The ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer's disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity.A literature review and meta-analysis were conducted to estimate the prevalence of APOE4 by geographic area among AD patients.Although estimates varied significantly by study design and case definition, AD patients recruited in Asian and southern European/Mediterranean communities seemed to have significantly lower E4 carrier status estimates (37 and 43%) than those recruited in North America (58%) or northern Europe (64%; all: p < 0.05).APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population. Study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.
The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs.
Objectives: This study evaluated the safety and effectiveness of dabigatran versus warfarin for stroke risk reduction in NVAF patients in routine clinical care using the Department of Defense Military Health System database. Methods: In this retrospective cohort study, patients were included if they had an AF diagnosis within 12 months prior to first OAC treatment, were 18-89 years, and had a first prescription claim for either dabigatran or warfarin between 01-Oct-2010 and 31-Jul-2012 (index date). Patients were excluded if they had heart valve disorders or prosthetic heart valves, transient causes of AF, or any OAC use during the baseline period. Patients were censored when their prescriptions exceeded a 30 day allowable gap, at OAC switch, at disenrollment, at death, or at study end. A total of 14,813 dabigatran and 24,500 warfarin patients were available for propensity score matching (PSM). PSM based on baseline demographics and clinical characteristics was achieved 1:1 with 12,793 matched subjects per group (within a 0.20 caliper of standard deviation). Comparisons of safety and effectiveness outcomes were made based on Cox-proportional hazards models of PSM groups. All FDA-approved dosages were included in this analysis. Results: Results are summarized in Table 1. Conclusions: Hazard ratios in the post-PSM dabigatran cohort suggest that there is a lower likelihood for stroke, hemorrhagic stroke, major intracranial bleeding, major urogenital and other bleeding, MI, and death than in the warfarin cohort. The hazard ratio in the post-PSM dabigatran cohort suggests a higher likelihood for major lower GI bleeding, but a lower likelihood for intracranial, urogenital, and other bleeding than seen with warfarin. These results are generally consistent with findings of the randomized controlled clinical trial, RE-LY, and support that the benefits of dabigatran demonstrated in clinical trials also may be achieved in a broad population receiving routine clinical care.
To examine the association of obesity with healthcare resource utilization (HRU) and costs among commercially insured individuals.This retrospective observational cohort study used administrative claims from 1 January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from 2008 to 2012 classified body mass index (BMI) into the World Health Organizations' BMI categories. The date of first observed BMI code was defined as the index date and continuous eligibility for one year pre- and post- index date was ensured. Post-index claims determined individuals' HRU and costs. Sampling weights developed using the entropy balance method and National Health and Nutrition Examination Survey data ensured representation of the US adult commercially insured population. Baseline characteristics were described across BMI classes and associations between BMI categories, and outcomes were examined using multivariable regression.The cohort included 9651 individuals with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%), overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class III (5.4%). Increasing BMI was associated with greater prevalence of cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics, analgesics and antidepressants rose with increasing BMI. Greater BMI level was associated with increased inpatient, emergency department and outpatient utilization, and higher total healthcare, medical and pharmacy costs.Increasing BMI was associated with higher prevalence of cardiometabolic conditions and higher HRU and costs. There is an urgent need to address the epidemic of obesity and its clinical and economic impacts.
Background:Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen.Objective:To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use.Methods:Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized.Results:Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose–response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users.Conclusions:Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful.
Irritable bowel syndrome (IBS) is often a diagnosis of exclusion, with poor diagnosis coding in primary care. This makes identification of eligible research participants challenging. We present the methodology development of a multi-centre, observational, retrospective research study ongoing in primary care, designed to overcome the challenges of IBS patient identification.
Methods
Study feasibility was conducted by pH Associates (research consultancy; study coordinators) for Almirall UK Ltd (Sponsor) using medical opinion, clinical coding searches and NIHR Clinical Research Network expertise. FARSITE, a software tool for identification of research participants in primary care developed by the Greater Manchester Comprehensive Local Research Network and North West e-Health, was used to screen anonymised primary care records for potential eligible patients. Search criteria: patients aged 18–60; combination READ code symptoms indicative of IBS and prescription of IBS drugs 01/01/2009–31/12/2011. GP practices with eligible patients were invited to participate, with GPs reviewing clinical records of the FARSITE-generated list of patients to apply full eligibility criteria for final patient selection. Inclusion criteria: medical diagnosis of IBS or meeting ROME III criteria; provision of consent. Exclusion Criteria: diagnosis excluding IBS; IBS symptoms secondary to other condition; IBS medications for non-GI symptoms. The study is ongoing in 8 GP practices in Salford and Greater Manchester (Ethical approval 13/LO/0692).
Results
FARSITE feasibility search using READ code for IBS identified 50 (0.02%) patients. Combining READ codes with symptom and prescriptions criteria selected 4714 (1.9%) From these, 3 GP practices each screened 10 random patient records for eligibility and 12/30 (40%) were found eligible. Eligibility READ codes were revised following feasibility. Following study approvals, FARSITE identified 1089 potential eligible patients at the 8 participating practices, of which 297 (27.3%) were eligible and approached for consent for participation. Main reasons for non-eligibility were symptom characteristics not meeting ROME III criteria or not confirmed as IBS by medical opinion.
Conclusion
Identification of patients with IBS using READ code is sub-optimal in primary care. A combination search of READ codes with symptom and prescription data via FARSITE has enabled potential participants to be identified with a reasonable screening failure rate. FARSITE is a valuable research tool aiding study feasibility by reducing the need for manual patient identification.
Disclosure of Interest
I. Caldwell: None Declared, J. Collins: None Declared, M. Rance Employee of: Almirall UK Limited, R. Dew Conflict with: Commissioned by Almirall UK to provide research design, conduct analysis and scientific editorial services.
1563 Background: Limited data exist on the real-world treatment patterns and effectiveness of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the germline BRCA (g BRCA) mutated breast cancer population. Methods: Adults with human epidermal growth factor receptor 2 negative (HER2-), hormone receptor positive (HR+) metastatic breast cancer (mBC) treated with a CDK4/6 inhibitor from 01Jan2013–31Jan2018 were retrospectively selected from the Flatiron Health Oncology electronic medical record database. Patients with known g BRCA status were classified as having g BRCA mutated (g BRCAm) or wild type (g BRCAwt) disease. Time to first subsequent therapy or death (TFST) and overall survival (OS) were calculated from start of the earliest line of therapy with a CDK4/6 inhibitor. Kaplan-Meier (KM) medians were estimated, and TFST and OS compared between g BRCA groups with Cox models stratified by line of therapy and adjusting for demographic and clinical characteristics that modified hazard ratios (HRs) for g BRCA status by > 10%. Results: Of 2968 HER2- HR+ patients with mBC receiving a CDK4/6 inhibitor, g BRCA status was known for 859 (28.9%). Patients with g BRCAm and g BRCAwt received letrozole plus palbociclib (42.4 and 39.8%, respectively), fulvestrant plus palbociclib (32.9 and 30.7%), or other CDK4/6 regimens (24.7 and 29.5%) across all lines. The g BRCAm group had a non-significant, shorter TFST than g BRCAwt (stratified HR 1.24; 95% CI 0.96–1.59). OS was significantly shorter in g BRCAm than g BRCAwt patients (stratified HR 1.50; 95% CI 1.06–2.14). Conclusions: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be poorer in patients with g BRCAm compared with g BRCAwt disease. These findings indicate a higher unmet need among patients with g BRCAm, potentially requiring alternative treatment options. [Table: see text]
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