Creating an Inventory of Risk Factors for Predicting Stroke among Atrial Fibrillation Patients: A Systematic Review

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Objectives: Since 1997 with the Law to modernize the Social Security Health Service (EsSalud), Peru workers contribute 9% of their income in exchange for health, economic and social benefits. The workers of high-risk companies also have a Complementary Insurance for Hazardous Work that can be purchased for the same EsSalud or private insurers. This study aims to demonstrate that regulation in the Hazardous Work Supplement Insurance is necessary because there are high-risk companies that are not regulated generate economic losses to EsSalud.  Methods: We search for all patient with pneumoconiosis diagnosis in Social Security of Peru database, information was sought in national database of companies belonging to these workers and a review of medical records was performed to cost evaluation.  Results: A total of 148 patients nationwide were found. Finding 29 cases in the La Libertad Assistance Network, 27 cases in the Assistance Network Arequipa and 25 cases in Puno-Juliaca Assistance Network (mining areas).The diagnoses found were unspecified pneumoconiosis with CIE X J64 and J64.X at 7 and 50 respectively , followed by pneumoconiosis due to dust containing silica ( J63.8 ) and Pneumoconiosis due to other specified inorganic dusts ( J63.8 ) both with 34 cases each. It was found that 70 % of the cases studied had the kind of Pensioner insurance , while 27 % had a regular insurance . There was a worker with home insurance. The costs incurred by patients in 2014 were: $ 1017.62 in 2014 per patient, $ 150609.10 in total.  Conclusions: There are high-risk companies whose workers are presenting occupational diseases who are treated as common diseases which generates costs to Social Security in Peru and should be covered by a Hazardous Work Supplement Insurance. PHS168 Examining Uncertainty around the American College of Medical Genetics Recommendation for Newborn Screening for 2-Methylbutyryll-Coa Dehydrogenase Deficiency (2mbg) Algatan R, Rittenhouse B MCPHS University, Boston, MA, USA

Objectives: In 2005 the American College of Medical Genetics (ACMG) conducted a survey to gather opinions of experts in various fields to evaluate 84 newborn diseases in the US. In its recommendations it ignored missing survey responses (implicitly using an invariance assumption – that missing were equal in expected value to observed responses). This research aims to estimate the potential influence of the missing data on the ACMG survey scoring and recommendations for the 2MBG condition by not making any assumption on the nature of the missing data and developing bounds on the possible score.  Methods: The survey for 2MBG was 1124. This determined the entry point to an algorithm (EPA) that determined the final recommendation. To alter the EPA, scores would need to change by +76 or –124. The missing data were identified from ACMG report. By applying boundary estimates (highest and lowest possible answers) for two questions (Burden if untreated and Efficacy of treatment) for which we have data in detail, Manski bounds were calculated (Manski 1989).  Results: The “Burden if untreated” question had 5 missing responses and “Efficacy of treatment” had 3. The total score changes were ±4 and -8/+14, respectively. Examined individually or jointly, the score changes did not reach the critical values needed to potentially alter the EPA and the 2MBG recommendation.  Conclusions: ACMG recommendations for this condition would not change based on these results. However, applying this method to the missing data from the remaining 16 survey questions (for which data were not available) could potentially result in a change in ACMG recommendations as the influence would be greater by incorporating effects of additional missing data. Also, additional exploration for other types of uncertainty like sampling variation may indicate further uncertainty around the ACMG point estimate for the total score and its recommendation. PHS169 Receipt of Guideline-Concordant Surveillance Care in Elderly Patients with Colorectal Cancer Goyal RK, Davis KL RTI Health Solutions, Research Triangle Park, NC, USA

