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Geriatrics Literature Updates

2016Eric Widera, MD

Kenneth Covinsky, MD

University of California San FranciscoSan Francisco VA Medical Center

Methods

• Search of leading journals• January 2015-December 2015• JAGS, NEJM, JAMA, JAMA-IM, Annals, Health

Affairs, Lancet, BMJ, Academic Medicine, JGIM, J Geron-Med Sci, JPM, JPSM

• Search of social media:• Twitter, Blogs, PC-FACS

• Selection Criteria• Impact and Interest

Disclosures

• No relevant financial relationships

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Vimovo• Naproxen and Esomeprazole

• 60 tabs = $1,700Duexis

• Ibuprofen and Famotidine

• 60 tabs = $1,100

*Costbasedongoodrx

What’s in Tussin & TonicTM

• Dextromethorphan• Dissociative hallucinogenic, sedative, and stimulant

properties at higher doses• Low-affinity NMDA receptor antagonist, Serotonin

reuptake, Sigma-1 receptor agonist• Quinine

• Stereoisomer of quinidine• Like quinidine, inhibits peripheral metabolism of

dextromethorphan• Flavor component of tonic water

Study

Cummings et al. JAMA. 2015;314(12):1242-1254

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Research Question

• Does Dextromethorphan-Quinidine Reduce agitation in patients with dementia?

• Quinidine inhibits degradation of Dextromethorphan, allowing higher brain concentration

• The combination of these two very cheap meds produces one very expensive pill ($824/30 day supply)

Who was included?

• 210 patients with Alzheimer Disease• Clinically significant agitation (such as aggressive physical or verbal behaviors)

• Mean age 78• 12% nursing home or assisted living

Study Design (URGH!!)

• “Proprietary” sequential parallel comparison • Phase 1: 5 weeks drug vs placebo• Phase 2: Take “placebo nonresponders” and Re-

randomized to drug vs placebo• This study design enriches your study with

patients who are less susceptible to placebo effect

• This ain’t real life at all. • Study design exaggerates the effectiveness of the

drug when used in real world

Results: Agitation

• Improved NPI Agitation score: 1.6 point improvement (12 point scale)

• Probably slight, but meaningful improvement

• Some evidence the change was noticeable to caregivers and clinicians

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Side Effects• Falls

• 8.6% dextromethorphan• 3.9% placebo• Absolute Difference: 4.7%, NNH= 21

• Diarrhea increased from 3.1% to 5.9% (NNH=36)

• UTI increased from 3.9% to 5.3% (NNH-71)• Dizziness increased from 2.4% to 4.6%

(NNH=45)• Investigators conclude drug was “generally well

tolerated” We beg to differ

Conclusion• Conclusion A:

• Dextromethorphan efficacious for reducing agitation with tolerable side effects

• Conclusion B: • Dextromethorphan efficacious in increasing falls

with some additional mild benefits of reduced agitation

• Should you consider Dextromethorphan for off-label use for patients with dementia agitation?

• Evidence of effectiveness is very modest, and risk for harm substantial

What Medicare Does and Doesn’t Cover

LongTermCareHomeCareServicesCaregiverSupport

Kelley et al. Ann Intern Med. 2015;163:729-736.

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What Do Health Conditions Cost?

• Typical Perspective• What insurers (ie, Medicare) pay

• The Truth: Patients and Families Pay a Lot• Out of pocket costs: stuff not paid by insurance

• Nursing home care, day health care, home health aides, home renovations, some medicines

• “Implicit” Costs: Family caregiving• May have no money exchanged, but incredibly valuable• Often leads to loss of employment• $ave$ Billion$ in public nur$ing home co$ts• Out of sight, out of mind: Failure to consider caregiver as

a cost devalues their contribution

What did they do ?

