Author Interviews, Hip Fractures, Medical Imaging, Osteoporosis / 25.01.2016

MedicalResearch.com Interview with: Margaret L. Gourlay, MD, MPH Assistant Professor UNC Department of Family Medicine Chapel Hill, NC 27599-7595 Medical Research: What is the background for this study? What are the main findings? Dr. Gourlay: While clinical practice guidelines universally recommend bone density screening for fracture prevention in women aged 65 years and older, minimal data exist to guide bone density screening in older men. We studied how often bone density screening tests should be ordered in men, using data from the Osteoporotic Fractures in Men (MrOS) Study. MrOS is the largest and longest-running (since 2000) US study of bone density and fracture in men aged 65 and older. After peak bone mass is reached in young adulthood, both men and women lose bone density as they get older. Based on our earlier findings in older women, we expected that men aged 65 and older with higher bone density T-score measurements (T-score >-1.50) on a first (baseline) bone density test would have a substantially longer estimated time to develop the lowest level of bone density (osteoporosis) than men with better baseline measurements. Clinicians want to know the time to osteoporosis because they prescribe osteoporosis treatments to prevent future fractures in elderly patients. As expected, we found that the men with higher baseline bone density had a much slower transition to osteoporosis compared to men with lower bone density. In fact, only nine out of 4203 (0.2%) of men with higher baseline bone density developed osteoporosis after an average of 8.7 years of bone density follow-up. That was much lower than we expected and is good news for men who have favorable scores on their first bone density test. Men who had lower baseline bone density measurements developed osteoporosis faster. Unfortunately, maintaining bone density above the osteoporosis range did not guarantee that men remained fracture-free.   Most of the major osteoporotic fractures (broken hip, spine, wrist or upper arm/shoulder) occurred in men who did not have osteoporosis. This might be because they had accidents or injuries that broke their bones despite their bone density being above the thinnest range. (more…)
Annals Internal Medicine, Author Interviews, Breast Cancer, Mammograms / 12.01.2016

MedicalResearch.com Interview with: Susan K. Boolbol, MD, FACS Chief, Division of Breast Surgery Chief, Appel-Venet Comprehensive Breast Service Co-Director, Breast Surgery Fellowship Mount Sinai Beth Israel Associate Professor of Surgery Icahn School of Medicine at Mount Sinai New York, NY 10003 Medical Research: What is the background for these new recommendations? Dr. Boolbol: To make this final recommendation, the Task Force conducted a comprehensive review of the science since its 2009 recommendation and considered the public comments it received on its 2015 draft recommendation statement. Based on all of this, the task force issued their recommendations. Medical Research: What are the main changes from current guidelines? Dr. Boolbol: Presently, there are several different guidelines and recommendations regarding screening mammography. Depending on the group issuing the guidelines, the recommendations vary from annual mammography beginning at 40 years old to biennial mammograms from 50 to 74 years old. The Task Force continues to find that the benefit of mammography increases with age, and recommends biennial screening in women ages 50 to 74. (more…)
Author Interviews, Breast Cancer, Geriatrics, Mammograms / 07.01.2016

MedicalResearch.com Interview with: Professor Charles Hennekens MD Dr.P.H Sir Richard Doll Professor Senior Academic Advisor to the Dean Charles E. Schmidt College of Medicine Florida Atlantic University 777 Glades Road Boca Raton, FL 33431 Medical Research: What is the background for this study? What are the main findings? Prof. Hennekens: Randomized evidence indicates clear benefits of mammography in middle age and, at present, most guidelines recommend regular mammography for women up to age 74.  In collaboration with colleagues at Baylor Medical College and Meharry Medical School we were able to link the Surveillance, Epidemiology, and End Results (SEER) data to the Medicare administrative claims data.  We found that, up to 84 years, screening was more common among whites than blacks and women receiving regular annual screening mammography had lower risks of mortality from breast cancer. (more…)
Author Interviews, Beth Israel Deaconess, CT Scanning, JAMA, Neurological Disorders, Stroke / 04.01.2016

MedicalResearch.com Interview with: Sandeep Kumar, MD Assistant Professor of Neurology Harvard Medical School Director, Inpatient Stroke Service Department of Neurology, Stroke Division Beth Israel Deaconess Medical Center Boston, MA 02215 Medical Research: What is the background for this study? What are the main findings? Dr. Kumar: Transient deficits that start suddenly and typically last for a few minutes to a few hours are the hallmark of a transient ischemic attack (TIA) or a minor ischemic stroke. In this single-center observational study, we have reported similar clinical presentation in some patients with intracerebral hemorrhage (ICH) that are difficult to distinguish from cerebral ischemia based only on clinical signs and symptoms. (more…)
Author Interviews, CT Scanning, JAMA, Lung Cancer / 02.01.2016