Objectives: To examine the proportion of elderly colorectal cancer (CRC) patients receiving guideline-concordant surveillance care and analyze predictors of guideline concordance using the Surveillance, Epidemiology, and End Results (SEER)Medicare linked database.  Methods: In this retrospective observational cohort study, early-stage CRC patients diagnosed between 2004 and 2008 and aged ≥ 66 years who survived at least 3 years were selected for study inclusion. Patients who received surveillance care concordant with the 2013 American Society of Clinical Oncology (ASCO) guidelines were identified. Guidelines were considered met if patients received ≥ 2 office visits for history/physical examination annually, ≥ 2 carcinoembryonic antigen (CEA) tests annually, ≥ 1 CT scan annually, and ≥ 1 colonoscopy in a three-year period. Multivariable logistic regression analysis was performed to examine predictors of guideline-concordant surveillance care.  Results: A total of 23,598 patients (mean age: 77 years) met the inclusion criteria. Overall, only 8.5% received guideline-concordant surveillance care during the study period. Individually, recommendation for office visits, CEA tests, CT scans, and colonoscopy were met by 82%, 23%, 15%, and 73% of patients, respectively. Guideline concordance was significantly higher among patients with regional-stage disease versus local-stage disease (15% vs. 4%, p< 0.0001). Based on the multivariable analysis, predictors of lower concordance included older age groups (75-84 vs. 66-74 years, odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.48-0.59) and black race (vs. white, OR: 0.63, 95%CI: 0.51-0.78). Patients with regional-stage disease and larger tumor sizes were associated with higher levels of concordance with recommended surveillance care guidelines.  Conclusions: Concordance with the current follow-up care and surveillance protocol for patients with early-stage CRC was substantially low, with older age, black race, and local-stage disease being the significant predictors of low concordance. Further research assessing barriers to access to guideline-recommended survivorship care is crucial to improve long-term outcomes among these patients.

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DISEASE – SPECIFIC STUDIES CARDIOVASCULAR DISORDERS – Clinical Outcomes Studies PCV1 Hmg-Coa Reductase Inhibitors (Statins) associated Tendon Rupture: An Analysis of Reports from the Food and Drug Administration’s Adverse Reporting System Rafi JA, Arabyat R, Chen C, Raisch DW University of New Mexico College of Pharmacy, Albuquerque, NM, USA

Objectives: To evaluate and summarize FAERS reports of tendon rupture associated with each HMG-CoA reductase inhibitors (statins) currently marketed in the United States.  Methods: FAERS data were reviewed for reports of tendon rupture associated with each statin from their respective approval date through January 2016. Data mining reporting signals, (proportion of tendon rupture events for the drug greater than the other drugs in FAERS) were estimated using proportional reporting ratios (PRR) with 95% confidence intervals (CI). A PRR is significant when a PRR is >  2.0 based upon at least 3 case reports and a chi square >  4.0.  Results: Therewere a total of 611 FAERS reports of tendon ruptures with currently approved statins as the primary suspected medication. The number of reports associated with each medications are as follows: atorvastatin (n =  218), simvastatin (n =  186), rosuvastatin (n=  104), pravastatin (n=  68), fluvastatin (n= 32), lovastatin (n= 2) and pitavastatin (n=  1). Signal detection results for the statins were significant for atorvastatin (PRR = 4.38, 95% CI=  3.83-5.01), simvastatin (PRR = 8.76, 95% CI =  7.5710.13), rosuvastatin (PRR = 4.03, 95% CI = 3.32–4.89), pravastatin (PRR = 12.97, 95% CI = 10.23 –16.45), fluvastatin (PRR =  18.18, 95% CI = 12.88 –25.67), but not for lovastatin (PRR = 1.70, 95% CI = 0.43 –6.81), and pitavastatin (PRR=  1.85, 95% CI = 0.26 –13.09). A search of the package inserts found that only atorvastatin and pravastatin identified tendon rupture as a possible adverse event.  Conclusions: Statin use may be associated with increased risk of tendon rupture. Recent guidelines recommend use of statins based upon cardiovascular risk, which may lead to an increase in use of these medications. Providers should therefore consider the potential for tendon rupture in their clinical decision making and patients should be made aware of early warning signs of tendon rupture, such as severe joint or heal pain or weakness. Pcv2 Associations of Comorbidities and Co-Medications with Angioedema during the Use of Angiotensin Converting EnzymeInhibitors within the United Kingdom Clinical Practice Research Datalink Mahmoudpour SH1, Baranova EV1, Souverein PC1, Asselbergs FW2, de Boer A1, Maitland-van der Zee A1 1Utrecht University, UTRECHT, The Netherlands, 2University Medical Centre Utrecht, UTRECHT, The Netherlands