• Identified everyone who died while in Health and Retirement Study (representative of US)

• Looked back 5 years to identify costs• Medicare claims

• Included all claims for inpatient, outpatient, skilled-nursing facility, hospice, home care

• Subject (and Family) reports of spending• Includes insurance, medication, nursing home, hired

helpers, in-home medical care, and other expenses• Caregiving costs (hours X home health aide wage)

• Compared those with dementia vs other diagnoses

Results• Average total cost per decedent in the last 5

years of life• Dementia $280 000• Heart disease $175 000• Cancer $173 000

• Medicare expenditures were similar across groups

• Average out-of-pocket spending • Dementia $62 000• Without dementia $34 000

• Average informal care costs• Dementia $83 000• Without dementia $38 000

Asset WIPEOUT

• % of assets obliterated in last 5 years of life

• Dementia 32%• Other diseases 11%

• Dementia destroys savings of most disadvantaged

• African American ethnicity: 84%• Less than high school education: 48%

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So, where should we spend our money?

• PET scans for early diagnosis of Alzheimer’s Disease?

• Pre-clinical Alzheimers?• Crazy idea

• Before plowing more $$ into early diagnosis of dementia, we could plow $$ into needs of patients and families that already have dementia

Conclusions

• Dementia is very expensive• Not so much from Medicare perspective

• But very much so from patient perspective

• Very large out of pocket expenses• Huge cost in terms of caregiver workload• Often wipes out family assets: Especially

in those who don’t start with much

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“Dr.Eckstrom,51,whospendsherdaysfocusedonthecomplexmedicalneedsofolderpatients,is,liketheCentralAfricanokapi,aspeciesthatisrevered,rareandendangered.She isageriatrician.”

www.nytimes.com/2016/01/26/health/where-are-the-geriatricians.html

JAGS. 2015 Nov;63(11):2227-46

Why potentially inappropriate medication use is important• Increases risk of adverse drug events, morbidity, and mortality

• Increases healthcare costs and utilization

• Increase use in the oldest and most vulnerable adults

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Polypharmacy is a growing issue

Qato, et al. JAMA Intern Med. 2016

8488

3136

53

67

0

10

20

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100

2005-2006 2010-2011

Prevelence,% >=1Medication

>=5Medications

>=5Medications orSuppliments

2015 Update Methods

• Background• Created in 1991 with updates in ‘97, ‘03, ‘12, and

’15• 2015 Update

• 13-member interdisciplinary expert panel• Systematic literature review

• SEARCH TERMS: ADE, inappropriate drug use, med errors, polypharmacyx age/human/Engl is h

• Initial Search (8/1/2001-7/1-2014) n=25,549 citations• Records Reviewed by Co-Chairs (3,387)• Records Screened by Full Panel (n=1,188 citations)• Studies Used to create Evidence Tables (n=335)

PIM’s(drugs toavoid)

Drugstoavoidinspecificdiseases

Anti-cholinergic

drugs

Drugs tousewithcaution

DangerousDrug–

DrugMixes

Drugs andKidney’s

Potentially Inappropriate Medications (examples)Med Important Changes

Nitrofurantoin Avoid in individuals with CrCl <30 or long term suppression (previously <60)

Digoxin Avoid as first line therapy for a fib and heart failure (continue to avoid >0.125mg)

Non-BDZ receptor agonists (eszopiclone, zaleplon, zolpidem)

Avoid as just as bad as BDZ’s

Anti-psychotics(1st and 2nd

generation)

Avoid as first-line treatment of delirium; Avoid in dementia unless all else fails; 1st line: non-pharm

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Potentially Inappropriate Medications (examples)Med Important changes

Insulin Sliding Scale Defined what ISS is (and continue to avoid)

Opioids Avoid in those with history of falls or past fracture

Proton-pump inhibitors

avoid use beyond 8 weeks without justification

Paroxitine Not just on anticholinergic list anymore -> avoid

Key Principle’s in using Beers Criteria

1. Meds listed are potentially inappropriate, not definitely inappropriate.

2. The rationale and recommendations statements give important caveats and guidance

Steinman et al. JAGS. 2015 Dec;63(12):e1-e7.