  MedicalResearch.com Interview with: Jan Marie Eberth, PhD Assistant Professor, Department of Epidemiology and Biostatistics Deputy Director, SC Rural Health Research Center Core Faculty, Statewide Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia, SC 29208 Medical Research: What is the background for this study? Dr. Eberth: With the breakthrough findings of the National Lung Screening Trial released in 2011, professional organizations have largely embraced population-based screening guidelines for patients at high risk for lung cancer. The diffusion of screening into broad clinical practice has been slow to be adopted, given concerns about the efficacy of screening in community settings, lack of insurance reimbursement and unclear billing logistics, and difficulty weighing the pros of screening against the known cons (e.g., high rate of false positives). Medical Research: What are the main findings? Dr. Eberth: Provisions of the Patient Protection and Affordable Care Act mandate that US Preventive Services Task Force-recommended screening tests with an A or B rating receive full insurance coverage by private payers. The Centers for Medicare and Medicaid (CMS) soon thereafter approved full coverage for lung cancer screening in high-risk patients (i.e., those aged 55-77 years, asymptomatic for lung cancer, tobacco smoking history of 30+ pack-years, is a current smoker or has quit smoking within the past 15 years). Coding is rapidly evolving; as of November 2015, CMS released HCPCS codes G0296 (pre-screening counseling visit) and G0297 (screening visit). These codes will be accepted retroactively starting January 4, 2016 to the date of the final coverage determination (back to February 5, 2015). No coinsurance or deductibles shall be charged to the patient for either the pre-screening counseling visit, or the screening visit itself. Quality of screening  is an important, but understudied, area of research. Several publications have focused on aspects of quality programs, and how to achieve quality benchmarks, but data is still being collected to assess variation across programs. In the future, data from screening registries, such as the American College of Radiology Lung Cancer Screening Registry (LCSR), can be leveraged to examine these quality metrics and improve risk-prediction models for lung cancer. (more…)
Author Interviews, CT Scanning, Heart Disease / 24.12.2015

MedicalResearch.com Interview with: Dr. Joan Pinto-Sietsma MD PhD Department of Clinical Epidemiology, Biostatistics and Bioinformatics Academic Medical Center Amsterdam, The Netherlands.  Medical Research: What is the background for this study? What are the main findings? Response: A positive family history for premature coronary artery disease is an important risk factor for coronary artery disease. Therefore, it is frequently proposed to be included in current risk assessment tools and clinical practice guidelines. On the other hand, a positive family history for coronary artery disease only identifies families at risk, whereas it fails to identify which specific individual within a family is at particular risk. Therefore, its applicability in clinical practice is limited. The detection of subclinical atherosclerosis as assessed by assessing coronary artery calcification, with CT scanning, has emerged as prognostic evaluation of coronary artery disease. Prospective follow-up studies have shown that coronary artery calcification predicts cardiovascular events, independent of risk factors. Therefore, assessing coronary artery calcifications in families with premature coronary artery disease might help in determining which individuals within such families are at particular risk and therefore help decide regarding treatment. We analysed the association between a positive family history for premature coronary artery disease and coronary artery calcifications in 704 asymptomatic individuals. Furthermore, we assessed the predictive value of coronary artery calcifications in individuals with a positive family history for premature coronary artery disease in a sub analysis in 834 individuals of the St. Francis Heart Study, in which subjects were followed for about 3.5 years. We observed, that individuals of high risk families (a positive family history of premature coronary artery disease) had a 2 time higher risk to have a calcium score > the 80th percentile as compared to individuals with a negative family history of premature coronary artery disease. Besides, individuals from high risk families with a high calcium score (> the 80th percentile) had a 2 time higher risk to get a cardiovascular event in 3,5 years, whereas individuals of high risk families without coronary calcifications did not have an increased risk at all. (more…)
Author Interviews, JAMA, MRI, Stroke / 22.12.2015

MedicalResearch.com Interview with: Sepideh Amin-Hanjani, MD FAANS FACS FAHA Professor & Program Director Co-Director, Neurovascular Surgery Department of Neurosurgery University of Illinois at Chicago Past Chair, AANS/CNS Cerebrovascular Section  Medical Research: What is the background for this study? What are the main findings? Dr. Amin-Hanjani: Posterior circulation strokes account for up to 30% of all ischemic strokes, and atherosclerotic occlusive disease of the vertebrobasilar (VB) is responsible for approximately one third of these cases. Symptomatic atherosclerotic VB occlusive disease is associated with a high risk of recurrent stroke despite medical therapy, in the range of 10-15% within 2 years. There have been advances in treatment options, particularly endovascular angioplasty and stenting, aimed at reverting the blockage; however these procedures themselves carry risks, and are likely to benefit only selected patients who are at highest risk without intervention. Our study, VERiTAS, aimed to determine if measurement of blood flow in the posterior circulation vessels could identify the high risk patients. Flow measurements were performed using the technique of quantitative magnetic resonance angiography (QMRA) relying on standard MR sequences and  the commercial software NOVA. These flow measurements were used to designate patients presenting with symptomatic vertebrobasilar disease as flow compromised or not, and patients were then followed for a median of 23 months in a blinded fashion to determine the risk of subsequent strokes. We found that among 72 such patients, only one quarter (18 patients) demonstrated flow compromise on QMRA, but that this group had a significantly higher risk of subsequent stroke at one year, 22% vs only 4% in the other group. The hazard ratio for subsequent stroke was markedly elevated at 11.5 even after adjusting for age and other stroke risk factors. (more…)
Author Interviews, JAMA, Mental Health Research, MRI, Neurological Disorders / 12.12.2015