Objectives: This study describes the occurrence of angioedema among patients initiating ACEI therapy and evaluates the association of this outcome with demographic factors, co-medication and chronic comorbidities.  Methods: A nested case-control study was conducted in a cohort of patients newly treated with ACEIs from 2007 to 2014 in the CPRD. Cases who had angioedema only during ACEI treatment were identified using medical codes and were matched on the duration of ACEI treatment at the angioedema date (index date) with up to 20 controls who never had angioedema recorded. The use of co-medication (anti-diabetics, antihistamines, anti-asthmatics, non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, calcium channel blockers and statins), was acquired from CPRD prescription records within a three months’ time window before the index date. The history of comorbidities (asthma, allergy, chronic obstructive pulmonary disease (COPD), diabetes mellitus and rheumatoid arthritis) was retrieved from medical records any time before the index date. Odds ratios (ORs) and p-values were estimated using univariate logistic regression analysis.  Results: The cohort included 276,977 patients aged ≥  45 years initiating ACEI therapy. The study population included 416 cases of angioedema during ACEI therapy matched with 4,335 controls. Age over 65 years was associated with angioedema. The proportions of asthma, allergy, COPD and rheumatoid arthritis were significantly higher in ACEI consumers who developed angioedema during ACEI therapy (ORs 1.83, 2.03, 2.08 and 2.83 respectively; p< 0.001), compared to controls. History of diabetes and use of anti-diabetic drugs were associated with a decreased risk for angioedema (OR 0.73, P= 0.034). Antihistamines, anti-asthmatic drugs and systemic corticosteroids were associated with angioedema during ACEI therapy (ORs 25.64, 2.19 and 7.15 respectively; p< 0.001).  Conclusions: Angioedema during ACEI therapy was more frequent in patients over 65 years old and in patients with history of inflammatory comorbidities, such as asthma and allergies. Pcv3 Creating an Inventory of Risk Factors for Predicting Stroke among Atrial Fibrillation Patients: A Systematic Review Oehrlein EM1, Perfetto EM2, Chung Y1, Ghafoori P1, Harris R3 of Maryland School of Pharmacy, Baltimore, MD, USA, 2University of Maryland, School of Pharmacy, Baltimore, MD, USA, 3University of Maryland, Health Sciences and Human Services Library, Baltimore, MD, USA

1University

Objectives: In determining which atrial fibrillation (AF) patients should receive anticoagulation therapy, clinical treatment guidelines recommend use of the CHADS2 and CHA2DS2-VASc risk-stratification schemes. While the CHADS2 considers congestive heart failure, hypertension, age ≥ 75 years, and diabetes mellitus, the CHA2DS2-VASc also considers gender, vascular disease, and patient’s age (65-74 years). Although these risk factors have been demonstrated to be highly predictive of stroke in elderly populations, these schemes may not be comprehensive, especially among younger populations. This systematic review examined published studies to create a comprehensive inventory of risk factors for stroke among AF patients.  Methods: A systematic review of studies identifying risk factors for

