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Background: In cancer outcome studies it is important to distinguish between effects of pre- and post-diagnostic exposures. A common approach to this is conduct a single analysis of fixed and time-varying exposures with naïve mutual adjustment. However, if changes in prognosis (i.e. recurrence) influence post-diagnostic exposure, this may introduce collider stratification bias (CSB). We conducted a simulation study to quantify the influence of CSB in studies of drug exposures and cancer outcomes.Methods: We simulated event times for 2000 observations with binomial pre-diagnostic exposure: p=0.25, null hazard ratio (HR)=1 (max time:5.5 years, event rate: 0.02%/day). Subsequently we generated a time-varying continuation of post-diagnostic exposure with fixed start/stop probabilities (start=10%/year, top=3%/year). To illustrate CSB we modified stop probabilities in the year prior to death by a pre-death probability factor (PDPF) 1x-5x. HR for pre-diagnostic (Pre-HR) and post-diagnostic (Post-HR) exposures were estimated using Cox regression.Results: In 50 simulated datasets, models with no PDPF had mean Post-HR=1.01, Pre-HR=1.01. Where stop probability was doubled (PDPF=2) effects were clear (Post-HR=0.78, Pre-HR=1.37). In the extreme (realistic) scenario (PDPF=5) effects were substantial (Post-HR=0.29, Pre-HR=2.11).Conclusions: In scenarios where post-diagnostic exposure is modified by changes in prognosis, naïve adjustment leads to spurious effect observations for pre-/post-diagnostic exposures.

Background: There is evidence in breast, colorectal and prostate cancer that patients who use statins have better cancer outcomes. There is biological evidence of similar benefits in ovarian tumour cells. We investigated whether stain use was associated with survival in ovarian cancer patients in Ireland. Methods: Women diagnosed with invasive ovarian cancer (C56) between 2001-2011 were identified from the National Cancer Registry. Those with at least one year medical card history (means tested) pre-diagnosis were identified and linked to community prescription records. Any statin use (ATC code: C10AA,C10B) in the year prior to diagnosis was determined. Association between statin use and cause-specific survival (end of follow-up: 31/12/2012) was estimated using Cox regression (adjusted for: age, smoking, marital status, year of diagnosis, urban/rural, local area deprivation, stage, grade, surgery at diagnosis). Secondary analysis accounting for competing risk was conducted. Results: Of 3097 invasive ovarian cancers diagnosed 2001-2011, 1823 (59%) had had a medical card history for at least one year prior to diagnosis and, of these, 490 (27%) had some exposure to statin in the year prior to diagnosis. 78% of women in the cohort had died by 31/12/2012 (median follow-up=5.8years). Pre-diagnostic statin use was not associated with ovarian cancer-specific survival (HR=1.06, 95%CI 0.92, 1.23) but was associated with better survival for other causes (HR=0.57, 95%CI 0.36, 0.93). When adjusting for competing risks, statin use was significantly associated with increased risk of ovarian cancer-specific death (HR=1.20, 95%CI 1.03, 1.40, p=0.02). Conclusion: In this, the largest ever study of statin use in ovarian cancer, we observed an association between pre-diagnostic statin use and cancer survival when adjusting for competing risks. Further work is being conducted to verify these results in United Kingdom populations. Research is needed to better understand the mechanisms by which prediagnosis statin use might influence cancer survival.

Background: There is evidence in breast, colorectal and prostate cancer that patients who use beta-blocker (BB) medication have better cancer outcomes. There is conflicting evidence of similar benefits in ovarian tumours. We investigated whether type of drug effected association between BB use and survival within Irish ovarian cancer patients. Method: Women diagnosed with invasive ovarian cancer (ICD code: C56) between 2001-2011 were identified from the National Cancer Registry Ireland. Those with continuous eligibility for a (means-tested) medical card in the year immediately prior to diagnosis were identified and linked to pharmacy claim records. Any BB exposure (WHO ATC: C07) in the year prior to diagnosis was determined. Associations between exposure and ovarian cause-specific survival (OvCSS) and all other causes was estimated using Cox regression (until follow-up 31/12/2012) adjusted for age, smoking, marital status, diagnosis year, urban/rural residence, deprivation, stage, grade, and surgery at diagnosis. Adjusted hazard ratios (AHR) and 95% CI are presented. Class of medication was a pre-planned subgroup and patients were classified as having exposure to: selective, non-selective, neither (reference category) or both. Results: Of 3097 invasive ovarian cancers diagnosed 2001-2011, 1823 (59%) had a medical card for at least one year prior to diagnosis. Of these, 432 (24%) had some BB exposure in that year. 78% of women in the cohort had died by 31/12/2012 (median follow-up 5.8 years). Pre-diagnostic use was not associated with improved OvCCS (AHR=1.08, 95%CI 0.93,1.23) or other-cause survival. Exposure to selective drugs (AHR=1.11, 95%CI 0.95,1.30) was not significantly different to that of non-selective drugs (AHR=0.88, 95%CI 0.56,1.38), drug class interaction p=0.55. Conclusions: In this large study of beta-blocker use in ovarian cancer, we observed no modification of association by drug class on cancer-specific survival.

