Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 11.06.2015

Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North CarolinaMedicalResearch.com Interview with: Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer.  The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients. (more…)
Author Interviews, Brigham & Women's - Harvard, General Medicine, Hospital Readmissions / 11.06.2015

Jeffrey C. Schneider, M.D. Medical Director, Trauma, Burn & Orthopedic Program Assistant Professor, Dept. of Physical Medicine and Rehabilitation Harvard Medical School Spaulding Rehabilitation Hospital Boston, MA 02129MedicalResearch.com Interview with: Jeffrey C. Schneider, M.D. Medical Director, Trauma, Burn & Orthopedic Program Assistant Professor, Dept. of Physical Medicine and Rehabilitation Harvard Medical School Spaulding Rehabilitation Hospital Boston, MA 02129 Medical Research: What is the background for this study? What are the main findings? Response: Hospitalizations account for the largest share of healthcare costs in the U.S., comprising nearly one-third of all healthcare expenditures.  In 2011, readmissions within 30 days of hospital discharge represented more than $41 billion in hospital costs.  Financial penalties for excess 30-day hospital readmissions were instituted by the Centers for Medicare and Medicaid Services in 20124; more than 2,200 hospitals were fined a total of $280 million in reduced Medicare payments in fiscal year 2013. Most readmission risk prediction models have targeted specific medical diagnoses and have utilized comorbidities and demographic data as the central risk factors for hospital readmission. Yet, large U.S. administrative datasets have demonstrated poor discriminative ability (c-statistics: 0.55-0.65) in predicting readmissions. However, few studies have considered functional status as potential readmission risk factors. There is increasing evidence that functional status is a good predictor of other health outcomes.  To date, acute care hospital administrative databases do not routinely include functional status measures.  Therefore, inpatient rehabilitation setting is an ideal population in which to examine the impact of functional status on readmission risk, because: (1) inpatient rehabilitation patients often have complex care transitions after acute care discharge, and represent a significant proportion of total readmissions; 2) inpatient rehabilitation facilities routinely document functional status using a valid instrument—the FIM®; and (3) a majority of U.S. IRFs participate in one of the only national datasets that contain standardized functional data—the Uniform Data System for Medical Rehabilitation. Limitations of prior work include small and single-center study designs, narrowly defined patient populations, and defining readmissions beyond the 30-day period.  Overall, there is a lack of literature on the utility of function as a readmission predictor in a large population of medical patients. Moreover, function is a modifiable risk factor with potential to impact readmission outcomes if function-based interventions are instituted early. Therefore, the objective of this study was to compare functional status with medical comorbidities as predictors of acute care readmissions in the medically complex rehabilitation population. We hypothesized that acute care readmission prediction models based on functional status would outperform models based on comorbidities,and that the addition of comorbidity variables to function-based models would not significantly enhance predictive performance. (more…)
Author Interviews, Cost of Health Care, Kaiser Permanente, Long Term Care, Medicare / 11.06.2015

Yan S. Kim, MD PhD Delivery Science Fellow Division of Research Kaiser Permanente Northern California Oakland, CA 94612MedicalResearch.com Interview with: Yan S. Kim, MD PhD Delivery Science Fellow Division of Research Kaiser Permanente Northern California Oakland, CA 94612 Medical Research: What is the background for this study? What are the main findings? Dr. Kim: Long-term care hospitals first emerged in the 1980s as an alternative to lengthy acute-care hospital stays for patients with complex medical problems who need prolonged hospital-level care.  In 2002, Medicare changed its payment method for these facilities from cost-based to a lump sum per admission based on the diagnosis.  Under this system, which is still in place, Medicare pays these hospitals a higher rate for patients who stay a minimum number of days based on the patient's condition.  Shorter stays are paid much less and longer stays do not necessary generate higher reimbursements. Using Medicare data, we analyzed a national sample of patients who required prolonged mechanical ventilation – the most common, and among the most costly, conditions for patients in long-term care hospitals – to examine whether this payment policy has created incentives to base discharge decisions on payments.  We found that in the years after the policy’s implementation there was a substantial spike in the percentage of discharges on and immediately after the minimum-stay threshold was met, while very few patients were discharged before the threshold. By contrast, prior to 2002, discharges were evenly distributed around the day that later became the short-stay threshold.  These findings confirm that the current payment policy has created unintended incentives for long-term care hospitals to base the timing of patient discharges on payments and highlight how responsive these hospitals are to payment incentives. (more…)
Author Interviews, Biomarkers, Lung Cancer, Wistar / 11.06.2015

