Louis Fiore - Academia.edu (original) (raw)

Papers by Louis Fiore

Circulation, Feb 5, 2002

; for the Combination Hemotherapy and Mortality Prevention (CHAMP) Study Group* Background-Both a... more ; for the Combination Hemotherapy and Mortality Prevention (CHAMP) Study Group* Background-Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy. Methods and Results-We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank Pϭ0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank Pϭ0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank Pϭ0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; PϽ0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups. Conclusions-In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy. (Circulation. 2002;105:557-563.

Clinical Trials

Background/Aims: The US Department of Veterans Affairs Point of Care Clinical Trial Program condu... more Background/Aims: The US Department of Veterans Affairs Point of Care Clinical Trial Program conducts studies that utilize informatics infrastructure to integrate clinical trial protocols into routine care delivery. The Diuretic Comparison Project compared hydrochlorothiazide to chlorthalidone in reduction of major cardiovascular events in subjects with hypertension. Here we describe the cultural, technical, regulatory, and logistical challenges and solutions that enabled successful implementation of this large pragmatic comparative effectiveness Point of Care clinical trial. Methods: Patients were recruited from 72 Veterans Affairs Healthcare Systems using centralized processes for subject identification, obtaining informed consent, data collection, safety monitoring, site communication, and endpoint identification with minimal perturbation of the local clinical care ecosystem. Patients continued to be managed exclusively by their clinical care providers without protocol specified s...

Orally administered questionnaire. (DOCX 26 kb)

The online version of this article, along with updated information and services, is located on the

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 2016

The program determines and disseminates precision oncology best practices; enhances patient and p... more The program determines and disseminates precision oncology best practices; enhances patient and provider engagement; and fosters collaboration among the VA, National Cancer Institute, academia, other health care systems, and industry to provide cancer patients with access to clinical trial participation.

Journal of the American Society of Nephrology, 2020

Significance Statement Most studies of Mesoamerican nephropathy have focused on regions in El Sal... more Significance Statement Most studies of Mesoamerican nephropathy have focused on regions in El Salvador and northwest Nicaragua and on agricultural workers, but information regarding prevalence and risk factors for CKD in Nicaragua’s general population is sparse. In a study of community-dwelling individuals in southwestern Nicaragua, the authors screened 1242 participants for CKD (defined as <60 ml/min per 1.73 m2). Risk factors for prevalent CKD included age, diabetes, and hypertension. Current or former workers in the sugarcane industry (but not other types of agriculture) had a twofold-increased odds of CKD. CKD prevalence in southwestern Nicaragua is about 5% among the general population but is not consistent across Nicaragua. Formal CKD surveillance programs in Nicaragua are needed to assess the overall burden of CKD nationally, with a focus on agricultural workers. Background Studies have described Mesoamerican nephropathy among agricultural workers of El Salvador and northw...

Journal of clinical epidemiology, Jan 3, 2015

To describe the design and ongoing conduct of the Million Veteran Program (MVP), as an observatio... more To describe the design and ongoing conduct of the Million Veteran Program (MVP), as an observational cohort study and mega-biobank in the Department of Veterans Affairs (VA) healthcare system. Data are being collected from participants using questionnaires, the VA electronic health record, and a blood sample for genomic and other testing. Several ongoing projects are linked to MVP, both as peer-reviewed research studies and as activities to help develop an infrastructure for future, broad-based research uses. Formal planning for MVP commenced in 2009; the protocol was approved in 2010, and enrollment began in 2011. As of 3 August 2015, and with a steady-state of ≈50 recruiting sites nationwide, N=397,104 Veterans have been enrolled. Among N=199,348 with currently available genotyping data, most participants (as expected) are male (92.0%) between the ages of 50 and 69 years (55.0%). Based on self-reported race, white (77.2%) and African-American (13.5%) populations are well represent...

Stroke, 1988

The association between elevated anticardiolipin antibody (ACA) titers and stroke has only rarely... more The association between elevated anticardiolipin antibody (ACA) titers and stroke has only rarely been reported. 1 We studied a patient with ACAs in whom recurrent cerebral ischemic events were the sole thrombotic manifestations of this hypercoagulable state during 23 years of follow-up. In May 1963, this previously healthy 39-year-old man presented with fever, malaise, weight loss, arthralgias, and Raynaud's phenomenon of 4 months duration. Blood pressure was 160/120 mm Hg. General and neurologic examinations were normal. Prothrombin time (PT) was 17.1 seconds with a control of 13.6 seconds. Erythrocyte sedimentation rate (ESR) was 25 mm; serum latex fixation test was positive. He was treated with aspirin. In August 1963, he had a generalized seizure followed by stupor, motor aphasia, and right hemiparesis predominating in his arm and face. Cardiovascular examination and routine laboratory tests were unremarkable. Bilateral carotid angiography showed mass effect in the left parietal area without arterial stenosis or evidence of vasculitis. The diagnosis of embolic stroke was made. He was discharged on diphenylhydantoin, phenobarbital, and hydrochlorthiazide but had to be readmitted 2 months later with transient binocular visual disturbance. A falsepositive VDRL and normal blood pressure were documented in 1966, and, at a routine follow-up visit in 1979, the partial thromboplastin time (PTT) was 42.3 seconds with a control of 31.0 seconds, but PT was normal. He presented in January 1985 with headache, lethargy, and a transient visual disturbance. He was slightly euphoric and unconcerned about his condition. New facial and arm weakness with sensory and visual neglect were noted on the left side in addition to the old mild aphasia and right hemiparesis. Blood pressure, PT, PTT, and echocardiogram were normal. Brain computed tomography (CT scan) was consistent with new right temporo-parietal and old left frontal and parietal infarcts. Cerebral angiogram showed moderate stenosis of the petrous segment of the right internal carotid artery, with nonfilling of the ipsilateral middle cerebral artery's inferior division branches. Warfarin was started. Follow-up ACA, ANA, anti-RNP, and anti-Sra antibodies were all positive. A diagnosis of systemic lupus erythematosus was made. Reevaluation in December 1986 confirmed the elevated ACA titers (Table 1). He was maintained on warfarin.