N Engl J Med 2015; 373:2103-2116

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Background What’s the optimum SBP target?• SBP < 150

• Systolic Hypertension in the Elderly Program (SHEP) and the

• Hypertension in the Very Elderly Trial (HYVET)

• Goal of <120 instead of <140?• Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure trial

• No benefit for treatment to the lower target for a composite cardiovascular disease outcome

• hazard ratio 0.88, 95% CI: 0.73 to 1.06, P =0.20

SPRINT Trial • Randomized, controlled, open-label trial comparing

a target goal of <120 mmHg vs <140 mmHg • 9361 people in the US and Puerto Rico

• 50 years and older• SBP 130 - 180 mmHg (*actually more complicated) • An increased risk of cardiovascular events

• Cardiovascular disease other than stroke.• CKD with eGFR of 20-59• Framingham 10-year risk CVD >=15% • Age > 75

• Excluded: stroke, diabetes, heart failure, protein in urine (>1g/d), Advanced CKD (eGFR <20), SPB<110 after 1 min of standing, nursing home, poor adherence (including dementia)

N Engl J Med 2015; 373:2103-2116

Who did they end up with?

• Demographics• Mean Age: 68 • 28% >75yrs old• 29.9% black, 10.5% Hispanic

• Mean baseline SBP: 139 mmHg • 90% already on HTN medications

• Only 16% of those taking one med were on a thiazide!

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What did thy do during the trial?

Visits• Startedmonthlyx3thenquarterly

SBP• Measuredx3andaveraged ateachvisit

Meds• BPmeds fromallmajorclassesavailable• Providedforfree

Start*:Beginw/2or3drugs: combothiazide +-ACEI/ARB +- CCB

Addanewdrugand seept monthlyuntil SBP<120

DBP>=100orDBP>=90onlast2visits

SBP>=120atvisit

Isitamilepostvisit

Titratedrugsor addnewdrug& seeparticipantmonthlyuntil SBP<120

Continue therapy

Titrateor addnewdrug

Monitor

Yes Yes

No

No

TreatmentAlgorithmforIntensiveGroup*oktostartw/1drugfor>75yearsofageifSBP<140

No

Yes

Did they reach the target?Standard Treatment:

Mean SBP134Mean #BPmeds 1.8

Intensive Treatment:Mean SBP122Mean #BPmeds 2.8

Outcome* Absolute RiskReduction

NumberNeeded toTreat

Combined MI,stroke,CHF,CVdeath

-1.6% 61

HeartFailure -0.8% 125CVMortality - 0.6% 167

All-CauseMortality -1.2% 83

• Allarestatisticallysignificant• Stoppedearly3.26yearsofplanned5years

The Good

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The BadOutcome Absolute Risk

IncreaseNumber

Needed toHarmHypotension 1.0% 100Syncope 0.6% 167

Electrolyteabnormalities 0.8% 125

Acute KidneyInjury 1.6% 62

Serious ADE** 2.2% 45*Allarestatisticallysignificant(nodiffinfallsorbradycardia)**Possiblyordefinitelyrelatedtotheintervention

2600Patients inageriatrics panel(age>50)2100withHypertension2000notinaNursing

Home

1000withnodiabetesor

historyofstroke;noissueswithpooradherence

tomeds

Out of these 1000 people treated over 3.2 years to an SPB goal <120 compared to <140

16Benefit-PrimaryOutcome 22Harmed

Out of these 1000 people treated over 3.2 years to an SPB goal <120 compared to <140

12Benefitinregardstoallcausemortality

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• We should consider a lower SBP target for patients over age 50 at increased cardiovascular risk but without diabetes, stroke, or other exclusions criteria

• Most never reached target of <120• There are harms• Be careful to generalize results of SPRINT

