MedicalResearch.com Interview with: Philipe de Souto Barreto (PhD) Toulouse University Hospital (CHU Toulouse) Gérontopole of Toulouse - Head of Department: Prof Bruno Vellas Medical...
MedicalResearch.com Interview with:
Ravi Mangal Patel, MD MSc
Assistant Professor of Pediatrics
Division of Neonatology
Emory University School of Medicine
Medical Research: What is the background for this study?
Response: We sought to understand the major causes of death and when these deaths occur among extremely premature infants (those born at 22 0/7 to 28 6/7 weeks of gestation). We evaluated a cohort of 22,248 extremely premature infants born at hospitals that were part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, a research network comprised of academic medical centers across the United States. We evaluated changes over time in survival by comparing in-hospital deaths among live births during three periods from 2000 to 2011.
MedicalResearch.com Interview with: Pravin U. Dugel MD Managing Partner, Retinal Consultants of Arizona Phoenix AZ Clinical Professor USC Eye Institute Keck School of Medicine ...
MedicalResearch.com Interview with:
Prof. David Mackey
Centre for Ophthalmology and Vision Science/Lions Eye Institute Perth
Managing Director/Chair of University of Western Australia,
Perth, Australia
Centre for Eye Research Australia, Melbourne University
MedicalResearch: What is the background for this study? What are the main findings?
Prof. Mackey: Too much or too little sun? Excessive sun exposure is associated with the eye disease pterygium, while lack of outdoor activity in childhood increases the risk of myopia (short sightedness).
Measuring the amount of early sun damage to a person’s eyes would be of great use to researchers and potential use in clinical practice.
Over the last few years we have developed a biomarker for sun exposure to the eye by photographing Conjunctival UV Auto-Fluorescence (CUVAF).
The study published in JAMA Ophthalmology looked at the genetic and environmental factors that contribute to CUVAF levels in three Australian studies from Tasmania, Perth and Brisbane.
People who live in sunnier environments closer to the equator have more evidence of sun damage using CUVAF. However, genetic factors also play a role.
MedicalResearch.com Interview with:
Thomas C. Tsai, MD, MPH
Departments of Surgery and Health Policy and Management
Harvard School of Public Health, Boston, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Tsai: Emerging evidence is suggesting that fragmented care is associated with higher costs and lower quality. For elderly patients undergoing major surgical procedures, fragmentation of care in the post-discharge period may be especially problematic. We therefore hypothesized that elderly patients receiving fragmented post-discharge care would have worse outcomes. We found that among Medicare patients who are readmitted after a major surgical operation, one in four are readmitted to a different hospital than the one where the original operation was performed. Even taking distance traveled into account, we find that this type of postsurgical care fragmentation is associated with a substantially higher risk of death.
MedicalResearch.com Interview with:
M. Justin Coffey MD
Associate Professor
Menninger Department of Psychiatry & Behavioral Sciences
Baylor College of Medicine
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Coffey: Although both the US Surgeon General and the Institute of Medicine have called on health care systems to reduce suicide, the few assessments of suicide in such systems have examined only specific patient groups and not the entire population of health plan members. Our study reports the first information on suicide for the entire membership of a large health maintenance organization (HMO). The findings provide a previously unavailable baseline data for health care systems who are engaged in important efforts to measure and prevent suicide.
We identified all suicides among the entire membership of our HMO network between 1999 and 2010, determining the date and cause of death using official state mortality records. In our sample, the annual suicide rate among all HMO members (including non-patient members) did not change over time, whereas the annual suicide rate in the general population of the state of Michigan increased significantly. Importantly, suicides actually decreased among HMO members who received specialty mental health services, whereas suicides increased among HMO members who accessed general medical services but not specialty mental health services.
MedicalResearch.com Interview with:
Dr. Juliane Kämmer Postdoctoral Researcher
on behalf of the authors
Max Planck Institute for Human Development
Center for Adaptive Rationality Berlin Germany
Medical Research: What is the background for this study? What are the main findings?