Nature Reviews Drug Discovery, 2019

Researchers, clinicians, policymakers and patients are increasingly interested in questions about... more Researchers, clinicians, policymakers and patients are increasingly interested in questions about therapeutic interventions that are difficult or costly to answer with traditional, free-standing, parallel-group randomized controlled trials (RCTs). Examples include scenarios in which there is a desire to compare multiple interventions, to generate separate effect estimates across subgroups of patients with distinct but related conditions or clinical features, or to minimize downtime between trials. In response, researchers have proposed new RCT designs such as adaptive platform trials (APTs), which are able to study multiple interventions in a disease or condition in a perpetual manner, with interventions entering and leaving the platform on the basis of a predefined decision algorithm. APTs offer innovations that could reshape clinical trials, and several APTs are now funded in various disease areas. With the aim of facilitating the use of APTs, here we review common features and issues that arise with such trials, and offer recommendations to promote best practices in their design, conduct, oversight and reporting. PersPectives Nature reviews | Drug Discovery N, no; NA , not applicable; RAR , response-adaptive randomization; TTE, time to event; Y, yes. a In the planning phase, with multiple experimental arms and a control arm proposed. b For corticosteroid, antibiotic and macrolide domains.

Journal of Clinical Oncology

6562 Background: Data on implementation of genetic diagnostic (GDx) tests are lacking yet are cru... more 6562 Background: Data on implementation of genetic diagnostic (GDx) tests are lacking yet are crucial to evaluate population differences in access and outcomes. Previous studies identified substantial underuse of GDx tests. Greater access existed in states with NCI cancer centers. This pattern of diffusion may exacerbate disparities. Since 2008, the 21-gene recurrence score (21-gene RS), which assesses the 10-year risk of breast cancer (BC) recurrence in ER+, node-negative, early-stage disease, has been recommended by ASCO/NCCN to guide chemotherapy decisions. This study examines regional and site-of-care differences in use. We report national implementation rate and state-level differences in utilization. Methods: Hospital level data on 2011 orders for the test were provided by Genomic Health. We aggregated this dataset at the state-level and linked it to public datasets (Census and CDC State Cancer Profiles). Using Surveillance Epidemiology End Results (SEER) data, we estimated nu...

Blood

Background: It has been hypothesized that chronic antigenic stimulation in response to chronic in... more Background: It has been hypothesized that chronic antigenic stimulation in response to chronic inflammation or infection may predispose to the development of plasma cell dyscrasias (PCD) including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Using Department of Veterans Affairs (VA) administrative databases we explored associations between PCD and chronic inflammatory diseases (CID) including rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), psoriasis, asthma, the chronic infections hepatitis C (HEPC) and hepatitis B (HEPB), as well as history of agent orange exposure (AO). Methods: To identify a source population of veterans who are regular users of the VA system for medical care, we gathered data on patients seen in the inpatient or outpatient setting with a diagnosis of hypertension (HTN), diabetes (DM) or coronary artery disease (CAD) between Oct 1, 1996 and Sept 30, 2003. This source population represents more than 70% of all ...

Heart (British Cardiac Society), Aug 1, 2017

Controlled trials provide the most valid determination of the efficacy and safety of an intervent... more Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some typ...

The American journal of cardiology, Jan 16, 2017

Hospitalization for acute decompensated heart failure (ADHF) is an important outcome in clinical ... more Hospitalization for acute decompensated heart failure (ADHF) is an important outcome in clinical trials and heart failure registries; however, the optimal strategy to identify these hospitalizations using International Classification of Diseases, Ninth Revision (ICD-9) codes is uncertain. We sought to identify diagnostic codes that improve ascertainment of ADHF hospitalizations. Heart failure-related ICD-9 principal discharge codes were used to identify 2,202 hospitalizations within the Minneapolis Veterans Affairs Medical Center from 2009 to 2014. Two independent reviewers adjudicated 447 of these hospitalizations to determine the accuracy of each code. We then applied our findings to an unadjusted nationwide sample containing the same ICD-9 codes of interest, from which overall positive predictive value (PPV), sensitivity, and accuracy were calculated. Use of 428.x alone resulted in a PPV of 91.3% (95% confidence interval [CI] 91.0 to 91.7), sensitivity of 97.5% (95% CI 97.3 to 97...