• Those with untreated SBP 120-129• Those with SBP >180, >170 on 2 HTN meds, >160 on 3

meds, or >150 on 4 meds• Nursing home patients• Diabetics• Frail older adults

ImportanceandConclusion Last Point - Measuring Matters

• How SPRINT did it• Average of 3 office BP readings taken with proper

cuff size• Participants seated with their back supported• 5 minutes of rest before measurement• No conversation during the rest period or BP

determinations.• Conventional Auscultatory SBP

• Up to 20mmHg higher than this technique• Potential for over-treatment

Myers MG, et tal. Hypertension. 2010;55:195–200

D 0

1000

2000

3000

4000

5000Pubmed ResultsPerYearforVitaminDandE

VitaminD VitaminE

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0

1000

2000

3000

4000

5000Pubmed ResultsPerYearforVitaminDandE

VitaminD VitaminE

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140Meta-analysesonVitaminDbyYear

Peak Vitamin DJAMA Intern Med. 2015;175(10):1612-1621.

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JAMA Intern Med. 2015;175(5):7 03 -71 1. JAMA Intern Med. 2016;176(2):175-183.

Exercise and Vitamin D to prevent falls

• Study question: In those with a history of falling

• Does Vit D prevent recurrent falls?• Does Exercise prevent recurrent falls?• Do both work better together than either one alone

• 409 persons in Finland, age 70-80• One fall in previous year• Not using Vit D supplements (Vit D deficiency not

required (mean level 27 ng/ml)

JAMA Intern Med. 2015;175(5):703-711.

Interventions

• Vitamin D 800 IU/day (vs placebo)• Exercise vs no Exercise

• Group training classes 2 times/week for first year, once a week second year

• Balance, strengthening, agility, weight training• Design: RCT with four groups

• Vit D + Exercise• Vit D alone• Exercise alone• Neither exercise or Vit D

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Results

Falls/100 py FallInjury/100py

Placebo/No Exercise 118 13

Vit D/ NoExercise 132 13

Placebo +Exercise 120 6.5

Vit D+Exercise 113 5.0

Conclusion

• In elders with a prior history of falls:• Vitamin D had no impact on falls or fall injury

• Exercise reduced the risk of fall injury

MegaDose Vitamin D in Fallers: Caveat Emptor

• Research question: Does high dose Vitamin D improve muscle function and prevent falls in elders with fall history?

• Study Design• 3 arm RCT in 200 fallers over age 70 (58% vitamin D deficient) rxed for 12 months with

• 24000 units of Vit D monthly• 60,000 units of Vit D monthly• 24000 units Vit D + 300 units calcifediol monthly

JAMA Intern Med. 2016;176(2):175-183.

Outcomes

Low D High D D+Calcifediol

Vit Dlevel>30

55% 81% 84%

SPPBchange

0.38 0.10 0.11

Fall 48% 67% 66%

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Conclusion

• Compared to low dose Vitamin D, High Dose Vitamin D

• Had no benefit on function• Markedly increased the risk of falling

• Do not use high dose Vitamin D

Cummings, Kiel, and Black:

• No evidence vitamin D supplements improve health outcomes in community-living seniors

• “The Vitamin D story seems to be following the familiar pattern with antioxidant vitamins”

• Recommendations for community living elders over age 70

• Aim for 800 IU Vit D/day from dietary sources

JAMA Intern Med. 2016 Feb 1;176(2):171-2

J Am Geriatr Soc 63:2472–2477, 2015. J Am Geriatr Soc 63:1084–1090, 2015.