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stroke among patients diagnosed with AF using PubMed, Embase, Scopus, Cochrane Register, and Clinical Trials.gov was performed by a research librarian in fall 2015. Abstracts were independently reviewed according to PRISMA guidelines by two research assistants with a third reviewer providing input when necessary.  Results: The systematic review yielded 5070 potentially relevant citations. Review of the abstracts identified the following risk factors as potentially important in predicting stroke among AF patients, but not considered in current risk schemes: race, low body weight, cancer, glycated hemoglobin level, brain natriuretic peptide, sleep disorders, breathing difficulties, C-reactive protein, inflammatory bowel disease, plasma von Willebrand factor, chronic kidney disease, renal impairment, plasma-D dimer, obstructive sleep apnea, left atrial appendage morphology, rheumatoid arthritis, troponin levels, smoking status, and platelet activity.  Conclusions: Although comparative effectiveness research of oral anticoagulants to date has accounted for comorbidities included in the CHADS2 and CHA2DS2-VASc risk scores, risk factors explaining heterogeneity of treatment effect may have been neglected. Future research should examine the strength of these additional risk factors or groupings of risk factors as they relate to patient outcomes in AF. PCV4 Prevalence of Inappropriate Prescribing of Antithrombotic Therapy in Ethiopian Elderly Population using Updated 2015 Stopp/Start Criteria Getachew H, Bhagavathula AS, Befekadu T, Admasu S University of Gondar, Gondar, Ethiopia

Objectives: The aim of this study was to assess the prevalence of inappropriate prescribing of antithrombotic therapy in hospitalized elderly patients.  Methods: A retrospective cross-sectional, single-center study was conducted at the Gondar University Hospital (GUH). Hospitalized elderly patients aged ≥ 65 years with Congestive Heart Failure, Venous Thromboembolism, Stroke, Atrial Fibrillation, Acute Coronary Syndrome, Peripheral Valvular Disease, elderly patients with a known co-morbidity of cardiovascular diseases, patients with a history of coronary, cerebral or PVDs, and patients prescribed with any of antithrombotics were included in the study. The STOPP/START criteria version-2 was applied to each patients’ data to identify the total instances of Inappropriate Prescription (IP) including potentially inappropriate medications (PIMs), potential prescribing omissions (PPOs).  Results: A total of 70 IPs were identified in 156 patients identified who fulfilled the inclusion criteria. Of which, 36 (51.4%) PIMs were identified by the STOPP criteria. The prevalence of IP per patient indicated that of the 156 patients, 58 (37.2%) were exposed to at least one IP. Of which, 32 (55.2%) had at least one PIM and 33 (56.9%) had at least one PPO. Patients hospitalized due to VTE (AOR= 29.87, 95% CI, 1.26-708.6), stroke (AOR= 7.74, 95% CI, 1.27-47.29) or ACS (AOR= 13.48, 95% CI, 1.4-129.1) were more likely to be exposed to an IP. An increase in CCI score was associated with reduced IP exposure (AOR= 0.60, 95% CI, 0.39-0.945). Patients prescribed with antiplatelet only therapy were about 6 times more likely (AOR=  6.23, 95% CI, 1.90 - 20.37) to have an IP than those with any other groups of antithrombotic.  Conclusions: The findings indicate that inappropriate prescribing of antithrombotic therapy were common among hospitalized elderly patients. Our study may guide further research to reduce high-risk prescribing of antithrombotics in older people. PCV5 Mono- And Combination Antihypertensive Therapy with Olmesartan is Associated with Enteropathy Risk Ali AK Eli Lilly and Company, Indianapolis, IN, USA