MedicalResearch.com Interview with: Qihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar InstituteQihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar Institute Medical Research: What is the background for this study? What are the main findings? Dr. Huang: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and results in more deaths globally than breast, prostate and colon cancers combined. While the five year survival rate for early stage non-small cell lung cancer (NSCLC) is above 50%, it is less than 5% in patients with metastatic disease.  Clearly, early detection can save lives, but accurate screening tests for high-risk individuals are still lacking. Although low dose computed tomography (LDCT) has been successfully used for screening in high-risk populations, multiple negative factors are associated with recurrent LDCT screening, including false-positives and false-negatives, unnecessary invasive procedures, radiation exposure, global availability of the technology and cost. Although several non-invasive tests for lung cancer using body fluids such as blood, urine or sputum are under investigation, none are currently available. When low dose computed tomography is used for screening, patients who are 50 years old or older are frequently diagnosed with pulmonary nodules.  However, only a small fraction of the nodules detected are subsequently diagnosed as lung cancer.  In cases where it is difficult to differentiate malignant from benign nodules, it is recommended that patients with these indeterminate nodules be followed with serial LDCT, which increases radiation exposure and financial cost. A simple, inexpensive blood test that differentiates malignant from benign nodules would fill an important clinical need. In this study, we validated AKAP4 as a highly accurate biomarker in a cohort of 264 blood samples from patients with known non-small cell lung cance and 135 controls samples from two different sites including a subset of controls with high risk lung nodules.   When all 264 lung cancers were compared with all 135 controls, the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC is 0.9795, and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules – a comparison of significant clinical importance – the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage but independently of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer, lung cancer recurrence, and distinguishing malignant from benign lung nodules. (more…)
Author Interviews, Heart Disease, Karolinski Institute, NEJM, Technology / 11.06.2015

Jacob Hollenberg M.D., Ph.D. Assistant Professor, Cardiologist Head of Research, Centre for Resuscitation Science Karolinska Institutet, Stockholm, SwedenMedicalResearch.com Interview with: Jacob Hollenberg M.D., Ph.D. Assistant Professor, Cardiologist Head of Research, Centre for Resuscitation Science Karolinska Institutet, Stockholm, Sweden Editor’s note: Dr. Hollenberg and colleagues published two articles in the NEJM this week discussing CPR performed by bystanders in out-of-hospital cardiac arrests. MedicalResearch: What is the background for the first study? Dr. Hollenberg: There are 10,000 cases of cardiac arrest annually in Sweden. Cardiopulmonary Resuscitation (CPR) has been taught to almost a third of Sweden’s population of 9.7 million. In recent years the value of bystander CPR has been debated, largely due to a lack of a randomized trial demonstrating that bystander CPR is lifesaving. In this study, which included all cases of emergency medical services (EMS) treated and bystander-witnessed out-of-hospital cardiac arrests recorded in the Swedish Cardiac Arrest Registry from January 1, 1990, through December 31, 2011, our primary aim was to assess whether CPR initiated before the arrival of EMS was associated with an increase in the 30-day survival rate. MedicalResearch: What were the main findings? Dr. Hollenberg: Early CPR prior to arrival of an ambulance more than doubled the chance of survival. (30-day survival rate was 10.5% among patients who underwent CPR before EMS arrival, as compared with 4.0% among those who did not (P<0.001).) This association held up in all subgroups regardless of sex, age, cause of cardiac arrest, place of arrest, EKG findings or time period (year analyzed). MedicalResearch: How did the patients who survived cardiac arrest do from a disability standpoint? Dr. Hollenberg: We had cerebral performance scores from 474 patients who survived for 30 days after cardiac arrest. (higher scores indicate greater disability). At the time of discharge from the hospital, 81% of these patients had a score of category of 1. Less than 2% had category scores of 4 or 5. MedicalResearch: What should patients and providers take away from this report? Dr. Hollenberg:
  • For patients with an out-of-hospital cardiac arrest, CPR performed by bystanders before the arrival of emergency medical personnel, saves lives. This has been validated by both the size of this study and the consistency of the results over three decades.
  • CPR education needs to continue and to increase. In Sweden about one-third of the population has been taught CPR.       Legislation has recently been passed that mandates CPR be taught to all teenagers in school which should allow an entire generation to become familiar with this lifesaving technique.
  • The willingness of the public to become involved also needs to increase. We need new ways of educating lay people to recognize cardiac arrest and to motivate them to perform it. The knowledge that bystander CPR saves lives may enhance that motivation.
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Author Interviews, Heart Disease, JACC, Yale / 10.06.2015

James V. Freeman MD, MPH, MS Yale University School of Medicine New Haven, CTMedicalResearch.com Interview with: James V. Freeman MD, MPH, MS Yale University School of Medicine New Haven, CT Medical Research: What is the background for this study? What are the main findings? Dr. Freeman: Atrial fibrillation (AF) substantially increases the risk of major adverse clinical outcomes such as stroke and death, but it can also cause frequent symptoms, affect patient’s functional status, and impair their quality of life. While prior studies have reported the range of AF-related symptoms in patient populations, these studies were generally from highly selected patients and referral based practices, and may not reflect results in community practice or results with contemporary AF management. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a large, contemporary, prospective, community-based outpatient cohort, we evaluated the type and frequency of symptoms in patients with Atrial fibrillation. In addition, we measured the degree to which physician assessed symptom severity (using the European Heart Rhythm Association [EHRA] classification system) was correlated with patient reported quality of life (assessed by the Atrial Fibrillation Effect on QualiTy-of-life [AFEQT] questionnaire). Finally, we association between symptoms or quality of life with clinical outcomes, including death, hospitalization, stroke and major bleeding. In our community-based study, the majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3-4). EHRA symptom class was well correlated with the AFEQT quality of life score (Spearman correlation coefficient -0.39). Over 1.8 years of follow-up, Atrial fibrillation symptoms were associated with a higher risk of hospitalization (adjusted HR for EHRA ≥2 vs EHRA 1 1.23, 95% CI 1.15-1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted HR for lowest quartile of AFEQT vs highest 1.49, 95% CI 1.2-1.84), but not other major adverse events including death. (more…)
Author Interviews, Blood Pressure - Hypertension, JAMA, Surgical Research, UCSF / 10.06.2015