Background There is some evidence in breast, colorectal and prostate cancer that patients who use nonsteroidal anti-inflammatory (NSAID) drugs have better survival. There is conflicting evidence of benefit in ovarian tumours. Our objective was to determine the association of pre-diagnostic NSAID use with survival in ovarian cancer patients in Ireland. Method Women diagnosed with invasive ovarian cancer (ICD-10 code C56) between 2001-2011 were identified in a retrospective cohort study from the National Cancer Registry. Those with continuous eligibility for a (means-tested) medical card in the year immediately prior to diagnosis were identified and linked to community prescription records. Any NSAID prescription in the year prior to diagnosis was determined. Date and cause of death was sourced from linked death-certificates. Association between exposure and cause-specific survival (end of follow-up: 31/12/2012) was estimated using Cox regression (adjusted for: age, smoking, marital status, year of diagnosis, urban/rural, local area deprivation, ovarian cancer stage and grade, surgery at diagnosis). Secondary analysis accounting for competing risks was conducted. Analysis by type of NSAID (aspirin/other) was pre-planned. Results Of 3097 invasive ovarian cancers diagnosed 2001-2011, 1823 (59%) had had a medical card history for at least one year prior to diagnosis and, of these, 1123 (62%) had some exposure to NSAIDs in that year. 78% of women in the cohort had died by 31/12/2012 (median follow-up=5.8years). Pre-diagnostic NSAID use was associated with improved ovarian cancer-specific survival (AHR=0.84, 95%CI 0.74, 0.96) as well as other causes (AHR=0.62, 95%CI 0.42, 0.93). Adjusting for competing risks, NSAID use was no longer significant (cancer-specific: 0.90 (0.78, 1.05), other causes: 0.75, (0.5, 1.11)). Effects were similar for aspirin and other NSAIDs. Conclusion In this, the largest ever study of NSAID use in ovarian cancer, we observed an association between pre-diagnostic NSAID use and cancer specific survival. The association was no longer observed after adjusting for competing risks. Acknowledgements Project funding, Health Research Board Ireland; Registry funding, Department of Health Ireland.

Background: There is evidence in breast, colorectal and prostate cancer that patients who use beta-blocker (BB) medication have better cancer outcomes. There is some evidence of similar benefits in ovarian tumours. We investigated whether BB use was associated with improved survival within Irish ovarian cancer patients. Method: Women diagnosed with invasive ovarian cancer (ICD code: C56) between 2001–2011 were identified from the National Cancer Registry Ireland. Those with continuous eligibility for a (means-tested) medical card in the year immediately prior to diagnosis were identified and linked to community prescription records. Any BB exposure (WHO ATC: C07) in the year prior to diagnosis was determined. Associations between exposure and ovarian cause-specific survival (OvCSS) and other causes until follow-up 31/12/2012 was estimated using Cox regression adjusted for: age, smoking, marital status, diagnosis year, urban/rural residence,deprivation, stage, grade, and surgery at diagnosis. Secondary analysis accounting for competing risks was conducted. Time-varying regression with ever/never status (6 month lag) was used to evaluate post-diagnostic BB use. Results: Of 3097 invasive ovarian cancers diagnosed 2001–2011, 1823 (59%) had a medical card for at least one year prior to diagnosis. Of these, 432 (24%) had some BB exposure in that year. 78% of women in the cohort had died by 31/12/2012 (median follow-up 5.8 years). Pre-diagnostic use was not associated with improved OvCCS (AHR = 1.08, 95% CI 0.93,1.23) or other-cause survival (AHR = 1.39, 95% CI 0.92,2.09). Results were similar adjusting for competing risks. Post-diagnostic BB use was associated improved OvCSS (AHR = 0.80, 95% CI 0.65, 0.99) but not other-cause survival(AHR = 1.61, 95% CI 0.85, 3.03). Conclusions: In this, one of the largest ever studies of beta-blocker use in ovarian cancer, we observed a post- (but not pre-) diagnostic association between exposure and cancer-specific survival.This analysis is being replicated in Northern Ireland and English populations. Acknowledgements: Project funding, Health Research Board; Registry funding, Department of Health.