Dr. Kämmer: Diagnostic errors contribute substantially to preventable medical error. Of the multiple reasons for diagnostic error (such as technical failures or poorly cooperating patients), cognitive error is among the most frequent. Although a vast amount of literature explores ways to reduce cognitive errors, for example, during data synthesis, the collaborative character of clinical decision making has been largely neglected so far. Thus, the aim of our study was to investigate the effect of working in teams as opposed to working alone on diagnostic accuracy and the diagnostic decision process as such (including the time to diagnosis, number of ordered diagnostic tests and calibration of diagnostic confidence to diagnostic accuracy).
In our study, we asked senior medical students to imagine being at the emergency ward and having to diagnose six simulated patients with respiratory distress on a computer – either working individually or in pairs. We indeed found that working in pairs reduced diagnostic error without requiring more diagnostic data gathering. Interestingly, neither differences in knowledge nor in amount and relevance of acquired diagnostic information could explain the superior accuracy of the pairs; neither did the statistically increased likelihood of containing a knowledgeable member. We thus have shown that – similar to other studies outside medicine – collaboration may help correct errors, fill knowledge gaps and counteract reasoning flaws – and thus save lives. Moreover, we found that reflecting on their personal confidence may point members of teams towards an increased probability of a diagnostic error.
MedicalResearch.com Interview with:
Sheree L. Boulet, DrPH, MPH
Division of Reproductive Health
Centers for Disease Control and Prevention, Atlanta, Georgia
Medical Research: What is the background for this study? What are the main findings?
Dr. Boulet: Intracytoplasmic Sperm Injection is generally considered a safe and effective treatment for male factor infertility; however, some studies have shown that ICSI is increasingly used in patients without male factor infertility without clear evidence of a benefit over conventional in vitro fertilization (IVF). In addition to increasing the cost of an IVF cycle, use of Intracytoplasmic Sperm Injection has been found to increase the risk for adverse infant outcomes such as birth defects, chromosomal abnormalities and autism. Using data from CDC’s National Assisted Reproductive Technology Surveillance System, we found that use of ICSI increased by fourfold from 1996 through 2012 (from 15.4% to 66.9%). Furthermore, we found that use of Intracytoplasmic Sperm Injection did not improve reproductive outcomes such as rates of pregnancy, miscarriage and live birth, when compared with conventional IVF, regardless of whether male factor infertility was present.
MedicalResearch.com Interview with:
Dr. Robert S. Rosenson, MD
Professor, Cardiology
Icahn School of Medicine at Mount Sinai
Cardiovascular Institute
New York, New York 10029
Medical Research: What is the background for this study? What are the main findings?
Dr. Rosenson: High intensity statin therapy is evidence-based and guideline directed for patients with acute coronary syndromes. In a 5 percent random sample of Medicare patients, we investigated the utilization of high vs low-moderate dosage statin in older adjusts who were admitted with an acute myocardial infarction of severe myocardial ischemia requiring hospitalization for a revascularization procedure (PCI or CABG).
We report that only 27 percent of hospitalized patients received high-intensity statin therapy based on their first outpatient fill for a statin medication. The most important determinant for the utilization of statin therapy is the dosage of the statin previously prescribed as an outpatient. When patients were started on a high-intensity statin, the continued use diminished in the ensuing year
MedicalResearch.com Interview with:
David Alter, MD, PhD FRCPC Senior Scientist
Toronto Rehabilitation Institute-University Health Network and Institute for Clinical Evaluative Sciences
Research Director, Cardiac Rehabilitation and Secondary Prevention Program Toronto Rehabilitation Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Alter: We knew going into the study that exercise was an important lifestyle factor that improved health. We also knew from studies that sedentary time was associated with deleterious health-effects. What we didn’t know was whether the health-outcome effects of sedentary time and exercise were really one and the same (i.e., albeit opposite ends of the same spectrum) or alternatively, whether the health effects of each were independent of one another. We explored over 9000 published studies to quantify the health-outcome effects associated with sedentary behaviour and extracted only those which took into account both sedentary time and exercise. We found a consistent association between sedentary time and a host of health outcomes independent of exercise. Specifically, after controlling for an individual’s exercising behaviour, sitting-time was associated with a 15-20% higher risk of death, heart-disease, death from heart disease, cancer-incidence, and death from cancer. Sitting time was also independently associated with a marked (i.e., 90% increase) in the risk for diabetes after controlling for exercise. In short, sedentary times and exercise are each independently associated with health outcomes. We hypothesize that the two may have different mechanism, and may require different therapeutic strategies. But, the health-outcome implications of both are each important in their own right.
