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They Shoulda Told Me
James W. Wright, MD
September 2015
Company Confidential ©2015 Genworth Financial, Inc. All rights reserved.
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CIMTCarotid Intima Media Thickness
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What is it?• B-mode ultrasound (cross-
section)• Distal 1 cm of the common
carotid artery far wall• Thickness of the intima and
media combined
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Atherosclerosis Progression
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Rationale for CIMT
CAD is leading cause of death in US (25% of all deaths)
Increased CIMT correlates with atherosclerosis progression in coronary and cerebral vessels
Detects disease at early (presymptomatic) stage
Assess early intervention strategies
Improves risk prediction beyond use of traditional risk factors
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How Results Are Reported
Mean thickness in mm, right and left
Percentile for age and sex
Percentiles >75th indicate increased risk
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Clinical Use
Most useful in middle age
Most useful for those at intermediate risk–Family history of premature CAD in 1st-degree relative
–Persons <60 with severe abnormality of a single risk factor
–Women <60 with at least 2 CAD risk factors
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Use in Life Insurance and LTC
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Traditional CVD Risk AssessmentFramingham Risk Score – 10-year risk
Age and Sex Women get CAD at older ages; risk may be underestimated
Race
Total Cholesterol With extreme levels of a single risk factor, FRS may underestimate risk
HDL Cholesterol With extreme levels of a single risk factor, FRS may underestimate risk
Systolic BP
BP Meds (Y/N) But risk is actually graded, not just present or absent
Diabetes (Y/N) But risk is actually graded, not just present or absent
Smoker (Y/N) But risk is actually graded, not just present or absent
Other factors (Meh!)CRP
Hyperhomocysteinemia
Lipoprotein a
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How to Use the CIMTin Insurance Underwriting
Underwriting Heuristic – create a rule that
modifies the current risk assessment
Replace chronological age with vascular age– Example 1: 45 yo man with low FRS (5% risk) and 50th percentile CIMT =
no adjustment
– Example 2: 45 yo man with low FRS (5% risk) but CIMT similar to 55 yo
man. Using 55 in the FRS calculation instead of 45 yields a 16% risk.
Thanks to Dr. Robert Pokorski
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“Chronic Lymes Disease”
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Dr. Irv SalitProfessor of MedicineUniversity of Toronto
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Thanks to:
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The Basics
Caused by the bacterium Borrelia burgdorferi
Transmitted to humans by infected ticks
Acute disease symptoms: rash (erythema migrans), fever,
headache, fatigue (days to weeks)
Early disseminated disease: cranial nerve palsies, radiculopathy,
peripheral neuropathy, lymphocytic meningitis (weeks to months)
Untreated disease late manifestations (months to years)
– Intermittent arthritis in a few large joints
– Subtle cognitive problems
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Reported Cases of Lyme Disease - United States, 2013
Source: CDC
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Diagnosis
Usually based on symptoms, characteristic rash, history of tick exposure
Blood tests (serologies) have problems– Negative is early stage of disease
– Often positive in endemic areas without evidence of active disease
– European forms of the disease require different tests
– Some labs use unreliable tests with high false-positive rate
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Treatment
Most cases are treated successfully with
a two-week course of an antibiotic.
Those with late, untreated disease may
require intravenous antibiotics.
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Outcomes
Close to 100% are cured with a 2-week course of an antibiotic
10–20% have lingering symptoms (PTLDS)– Fatigue, joint and muscle aches
– Persistent symptoms for 6 months or more
– Mechanism unknown
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“Chronic Lyme Disease”
Lyme Group – Persisting symptoms after treatment for Lyme disease, called “post-treatment Lyme disease syndrome” (PTLDS)
CFS Group – Never had Lyme disease but have symptoms similar to PTLDS. In their search for the cause, found serologic evidence of Lyme disease.
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CFS — Lyme Connection
Chronic fatigue syndrome (CFS) symptoms are common
Positive Lyme serology tests are common– Positive predictive value in patients with only nonspecific
symptoms is poor.– Some labs use non-validated tests
Leads to misdiagnosis based on a false-positive serologic test
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Misattribution Leads to Inappropriate Treatment
Some doctors believe CFS symptoms are caused by persistent B. burgdorferi infection
Treat with prolonged courses of antibiotics
Patients who receive prolonged courses of antibiotics fare no better than those treated with placebo.