BackgroundThere is evidence in breast, colorectal and prostate cancer that patients who use beta-blocker (BB) medication have better cancer outcomes. There is conflicting evidence of similar benefits in ovarian tumours. We investigated whether tumour histology played a role in the association between BB use and survival within Irish ovarian cancer patients. MethodsWomen diagnosed with invasive ovarian cancer (ICD code: C56) between 2001-2011 were identified from the National Cancer Registry Ireland. Those with continuous eligibility for a (means-tested) medical card in the year immediately prior to diagnosis were identified and linked to pharmacy claim records. Any BB exposure (WHO ATC: C07) in the year prior to diagnosis was determined. Associations between exposure and ovarian cause-specific survival (OvCSS) and all other causes was estimated using Cox regression (until follow-up 31/12/2012) adjusted for age, smoking, marital status, diagnosis year, urban/rural residence, deprivation, stage, grade, and surgery at diagnosis. Adjusted hazard ratios (AHR) and 95% CI are presented. Tumour histology was a pre-planned subgroup (test for interaction) and was classified as: serous carcinoma, adenocarcinoma, other carcinoma all remaining (unknown and other histology) tumours were grouped. ResultsOf 3097 invasive ovarian cancers diagnosed 2001-2011, 1823 (59%) had a medical card for at least one year prior to diagnosis. Of these, 432 (24%) had some BB exposure in that year. 78% of women in the cohort had died by 31/12/2012 (median follow-up 5.8 years). Pre-diagnostic use was not associated with improved OvCCS (AHR=1.08, 95%CI 0.93,1.23) or other-cause survival (AHR=1.39, 95%CI 0.92, 2.09). Tumour histology did not modify the association (Table 1, interaction p= 0.16).Conclusions: In this large study of beta-blocker use in ovarian cancer, we observed no effect overall or for modification of histology on cancer-specific survival. AcknowledgementsProject funding, Health Research Board; Registry funding, Department of Health.

Background Ireland has a mixed public-private healthcare system. Free healthcare within the public system is restricted to holders of general medical services (GMS) cards, eligibility for which is based on means-test and age. Cards may also be awarded on discretionary grounds due to extreme hardship (e.g. following cancer diagnosis). One-third of the female population under 70 have a card, and 97% of those aged 70 and older. Community prescribing data is only recorded systematically for card-holders. This restriction likely creates selection bias in pharmacoepidemiological studies conducted in RoI. This study aimed to quantify this bias within women with incident ovarian cancer. Methods Records for all women diagnosed with invasive ovarian cancer (ICD10 C56) 2001-2010 were linked to GMS card records. Characteristics of patients with and without cards (both at diagnosis, and after diagnosis) were compared. Health board of residence, deprivation category, age group at diagnosis, smoking status at diagnosis, employment and marital status were evaluated using logistic regression. Results Of the 3097 women diagnosed with ovarian cancer 1609 (52%) had a GMS card at the time of diagnosis. Most women with cards (92%) had them for at least >12months prior to diagnosis. As expected, age >70 strongly predicts card status (card holders, Conclusion Medical card coverage at diagnosis within the ovarian cancer population is similar to the general population. Half of patients without a card at diagnosis receive one subsequently. There is selection bias in linked cancer-prescribing datasets which needs to be considered when interpreting pharamcoepidemiological analyses.

A database has been derived from recently reported [60]fullerene derivatives, and their binding scores with HIV-1 PR have been computed using docking techniques. Computational methods have been used to predict which derivatives may have high binding affinities, and for these compounds biological tests have been performed with purified PR. Experimental results confirm the high binding scores of fullerene derivatives predicted from the docking calculations. Our measurements showed that the fullerene derivative (Fmoc-Baa) has about three times better inhibitory binding (Ki ) 36 nM) than the most active fullerene-based inhibitor (Ki ) 103 nM) currently available.