MedicalResearch.com Interview with: Stephane De Brito, PhD Birmingham Fellow School of Psychology Robert Aitken Building, Room 337a University of Birmingham  UK Medical Research: What is the background for this study? What are the main findings? Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date. Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems. (more…)
Author Interviews, Breast Cancer, Lancet, Mammograms, Radiology / 05.12.2015

MedicalResearch.com Interview with: Prof Stephen Duffy BSc MSc CStat Professor Of Cancer Screening Wolfson Institute Of Preventive Medicine Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Prof. Duffy: There is debate on the value of diagnosing and treating ductal carcinoma in situ (DCIS) of the breast, depending mainly on different theories about the risk of progression to invasive breast cancer if DCIS were untreated. No-one asserts that no DCIS is progressive and no-one asserts that all DCIS is progressive. There is, however, a range of opinions on the proportion of progressive disease. We found that those mammography screening units in the UK with higher detection rates of DCIS had lower subsequent rates of invasive cancers in the three years after screening. (more…)
Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, CT Scanning, Gender Differences, Lung Cancer / 04.12.2015

MedicalResearch.com Interview with: Phillip Boiselle, M.D. Staff, Cardiothoracic Imaging Beth Israel Deaconess Medical Center Associate Dean for Academic and Clinical Affairs Professor of Radiology, Harvard Medical School Boston, Mass Medical Research: What is the background for this study? What are the main findings? Dr. Boiselle: Previous studies have shown that women have a greater mortality benefit from lung cancer screening then men, and that this test (CT screening) is more cost-effective for women than men. Our purpose was to determine whether the relative risk of lung cancer for women and men differed depending on the specific type of lung nodule that was discovered at screening. Such differences could potentially help to influence a more personalized approach to patient management in lung cancer screening. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, MRI, Yale / 02.12.2015

MedicalResearch.com Interview with: Shiyi Wang, MD, PhD Assistant Professor of Epidemiology (Chronic Diseases) Yale School of Public Health Medical Research: What is the background for this study? Dr. Wang: As magnetic resonance imaging (MRI) of the breast has become part of medical care, there is increasing concern that this highly sensitive test might identify health problems that otherwise would not have had an impact on the patient – so called “overdiagnosis”. However, even if MRI use leads to overdiagnosis, the main “theoretical” benefit of early detection by MRI is to prevent future advanced diseases, the prognosis of which is deleterious. A systematic literature review found that, compared to mammography and/or ultrasound, MRI had a 4.1% incremental contralateral breast cancer (breast cancer in the opposite breast) detection rate. At this point, the impact of MRI on long-term contralateral breast cancer outcomes remains unclear.  Medical Research: What are the main findings? Dr. Wang: Analyzing the Surveillance, Epidemiology, and End Results-Medicare dataset, we compared two groups of women who had breast cancer (one group receiving an MRI, and the other not) in terms of stage-specific contralateral breast cancer occurrences. We found that after five years, the MRI group had a higher detection rate of cancer in the opposite breast than the non-MRI group (7.2 % vs. 4.0%). Specifically, MRI use approximately doubles the detection rate of early stage contralateral breast cancer, but does not decrease the incidence of advanced stage contralateral breast cancer occurrences after a 5-year follow-up. Our results indicate that nearly half of additional breast cancers detected by the preoperative MRI were overdiagnosed, which means that many of these occult cancers not detected by MRI would not have become clinically evident over the subsequent 5 years. There was no evidence that MRI use was benefiting women because the rate of advanced cancer was similar in the MRI and the non-MRI groups. (more…)
Author Interviews, Breast Cancer, Chemotherapy, MRI / 14.11.2015

MedicalResearch.com Interview with: Dr. Franca Podo, Dr Sci Former Director of the Molecular and Cellular Imaging Unit Department of Cell Biology and Neurosciences Istituto Superiore di Sanità Rome, Italy Medical Research: What is the background for this study? What are the main findings? Dr. Podo: Population-based studies showed that triple negative breast cancers (TNBCs), i.e. those which are negative for estrogen and progesterone receptors without HER-2/neu overexpression, have a more aggressive clinical course and a 2-to-3 fold higher likelihood of distant recurrence and death from breast cancer within 5 years from diagnosis, compared with non-TNBCs. In a study published in Clinical Cancer Research (Online First 26 October 2015) Dr. F. Podo and Dr. F. Santoro (Istituto Superiore di Sanità, Rome) and Prof. F. Sardanelli (Università degli Studi di Milano, IRCCS Policlinico San Donato) in collaboration with other Italian co-authors, compared phenotype features and survival rates of invasive TNBCs versus non-TNBCs detected during the HIBCRIT-1 screening study of 501 asymptomatic women at high genetic-familial risk for breast cancer. The screening included BRCA1 and BRCA2 mutation carriers, as well as women with a strong family history of breast and/or ovarian cancer, enrolled between 2000 and 2008 in 18 centers. Data analysis from a median 9.7-year follow-up until June 2015 showed that, combining an annual screening including magnetic resonance imaging (MRI) with adequate treatment options, the mean 5-year overall survival of triple negative breast cancers was not significantly different from that of non-TNBCs (86% vs 93%), in spite of a 3-fold higher rate of cases of grade 3 invasive ductal carcinoma in the former subgroup (71% in TNBCs vs 23% in non-TNBCs). The mean disease-free survival rates were also very similar (77% vs 76%, respectively). (more…)
Author Interviews, Breast Cancer, JAMA, Mammograms, UC Davis / 21.10.2015

