Poster Session I (PI 1-106)Displayed 8:00 am – 3:00 ... - Nature

aBsTraCTs nature publishing group
PI-15
FOLIC ACID AND COLORECTAL ADENOMA RECURRENCE:
A SYSTEMATIC REVIEW OF RANDOMIZED CONTROL TRI-
ALS. D. A. Kennedy, S. J. Stern, I. Matok, M. Moretti, M. Sarkar,
T. Adams-Webber, G. Koren; The Hospital for Sick Children, Toronto,
ON, Canada. D.A. Kennedy: None. S.J. Stern: None. I. Matok:
None. M. Moretti: None. M. Sarkar: None. T. Adams-Webber:
None. G. Koren: None.
BACKGROUND: The theory of ‘‘dual effect of folate’’ in cancer
postulates that in healthy persons folate supplementation decreases
the rates of cancer, while heightened folate exposure may increase the
rate of malignant transformation of precancerous cells. Our aim was to
examine the risk of colorectal adenoma recurrence under a high intake
of folic acid in the context of folic acid supplementation.
METHODS: MEDLINE, Embase, and SCOPUS were searched
from inception to April, 2011: using the following ‘‘folic acid,’’ ‘‘folate,”
‘‘colorectal adenomas,’’ ‘‘recurrence.’’ Randomized control studies
reporting on colorectal adenoma recurrence and folic acid supplementation
of at least 1 mg/day were selected. Studies were excluded if supplementation
was combined with other vitamins or pharmaceutical drugs.
RESULTS: Out of the 4013 records retrieved, 4 articles met the
inclusion criteria. Three of the studies were conducted in the United
States either during, or overlapping with, mandatory folate fortification.
Three of the studies supplemented with 1 mg/day for up to 6 years.
The remaining study used 5 mg/day for three years. The reported risk
ratio of colorectal adenoma recurrence with 1 mg/day after one year
was 0.60 (CI 95% 0.27-1.33), after 3 years, 1.20 (CI 95% 0.95-1.51)
and 0.82 (CI 95% 0.59-1.13). A risk ratio was not reported after 5 mg/
day for 3 years, rather the risk was described as “twice as high in the
placebo group versus the folic acid group.”
CONCLUSION: Supplementation of folic acid at either 1 mg/day
or 5 mg/day for a period of three years in an environment of mandatory
folate fortification did not increase nor decrease the risk of colorectal
adenoma recurrence in those individuals with a previous history of
colorectal adenomas. Pregnant women, at higher risk for neural tube
defects or other folate-dependent malformations, who may need a high
daily dose of folate (up to 5 mg/day) can use these doses safely for the
short period of first trimester of pregnancy.
PI-16
HIGH RISK PRESCRIBING AND INCIDENCE OF FRAILTY
AMONG OLDER COMMUNITY-DWELLING MEN. D. Gnjidic, 1 S.
N. Hilmer, 1 D. G. Le Couteur, 2 D. R. Abernethy 3 ; 1 Royal North Shore
Hospital and University of Sydney, Sydney, Australia, 2 Centre for Education
and Research on Ageing (CERA) and University of Sydney,
Sydney, Australia, 3 Food and Drug Administration, Silver Spring, MD.
D. Gnjidic: None. S.N. Hilmer: 4. I hold a patent for; Company/
Drug; Drug Burden Index. D.G. Le Couteur: None. D.R. Abernethy:
4. I hold a patent for; Company/Drug; Drug Burden Index.
BACKGROUND: Evidence on the association between treatment
with high risk medicines and frailty in older adults is limited. We aimed
to investigate the relationship between high risk prescribing and frailty
at baseline, and 2-year incident frailty in older adults.
METHODS: A total of 1662 community-dwelling males, aged ≥70
years enrolled in the Concord Health and Ageing in Men Project were
studied. Measurements were obtained at baseline (2005-2007) and
2-year follow-up (2007-2009). High risk prescribing was defined as
polypharmacy (use of ≥ 5 medicines), hyperpolypharmacy (use of ≥ 10
medicines) and by the Drug Burden Index (DBI), a dose-normalized
measure of anticholinergic and sedative medicines. Frailty was defined
according to validated criteria. Odds ratios of frailty were modeled
using logistic regression, and adjusted for age, education, marital status
and multiple comorbidities.