Objectives: Sprue-like enteropathy is an identified risk of olmesartan monotherapy. It is unknown if this risk is different across single-pill combination formulations. This analysis describes the pattern of enteropathy signals across olmesartan formulations.  Methods: Adverse event reports submitted to the FDA Adverse Events Reporting System through June 2015 were used to calculate the Empirical Bayes Geometric Mean (EBGM) and 95% confidence interval (EB05-EB95) as measures of association between olmesartan and enteropathy events. Treatment with olmesartan formulations was defined by corresponding generic names: “olmesartan”, “amlodipine-olmesartan”, and “hydrochlorothiazide-olmesartan”; and enteropathy events were defined by the following Preferred Terms of MedDRA 18.0: “diarrhoea”, “coeliac disease”, and “intestinal villi atrophy”.  Results: Overall, 836 enteropathy reports were submitted for olmesartan, corresponding to 77% diarrhea (n= 644); 15% celiac disease (n= 123); and 8% intestinal villi atrophy (n= 69). Monotherapy accounted for the 67% of enteropathy reports (diarrhea, n= 440; celiac disease, n= 79; and villi atrophy, n= 45). The distribution in hydrochlorothiazide-based and amlodipine-based combination therapies were (diarrhea, n= 132 and n= 72; celiac disease, n= 37 and n= 7; and villi atrophy, n= 10 and n= 14), respectively. Signals of enteropathy were detected for olmesartan as monotherapy and combination therapy, and signal ranking among the 3 enteropathy events was consistent across the 3 olmesartan formulations (villi atrophy >  celiac disease >  diarrhea). Nonetheless, combination therapy was associated with the strongest signals. Amlodipine-based formulation was associated with the strongest signals for villi atrophy (EBGM= 161; EB05-EB95= 120-292) and diarrhea (EBGM= 3.4; EB05-EB95= 2.8-4.1), and hydrochlorothiazide-based formulation was presented with the strongest celiac disease signal (EBGM= 44.2; EB05-EB95= 33.4-57.6).  Conclusions: Antihypertensive treatment with olmesartan is associated with enteropathy signs and symptoms; and the risk appears more significant in single-pill combination formulations than monotherapy. Prescribers should evaluate patients for intestinal disorders before and during olmesartan therapy. Pharmacoepidemiologic studies are required to evaluate the risk-modifying effects of diuretics and calcium channel blockers when added to olmesartan in relation to enteropathy. Pcv6 Examining the Mortality and Readmission Rates of Patients Diagnosed with Stroke in the United States Medicare Population

Bashyal R1, Du H1, Wang L1, Yuce H2, Baser O3 Research, Plano, TX, USA, 2New York City College of Technology-CUNY and STATinMED Research, New York, NY, USA, 3Columbia University and STATinMED Research, New York, NY, USA

1STATinMED

Objectives: To examine the mortality and readmission rates of patients diagnosed with stroke in the US Medicare population.  Methods: Using Medicare data, mortality and readmission rates were calculated among patients diagnosed with stroke (International Classification of Diseases, 9th Revision, Clinical Modification codes: 433, 434, 436). Patients with continuous enrollment in a Fee-for-service Medicare health plan during the calendar year and ≥ 2 years prior were restricted. Using sex-specific age groups, the age- and sex-adjusted readmission rates were calculated using direct standardization for the US population aged ≥ 65 years in 2010.  Results: The 30-day and 1-year mortality rates increased by 22.2% (9 to 11 per 1000 persons) and by 18.2% (22 to 26 per 1000 persons), respectively, from 2008 to 2013. The overall adjusted readmission rates were 8.70% (2008), 8.60% (2009), 8.58% (2010), 9.53% (2011), 9.12% (2012), and 7.43% (2013). Male patients had higher readmission rates than female patients across all study years. Readmission rates were highest among patients aged 65-69 years during 2008 (9.72%), 2011 (10.25%), and 2012 (10.04%), whereas readmission rates were highest among patients aged 70-74 in 2009 (9.65%) and among those aged 75-79 in 2010 (10.11%) and 2013 (7.96%). Readmission rates were highest among Hispanic patients in 2009 (9.07%), other race in 2008 (13.94%), North American Native in 2010 (15.03%) and 2011 (12.69%), and Asian patients in 2012 (11.10%) and 2013 (9.24%). Readmission rate results varied according to state.  Conclusions: Compared to 2008, Medicare beneficiaries diagnosed with stroke had higher mortality rates from 2009 to 2013, with the highest 1-year mortality rate in 2012. Overall readmission rates were highest during 2011 and decreased in 2012 and 2013. Readmission rate results varied by age group, race, and state. PCV7 Insulin and Higher Odds of a Positive History of Cardiovascular Disease among Diabetic Individuals GeneusCJ , DavisRE Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA

