.g. sleep intervention)

• Can – Higher risk patients get more intense interventions? – Lower risk patients not receive as much intervention?

• Can we risk stratify for post-op delirium (POD) prior to surgery? – Olfaction (!) – Standardized metrics

Impaired olfaction

Olfaction Short-term memory processing

Impaired Olfaction & POD

• Neuropsych testing

– 1-3d before cardiac surgery in 165 adults

– 4-6 weeks after surgery in 122 / 165

• Baseline brief smell identification (BSIT)

– Scratch test, 12 item, 4 multiple choice each

• Outcome:

– Delirium using validated chart-review

Brown. JAGS. 2015

Results of Olfaction study Normal

Olfaction n = 111

Impaired Olfaction

N = 54

P-value

Age (years) +/- std deviation 69 +-8 72 +-8 .05

Female n (%) 40 (36) 18 (33.3) ns

Black n (%) 15 (13.6) 10 (18.9) ns

Stroke n (%) 11 (9.9) 5 (9.3) ns

Current smoker n(%) 10 (9) 7 (13) ns

Previous smoker n (%) 47 (42.3) 25 (46.3) ns

Hypertension n (%) 96 (86.5) 45 (83.3) ns

Diabetes n(%) 60 (54.1) 24 (44.4) ns

CABG alone n (%) 65 (58.6) 32 (59.3) ns

AVR alone n (%) 2 (1.8) 4 (7.4) ns

Cardiopulm bypass duration min (IQR) 98 (79 – 130) 106 (77 – 139) ns

Aortic cross-clamping duration min (IQR) 63 (49 – 83) 61 (50 – 88) ns Brown. JAGS. 2015

• 33% had baseline impaired olfaction

• Incidence delirium 31%

• Odds risk delirium (adjusted to age, prior stroke, baseline cognition) if impaired olfaction

– 1.90 (1.17 – 3.09) p = .009

• For every 1-unit loss in olfaction, adjusted risk of delirium increased by 11% (1-21%, p = .03)

Results of Olfaction study

Brown. JAGS. 2015

Cleveland Clinic Confusion Score! Preoperative screening for delirium risk

• Elective orthopedic surgery at main campus

• Preoperative testing 114 persons 50+

• See next slide for CCCS

• Post-op delirium defined as composite: – Positive Nu-desc OR

– Positive chart review OR

– Positive family or patient report

• Outcome: predictive value of the CCCS to predict delirium

Vanderbilt. JARCP. 2015

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Cleveland Clinic Confusion Score Across all non-cardiac surgeries: • Score of 0-1 was associated

with <10% risk of delirium • Score of > 3 was associated

with a 35% risk of delirium • Score of 2 was associated

with a 27% risk of delirium SN 73.7%; Sp 73.8% PPV 26.6%; NPV 95.6%

Variable aOR Point

value

Age ≥ 70 3.2 1

History of delirium 4.1 1

Baseline cognitive

impairment - TICS

2.2 1

Self-report ETOH

Based on CAGE scale

6.5 2

Pre-operative use of

narcotic analgesic

2.7 1

Admission to neurosurgery

service

2.7 1

Litaker. General Hospital Psychiatry. 2001

Telephone Interview for Cognitive Status (TICS)

• Validated form of the Folstein Mini Mental Status Exam

• Proprietary Scale for purchase

• Estimated 10 minutes to complete

• 11 questions possible 41 points

• For this study < 30 was considered cognitive impairment

Results of pre-operative screening for delirium risk following ortho surgery

• Data available on 111 patients

• Mean age 65.3 (50-88), 59% female

• Knee (v. hip) 68.5%

• Prevalence of + CCCS: 31 (27.9%)

• Prevalence of POD: 12 (10.8%)

Vanderbilt. JARCP. 2015

Postoperative delirium Predictive Value

Yes (n=12) No (n=99)

Positive (n=31) 9 (true positive) 22 (false positive) 29% PPV

Negative (n=80) 3 (false negative) 77 (true negative) 96% NPV

Summary

• NPMIs reduce delirium incidence but not LOS

• NPMIs are time/staff intensive

• Preoperative testing (by smell and/or CCCS) may select cohort w/higher (or lower) delirium risk

• Intensive interventions (select or multicomponent, pharmacological or NPMI) may be focused on those who are at “higher” risk

• More research needed

Vanderbilt. JARCP. 2015

Brown. JAGS. 2015

American Geriatrics Society Expert Panel Post-Operative Delirium

• 23 member panel, multidiscipline

• Scope: interventions to prevent and treat post-op delirium

• Exclude: post-acute, nursing home, hospice

• November 2014

– Post-operative clinical practice guideline

• February 2015

– Postoperative delirium best practice statement

Post-op Delirium Best Practices

1. Pre-op risk factors

2. HCP able to diagnosis delirium

3. Nursing staff screen at least daily

4. Intra-op EEG

5. Avoid hi-risk meds

6. Pharmacological prevention?

– Antipsychotics? AChI ?

– Regional block?

7. Non-pharm prevention & treatment

8. Full medical eval of POD

9. Pharm tx of POD

– Benzo’s not first choice in general

9/27/2015

14

Summary

• Multiple Chronic Conditions: • Patient centered care goals

• Safe and thoughtful deprescription • Progression of cognitive impairment

• reversing dementia is in the future • now is the time to delay cognitive aging

• Care coordination- focus on dyads • Delirium research continues for

• NonPharm Multicomponent Intervention • Pharmacological treatment • Pre-operative delirium risk assessment

• And what to do if risks are found

THE END!