venous thromboembolic disease

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Venous Thromboembolic Disease. Chris Hall, MD, FRCPC Emergency Medicine Resident Rounds January 12, 2012. One Night in the ED…. 36 yo Female Sudden onset right-sided pleuritic CP Feels SOB Physical examination ‘normal’ PMHx : Nil Meds: None ECG, CXR normal. WHY I HATE PE…. - PowerPoint PPT Presentation

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Page 1: Venous  Thromboembolic  Disease
Page 2: Venous  Thromboembolic  Disease

Venous Thromboembo

lic DiseaseChris Hall, MD, FRCPC

Emergency Medicine Resident RoundsJanuary 12, 2012

Page 3: Venous  Thromboembolic  Disease

One Night in the ED…

36 yo Female Sudden onset right-sided pleuritic CP Feels SOB Physical examination ‘normal’ PMHx: Nil Meds: None ECG, CXR normal

Page 4: Venous  Thromboembolic  Disease
Page 5: Venous  Thromboembolic  Disease

WHY I HATE PE…

Potentially fatal (“can’t miss”)

Challenging to diagnose

Evidence base is HUGE… and growing

Rapid advances in technology: evidence is obsolete (?!)

Page 6: Venous  Thromboembolic  Disease

Objectives

To simplify YOUR life when it comes to PE in the ED

To provide an update on the latest state of the evidence regarding PE: Diagnosis Management Risk Stratification

Page 7: Venous  Thromboembolic  Disease

Epidemiology

PE Incidence 115 cases per 100,000 population / yr

Mortality Rate 12 per 100,000 / yr

Case Fatality 8% overall (30% if untreated!)

Page 8: Venous  Thromboembolic  Disease

Pathophysiology

Virchow’s Triad Stasis Injury Hypercoagulability

> 90% Deep venous source Iliofemoral > Pelvic > Renal > IVC Calf veins (< 10%)

Page 9: Venous  Thromboembolic  Disease

Pathophysiology

Multiple mechanisms of hypoxia V/Q mismatch Inflammatory cascade surfactant dysfxn Functional intrapulmonary shunting

75% obstruction of PA bed = reduced CO

Page 10: Venous  Thromboembolic  Disease

Risk Factors

Malignancy Immobilization / Paresis Surgery / Trauma Prior hx of VTE Thrombophilia Family history Pregnancy Estrogen use

Page 11: Venous  Thromboembolic  Disease

PE: Our Worst Nightmare…?

Presentation often non-specific

Many clinical mimics

Up to 40% of fatal PE < 35 yo missed on first MD contact

Page 12: Venous  Thromboembolic  Disease

…or an iatrogenic epidemic?

1998 – 2006: PE Indicence 86% Case Fatality 36% CTPA use > 10-fold Pop’n Mortality: NO CHANGE More testing / treatment to

get the same result?

Page 13: Venous  Thromboembolic  Disease

A Balance of Risks

PE mortality: 8% (?? 25-30% if

untreated)

LAR for cancer from one CTPA 25yF: 1 / 400 55yF: 1 / 950 25yM: 1/ 2000

Contrast nephropathy

Overanticoagulation

Page 14: Venous  Thromboembolic  Disease

More investigation

Fewer missed PE

Less Investigation

More missed PE??

??

Page 15: Venous  Thromboembolic  Disease

What Risk is ‘Acceptable’?

At what pre-test probability would you discharge your patient without further testing? 10% 5% 2% 1% 0.5% 0.1%

Page 16: Venous  Thromboembolic  Disease

What Risk is ‘Acceptable’?

Lessler et al, Ann Emerg Med 2010 Theoretical decision analysis Risk of missed PE vs. risk of investigation /

overtreatment At 1.4% probability, risks are equal

If probability of PE < 1.4%, do not test

Page 17: Venous  Thromboembolic  Disease

Can clinical exam achieve PTP < 1.4%?

Page 18: Venous  Thromboembolic  Disease

PE: Clinical Presentation

What symptoms / signs make you think of PE?

What is the most common symptom / sign?