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JAMA Intern Med. 2015;175(8):1 33 1- 13 39

Background

• 2 out of 3 nursing home residents receive antibiotics each year (mostly for suspected UTIs)

• Many are inappropriate, unnecessary, or unnecessarily prolonged

• Antibiotics have benefits but also harms• Clostridium difficile • Polypharmacy• Medication side effects• Potential for antibiotic-resistant organisms

Methods

• Linked multiple healthcare datasets from province of Ontario, Canada

• Included information on medication prescriptions, physician visits, emergency room visits, and hospitalizations

• Inclusion• >= 66 years of age• Resident in Ontario nursing home from 2010-2011

• Excluded• Nursing homes with < 25 beds• Switched homes more than once in the study period

Methods

• Nursing homes classified into three use

• low, medium, and high antibiotic users based on days of use

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Potential antibiotic-related adverse outcomes

• Clostridium difficile • Diarrhea or gastroenteritis• Antibiotics resistant organisms• Allergic reactions to antibiotics• General medication adverse events

Lots of Antibiotics, Lots of Variability• 111,656 residents in 607 nursing homes

• 70% female, 56% with dementia• Participants used antibiotic Use

• 5 out of every 100 days spent in a nursing home • Ranged 2-20 out of every 100 days spend in a

nursing home• Antibiotic Adverse Events*

• High-use nursing homes: 13%• Medium-use nursing homes:12%• Low-use nursing homes: 11%

* NNH between high and low utilizers: 53

Association remained true even for residents who didn't get antibiotics

• Antibiotic Adverse Events*• High-use nursing homes: 9.9%• Medium-use nursing homes: 9.6%• Low-use nursing homes:8.7%

* NNH between high and low utilizers: 83

Second-Hand Antibiotic Exposure

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Geriatric care improves hip fracture outcomes!

Lancet. 2015 Apr 25;385(9978):1623-33

Study Question

• Does providing comprehensive geriatric care (“orthogeriatric care”) on a dedicated ward lead to better outcomes than usual orthopedic care?

• General concept: Treat hip fracture as a geriatric condition rather than a surgical condition (other than hip surgery)

Study Design

• RCT in Norway: • Elders randomized to care on usual unit vs

dedicated orthogeriatrics unit• Subjects=400 patients

• Age 70 + (mean 83)• Able to walk 10 meters pre-fracture• Not in nursing home (nearly 25% of patients

excluded on this basis)

What is orthogeriatrics?• Admission to ward staffed by Geriatricians

• Managed care both before and after surgery• Interdisciplinary Team (Geriatrics, Nursing, PT,

OT)• Diagnostic and treatment algorithms grounded

in comprehensive geriatric assessment• Assessment of multimorbidity, medication reviews,

pain, nutrition, depression, social situation• Protocols focused on delirium prevention and

functional improvement (early mobilization)• Early discharge planning

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Primary Outcome

• Short physical performance battery (SPPB)• Chair stands (stand up from chair 5 times without

using arms)• Standing balance (stand tandem for 10 seconds for

best score)• 8 foot walk at usual pace• Each scored 0-4, maximum total 12

• Strongly correlated with mortality and NH need

Results: Good new for the Geriatrics Team

• SPPB at 4 months• 5.1 vs 4.4 favoring geriatrics

• SPPB at 12 months• 5.3 vs 4.6 favoring geriatrics

• MMSE at 12 months• 24.1 vs 22.7 favoring geriatrics

• Barthel ADL score• 16.5 vs 15.3 favoring geriatrics

• Discharged directly home• 25% vs 11% favoring geriatrics

• Quality of life score favor Geriatrics

Conclusion

• A Geriatric care model following hip fracture led to clinically meaningful improvement in outcomes

• Hard to justify this not being the care model for hip patients with fracture

But, a little footnote to our applause

• Study did not include nursing home patients severe prefracture mobility impairment before fracture

• A LOT of people• Even with the best care hip fracture has

• High mortality• High rates of functional decline

• Geriatrics not only about preventing functional decline. We also help patients and their care givers have good quality of life despite disability

• Time for a hip fracture intervention aimed at those who have little hope for independent functional recovery

• ?OrthoGeriatricsPalliative Care??

