SEAC 2012 Medical Director Potpourri BANNER. WILLIAM PENN. YOUR COMPANY FOR LIFE

(1)

SEAC 2012

Medical Director Potpourri

BANNER. WILLIAM PENN. YOUR COMPANY FOR LIFE™

(2)

Legal & General America

SEAC

ML ENGMAN, MD Vice President and Chief Medical Director

(3)

UNDERWRITING

SLEEP APNEA 2012.

(4)

11/17/2012

Observation vs

Polysomnography

• Spec = 100% Sens = 64.5% (Miss 35%)

• PVP = 100% NPV = 64.7%

• Accuracy = 70.3%

• Severity as judged clinically did not

correlate with polysomnography

(5)

(6)

(7)

NORMAL DISTRIBUTION OF

SLEEP STAGES.

REM: 25% Activated sleep Dream sleep Stage 1: 5% drowsiness Stage ¾: 25% deep sleep

slow wave sleep

Stage 2:

(8)

SLEEP STAGE DISTRIBUTION

THROUGH THE NIGHT.

REM Wake Stage 1 Stage 2 Stage 3 Stage 4 0 1 2 3 4 5 6 7 8 Hours of Sleep

(9)

(10)

SLEEP APNEA.

• Apnea: Cessation of airflow >10 secs

• Central (uncommon) • Obstructive • Mixed • Hypopnea • Partial Apnea • >30% or 50% reduction in airflow • 3% or 4% Desaturation

(11)

CENTRAL SLEEP APNEA.

THORACIC RESPIRATION O₂ SATURATION NASAL/ORAL AIRFLOW 100% SaO2 0% 10 SECONDS

(12)

OBSTRUCTIVE Sleep Apnea.

(13)

MIXED SLEEP APNEA.

(14)

SLEEP APNEA SYNDROME.

Apnea Index (AI)

Total # Apneas Apneas Total Sleep Time Hour Hypopnea Index (HI)

Tot # Hypopneas Hypopneas Total Sleep Time Hour

Apnea Hypopnea Index (AHI) AHI = AI + HI

Respiratory Disturbance Index (RDII) RDII = AI + HI + RERA

11/17/2012

AI =

=

HI =

(15)

SLEEP APNEA, SEVERITY.

• Normal: AHI <5

• Mild: AHI 5-15

• Moderate: AHI 15-30

(16)

(17)

SPECTRUM OF SLEEP

RELATED OBSTRUCTIVE

BREATHING

DISORDERS.

11/17/2012 SEVERITY

Other excess mortality

Cardiovascular disease

Cognitive dysfunction Excessive daytime sleepiness

Diurnal hypertension Nocturnal hypertension

Social isolation

Accidents

Sleep fragmentation

UARS: upper airway resistance syndrome; OSAS: obstructive sleep apnea syndrome;

OHS: obesity-hypoventilation syndrome

(18)

COMPLICATIONS OF SAS.

• Excessive daytime sleepiness (EDS) • Cognitive dysfunction • Polycythemia • Hypertension • Pulmonary • Systemic • Cor Pulmonale • Elevated NTproBNP

• Arrhythmias (Atrial and Ventricular)

• LVH

• Left Heart Failure

• Sudden Death

(19)

11/17/2012

Treatment for OSAS

Position therapy Weight loss Medications protriptyline medroxyprogesterone theophylline almitrine oxygen modafinil Surgery uvulopalatopharyngoplasty (UPPP) nasal surgery maxillary surgery mandibular surgery tracheostomy Oral Appliances

Positive airway pressure (nCPAP, BiPAP, etc) Hypoglossal Nerve Pacemaker

Effectiveness +/- +/- No No No No ?

May help EDS +/- +/- +/- +/- + +/- + Experimental

(20)

11/17/2012

POSITIVE AIRWAY

PRESSURE (PAP).

(21)

NCPAP IMPROVES APNEAS.

11/17/2012 0 10 20 30 40 50 60

OSA CSA All

ev ents Control NCPAP OSA CSA E v ents per hour Rajagopal: Chest 1986;90:172

(22)

11/17/2012

NCPAP IMPROVES SLEEP.

Stage 3/4=25% Stage 1=5% Stage 2 =45% REM=25%

_NORMAL

48% 16% 31% 12% 1% 5%

OSAS

NCPAP

(23)

NCPAP IMPROVES SLEEPINESS.

11/17/2012 0 1 2 3 4 5 6 Control NCPAP

Patients

Sleep iness Sc ore Rajagopal: Chest 1986;90:172

(24)

NCPAP COMPLIANCE IS

POOR.