Page 19: Venous  Thromboembolic  Disease

Clinical PresentationSymptom % of PEDyspnea At rest Exertional only

61%16%

Chest Pain Pleuritic Non-pleuritic

47%17%

Cough No blood Hemoptysis

32%11%

Orthopnea 36%Syncope 12%

Page 20: Venous  Thromboembolic  Disease

Clinical PresentationSign % of PE

Tachypnea 57%Signs of DVT 47%Tachycardia 29%Abn. Lung Sounds

26%

Fever 2%

Page 21: Venous  Thromboembolic  Disease

One Night in the ED…

36 yo Female Sudden onset right-sided pleuritic CP Feels SOB Physical examination ‘normal’ PMHx: Nil Meds: None ECG, CXR normal

Page 22: Venous  Thromboembolic  Disease

Would You…

Send a d-dimer?

Proceed directly to imaging?

Do nothing?

Page 23: Venous  Thromboembolic  Disease

Is this patient’s pre-test probability of PE below the “no-test” threshold?

Page 24: Venous  Thromboembolic  Disease

Wells Rule

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Geneva Rule

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55,268 patients

10 CDRs + MD gestalt reviewed

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CDR SN SP NLR PLR

Wells 84 % 58 % 0.3 2.0

Geneva 84 % 50 % 0.3 1.7

Revised Geneva

91 % 37 % 0.2 1.4

MD Gestalt 85% 51 % 0.3 1.7

Page 29: Venous  Thromboembolic  Disease

PERC

Pulmonary Embolism Rule-out Criteria Derived 2004 Validated 2008 (multi-center) Provides CLINICAL basis to rule out PE GOAL: < 1.5% probability

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PERC

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PERC Validation 8138 patients Results:

SN 97.4% (if MD gestalt ‘low-risk’) Post-test prob: 1.0%

PE prevalence 7% (3% in low-risk pts) Only useful in ‘low-risk’ population (MD

gestalt)

(BUT - who qualifies?? < 5% PTP?? )

Page 32: Venous  Thromboembolic  Disease

Caveat Emptor…

Hugli et al. J Thromb Haemost., Feb 2011 1675 consecutive patients 21.3% prevalence of PE

Low-risk revised Geneva: 6.4% PE Low-risk Geveva + PERC (-): 5.8% PE

PERC NLR = 0.63 in LOW RISK pop’n

Page 33: Venous  Thromboembolic  Disease

PERC Bottom Line

Achieves ‘no-test’ threshold in ‘low-risk’ patients

Endorsed in ACEP Clinical Policy (2011)

Select patients carefully

Page 34: Venous  Thromboembolic  Disease

Back to our case

How many will now send a d-dimer?

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The test you love to hate…

D-dimer = FDPSN 75 – 97%SP 43 – 99%Depends on assay typeDepends on clinical context (CDRs)

Higher PTP = Lower SN

Page 36: Venous  Thromboembolic  Disease

Low

Not Low

(-)

(+)

Page 37: Venous  Thromboembolic  Disease

‘Wells Rule’

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Quantitative D-dimer + CDR

CDR Failure Rate Efficiency

Simplified Wells (≤4)

0.5 % 39 %

Geneva 0.0 % 21 %

MD Gestalt ** 0.7 % 52 %

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D-dimer: Bottom Line

In low-intermed. probability patients, d-dimer rules out PE

ACEP Clinical Policy 2011

Efficiency of PERC + CDR / d-dimer strategy unknown

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Not HighHigh

Yes No

Positive Negative

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Back to our case…

D-dimer result = 0.89 Patient remains stable Do you now:

Order a V/Q scan? Order a CTPA? Order U/S dopplers of the legs?

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PE: Imaging

What is the ideal strategy for imaging in suspected pulmonary embolism?

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V/Q Scan

Advantages Lower radiation dose (7 – 10 x less than CTPA) No iodinated contrast

Disadvantages Harder to obtain ‘after hours’ Higher rate of non-diagnostic scans Cannot diagnose other causes for symptoms

Page 45: Venous  Thromboembolic  Disease

CT diagnosed more PE 19.2% vs 14.2%

LARGE non-diagnostic V/Q scan rate (> 50%) V/Q noninferior to CT

VTE @ 3 mos 1.0% vs 0.4%

Page 46: Venous  Thromboembolic  Disease

V/Q Scan: Don’t Bury it Yet!