RESULTS: There were 9.4% participants who were identified as
frail at baseline. At baseline, frail participants had adjusted odds ratios
(ORs) of 2.55 (95% confidence interval, CI: 1.69-3.84) for polypharmacy,
5.80 (95% CI: 2.90-11.61) for hyperpolypharmacy and
2.33 (95%CI: 1.58-3.45) for DBI exposure, compared with non-frail.
Among the 1242 men who were non-frail at baseline, 6.2% developed
frailty over two years. Adjusted ORs of incident frailty were 2.45
(95%CI: 1.42-4.23) for polypharmacy, 2.50 (95%CI: 0.76-8.26) for
hyperpolypharmacy, and 2.14 (95%CI: 1.25-3.64) for DBI exposure.
CONCLUSION: Older frail men were significantly more likely to
be exposed to high risk prescribing than non-frail older men at baseline,
and exposure to high risk medicines was significantly related to
the development of frailty over two years.
PI-17
POLYPHARMACY AND ADVERSE OUTCOMES: DETER-
MINING THE BEST CUT-OFF FOR POLYPHARMACY
ASSOCIATED WITH GERIATRIC SYNDROMES, FUNC-
TIONAL OUTCOMES AND MORTALITY IN OLDER ADULTS.
D. Gnjidic, 1 D. G. Le Couteur, 2 S. N. Hilmer 1 ; 1 Royal North Shore
Hospital and University of Sydney, Sydney, Australia, 2 Centre
for Education and Research on Ageing (CERA) and University of
Sydney, Sydney, Australia. D. Gnjidic: None. D.G. Le Couteur:
None. S.N. Hilmer: None.
BACKGROUND: There is lack of agreement about the best cut-off
value for the number of concomitant medications that should be used
to define polypharmacy. We aimed to determine an optimal discriminating
number of concomitant medications for the associations with
adverse outcomes in older adults.
METHODS: Males aged ≥ 70 years (n=1705), participating in
the Concord Health and Ageing in Men Project were studied. Measurements
were obtained at baseline (2005-2007) and follow-up
assessments. Frailty was ascertained according to the validated criteria.
Disability was assessed using the Activities of Daily Living
scale. Participants were categorized as cognitively impaired (mildcognitive-impairment
or dementia) using clinical diagnostic criteria.
Prospective data on mortality and incident falls were collected
by 4-monthly telephone calls. Receiver operating characteristics
curve analysis using the Youden Index and the area under curve was
performed to determine discriminating number of medications in
relation to each outcome. Odds ratios were calculated for the association
of the number of concomitant medications with each of the
outcomes.
RESULTS: The highest value of the Youden Index for frailty was
obtained for a cut-off point of 6.5 medications, compared to a cut-off
of 5.5 for disability and 3.5 for cognitive impairment. For mortality
and falls, the highest value of Youden Index was obtained for a cut-off
of 4.5 medications. For every one increase in number of medications,
the adjusted odds ratios for age and multiple comorbidities, were 1.13
(95% confidence interval (CI): 1.06-1.21) for frailty, 1.08 (95%CI:
1.00-1.15) for disability, 1.02 (95%CI: 0.96-1.09) for cognitive impairment,
1.09 (95%CI: 1.04-1.15) for mortality and 1.07 (95%CI: 1.03-
1.12) for falls.
CONCLUSION: This study justifies the widespread definition of
polypharmacy, which is linked to adverse outcomes, as five or more
medications.
PI-18
A REVIEW OF FOOD AND DRUG ADMINISTRATION (FDA)
LABELING FOR OVERDOSE TREATMENT AND TOXICITY
DATA. M. E. Mazer, 1 G. Sokol, 2 L. Cantilena 2 ; 1 George Washington
University, Washington, DC, 2 Uniformed Services University of the
Health Sciences, Division of Clinical Pharmacology, Bethesda, MD.
M.E. Mazer: None. G. Sokol: None. L. Cantilena: None.
BACKGROUND: Adverse drug reactions, including overdose, are
a major cause of morbidity and mortality. The goal of the FDA is to
ensure approved pharmaceuticals are safe and effective yet clinical
toxicology data is often limited at the time of approval. There may also
be a lag time until toxicology data is available and incorporated into
labeling revisions. In order to determine the type and quality of clini-
s14 volume 91 supplemenT 1 | marCh 2012 | www.nature.com/cpt