MedicalResearch.com Interview with:
Dr. P. Michael Ho, MD PhD
Denver Veteran Affairs Medical Center,
University of Colorado, Denver, Section of Cardiology
Denver, Colorado 80220.
Medical Research: What is the background for this study? What are the main findings?
Dr. Ho: There is increasing interest in measuring health care value, particularly as the healthcare system moves towards accountable care. Value in health care focuses on measuring outcomes achieved relative to costs for a cycle of care. Attaining high value care - good clinical outcomes at low costs - is of interest to patients, providers, health systems, and payers. To date, value assessments have not been operationalized and applied to specific patient populations. We focused on percutaneous coronary intervention (PCI) because it is an important aspect of care for patients with ischemic heart disease, is commonly performed and is a costly procedure. In this study, we evaluated 1-year risk-adjusted mortality and 1-year risk-standardized costs of care for all patients who underwent PCI in the VA healthcare system from 2008 to 2010.
We found that median one-year unadjusted hospital mortality rate was 6.13% (interquartile range 4.51% to 7.34% across hospitals). Four hospitals were significantly above the one-year risk standardized median mortality rate, with median mortality ratios ranging from 1.23 to 1.28; no hospitals were significantly below median mortality. Median 1-year total unadjusted hospital costs were $46,302 (IQR of $37,291 to $57,886) per patient. There were 16 hospitals above and 19 hospitals below the risk standardized average cost, with risk standardized ratios ranging from 0.45 to 2.09 reflecting much larger magnitude of variability in costs compared to mortality. These findings suggest that there are opportunities to improve PCI healthcare by reducing costs without compromising outcomes. This approach of evaluating outcomes and costs together may be a model for other health systems and accountable care organizations interested in operationalizing value measurement.
MedicalResearch.com Interview with:
Andreas Kalogeropoulos, MD MPH PhD
Assistant Professor of Medicine (Cardiology)
Emory University School of Medicine Emory Clinical Cardiovascular Research Institute
Atlanta GA 30322
Medical Research: What is the background for this study? What are the main findings?
Dr. Kalogeropoulos: There is ongoing debate on how low should we go when it comes to dietary sodium (salt) restriction recommendations. In this study, we examined the association between self-reported dietary sodium intake and 10-year risk for death, cardiovascular disease, and heart failure in approximately 2,600 adults 71-80 years old. The subjects (women: 51.2%; white: 61.7%; black: 38.3%) were participants of the community-based Health, Aging, and Body Composition Study, which is sponsored by NIH and focuses on aging processes, i.e. was not specifically designed to address the issue of dietary salt intake. Also, it is important to note that salt intake was self-reported (not objectively measured) using a food frequency questionnaire, which underestimates salt intake. Keeping these limitations in mind, we did not observe a significant association between self-reported sodium intake and 10-year mortality, cardiovascular disease, and heart failure. Ten-year mortality was lower in the group reporting 1500–2300 mg daily sodium intake (30.7%) compared to those reporting daily intake less than 1500 mg (33.8%) or over 2300 mg (35.2%); however, this difference was not statistically significant. The 10-year event rates for cardiovascular disease (28.5%, 28.2%, and 29.7%) and heart failure (15.7%, 14.3%, and 15.5%) were also comparable across the <1500-mg, 1500-2300-mg, and >2300-mg dietary sodium intake groups.
MedicalResearch.com Interview with:
Jose Gutierrez MD, MPH
Assistant Professor of Neurology
Division of Stroke and Cerebrovascular Disease
Columbia University Medical Center NY, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Gutierrez: There is growing interest in the effects of vascular health in cognition. The prevailing thought is that vascular disease leads to worse cognition due to direct structural damage of the brain, as in the case of brain infarcts, microhemorrhages or white matter hyperintensities, which are themselves associated with traditional cardiovascular risk factors such as hypertension, diabetes, smoking etc. Arterial stiffness, particularly of the aorta, has gained interest among researchers as predictors of vascular disease and worse cognition, but it is not clear whether arterial stiffness in the absence of traditional definition of vascular disease may be associated with worse cognition.