MedicalResearch.com Interview with: Diana L. Miglioretti, PhD Dean's Professor in Biostatistics Department of Public Health Sciences UC Davis School of Medicine Davis, CA  95616 Medical Research: What is the background for this study? What are the main findings? Dr. Miglioretti: Screening mammography intervals remain under debate in the United States. The US Preventive Services Task Force recommends biennial (every other year) screening, whereas other organizations recommend annual screening. To help inform their updated screening guidelines, the American Cancer Society guideline development group requested that the US Breast Cancer Surveillance Consortium conduct a study comparing cancer outcomes among women screened annually vs. biennially. Prior studies conducted by the consortium used wide intervals for defining annual and biennial mammograms. We wanted to evaluate cancer outcomes for women who more closely adhere to screening intervals. Our goal was to determine if women diagnosed with cancer following biennial screening have tumors with less favorable prognostic characteristics compared to women diagnosed after annual screening. We evaluated outcomes separately by age and by menopausal status because evidence suggests that younger women and premenopausal women may have more aggressive tumors and thus may benefit from more frequent screening. We found from this study that premenopausal women diagnosed with invasive breast cancer following biennial versus annual screening mammography were more likely to have tumors with less-favorable prognostic characteristics (e.g., later stage, larger size). For example, women with an invasive breast cancer diagnosed after a biennial screen had a 28% increased risk of a stage IIB or higher tumor, a 21% increased risk of being diagnosed with a tumor >15 mm, and an 11% higher risk of being diagnosed with a tumor with any less-favorable prognostic characteristic compared women diagnosed with breast cancer following an annual mammogram. In contrast, we found postmenopausal women not using hormone therapy and women 50 years of age or older had similar proportions of tumors with less-favorable prognostic characteristics regardless of screening interval. Relative risk estimates were close to one with no significant differences between biennial and annual screeners. Among postmenopausal women using hormone therapy at the time of the mammogram and women age 40-49, results were less clear. Relative risk estimates for biennial versus annual screeners were consistently above one, but were not as large as for premenopausal women and were not statistically significant. (more…)
Author Interviews, Medical Imaging, NYU, Surgical Research / 19.10.2015

MedicalResearch.com Interview with: Nolan S. Karp, MD  Associate Professor, Hansjorg Wyss Department of Plastic Surgery NYU Langone Medical Research: What is the background for Three-dimensional imaging? Dr. Karp: This was really developed for industry in product engineering.  We and others applied this to medicine. Medical Research: What kind of technology is required? Dr. Karp: This is a fancy picture.  We obtain a 3D surface scan of the person or an object, which corresponds to a digital data set. Medical Research: How does Three-dimensional imaging help the physician and patient plan for better surgical outcomes? Dr. Karp: It lets you simulate the surgery.  For the surgeon, we can plan the surgery better.  For the patient, they can see the expected outcome better, before surgery. (more…)
Author Interviews, Autism, Medical Imaging, OBGYNE / 14.10.2015

MedicalResearch.com Interview with: Alex Ure MPsych(Clin) PhD Psychologist & Postdoctoral Fellow, CRE in Newborn Medicine Research Officer, VIBeS Group, Clinical Sciences Murdoch Childrens Research Institute The Royal Children’s Hospital Flemington Road Parkville Victoria 3052 AUS Medical Research: What is the background for this study? What are the main findings? Dr. Ure: Children born very preterm (<30 weeks gestation) are at increased risk of autism spectrum symptoms and disorder (ASD) compared with their term born peers. It has been suggested that this increased prevalence is due to abnormal brain development or injury associated with preterm birth.   But, until now, there has been limited research using neonatal brain imaging, a period of key brain development, and later ASD diagnosis. Our study included 172 children born very preterm who were recruited at birth and underwent structural brain imaging at term equivalent age (40 weeks gestation). We used a standardized diagnostic interview with parents to diagnose children with autism spectrum symptoms and disorder during their 7 year follow up visit. The diagnoses were confirmed via an independent assessment. Our results suggest there are subtle differences in the brain structure of very preterm newborns later diagnosed with autism spectrum symptoms and disorder, compared with very preterm children without autism spectrum symptoms and disorder. Specifically, we found newborns later diagnosed with ASD had more cystic lesions in the cortical white matter and smaller cerebellums. This latter result is consistent with findings from previous research, including studies that have used positive ASD screening tools with very preterm toddlers, and others who have reported reduced cerebellar volumes in older children with ASD. (more…)
Author Interviews, Cancer Research, CT Scanning, JAMA, Melanoma, Radiology, University of Michigan / 25.09.2015