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Treatment of PTLDS
Treat like fibromyalgia or CFS
Encourage patients to stay active
Rest, healthy diet
Cognitive behavioral therapy
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Chronic Lyme Subculture
Similar to CFS, chronic candidiasis,
chronic EBV infection, etc.
Pseudoscience
Internet-based:– support groups– meetings– literature– activist groups
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Bottom Line
10–20% of Lyme patients have post-treatment
symptoms that may last months
This does not mean persistent infection
No proof that chronic Lyme disease exists
Chronic antibiotic therapy is not needed
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“Newer” Diabetes Medicines
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Type 2 Diabetes
Insulin Resistance
o Muscle
o Liver
Impaired insulin secretion
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Noninsulin Antidiabetes Medications
Insulin secretagogues
Sulfonylureas
Meglitinides
Insulin sensitizers
Biguanides
Thiazolidinediones
Glucosidase inhibitors
Peptide analogs
Glucagon-like peptide-1 analogs
Dipeptidyl peptidase-4
inhibitors
Amylin analogs
Glucosurics (SGLT-2
inhibitors)
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Insulin secretagogues
Sulfonylureas• Glyburide
(Glucotrol)• Glipipzide
(Diabeta)• Glimepiride
(Amaryl)
Meglitinides• Repaglinide
(Prandin)• Nateglinide
(Starlix)
Insulin sensitizers
Biguanides• Metformin
(Glucophage)
Thiazolidinediones• Rosiglitazone
(Avandia)• Pioglitazone
(Actos)
∝-Glucosidase inhibitors
Miglitol (Glyset)
Acarbose (Precose)
Peptide analogs
Glucagon-like peptide-1 analogs•Exenatide (Byetta)•Liraglutide (Victoza)•Albiglutide (Tanzeum)•Dulaglutide (Trulicity)
Dipeptidyl peptidase-4 inhibitors•Sitagliptin (Januvia)•Vildagliptin (Galvus)•Saxagliptin (Onglyza)•Linagliptin (Tradjenta)•Alogliptin (Nesina, Vipidia)
Amylin analogs•Pramlintide (Symlin)
Glucosurics (SGLT-2 inhibitors)
Canagliflozin (Invokana)
Empagliflozin (Jardiance)
Dapagliflozin (Farxiga)
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Peptide Analogues
GLP-1 Analogues
DPP-4 Inhibitors
Amylin Analogues
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Exenatide (Byetta) – “lizard spit” GLP-1 Analogue Isolated from gila monster saliva Approved 2005 Injection only Now available in one weekly dosing (Bydureon) Others in this class: liraglutide (Victoza), albiglutide (Tanzeum),
dulaglutide (Trulicity)
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Peptide Analogues
GLP-1 Analogues
DPP-4 Inhibitors
Amylin Analogues
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Sitagliptin (Januvia)
Inhibits DPP-4, thereby increasing levels of GLP-1
Approved 2006 Taken orally Others in this class
– Saxagliptin (Onglyza)– Linagliptin (Tradjenta)– Alogliptin (Takeda)– Vildagliptin (Galvus) - pending
Others in other countries and others in development
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Peptide Analogues
GLP-1 Analogues
DPP-4 Inhibitors
Amylin Analogues
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Pramlintide (Symlin)
Amylin is secreted from the beta cell with
insulin Actions:
– Delays gastric emptying
– Promotes satiety
Synthetic analogue pramlintide approved 2005 Must be injected
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Glucosurics (SGLT-2 Inhibitors)
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SGLT-2 Inhibitors
canagliflozin (Invokana) – 2013
empagliflozin (Jardiance) – 2014
dapagliflozin (Farxiga) – 2014
All are taken orally.
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Combination Meds - 1
Metformin+ glipizide = Metaglip+ glyburide = Glucovance+ pioglitazone = Actoplus Met+ rosiglitazone = Avandamet+ repaglinide = Prandimet+ saxagliptin = Kombiglyze+ sitagliptin = Janumet+ linagliptin = Jentadueto+ alogliptin = Kazano+ dapagliflozin = Xigduo
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Combination Meds - 2
Glimepiride (Amaryl)+ rosiglitazone = Avandaryl+ pioglitazone = Duetact
Pioglitazone (Actos)+ alogliptin = Oseni
Sitagliptin (Januvia)+ simvastatin = Juvisync
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