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J Gen Intern Med 30(8):1071–80

Methods

• Randomized controlled trial in 2 teaching hospitals

• Participants (n=150):• Hospitalized adults >60 years of age• Advanced illness with prognosis of ≤1 year

Intervention(3 minute video on CPR/Intubation)

Assessment:1) Knowledge, 2) code status on

admission and d/c, 3) Repeat ? On preferences for CPR/Intubation

Communicated post-video preference to MD

Enrollment & Questionnaire(demographics, preferences CPR/Intubation)

Usual Care

Assessment:1) Knowledge

2) Code status on admission and d/c

Randomized

Watching a Video Changes Preference

NoVideo Video pStated Preferencefor:DNR 32% 64% <0.0001DNI 43% 72% <0.0001

DocumentedOrdersat D/Cfor:DNRorder 19% 57% <0.0001DNIorder 19% 64% <0.0001

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Other Secondary Outcomes

• Higher mean knowledge scores after viewing the video compared to control

• 4.1 vs 2.4, p<0.001

• Only 3% not comfortable watching the video

1 Year Outcomes on Re-admission

NoVideo Video pDNRorders 13% 49% <0.001DNIorders 13% 53% <0.001

*1-year follow-up basedon 65%ofvideoand 73%ofcontrolpatients whowere readmitted at least once

N Engl J Med. 2015 Oct 22;373(17):1597-606

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Study Design• Randomized Controlled Trial of TKR vs 12

week Non Surgical Treatment• Eligibility:

• Radiographically confirmed knee OA• Deemed by orthopedic surgeon as being eligible for

TKR• Subjects

• Mean age 67• 60% women• Mean BMI 32• 90% Kellgren-Lawrence score of 3 or greater

What is Non-Surgical Treatment

• Exercise/PT• 2 hour long sessions/week X 12 weeks• Restore functional alignment, compensatory

exercises, improved sensorimotor control• Education

• Promote active engagement, self-management• Diet and Weight loss intervention

• Goal 5% weight loss (actual 6 lbs)• Insoles• Pain meds

Improvement in Surgery and Non Surgery GroupsSurgery NoSurgery Difference

Pain 34 17 17Symptoms 26 11 15Activities ofDailyLiving

30 18 12

Quality ofLife 38 18 20

13(26%)ofPatientsrandomizedtonosurgerychosesurgeryover12months

Complications of Surgery

• 24 serious adverse events in surgery vs6 in Non Surgery

• Examples of Complications• 3 DVTs• 3 GI bleeds• 3 brisement forcee procedures needed• 1 deep infection• 1 femur fracture

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Conclusion

• Knee replacement works!• But complications are common• Rigorous Non Surgical Management

leads to significant improvement• Most patients with severe knee OA will

do better with surgery• But trial of non surgical management appropriate for those reluctant to have surgery

• ELPHANENT

Pediatrics. 2015 Sep;136(3):487-95

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Study Design / Participants• 24 NICU teams

• 72 Israeli NICU professionals (physicians and nurses)

• Mean tenure of of 11 years• Placed in a training simulation involving a

preterm infant whose is getting sicker due to necrotizing enterocolitis.

• Teams were evaluated in their performance by 3 independent judges who assessed

• diagnostic performance• procedural performance• information-sharing, and help-seeking.

I’mnotimpressedwiththequalityofmedicineinIsrael

“medicalstafflikethoseobservedinIsrael“wouldn’tlastaweek”inhisdepartment

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“IhopethatIwon’tgetsickwhileinIsrael.”

Results

• Teams exposed to the mildly rude comments had significantly:

• worse diagnostic scores • 2.6 vs 3.2 [P = .005])

• procedural performance scores • 2.8 vs 3.3 [P = .008]

• Rudeness negatively influenced team information sharing and help-seeking.

Rudeness

InformationSharing

HelpSeeking

DiagnosticPerformance

ProceduralPerformance

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