MedicalResearch.com Interview with: Benjamin Y. Scheier, MD Division of Hematology/Oncology Department of Internal Medicine University of Michigan, Ann Arbor Medical Research: What is the background for this study? What are the main findings? Dr. Scheier: Existing data suggests that PET/CT has use in the detection of metastases from multiple primary tumor types. However, PET/CT lacks data supporting its use in staging asymptomatic patients with early-stage melanoma, may inconsistently impact treatment decisions, and carries a false-positive finding risk that may detract from its use. To evaluate an evolving practice, this study aims to assess the use of PET/CT in detecting occult metastases in SLN-positive melanoma prior to resection. In this retrospective evaluation of patients with melanoma and clinically silent regional lymph nodes treated at the University of Michigan, only 7% had PET/CT findings that ultimately identified metastatic melanoma and precluded LND. Of the 46 patients who underwent a preoperative PET/CT, 15 (33%) had intense uptake distant from the primary tumor and local lymph node basin. Nine of those 15 patients (60%) had abnormalities biopsied prior to LND. Three of the 9 biopsies yielded metastatic melanoma, a false-positive rate of 67% for PET/CT in identifying distant metastases in asymptomatic patients. (more…)
Author Interviews, Clots - Coagulation, CT Scanning, Emergency Care, Geriatrics / 24.09.2015

MedicalResearch.com Interview with: Dr Lim Beng Leong MBBS, MRCS (A&E), FAMS Jurong Health Services Emergency Department, Singapore  Medical Research: What is the background for this study? What are the main findings? Dr. Leong: It is common in the emergency department to see patients with warfarin who suffer a minor head injury (HI) with GCS >13. It is standard practice according to international guidelines to perform a plain CT scan of the head. What is contentious in the literature is the subsequent management of those patients with a normal initial CT scan. Practice is heterogeneous and includes a mandatory second CT scan at 24 hours mark or observation and repeat CT scan at the discretion of the attending doctor. We have found in our study that the "observe and repeat CT scan for symptomatic cases" approach only was safe as abnormal second CT scans were rare (1 in 295 cases). We traced the patients' course 2 weeks post discharge and none of the patients were re-admitted for reasons of delayed intra-cranial hemorrhage (ICH). However, the cohort of patients consist largely of geriatric patients with falls. More than 50% of these patients were hospitalized for more than 3 days; the longest of 2-3 weeks. They were likely to have various reasons that required longer hospitalizations apart from observation for delayed ICH, such as assessing for risk, etc. (more…)
AHA Journals, Author Interviews, Blood Clots, Brigham & Women's - Harvard, Medical Imaging / 17.09.2015

Peter Caravan, PhD Co-Director, Institute for Innovation in Imaging (I3) Martinos Center for Biomedical Imaging Massachusetts General Hospital Associate Professor of Radiology Harvard Medical SchoolMedicalResearch.com Interview with: Peter Caravan, PhD Co-Director, Institute for Innovation in Imaging (I3) Martinos Center for Biomedical Imaging Massachusetts General Hospital Associate Professor of Radiology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Caravan: The motivation for this work was to develop a technique that would allow the detection of thrombus (clot) anywhere in the body after injection of a molecular probe called 64Cu-FBP8.  Current techniques for thrombus detection are limited to specific vascular territories.  In instances where the location of the thrombus is unknown or if there is suspicion of multiple thrombi, then multiple imaging tests must be performed.  We sought to develop a test that could be used to find clots anywhere:  brain, thorax, abdomen, legs and in arteries, veins, or the cardiac chambers.  In addition to whole body thrombus detection, we sought a technique that could address some of the limitations with current thrombus imaging techniques.  For example computed tomography (CT), which is used to detect pulmonary emboli, requires a contrast agent that cannot be used in patients with poor kidney function.  Transesophageal echocardiography used to identify thrombus in the chambers of the heart requires that the patient be sedated. Our approach is to use a small peptide that recognizes the protein fibrin, which is a key component of blood clots.  We tagged the peptide with an isotope of copper, Cu-64, that allows the peptide to be detected by positron emission tomography (PET). 64Cu-FBP8 binds specifically to fibrin but not to other proteins in the blood and this means that the uptake in the clot is high while background signal is very low.  We combined PET imaging which finds the clot with CT imaging or magnetic resonance imaging (MRI).  By overlaying the PET image with the CT or MRI image, we could precisely localize the clot within the We were interested to see if the age of the clot impacted our ability to detect it.  We imaged animals with a total of 42 arterial or venous clots and then the images were analyzed by two reviewers who had no prior knowledge of the location of the clot.  Overall the accuracy was 98% for detection. Another key finding was that the uptake of 64Cu-FBP8 strongly correlated with the amount of fibrin in the clot and that younger, fresher clots had more fibrin than older clots.  This could be very useful in distinguishing newer clots which may be the source of cardiovascular events from older, clots that may pose less risk. We also showed using combined PET-MRI that we could detect multiple blood clots in the animal in a single whole body scan.  The procedure involves a single intravenous administration of 64Cu-FBP8 and clots in the deep veins of the legs or in the carotid arteries were readily detected. (more…)
Author Interviews, Education, MRI, Pediatrics / 10.09.2015