Objectives: This study examined associations between positive history of cardiovascular disease (CVD) and insulin, socio-demographic, and psychological determinants among diabetic respondents.  Methods: Data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) were analyzed for 9,506 self-reported diabetic survey participants aged ≥ 18 years. Both weighted multivariable and multinomial logistic regression models assessed history of CVD.  Results: The adjusted multivariable model revealed that the odds of a positive self-reported history of CVD were 1.43 (95% CI: 1.22-1.68) times higher among individuals who reported using insulin compared to non-users. Older individuals (aged ≥  55 years) had higher odds (aOR =  2.72; 95% CI: 1.30-5.67) of history of CVD compared to younger peers (aged 18-24 years). Furthermore, males had higher odds compared to females (OR =  1.35; 95% CI: 1.15-1.60). Interestingly, alcohol users had 21.2% (aOR =  0.79; 95%: 0.66-0.95) lower odds compared lifetime abstainers. Although positive self-reported frequent mental distress (≥ 14 mentally unhealthy days) (aOR =  1.11; 95% 0.89-1.39) and depression (aOR =  1.10; 95% CI: 0.91-1.33) both increased the odds of a positive self-reported history of CVD, only self-reported physical health (≥ 30 days of physical health not good) was statistically significant (aOR =  1.64; 95% CI:1.40-1.93). The adjusted multinomial logistic regression model showed that, compared to individuals without a history of CVD, insulin users had higher odds of self-reporting coronary heart disease (CHD) (aOR =  1.53; 95% CI: 1.22-1.68). Moreover, insulin users had 8% lower odds of self-reporting stroke, (aOR =  0.92; 95%CI: 0.69-1.24) and had 1.30 times (OR =  1.30; 95% CI: 0.94-1.80) higher odds of self-reporting myocardial infarction but such trend were not statistically significant.  Conclusions: Selfreported diabetic individuals who use insulin had higher odds of a self-reported history of CVD, particularly CHD. Future research should determine whether other medical and cardiometabolic mechanisms interact with insulin to better understand CVD outcomes. PCV8 Accelerated/Malignant Hypertension with a Diagnostic Ambugity: A Retrospective Cohort Study Srujitha M manipal university, manipal, India

Objectives: To investigate the incidence, TOD of patients presenting with A/MH, and its management.  Methods: A retrospective cohort analysis was carried out at our 2500 bedded tertiary care teaching hospital on patients admitted with essential HTN or hypertensive retinopathy during 2010 with ICD – 10 ( I.10 /H 35) coding with no comorbidities, were considered for the study. A 4 – year follow-up to evaluate their clinical outcomes of those diagnosed with A/MH was carried out.  Results: Of the 480 in-patients diagnosed with essential HTN or hypertensive retinopathy, 52 (10.8%) were found to have Grade III HTN (ESH/ESC 2013) which were documented as A/MH. Male predominance was found to be higher with 63.5% with a mean age of 49.58 years (±13.6 SD) and mean BMI of 25.0 (±5.6 SD).The Mean Arterial Pressure on admission was found to be 166.3(±16.6) mmHg and on discharge found to be 122.5(±10.9)mmHg. TOD was identified in 42 patients among them 22(42.3%) patients had retinal damage, 15(28.8%) had left ventricular failure, 2(3.8%) patients had renal damage and 3(5.7%) reported to have cerebral damage.  Conclusions: Our experience suggests that malignant hypertension is still common, with a small proportion of hypertensive’s presenting each year. We consider ours is the first study to report the incidence of A/MH in patients previously diagnosed with essential HTN from an Indian sub-population. We observe through our study that diagnosis of A/MH is not fulfilling the standard criteria. Thus we strongly believe that patients presenting with BP >  180/110 mm Hg should undergo ophthalmic evaluation, before being diagnosed as A/MH.