Good option if:

Normal CXR

Younger patients

Lower PTP

Contraindications to CT

Page 47: Venous  Thromboembolic  Disease

CT Pulmonary Angiogram

Advantages Speed Available after hours (in Calgary) Confirms alternative diagnoses

Disadvantages Contrast load Radiation dose

Our ‘de facto’ gold standard

Page 48: Venous  Thromboembolic  Disease

3306 consecutive patients Utilized dichotomous Wells (≤ 4 = “low”)

D-dimer if Wells low; MDCT if d-dimer (+) or Wells high

No Rx if d-dimer (-) or MDCT (-)

VTE rate @ 3 months: 0.5% for Wells / d-dimer (-) 1.3% for CT (-)

Page 49: Venous  Thromboembolic  Disease

PIOPED II CTPA SN: 85% VTE @ 6 mos: 14% for Int. / High PTP if CTPA

(-)

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CTPA Bottom Line:

For Wells ≤ 4, CTPA (-) rules out PE If PTP ‘intermediate’, consider additional

testing** if still ‘concerned’ about PE If PTP ‘high’, obtain additional testing**

ACEP Clinical Policy, 2011

**(D-dimer acceptable)

Page 51: Venous  Thromboembolic  Disease

What if I add CTV?

~ 2 – 4% pick-up of isolated DVT

Universal CTV use still controversial Intermediate – High PTP would benefit if CTPA

(-)

More studies using newer technology are needed

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U/S: 1st-Line Imaging?

Righini et al., Lancet 2008 1819 patients with suspected PE U/S eliminated need for CTPA in 10%

“NNI” = 10

In both trial arms 3-month VTE risk = 0.3% CT-only arm 24% less expensive

Page 53: Venous  Thromboembolic  Disease

Venous Imaging: Bottom Line

Routine venous imaging not usually recommended

Consider U/S first if: Leg symptoms present CT contraindicated or unavailable

Page 54: Venous  Thromboembolic  Disease

Our Case…

CT refused RE: pregnancy test (+)

Page 55: Venous  Thromboembolic  Disease

Diagnostic Controversy: PE in Pregnancy

Pregnancy = PE Risk factor Overall risk still low: 10.6 / 100,000 Risk greatest in post-partum period 3-6% of suspected cases are PE (+) PE symptoms overlap with changes of

pregnancy Strong desire to avoid ionizing radiation in

workup

Page 56: Venous  Thromboembolic  Disease

PE in Pregnancy: D-dimer

True prognostic value unkown EVIDENCE IS WEAK on either side ESC Guidelines: USE D-DIMER TO R/O PE! ATS Guidelines: DO NOT USE D-DIMER TO R/O PE! “Kline” protocol:

PERC + TM-specific cut-offs

PERC alone may be good enough (~5% PTP)

Page 57: Venous  Thromboembolic  Disease

PE Imaging in Pregnancy

U/S 1st-line if DVT symptoms; if no leg symptoms – skip it

V/Q If CXR normal, > 90% of scans are “definitive” Fetal radiation similar / maternal lower than CT *** Preferred 1st-line test

CT 30% of scans ‘non-diagnostic’ 1st-line if CXR abnormal

Page 58: Venous  Thromboembolic  Disease

1/10,000 risk 10 mSv

of CA by age 25

NCRPM Cut-off 50 mSv

Background 5 mSv

radiation over 9 mos

V/Q scan0.32-0.74

mSvCTPA0.03-0.66

mSv

CXR0.002 mSv

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You Call THAT Simplified??!!

MY approach

‘PERC’ them

D-dimer w/ ‘standard’ cut-offs

CXR

V/Q

(U/S first if leg symptoms)

Page 61: Venous  Thromboembolic  Disease

Case

CTPA result: Several right-side PE Moderate clot burden RV normal

Treatment? Disposition?