Journal of Clinical Psychopharmacology, Dec 1, 2005

To characterize long-term prescriptions for commonly prescribed anxiolytic benzodiazepines to vet... more To characterize long-term prescriptions for commonly prescribed anxiolytic benzodiazepines to veteran patients and to identify factors associated with high daily doses, we analyzed the linked pharmacy and administrative databases from New England Veterans Healthcare System (VISN 1). We analyzed treatment episodes of 3 months or longer with the 4 most commonly prescribed agents: alprazolam, clonazepam, diazepam, and lorazepam. Descriptive statistics and univariate and multivariate analyses described the sample and tested associations of pharmacological and clinical variables for patients prescribed the top 5% of average daily doses (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;high-dose&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; prescriptions). From 16,630 full or partial treatment episodes for all 4 agents analyzed within a 42-month window, average daily doses were predominantly moderate, age-sensitive, and stable; refill lag intervals were short. Patients on &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;high-dose&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; prescriptions for the 4 agents combined, compared with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;middle quartile&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; dose prescriptions, in adjusted analyses, were younger, more likely to have posttraumatic stress disorder (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.17-3.13), substance abuse (OR, 1.50; 95% CI, 1.25-1.80), and anxiety (OR, 1.33; 95% CI, 1.11-1.60) and were more likely to be receiving concurrent oxycodone/acetaminophen (OR, 2.05; 95% CI, 1.64-2.56), anxiolytic benzodiazepine (OR, 1.51; 95% CI, 1.12-2.03), antidepressant (OR, 2.15; 95% CI, 1.80-2.58), and neuroleptic (OR, 2.03; 95% CI, 1.69-2.44) prescriptions. These results indicate that veteran patients prescribed anxiolytic benzodiazepines typically receive modest, nonincreasing doses over long-term treatment episodes. However, those on the highest average daily doses, typically more than recommended guidelines, are more likely to have clinical diagnoses and concurrent prescriptions for psychoactive medications indicative of more complex and, perhaps, problematic management.

BMC Nephrology, 2016

Background: A lack of advanced healthcare information systems and validated scientific cohorts in... more Background: A lack of advanced healthcare information systems and validated scientific cohorts in Nicaragua makes it difficult to estimate disease prevalences and other public health statistics. Although there is concern of an "epidemic" of chronic kidney disease (CKD) in this country, statistics regarding its magnitude are derived from only a small number of non-representative studies. Budgetary constraints and the logistical problems of maintaining a study cohort make longitudinal studies difficult. The Rivas Cohort was created to measure disease burden of CKD and other public health priorities in the Department of Rivas, Nicaragua. Using primarily volunteer research students and technologic innovation including GPS, digital photography and point of care biochemical analysis, the ability to establish a longitudinal chronic disease cohort is demonstrated. Methods: Subjects were recruited from consecutive adjacent households in thirty-two randomly selected communities in the ten municipalities that comprise the Department of Rivas in southern Pacific coastal Nicaragua. The study was conducted in two phases. In the first phase, subjects were enrolled into the cohort and consented for future re-contact. In Phase II, conducted two years later, attempts were made to re-contact 400 of these subjects for additional data collection. Demographic, lifestyle, occupational, exposure and health data was collected for both phases of the study. Blood and urine testing and height, weight and blood pressure measurements were also performed. GPS coordinates of homes were recorded and maps of remote communities created. Results: Of 1397 adults living in 533 households approached for participation a total of 1242 (89 %) were enrolled in the cohort. The median age is 41 years and 43 % are male, demographics in agreement with Nicaraguan census data for the Department of Rivas. During Phase II we attempted to re-contact 400 subjects for a follow-up study of CKD. It was possible to re-contact 84 % of these participants and of those re-contacted 95 % agreed to participate in the follow-up study. Of subjects that were not successfully re-contacted the majority had either moved (32) or were not at home (22) at the time of the study team visits.

Amia Joint Summits on Translational Science Proceedings Amia Summit on Translational Science, 2013

ACC Current Journal Review, 1997

year) at an interim analysis, an absolute reduction of 6.0% per year by adjusted-dose warfarin. T... more year) at an interim analysis, an absolute reduction of 6.0% per year by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p ϭ 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p ϭ 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Interpretation: Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) developed a SharePo... more Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) developed a SharePoint / InfoPath based electronic data capture for clinical trials within the Veterans Affairs Cooperative Studies Program (CSP). A declarative study specification includes all questions, element names, element types, repeating elements, and simple constraints plus specifications for visits, sites, question hiding, and randomization. The CSP eDC tool transforms a declarative data model into an operational data collection and storage mechanism including data dictionaries, forms, and databases. CSP is creating extendable standardized forms relating to adverse events, contact information, demographics, drug accountability, medication history, military history, patient termination, protocol deviation, and vital signs.

Proceedings of the ACM international conference on Health informatics - IHI '10, 2010

ABSTRACT