We investigated in a representative sample of the US among adults 60 years or older who underwent cognitive testing with the Digit Symbol Subtraction test and who also had other measures of vascular disease, including blood workup, blood pressure measurement and Pulse pressure. We hypothesized that indirect measures of arterial stiffness such as ABI > 1.3 or pulse pressure would be associated with worse cognition, even among those without any clinical vascular disease or traditional vascular risk factors. We Included 2573 US adults in the sample, segregated those with any self-reported vascular disease or vascular risk factors and we found that among those without vascular disease or risk factors, an ABI > 1.3 and increased intra-visit blood pressure variability were predictors of worse cognitive performance compared with those without these indicators. Among participants with both indirect markers of arterial stiffness, their cognitive performance was worse that having only one of them suggesting additive effects of these two variables.
MedicalResearch.com Interview with:
Jane Wardle
University College London
Medical Research: What is the background for this study? What are the main findings?
Dr. Wardle: Previous studies have shown that couples tend to have similar health behaviours to one another, but no studies had compared having a partner who takes up a healthy behaviour (e.g. quits smoking) with having one whose behaviour is consistently healthy (e.g. never smoked). Nor have there been other studies in the older age group – our participants were over 60 on average. We used data from 3722 couples participating in the English Longitudinal Study of Ageing (ELSA) to explore this issue for three behaviours: smoking, physical activity, and weight loss. For each behaviour, we found that when one partner changed their behaviour, the other partner was more likely to make a positive change, and the effect was stronger than having a partner whose behaviour was consistently healthy (i.e. never smoked/always exercised).
MedicalResearch.com Interview with:
Jinnie J. Rhee MSc, ScD
Department of Medicine, Stanford University School of Medicine Palo Alto, CA
Medical Research: What is the background for this study? What are the main findings?
Response: The goal of this study was to see if the dietary determinants of type 2 diabetes observed in predominantly white populations were similar to those in other racial and ethnic groups. We created a dietary diabetes risk reduction score using eight different dietary factors found to be associated with risk of type 2 diabetes, where a higher score indicates a healthier overall diet (A higher score included low intakes trans fat, sugar-sweetened beverages, and red and processed meats; lower glycemic index; and higher intakes of cereal fiber, nuts, and coffee; and higher polyunsaturated to saturated fat ratio). We found a protective association of similar magnitude between a healthy overall diet and type 2 diabetes risk in all racial and ethnic groups. However, in terms of the actual number of preventable cases, a healthier diet conferred even greater benefit for minority women because they were initially at higher risk than white women.
This study is significant because diabetes is a rapidly growing epidemic in most parts of the world, but most previous studies of diet and diabetes have been conducted in populations of European origin. This analysis was very powerful because it combined two large populations with a total of 156,030 women who were followed for up to 28 years with many repeated assessments of diet. This allowed us to conduct detailed analyses within specific racial and ethnic groups.
MedicalResearch.com Interview with:
Lee Zou, Ph.D.
Professor of Pathology, Harvard Medical School
The Jim & Ann Orr MGH Research Scholar
Associate Scientific Director, MGH Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on alternative lengthening of telomere can be exploited therapeutically was not known.
In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer. 
MedicalResearch.com Interview with:
Soko Setoguchi, MD DrPH
Assistant Professor of Medicine
Harvard Medical School and Harvard School of Public Health
Director of Safety and Outcome Research in Cardiology
Associate Physician in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Setoguchi: Medicare made a decision to cover Carotid Artery Stenting (CAS) in 2005 after publication of SAPPHIRE, which demonstrated the efficacy of Carotid Artery Stenting (CAS) vs Carotid endarterectomy (CEA) in high risk patients for CEA. Despite the data showing increased carotid artery stenting dissemination following the 2005 National Coverage Determination, peri-procedural and long-term outcomes have not been described among Medicare beneficiaries, who are quite different from trial patients, older and with more comorbidities in general population.