Page 62: Venous  Thromboembolic  Disease

PE: Treatment

LMWH is preferred Warfarin is OAC of choice Dabigatran: ? Non-inferior to warfarin IVC Filters:

Absolute CI to anticoag Failure of warfarin

Page 63: Venous  Thromboembolic  Disease

Treatment Duration

Condition Duration of TherapyReversible cause

3 months

Idiopathic (1st)

3 months minimum; indefinite if low bleed risk

Idiopathic (2nd +)

Indefinite

Cancer LWMH x 3-6 mos, then warfarin until CA “cured”

Source: ESC PE Guidelines, 2008

Page 64: Venous  Thromboembolic  Disease

Management:Sub / Massive PE

Massive PE: SBP < 90 mmHg (w/o other cause) Pulselessness HR < 40 with shock

Submassive PE: Not hypotensive RV dysfunction (+) Myocardial necrosis (+)

Page 65: Venous  Thromboembolic  Disease

Supportive Care

IV Fluids Use caution: 250-500cc then consider echo

Pressors Levophed or dopamine OK; phenylephrine less

OK

Intubation Keep PEEP low (< 6) Use low TV (6cc/kg)

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Thrombolysis

Indicated in massive PE AHA & ACEP endorsed NNT = 10

Subset of submassive PE may benefit Progressive deterioration (AHA) Insufficient evidence (ACEP)

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Thrombolysis

Secure Dx before Rx CT vs echo

Alteplase 100mg IV preferred Bolus vs infusion / 2hr UFH infusion after

Avoid in undifferentiated VSA

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Adjuncts

Catheter fragmentation Surgical Embolectomy Pulmonary vasodilators

NOx Sildenafil Inhaled prostacyclin

IVC Filters

Page 69: Venous  Thromboembolic  Disease

Risk Stratification

Many (most?) jurisdictions practice universal admission

Calgary (Canadian?) practice heavily outpatient-based

Who is safe to d/c home?

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Risk Stratification

Potential Tools Biomarkers

Imaging

Clinical risk scores

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Troponin

Conventional Tn useful if positive: OR = 5.3 (short term death) SN = 70.5, NLR = 0.42

Becattini et al, Circulation 2008

hs TnT better for rule-out use: OR = 5.0 SN = 87.0, NLR = 0.31

Lankeit et al, Circulation 2011

Page 72: Venous  Thromboembolic  Disease

Imaging

RV Dysfunction CT: debated Echo: gold standard ECG Useful if positive, less so if negative

CT ‘clot burden’ not predictive

Page 73: Venous  Thromboembolic  Disease

Pulmonary Embolism Severity Index

Prospectively validated Purely clinical variables For STABLE patients SN ~ 95%; NLR ~ 0.1 for 30-day mortality

< 1% in low-risk 8-9% in non-low-risk

30-40% of patients are low-risk

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Simplified PESI

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PESI in Practice

Lancet, 2011 RCT of inpatient vs outpatient for PESI class

I / II 30-day mortality very low (< 1% overall) No difference between groups

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Risk Stratification Pearls

Outpatient Rx: Low-risk PESI / sPESI

No RV dysfunction on echo / CT / ECG

Negative TnT / hsTnT

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Case Conclusion…

Patient does not have a GP

What follow-up is needed?

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Anticoagulation Clinic

Single visit; subsequent follow up on phone

Rely on GP for additional work-up

Director (MD) available for help if needed

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Malignancy Screening

10% risk of malignancy in ‘idiopathic’ VTE Highly age-dependent Aggressive screening identifies more CA

sooner Guidelines suggest symptom-based

screening DO A THOUROUGH Hx & P/E Consider aggressive screen if > 60yo

Page 81: Venous  Thromboembolic  Disease

Summary

PERC is useful if low-risk population D-dimer + CDR highly sensitive and moderately

efficient Don’t bury the V/Q yet! Routine venous imaging generally low-yield V/Q is preferred 1st-line image in pregnancy PESI can identify low-risk patients for outpatient Rx Consider a malignancy screen in older idiopathic VTE

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Questions?