Henrik Ullman, MD, PhD Candidate Department of Neuroscience Karolinska Institutet Stockholm, Sweden MedicalResearch.com Interview with: Henrik Ullman, MD, PhD Candidate Department of Neuroscience Karolinska Institutet Stockholm, Sweden Megan Spencer-Smith, PhD School of Psychological Sciences Monash University Melbourne, AustraliaMegan Spencer-Smith, PhD School of Psychological Sciences Monash University Melbourne, Australia     Medical Research: What is the background for this study? What are the main findings? Response: Infants born preterm are at risk for school-age cognitive and academic impairments. While some will suffer severe impairments, many more will experience mild impairments, and it is these children who might not raise sufficient concern for referral and intervention. Identifying early markers and methods for classifying preterm infants at risk for school-age impairments, many years before difficulties emerge, would provide important information for clinicians in advising families regarding intervention and ongoing monitoring. Brain alterations are common in preterm populations. Any brain alterations associated with school-age impairments are likely already present in the neonatal period but are not detected with the current standard clinical and radiological evaluations. In this study we wanted to see how well we could use advanced analysis of volumetric and diffusion MRI collected in the neonatal period from 224 very preterm children to predict cognitive functions at five and seven years of age. We used statistical models to look for localised regions as well as machine learning methods to correlate patterns in the neonatal MRI data that could predict school-age outcomes. We found that localised volumes in the insula and basal ganglia as well as a distributed patterns of diffusion MRI could predict working memory and early mathematical skills even after co-varying for important perinatal clinical factors. It has previously been shown that quantitative and pattern analysis can catch subtle patterns in MRI data not easily detected by eye and may predict cognitive development. The current study builds further on these results showing clinically relevant predictions in preterm children. (more…)
Author Interviews, Medical Imaging, Outcomes & Safety, Pulmonary Disease, Radiology / 29.05.2015

Evgeniya Sokolovskaya, DO, MD Monmouth Medical Center Long Branch, NJ 07740.MedicalResearch.com Interview with: Evgeniya Sokolovskaya, DO, MD Monmouth Medical Center Long Branch, NJ 07740. Medical Research: What is the background for this study? What are the main findings? Dr. Sokolovskaya: As the utilization of diagnostic imaging has continued to increase in recent years, the workload of radiologists has correspondingly risen. Radiologists are under pressure to increase productivity by increasing workload volume. Previous studies have shown that increasing the number of reporting exams per day can affect the accuracy of radiologic interpretations, increase an error rate and degrade radiologists’ performance in the detection of pathology as viewing time per study decreases. The purpose of this pilot study was to determine if faster reporting speed when reading CT imaging studies of the Abdomen and Pelvis, results in higher number of misses and interpretation errors. The results of our study showed that the number of major misses and interpretation errors significantly increased at the faster reporting speed. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, UCSF / 20.05.2015

Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging CenterMedicalResearch.com Interview with: Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging Center MedicalResearch: What is the background for this study? Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database. MedicalResearch: What are the main findings? Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of 1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype), 2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and 3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”). The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials. In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect 1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or 2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander. (more…)
Author Interviews, Cost of Health Care, MRI, Radiology / 18.05.2015

Jalal B. Andre, MDDirector of Neurological MRI Harborview Medical Center Assistant Professor of Radiology University of Washington Seattle, WA 98195-7115MedicalResearch.com Interview with: Jalal B. Andre, MD Director of Neurological MRI Harborview Medical Center Assistant Professor of Radiology University of Washington Seattle, WA  98195-7115 Medical Research: What is the background for this study? What are the main findings? Dr. Andre: Patient motion during clinical magnetic resonance (MR) examinations occurs frequently, can result in artifacts that degrade image quality, and has the potential to mask underlying pathology and affect patient care.  Surprisingly, the frequency of motion artifacts in clinical MR examinations has been poorly documented in the literature, as has been the cost associated with obtaining such exams, specifically those that do not meet diagnostic criteria. To better quantify these observations, we performed a retrospective study evaluating the prevalence of motion artifacts during a randomly selected week of clinical MR examinations. We devised a graded 5-tier scale to quantify patient motion, which incorporated the potential for clinical impact  Using this scale, two neuroradiologists performed a consensus evaluation at a picture archiving and communication system station of 192 MR examinations performed during a single calendar week.  This evaluation revealed that significant motion artifact (defined as artifact that could impact image interpretation and potentially change diagnosis) was present in 7.5% of outpatient and nearly 30% of inpatient and/or emergency department MR examinations, and that repeated sequences (subcomponents of an MR examination) were present in nearly 20% of completed MR examinations.  In addition, we found that the specific imaged body part was less predictive of subsequent patient motion than was patient disposition (if they were imaged as a hospital inpatient and/or emergency department patient).  Using a base-case cost estimate derived from fiscal year 2012 outpatient Medicare reimbursement rates and institutional cost estimates, our analysis suggested that a potential cost of $592 per hour could be lost in hospital revenue secondary to patient motion. Extrapolated over a calendar year, the cost of patient motion (as potential forgone institutional revenue) approached $115,000 per scanner per year. (more…)
Author Interviews, MRI, Neurology, Stroke / 14.05.2015