Understanding the outcomes in these population is particularly important in the light of more recent study, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), which established CAS as a safe and efficacious alternative to CEA among non-high-surgical risk patients that also expanded the clinical indication of carotid artery stenting.
Another motivation to study ‘real world outcomes in the general population is expected differences in the proficiency of physicians peforming stenting in trial setting vs. real world practice setting. SAPPHIRE and CREST physicians were enrolled only after having demonstrated CAS proficiency with low complication rates whereas hands-on experience and patient outcomes among real-world physicians and hospitals is likely to be more diverse.
We found that unadjusted mortality risks over study period of 5 years with a mean of 2 years of follow-up in our population was 32%. Much higher mortality risks observed among certain subgroups with older age, symptomatic patients and non-elective hospitalizations.
MedicalResearch.com Interview with:
Jonathan Thigpen, PharmD
Assistant Professor
Clinical and Administrative Sciences
Notre Dame of Maryland University School of Pharmacy
Medical Research: What is the background for this study? What are the main findings?
Dr. Thigpen: This effort assessed the accuracy of International Classification of Disease 9th Edition (ICD-9) stroke codes in identifying valid stroke events in a cohort of atrial fibrillation (AF) patients. The initial electronic search yielded 1,812 events across three stroke centers (Boston Medical Center, Geisinger Health System, and University of Alabama). All ICD-9 identified stroke events were vetted through manual chart review with final adjudication by a stroke neurologist. Atrial fibrillation was verified by evidence via electrocardiogram at stroke admission, 6 months prior to, or 90 days after stroke admission.
In addition to assessing the accuracy of the stroke codes alone, we also assessed the accuracy of stroke and Atrial fibrillation codes combined as well as the accuracy of stroke codes when seeking for stroke associated with Atrial fibrillation. These additional steps give readers insight as to the accuracy and reliability of using ICD-9 codes alone to create a stroke plus AF cohort. We feel that this effort is extremely important given the increasing reliance on ICD-9 codes as a means of identifying stroke events and covariates in research, especially research using administrative data.
The positive predictive value (PPV) of stroke codes alone was 94.2%. PPVs did not differ across clinical site or by type of event (ischemic vs. intracranial hemorrhage). PPV of stroke codes did differ by event coding position (primary vs. other; 97.2% vs. 83.7%) and by ischemic stroke code (433 vs. 434; 85.2% vs. 94.4%). When combined with validation of Atrial fibrillation codes, the PPV of stroke codes decreased to 82.2%. After excluding ischemic stroke due to a different mechanism (eg, vascular procedure, tumor, sepsis) the PPV dropped further to 72.8%. As a separate exercise, manual review confirmed 33 (7.2%) ischemic strokes in 458 events coded as "without infarction".
MedicalResearch.com Interview with:
Dr. Jeanne Madden PhD
Instructor, Department of Population Medicine
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Madden: When Medicare Prescription Drug Coverage started in 2006, many experts voiced concerns about disabled patients with serious mental illness making the transition from state Medicaid coverage to Medicare. Our study is one of the first to examine the impact of the transition in mentally ill populations. People living with schizophrenia and bipolar disorder are at high risk of relapse and hospitalization and are especially vulnerable to disruptions in access to their treatments.
We found that the effects of transitioning from Medicaid to Medicare Part D depended on where patients lived. Transition to Part D in states that put limits on Medicaid drug coverage resulted in fewer patients going without treatment.
By contrast, in states with more generous drug coverage, we saw reductions in use, of antipsychotics in particular, after patients shifted to Medicare Part D. This may have been due to new cost controls used within many private Medicare drug plans. Given that most states in the US are in this latter category, with the relatively generous Medicaid drug coverage, we also found reductions in antipsychotic use nation-wide.
Although a very large group of people made that transition from Medicaid to Medicare in 2006, thousands more still transition every year because when disabled people qualify for Medicare, they must wait 2 years for their benefits kick in. Also, many other disabled patients are on Medicaid only and don’t qualify for Medicare. They are of course affected by restrictions on Medicaid coverage, which vary from state to state.