Page 83: Venous  Thromboembolic  Disease

CASE 2

56 yo male 3 weeks post-op for TKA Unilateral calf swelling, erythema, and

tenderness x 2 days No trauma No chest pain / SOB No fever

Page 84: Venous  Thromboembolic  Disease

Deep Vein Thrombosis

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DVT: Objectives

Diagnosis of DVT Diagnostic algorithms

Novel ED-based imaging strategies

Treatment of DVT Complications / special scenarios

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Epidemiology

Risk = 1.92 / 1000 person-years Higher risk in men 50% will embolize eventually (PE) 30% have silent embolism at diagnosis

Page 87: Venous  Thromboembolic  Disease

Pathophysiology

Virchow’s Triad

50% will embolize eventually

30% have silent emboli @ diagnosis

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Classification

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Risk Factors

See PE… PLUS:

IVC anomalies

May-Thurner Syndrome

Page 90: Venous  Thromboembolic  Disease

Clinical Presentation

Pain / tenderness Erythema / warmth Swelling / edema Venous distension

+/- ‘palpable cord’

Homan’s Sign “Phlegmasia Cerulea Dolens” / “Phlegmasia Alba

Dolens”

Page 91: Venous  Thromboembolic  Disease

Differential Diagnosis

Baker’s Cyst Cellulitis Venous Insufficiency Swelling due to paralysis Lymphangitis / lymphatic obstruction Non-specific swelling

Page 92: Venous  Thromboembolic  Disease

Our Case

Does this patient have a DVT?

Can clinical features r/o DVT?

Page 93: Venous  Thromboembolic  Disease

Wells’ DVT Criteria

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Predicting DVT Clinically

Wells Score

PTP of DVT

Low 5%

Intermediate 17%

High 53%

Page 95: Venous  Thromboembolic  Disease

D-dimer

Wide range of sensitivities / specificities ELISA generally higher SN / lower SP than

SimpliRED Primary utility is when combined with PTP

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D-dimer

Wells Score

SN SP LR (+) LR (-)

Low 95% 58% 2.4 0.10

Moderate 98% 41% 1.7 0.06

HIgh 97% 36% 1.5 0.07

Page 97: Venous  Thromboembolic  Disease

D-dimers: Bottom Line

In Low-Risk group, NLR is sufficient to R/O DVT

In other groups, d-dimer insufficent to change decision to image

Page 98: Venous  Thromboembolic  Disease

DVT: Imaging

Venography Impedance Plethysmography CT Venogram MRI Venogram

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U/S for DVT

Defacto ‘gold standard’ No ionizing radiation No IV contrast Generally widely available Variable techniques

Whole-leg Doppler 2-point proximal vein compression

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Whole-Leg U/S

Detects calf vein DVTs Equivalent to strategy of serial proximal

compression U/S plus d-dimer May eliminate need for serial U/S Not performed routinely at AHS sites

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ED Ultrasound

Available “24 / 7” Easy to learn Variable SN: 70-100% depending on author Accuracy likely improved w/ clinical risk

stratification

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DVT Treatment

LMWH UFH Fondaparinux Warfarin Dabigatran

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LMWH

Preferred 1st-line agent Better outcomes than IV UFH OD / BID dosing Predictable anticoagulation effect No monitoring needed Lower risk of HIT SAFE in pregnancy

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SubQ UFH

Equivalent to LMWH BID dosing (weight-adjusted, fixed-dose) Monitoring of APTT likely NOT needed Less concern in renal failure Risk of HIT Less expensive than LMWH

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Fondaparinux

Non-inferior to LMWH OD dosing (weight-based, fixed-dose) No monitoring needed Can be used (with limits) in renal failure (CR

< 260)

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Wafarin

OAC of choice Initial 5-7 days need overlap with an anti-

thrombin INR monitoring required UNSAFE in pregnancy

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Dabigatran

Oral anticoagulant; Non-inferior to warfarin No monitoring required Not yet approved for use in VTE

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Other Therapies

IVC Filter Failed anticoagulation Contraindications to A/C

Catheter procedures (incl. thrombolysis) Circulatory compromise (PCD) IFDVT w/ rapid progression despite A/C “Selected” patients w/ IFDVT

Stenting Advanced PTS / venous ulcers in setting of IFDVT

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Condition Duration of TherapyReversible cause

3 months

Idiopathic (1st)

3 mos minimum (6 mos IFDVT); indefinite if low bleed risk

Idiopathic (2nd +)

Indefinite

Cancer LWMH x 3-6 mos, then warfarin until CA “cured”

Calf DVT 6 wks – 3 mos

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Summary

Clinical exam insufficient when used alone D-dimer useful only in lowest-risk group Consider serial U/S if d-dimer (+) in non-

low-risk patients LMWH / Warfarin are first-line agents

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Questions?