11/17/2012 Pe rcent Comp li ant 100 91 ₈₀ 73 ₇₀ ₆₈ 66 ₆₄ 0 20 40 60 80 1 3 5 9 12 15 18 Months of Follow-up Somniloquy, V3,No3

(25)

He (1988): Age < 50 425% compared to 1979-81 USLT

Age 50+ No XS mortality

Lavie (1995): Age 20-30 No XS mortality

Age 30-50 350% compared to pop (Univariate)

Age 50+ No XS mortality

Bliwise (1988): Age 66 No XS mortality

Mant (1995): Age 80 No XS mortality

Ancoli-Israel (1989): Nursing Home XS mortality in women

Pollack (1990): Community Dwelling

Elderly, Questionnaire.

No XS Mortality

(26)

Legal & General America Marti (2001): Ages 17-50: RMR=1,606 (603%-4,280%) Ages51-60 RMR=595% (2.97-11.89) Age 60+ RMR=336% (1.95-5.79) Marin (2005): Snoring RMR=103% (31%-184%)) Mild-Mod (AHI=5-30) RMR=115% (34%-260%) Severe (AHI>30) RMR=287% (117%-751%) nCPAP RMR=105% (59%-221%)

Young (2008): Mild (AHI 5-15) RMR=150% (80%-280%)

Moderate (AHI 15-30) RMR=130% (50%-320%)

Severe (AHI >30) RMR=270% (130%-570%)

Johansson (2011): Ages 71-87 No XS Mortality

(27)

An 18 year follow-up of the Wisconsin Sleep Cohort

Young: Sleep. 2008;31:1075-1078

Observational study of 1522 subjects begun in 1988

Random sample of men and women age 30-60 recruited from several Wisconsin State agencies

Mostly untreated (126 treated with nCPAP)

RMR = 1.5 (0.8-2.8)

RMR = 1.3 (0.5-3.2)

RMR = 2.7 (1.3-5.7)

RMR adjusted for age, sex, BMI, BP, SBP, DBP, use of antihypertensive mediations, diabetes, CAD, CV disease, CHF, MI, cardiac surgery, stroke RMR = 1.0 (reference group) 27

(28)

Campos-Rodriguez. Chest 2005;128:624-633

871 Patients with OSAS followed for mean of 4 years Mean Age = 55.4 + 10.6; 80% Males

CPAP compliance: <1h/d; 1-6h/d; >6h/d CPAP <1h/d RMR = 4 (2.2-6.1) AHI=48.8+27.3 CPAP 1-6h/d RMR = 2.4 (1.67-3.33) AHI=52.1+26.8 CPAP >6h/d; AHI=60 + 29.6 28

(29)

Summary

• Types of Sleep Apnea:

• Central, Mixed, Obstructive

• Central Sleep Apnea:

• Rare

• Mortality risk is largely that of underlying cause

• Diagnosis:

• Observation is 90% accurate;

• Polysomnography is necessary to quantify severity

• Treatment:

• Medications are ineffective

• Tracheostomy is universally effective

• nCPAP is almost universally effective

• All other treatments may be effective in selected patients

(30)

Summary

• Weight Loss:

• 10% reduction in BMI = 20% reduction in AHI

• UPPP:

• Cures snoring in 100%

• Improves Sleep Apnea in 50% (carefully selected patients))

• Cures Sleep Apnea in 25% (carefully selected patients)

• nCPAP compliance:

• First 6 months: 6% quit per month

• Then then 6% quit per year

• Mortality (OSAS)

• Pickwickian : Very high

• Untreated: ~ 150% if mild to 300%+ if severe

• Inversely related to age (Higher in younger subjects)

(31)

Family History of Cancer

(32)

Cancer Genetics

• The etiology of Cancer is Multifactorial

• Interaction of Environmental and Genetic Factors

• Environmental Factors • Chemicals and Toxins

• Benzene

• Radiation

• UV, Radon, X-ray

• Tobacco Smoke

• Cigarette Smoke • Passive Exposure

• Silicates (Asbestos, Silicates)

(33)

Proteins: the product of genes

• Proteins

• Responsible for all anatomic and metabolic characteristics

• Formed by combining amino acids

• Sequence of DNA base pairs determines the order that amino acids are combined to form a protein

• Transcription and Translation • Gene

• Portion of DNA forming coding sequence

• 20,000 to 25,000 genes • Chromosome

• Coiled strand of DNA,

• 23 pairs of chromosomes, one of each pair inherited from each parent

(34)

The Genetic Code

Amino Acid Abb. mRNA codons

Stop codons UAA UAG UGA Alanine Ala GCA GCC

GCG GCU Arginine Arg AGA AGG CGA

CGC CGG CGU Asparagine Asn AAC AAU

Aspartic

acid Asp GAC GAU

Cysteine Cys UGC UGU Glutamic

acid Glu GAA GAG

Glutamine Gln CAA CAG Glycine Gly GGA GGC

GGG GGU Histidine His CAC CAU Isoleucine Ile AUA AUC AUU

Amino Acid Abb. mRNA codons

Leucine Leu CUA CUC CUG CUU UUA UUG

Lysine Lys AAA AAG

Methionine* Met AUG

Phenylalanine Phe UUC UUU

Proline Pro CCA CCC

CCG CCU Serine Ser AGC AGU UCA

UCC UCG UCU

Threonine Thr ACA ACC

ACG ACU

Tryptophan Trp UGG

Tyrosine Tyr UAC UAU

Valine Val GUA GUC

(35)