Amie W. Hsia, MD Medical Director, Comprehensive Stroke Center MedStar Washington Hospital Center NIH Stroke Program at MWHC Associate Professor, Neurology Georgetown University Washington, DC 20010MedicalResearch.com Interview with: Amie W. Hsia, MD Medical Director, Comprehensive Stroke Center MedStar Washington Hospital Center NIH Stroke Program at MWHC Associate Professor, Neurology Georgetown University Washington, DC 20010   Medical Research: What is the background for this study? What are the main findings? Dr. Hsia: Acute stroke is a common presenting problem in the emergency department. We know that “time is brain” and that for patients experiencing an ischemic or “blockage” type of stroke, the most common type, the sooner we can administer tPA, a clot-busting medication and the only FDA-approved medication to treat acute stroke, the better chance for a good outcome. Therefore, there is a goal national benchmark time of administering the drug to appropriate acute stroke patients within 60 minutes of their arrival to the emergency department. There are many steps that are necessary in the evaluation of an acute stroke patient in the emergency department before tPA can be given. This includes a brain scan to make sure a patient is not having the less common bleeding type of stroke. A CT or “CAT” scan is the typical type of brain scan that is performed in emergency departments across the country and the world to screen a patient before giving tPA. The primary purpose of the CT scan is to exclude bleeding; it is difficult to visualize an early stroke on CT. Though an MRI can give more complete information including showing the stroke as it is happening in these first few hours and though most hospitals have an MRI scanner, an MRI takes longer to perform and has not traditionally been used in an emergency setting. At the two hospitals included in this study, MedStar Washington Hospital Center in D.C. and Suburban Hospital in Maryland, we are fortunate to serve as the sites for the NINDS intramural stroke clinical research program and use MRI routinely to screen acute stroke patients to learn more about stroke and develop new treatments for stroke. It is upon this foundation that we performed independent hospital-wide quality improvement initiatives engaging multidisciplinary committees with leadership from all the departments involved in the care of the acute stroke patient in that critical first 60 minutes. Inspired by our colleagues at Washington University in St. Louis led by Dr. Andria Ford who used similar methods in reducing treatment times with CT screening, we used lean manufacturing principles to streamline our processes that include MRI screening and dramatically reduced our treatment times from a baseline of 93 minutes down to 55 minutes while still maintaining safety. Through these efficiency improvements, we were able to achieve a 4-fold increase in the percentage of stroke patients treated with tPA within 60 minutes. (more…)
Author Interviews, CT Scanning, Duke, Heart Disease, NEJM / 02.04.2015

Pamela S. Douglas, M.D. Duke University School of Medicine Duke University Medical Center Durham, NC 27715MedicalResearch.com Interview with: Pamela S. Douglas, M.D. Duke University School of Medicine Duke University Medical Center Durham, NC 27715 Medical Research: What is the background for this study? Dr. Douglas: The primary objective of the PROMISE study was to compare the health outcomes of people who went to the doctor with new symptoms such as shortness of breath and/or chest pain that were suggestive of coronary artery disease and that required additional evaluation. This was an important investigation because no large research trial has ever been conducted to help guide the care of such patients. Instead, the selection of tests for such patients—which constitutes at least 4 million patients in the United States each year—has been largely left up to physician and patient preference rather than proven results. Medical Research: What are the main findings? Dr. Douglas: 10,003 patients from 193 different medical facilities across the US and Canada agreed to be part of the PROMISE study and  were randomized to a functional stress test or an anatomic test Using CT angiography.  The study found that the clinical outcomes of participants with suspected coronary artery disease were excellent overall, and were similar in terms of death and major cardiac conditions regardless of whether patients had a functional stress test or a computed tomographic scan. However, the CT scan may be better at ruling out the need for subsequent tests and procedures in patients who are free of heart disease, and involved a lower radiation exposure relative to a stress nuclear study. We also found, in a separately reported study, that the costs of the two diagnostic strategies were similar. (more…)
Alzheimer's - Dementia, Author Interviews, Johns Hopkins, Medical Imaging / 20.03.2015

Arnold Bakker, Ph.D. Assistant Professor Division of Psychiatric Neuroimaging Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD 21287MedicalResearch.com Interview with: Arnold Bakker, Ph.D. Assistant Professor Division of Psychiatric Neuroimaging Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD 21287 Medical Research: What is the background for this study? What are the main findings? Dr. Bakker: Patients who are at increased risk for developing dementia due to Alzheimer’s disease show hyperactivity in an area of the brain called the hippocampus, which is critically important for memory function. This study investigated the functional significance of this hyperactivity and determined if, similar to animal studies, treatment with low dose levetiracetam would reduce this increased activation and improve memory function in these patients. Results showed that this overactivity is a dysfunctional condition that contributes to the memory impairment such that treatment with very low doses of levetiracetam both reduces this overactivity and improves memory function in these patients. (more…)
AHRQ, Author Interviews, Cost of Health Care, JAMA, Medical Imaging, Pain Research / 17.03.2015

