1. Excess mortality and hospitalized morbidity in newly treated epilepsy patients
Chen Z, Liew D, Kwan P
Published in Neurology online before print 07/15/2016
doi: /WNL
Presented by Kurt Qing, MS4

2. Outline Epilepsy overview Study overview Study methods Study results
Study discussion
Study Limitations
Ponderings

3. Epilepsy overview
Definition: Two or more (24 hours apart) unprovoked epileptic seizures
Types
Partial (focal) : simple vs complex
Partial with secondary generalization
Generalized
Worldwide stats: prevalence: 2.7 – 17.6 per incidence: 16 – 51 per 100,000 per year (WHO & Epilepsy Foundation similar numbers)
Banerjee PN, Filippi D, Hauser WA, The descriptive epidemiology of epilepsy—A review. Epilepsy Research. 85(1) July 2009:

4. Study overview
“Quantify the burden of mortality and hospitalized morbidity” in patients with newly diagnosed and treated epilepsy
Exposure to CYP450-inducing AED
Retrospective cohort
Mortality, hospitalizations, new comorbidities
Baseline comorbidities, mono vs multi AED, CYP450-inducing AED

5. Study Methods Hong Kong Hospital Authority (HKHA) In-patient records
Public health care
Covers >90% of population
In-patient records
Discharge summaries 9/16/2005 – 9/15/2010
Followed until 9/15/2011
ICD-9-CM
No previous epilepsy diagnosis or treatment

6. Study Methods Standardized mortality ratio (SMR)
Obs/Exp (Census 2006 – 2011)
Standardized hospitalization rate (SHR), length of stay ratio (SLR), and SLR per admission (SLRA)
Obs/Exp (HKHA 2006 – 2011)

7. Study Methods Standardized incidence ratios (SIR) Statistics w/ STATA
Obs/Exp (HKHA – 2011) Only in patients w/o prior comorbidity
>30 days after starting AED
Statistics w/ STATA
Byar approximation for 95% CIs
Glm w/ log-binomial regression
Photo from Wikipedia

8. Study Results

9. Study Results

10. Study Results

11. Study Results low n Cohort SMR 5.09 (4.88 – 5.31)
Supplementing table e-3 data

12. Study Results

13. SMR also higher with psych and physical + psych comorbidities
Study Results
Multi AEDs, SMR = 5.98 (5.53 – 6.47)
Single AEDs, SMR = 4.80 (4.56 – 5.05)
SMR also higher with psych and physical + psych comorbidities

14. Study Results

15. Study Results

16. 63% non-seizure-related
Study Results
63% non-seizure-related
Physical only

17. Study Results

18. Study Results Overall RR mono vs multi 1.02 (0.85 – 1.23)
Age >35 SIR acute stroke
4.96 (4.19 – 5.84), esp in age 35-44
Overall RR enzyme vs none 1.48 (1.19 – 1.85)
Total SIR cancer
1.97 (1.56 – 2.46), higher in men only
Total SIR MI
4.18 (3.54 – 4.91), female > men

19. Study Results (summary)
Higher SMR in…
Hong Kong overall
Young age
Pts with baseline comorbidities
Pts taking multiple AEDs
Higher SHR
Higher SIR for stroke, cancer, and ischemic heart disease

20. Study Discussion/Conclusions
Epilepsy and cancer may have common etiology factors
No association b/w AED and cancer
EIAEDs may increase stroke and coronary disease by affecting cholesterol metabolism
Bidirectional relationship between epilepsy and psychiatric disorders

21. Study Limitations Surveillance bias
e.g. occult cancer
Public hospitals records only – underestimating
Older, sicker patients
Starting AED
Requiring hospitalization
No cause of death data (future)

22. Study Limitations (critique)
Varying length of follow-up (1 to 6 years)
Study population not representative
Mean onset age 20 in HK in general (Fong 2003)
Median onset age 60 in study
Control M&M data for hospitalized patients
Comparing standardized ratios indirectly rather than relative risks (only table 4)
No data on seizure control (refractory?)
Fong GCY, et al. "A prevalence study of epilepsy in Hong Kong." Hong Kong Med J. 9(4) 2003:

23. Study Limitations (critique)
Exposure to other enzyme-inducing agents (i.e. for comorbidities)
EIAED and liver disease
No data on adverse effects or toxicity
EIAED and stroke
Ischemic, embolic, hemorrhagic

24. Study Limitations (critique)
Olesen JB et al. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study. Pharmacoepidem Drug Safe. 20 (2011): 964–971. 

25. Ponderings Multiple logistic regression (n = 7,461)
Relationships among age, specific baseline and new comorbidities, AED use, mortality, morbidity
Quickly determine predictive factors and interactions
Predictive factors plus cause of death
Ex: young health patients on mono-AED tend to die of sudden death whereas older patients tend to die of stroke.

26. Thank you!