Mutations

• Permanent Changes in DNA sequence

• Inherited

• Changes carried in gem cells (sperm and egg)

• All resulting cells in the body will carry the mutation

• Acquired

• Caused by DNA damage:

• Radiation • Chemicals • Toxins

• Spontaneous during replication

(36)

Karyotype: the Normal Set of

Chromosomes:

Normal Male

Karyotype

Normal Female

Karyotype

One of each pair of chromosomes from

each parent means 2 copies of each gene,

one from each parent

(37)

Cancer Genes

• Oncogenes

• Mutation of a proto-oncogene to an active oncogene promotes cancer development

• Tumor suppressor Genes

• Inactivation of a tumor suppressor gene allows cancer to develop

• Mismatch Repair Genes

• Failure to repair spontaneous gene mutations allows cancer to develop

(38)

Hereditary Cancer Syndromes,

some examples

Syndrome Gene Cancer Lifetime Risk Other Cancers

Hereditary Breast – Ovarian Cancer Syndrome BRCA1 Breast Ovarian 50-80% (Breast) 20-40% (Ovarian) Ovarian, prostate, pancreatic, peritoneal BRCA2 Breast Ovarian 50-80% (♀ Breast) 6-10% (♂ Breast) 10-20% (Ovarian) Prostate HNPCC MLH1 MSH2&6 PMS1&2

Colon 80% Endometrial, Ovarian, GI, Urinary Tract

FAP APC Colon 100% Duodenal, Gastric, Desmoid

Familial Melanoma

5-7% Dysplastic Nevi, Pancreatic, neural

(39)

Family History, a primary

risk assessment tool

Br 65 A 67 A 35 A 42 A 65 A 37 Male Female

(40)

Family History, a primary

risk assessment tool

Br 65 A 67

A 35 A 42 A 65

(41)

Family History, a primary

risk assessment tool

Br 50s D 60s Pr 70 D 78 D Unk Br 65 A 67 A 35 A 42 D Unk Ov 50 D 52 Br 55 D 56 Br 40 Ov 45 D 45 CRC 50 D 95 MI 80 D 80 A 65 A 87 A 37 Br 50s D 50s A 90

•Breast and/or Ovarian

Cancer affecting every generation

•Male breast cancer

(42)

Family Histories

• Size

Age

Density

• Large

Young

• Small

Small

•

• Smaller Families

Larger Families

Younger Families

Older Families

• Fewer Cancers

• More Cancers

(43)

Prevalence of Any Family

History of Cancer

Ages Sex Lung Colon Breast Ovarian Prostate Total

20-29 M 1.4% 0.4% 2.9% 0.7% 0.7% 5.7% F 1.8% 1.0% 2.7% 1.8% 1.2% 7.9% 40-49 M 7.5% 4.6% 7.2% 2.0% 6.4% 24.5% F 8.0% 6.3% 8.7% 2.0% 5.7% 26.7% 60-69 M 10.7% 10.5% 14.1% 2.2% 7.0% 36.0% F 11.7% 9.6% 13.1% 2.3% 7.0% 34.4% 70-79 M 10.0% 9.3% 13.1% 1.8% 8.3% 34.8% F 12.1% 10.2% 15.5% 2.7% 7.9% 38.2% Total M 6.7% 4.5% 7.1% 1.5% 4.8% 21.2% F 7.5% 5.4% 8.4% 2.0% 4.6% 23.5%

(44)

Percentage of Cases based

on Number of First Degree

Relatives with Cancer

Cancer One first

degree Relative Two first degree Relatives Three or more first degree Relatives Lung 93.6% 5.2% 1.2% Colon 93.1% 5.0% 1.8% Breast 91.8% 7.2% 1.0% Ovarian 94.9% 4.5% 0.6% Prostate 93.5% 5.5% 1.0%

(45)

Odds Ratios for Developing

Specific Cancers based on

Family History

Ages Family History

Prevalence Odds Ratio relative to no family history (95% CI) Breast Strong 5.0% 1.51 (1.34-1.72) Moderate 5.0% 1.97 (1.75-2.21) Ovarian Strong 6.7% 2.6% (1.78-3.80) Moderate 1.6% 3.27 (2.66-4.03) Prostate Strong 0.7% 1.59 (1.35-1.87) Moderate 4.5% 2.03 (1.76-2.35) Colon Strong 1.1% 1.47 (1.28-1.67) Moderate 4.2% 1.76 (1.60-1.94)