'Tiger Mosquito'
MedicalResearch.com Interview with:
John M. Drake, Ph.D.
Associate Professor, Odum School of Ecology
University of Georgia
Director, Population Biology of Infectious Diseases REU Site
Medical Research: What is the background for this study? What are the main findings?
Dr. Drake: Ebola virus disease is a deadly illness caused by infection with the zoonotic Ebola virus. The world's largest epidemic of Ebola virus disease is currently ongoing in West Africa, concentrated in the countries of Liberia, Sierra Leone, and Guinea. Ebola emerges in a human population after contact with an infected animal host and persists through human-to-human transmission. Persons with late stage illness are especially infectious. Ebola outbreaks are typically contained by outbreak investigation and patient isolation. But, as the current epidemic shows, containment may be very difficult to achieve in areas of high population density or where there is little health infrastructure.
During the second half of 2014, the West African nation of Liberia suffered the greatest rates of Ebola transmission. Slowing the spread of Ebola was found to be especially difficult after the virus reached the urban areas around Monrovia, particularly the township of West Point. The United States, other nations, and non-governmental organizations promised aid and developed a plan to improve Liberia's health infrastructure, but many aspects of urban Ebola transmission were then unknown, including the relative importance of hospital- and community-acquired infection, how much hospital capacity must be increased to provide care for the anticipated patient burden, and what level patient of isolation would be required to contain the outbreak. To address these issues, we developed a model for Ebola transmission that accounted for the separate sites at which infection could occur, for instance in the home, in public places (particularly at funerals), or in health facilities. Based on information available by mid-October, it was not clear whether enough was being done to contain the epidemic in Liberia. But, through public vigilance and community participation, particularly the willingness of infected persons to be treated in health facilities and to allow safe handling of the bodies of the deceased, transmission dropped dramatically in the last quarter of the year. An updated version of our model developed in early December suggests that if these gains can be maintained then the epidemic may be over by the middle of 2015.
MedicalResearch.com Interview with:
Leora Horwitz, MD, MHS
Director, Center for Healthcare Innovation and Delivery Science
New York University Langone Medical Center
Director, Division of Healthcare Delivery Science
Department of Population Health, NYU School of Medicine
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Horwitz: We reviewed over 1500 discharge summaries from 46 hospitals around the nation that had been collected as part of a large randomized controlled trial (Telemonitoring to Improve Heart Failure Outcomes). All summaries were of patients who were admitted with heart failure and survived to discharge. We found that not one of them met all three criteria of being timely, transmitted to the right physician and fully comprehensive in content. We also found that hospitals varied very widely in their average quality. For instance, in some hospitals, 98% of summaries were completed on the day of discharge; in others, none were. In the accompanying Data Report, we show that summaries transmitted to outside clinicians and including more key content elements are associated with lower risk of rehospitalization within 30 days of discharge. This is the first study to demonstrate an association of discharge summary quality with readmission.
MedicalResearch.com Interview with:
Jean-Claude Tardif MD
Professor of Medicine
Director of the Research Centre
Montreal Heart Institute Montreal, Quebec Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Tardif: Epidemiological and mechanistic studies have suggested that high-density lipoproteins (HDL) could have beneficial cardiovascular properties. However, several medications targeting HDL have failed in recent clinical trials, including the CETP inhibitor dalcetrapib in the dal-Outcomes trial. We hypothesized that dalcetrapib would be beneficial in the subset of patients with the appropriate genetic profile. We conducted the pharmacogenomic analysis of approximately 6000 patients from the dal-Outcomes study which showed that patients with the AA genotype at a specific genetic location (rs1967309) of the adenylate cyclase (ADCY9) gene benefited from a 39% reduction in cardiovascular events including cardiovascular death, myocardial infarction, stroke, unstable angina and the need for coronary revascularization when treated with dalcetrapib compared to placebo. In contrast, patients with the GG genotype had a 27% increase in cardiovascular events. We then obtained confirmatory evidence from the dal-Plaque-2 imaging study which revealed that patients with the protective genotype (AA) had a reduction in their carotid artery wall thickness and that those with the genotype associated with clinical harm (GG) had an increase in their wall thickness.