Jeffrey (Jerry) G. Jarvik MD MPH Professor, Radiology, Neurological Surgery and Health Services Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine Director, Comparative Effectiveness, Cost and Outcomes Research Center University of Washington Seattle, WA 98104-2499MedicalResearch.com Interview with: Jeffrey (Jerry) G. Jarvik MD MPH Professor, Radiology, Neurological Surgery and Health Services Adjunct Professor, Pharmacy and Orthopedics & Sports Medicine Director, Comparative Effectiveness, Cost and Outcomes Research Center University of Washington Seattle, WA Medical Research: What is the background for this study? Dr. Jarvik:  When I arrived at the Univ of WA over 20 years ago, my mentor, Rick Deyo, had just finished leading a project that was responsible for developing one of the first set of guidelines for the diagnosis and treatment of acute low back pain. These guidelines, published in a booklet by AHRQ (then called AHCPR), recommended that patients with acute low back pain not undergo imaging for 4-6 weeks unless a red flag was present. One of the exceptions was that patients older than 50 could get imaged immediately, the rationale being that older adults had a higher prevalence of potentially serious conditions such as cancer, infections, etc, that would justify the early imaging. As a practicing neuroradiologist, it was clear that a potential problem with this strategy is that the prevalence of age-related changes, which may or may not be related to back pain, also increases with age. So earlier imaging of older adults would almost certainly reveal findings, and these could easily start a series of unfortunate events leading to potentially poor outcomes and more healthcare resource use. Thus this policy of early imaging of older adults didn’t entirely make sense. About 5 years ago, these guidelines hit home when I developed acute low back pain and since I was over 50 (barely) my doctor recommended that I get an imaging study. Being a knowledgeable patient and having a reasonable doctor, we mutually agreed not to get the study. I improved but that wasn’t the end of it. When we had the chance to apply for one of the CHOICE ARRA awards funded by AHRQ, we made answering this question of early imaging in older adults one of our primary goals. (more…)
Author Interviews, CT Scanning, Heart Disease / 16.03.2015

Prof. David Newby British Heart Foundation Professor of Cardiology University of Edinburgh Director of the Wellcome Trust Clinical Research FacilityMedicalResearch.com Interview with: Prof. David Newby British Heart Foundation Professor of Cardiology University of Edinburgh Director of the Wellcome Trust Clinical Research Facility MedicalResearch: What is the background for this study? What are the main findings? Dr. Newby: The diagnosis of angina (chest pain) due to coronary heart disease can be very challenging and we often get it wrong. We have a wide range of tests that can try and identify patients with angina due to coronary heart disease. However, even with these tests, we fail to identify 1 in 3 patients who go on to have heart attacks. So we need better tests. The study shows that if you add CTCA to a clinic consultation, you clarify the diagnosis in 1 in 4 patients, alter the investigations in 1 in 6 and change the subsequent treatments in 1 in 4. This did appear not only to increase the use of coronary revascularisation but also reduce the risk of subsequent heart attacks by 38-50%. (more…)
Author Interviews, Cost of Health Care, JAMA, Medical Imaging, NYU / 12.03.2015

Danil Makarov, MD Lead Investigator Assistant Professor, Departments of Urology, Population Health and Health Policy Member, Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center, New York, NYMedicalResearch.com Interview with: Danil Makarov, MD Lead Investigator Assistant Professor, Departments of Urology, Population Health and Health Policy Member, Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center, New York, NY Medical Research: What is the background for this study? Dr. Makarov: The background for this study is that regional variation in patterns of care and healthcare spending is widely known.  The drivers of this regional variation, though, are poorly understood.  Certain policy groups like the IOM have suggested that policy efforts be focused on individual providers and patients. Programs such as Choosing Wisely, which encourage a dialogue between physicians and patients, are a great example of such efforts.  However, some of our prior research suggests that regional variation is not random and that there might be are regional-level factors which drive variation. To test out our hypothesis, we wanted to see whether inappropriate imaging for two unrelated cancers was associated at a regional level (it should not be). Medical Research: What are the main findings? Dr. Makarov: We found that, at a regional level, inappropriate breast cancer imaging was associated with inappropriate prostate cancer imaging. (more…)
Author Interviews, Lung Cancer, Medical Imaging / 05.01.2015

Joao R. Inacio, MD Cardiothoracic Radiologist Director Visiting Professor Program Assistant Professor of Radiology, University of Ottawa Medical Imaging, The Ottawa Hospital Ottawa, ONMedicalResearch.com Interview with: Joao R. Inacio, MD Cardiothoracic Radiologist Director Visiting Professor Program Assistant Professor of Radiology, University of Ottawa Medical Imaging, The Ottawa Hospital Ottawa, ON Medical Research: What is the background for this study? What are the main findings? Dr. Inacio: Lung cancer is the most common and most lethal cancer worldwide. Its prognosis remains poor with a 5-year survival rate of 6–18%. Adenocarcinoma has surpassed squamous cell carcinoma as the leading histologic type. The presence of metastases carries the worst prognosis in lung cancer and is the most important in determining staging and management. Hematogenous spread (i.e., carried by blood) is the most common mechanism of intrapulmonary metastasis. Cumulative evidence suggests that intrapulmonary aerogenous spread may exist and is under recognized. Deriving from our clinical experience, we performed a literature review that supports the hypothesis that lung cancer, particularly adenocarcinoma, may spread through the airways. With aerogenous metastases, it has been postulated that cancer cells growing along the alveolar septa at the primary site detach from the basal membrane, spread through the airways and re-attach and grow along alveolar septa away from the primary focus. Radiology-pathology correlation studies, using Chest Computed Tomography (CT), have documented the radiological evolution from focal adenocarcinoma to multifocal airspace disease and demonstrated cytologic and histologic findings supportive of aerogenous spread. (more…)