(46)

Hazard Ratio for Concordant

Cancer Death in Offspring

Ages Family

History

Hazard Ratio relative to no family history (95% CI) Breast Nonfatal 1.51 (1.34-1.72) Fatal 1.97 (1.75-2.21) Ovarian Nonfatal 2.6% (1.78-3.80) Fatal 3.27 (2.66-4.03) Prostate Nonfatal 1.59 (1.35-1.87) Fatal 2.03 (1.76-2.35) Colon Nonfatal 1.47 (1.28-1.67) Fatal 1.76 (1.60-1.94)

(47)

Hazard Ratio for Concordant

Cancer Death in Offspring

Number of Affected Family Members Family History Score 0 1 2 >=3 Total 0 420,136 0 0 0 420,136 Low 0 0 0 0 10,979 Medium 0 10,871 104 0 10,975 High 0 9,266 1,585 130 10,983 Total 420,136 31,118 1,689 130 453,073 Yang: Am J Epidemiol 1998; 147:652-9

(48)

Hazard Ratio for Dying from

Breast Cancer

based on Number Family

Members with Breast Cancer and Family History Score

Number of Breast Cancers in Family

1 2

Ages HR (95% CI) HR (95% CI)

<=40 4.9 (2-11.8) ----

40-49 2.3 (1.6-3.4) 1.0 (0.3-4.2) 50-59 1.8 (1.4-2.4) 1.1 (0.3-4.2) >=60 1.3 (1.0-1.6) 1.1 (0.4-2.9) All Ages 1.6 (1.4-1.9) 1.7 (0.9-3.1)

Family History Score

Low Med High

HR (95% CI) HR (95% CI) HR (95% CI)

---- ---- 5.1 (2.1-12.4) 0.8 (0.1-5.4) 1.7 (1.3-2.8) 3.3 (2.2-4.9) 1.4 (0.8-2.3) 1.9 (1.3-2.8) 1.9 (1.3-3.0) 1.0 (0.7-1.5) 1.5 (1.0-2.2) 1.7 (1.0-2.9) 1.0 (0.8-1.4) 1.6 (1.3-2.1) 2.3 (1.8-2.9) Yang: Am J Epidemiol 1998; 147:652-9

(49)

Family History, Summary

• All Cancer is ultimately Genetic

• A Moderate to Strong Family History of Cancer is associated a 1.5 to 2 fold increased risk of a family member developing cancer

• Hereditary Cancer syndromes are uncommon

(prevalence = 1% to 2%) but are associated with a 6 to 8 fold or higher relative risk of developing cancer

• Not all Family Histories are created equal

• The Significance of a Family History depends on the age and size of the family, the density of the impairment and the lineage

(50)

SEAC 2012

Medical Director Potpourri

(51)

Medical Underwriting –

Actuarial Collaboration

• Actuaries decide on the desired composition and mortality parameters defining a block of business or class – the “blueprint”

• Underwriters and Medical Directors build that block of business or class, one case at a time

• It is surprising how closely the closely the completed block of business resembles the desired outcome

considering the builders usually never see the “blueprint”

(52)

Areas for Further Dialogue

and Collaboration

• Mortality Assumptions

• Impairment Ratings

• EDR

• Mortality Multiples (Table Ratings)

• Mortality Modeling

• Uncommon Impairments

• Genetic Impairments

• Life Expectancies

• Back Calculate Mortality Multiples

• Protective Value Projections and Studies

• Mortality Savings

• Claims Analysis

• Data Mining

(53)

Areas for Further Dialogue

and Collaboration

• Mortality Assumptions

• Impairment Ratings

• EDR

• Mortality Multiples (Table Ratings)

• Mortality Modeling

• Uncommon Impairments

• Genetic Impairments

• Life Expectancies

• Back Calculate Mortality Multiples

• Protective Value Projections and Studies

• Mortality Savings

• Claims Analysis

• Data Mining

(54)

Protective Value, Caveat

Mortality Savings Can Be Demonstrated for Almost Every underwriting Requirement

The Cost of Good Business Lost due to false positive results must be considered

Test Sensitivity = TP/(TP+FN) = TPR

Test Specificity = TN/(TN+FP); FPR= 1-Specificity= FP/(TN+FP)

0 1.0 1.0 Ideal Test Worthless Test FPR TPR Mediocre Test

(55)

DISCLOSURE.

Legal & General America life insurance products are underwritten and issued by Banner Life Insurance Company, Urbana, MD and William Penn Life Insurance Company of New York, Garden City, NY. Banner products are distributed in 49 states and in DC. William Penn products are available exclusively in New York; Banner does not solicit business there. Not for public distribution. For agent/broker use only.