MedicalResearch.com Interview with: Susan Ming Lee, MD, FRCPC, MAS (Clinical Research) Clinical Instructor, Dept. of Anesthesia and Perioperative Care University of California, San Francisco Medical Research: What are the main findings? Dr. Lee: Angiotensin receptor blockers (often referred to as ARBs) are common medications used to treat high blood pressure, heart disease, and kidney disease.  Doctors sometimes stop these medications briefly around the time of surgery, since they are known to cause low blood pressure under general anesthesia.  Doctors may hesitate to restart ARBs after surgery because they are worried about low blood pressure or kidney function.  Prior to our research, there was little information to guide the optimal timing of restarting ARBs after surgery. Medical Research: What are the main findings? Dr. Lee: Our study of over 30,000 veterans shows that nearly one third of veterans admitted to hospital for non-cardiac surgery are not restarted on their usual ARBs within two days of their operation.  This delay in resuming ARBs is associated with increased death rates in the first month after surgery.  In fact, even accounting for factors that might contribute to why doctors would withhold ARB (such as low blood pressure, kidney dysfunction, or other comorbidities), 30-day postoperative mortality was increased approximately 50% in those without resumption of ARBs, and this effect was even greater in younger patients under age 60.  Our findings of reduced rates of infections, pneumonia, heart failure, and kidney failure in those that resumed ARBs soon after surgery suggest that early resumption may also reduce complications after surgery. (more…)
Author Interviews, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, MarylandMedicalResearch.com Interview with: Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, University of Michigan / 06.06.2015

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of MichiganMedicalResearch.com Interview with: Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Michigan Medical Research: What is the background for this study? Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes. Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma. Medical Research: What are the main findings? Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes. In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases. (more…)
AHA Journals, Author Interviews, Compliance, Duke, Heart Disease / 06.06.2015

Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NCMedicalResearch.com Interview with: Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NC Medical Research: What is the background for this study? What are the main findings? Dr. Mathews: Though treatment for patients with an acute myocardial infarction with evidence based therapies has increased significantly over the years, adherence to these therapies after discharge remain sub optimal. We used a validated instrument, the Morisky scale, to assess patient medication adherence.  We found that in a contemporary population of 7,425 patients across 216 hospitals, about 30% of patients were not adherent to prescribed cardiovascular medications as early as 6 weeks after discharge. Patients with low adherence were more likely to report financial hardship as well as have signs of depression. In addition, we found that patients who had follow up arranged prior to discharge and those that received explanations from the provider on the specific medications, were more often adherent to therapies. There was a non significant increase in risk of death or readmission at 2 months (HR [95% CI]: 1.35 [0.98-1.87]) among low adherence patients. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA, Johns Hopkins / 05.06.2015

MedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John HopkinsMedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John Hopkins Medical Research: What is the background for this study? Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status  recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies. We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies. Medical Research: What are the main findings? Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort. (more…)
Author Interviews, HIV, Sexual Health, UCSD / 05.06.2015

MedicalResearch.com Interview with: Dr. Martin Hoenigl Center for AIDS Research University of California, San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP). By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu. (more…)
Author Interviews, Fertility, Genetic Research, NEJM, University of Pittsburgh / 04.06.2015

Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213MedicalResearch.com Interview with: Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213 Medical Research: What is the background for this study? What are the main findings? Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem. We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies. (more…)
Annals Internal Medicine, Author Interviews, Beth Israel Deaconess, Hospital Readmissions / 04.06.2015

MedicalResearch.com Interview with: Kelly L. Graham, MD, MPH Instructor in Medicine Harvard Medical School Division of General Medicine and Primary Care Beth Israel Deaconess Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Graham: 30-day readmissions have become a standard quality metric used to represent inpatient quality of care and unnecessary healthcare utilization.  Effective 10/1/2009, hospitals with excess 30-day readmissions have been faced with financial penalties.  Experts have questioned the validity of this metric, and have raised concerns about the potential unintended consequence of creating health disparities, as critical access hospitals caring for the most socioeconomically burdened patients have faced the highest penalties. We were interested to see if factors associated with readmissions in the early part of the 30 day window (0-7 days post-discharge) differed from those associated with the later window (8-30 days post-discharge), ultimately attempting to better understand the "pathophysiology" of a readmission. Our findings suggest that early readmissions are associated with many factors, including those related to the index admission (acute illness burden and suboptimal discharge timing), and factors that are not related to the index hospitalization, such as chronic illness burden and social determinants of health.  In contrast, late readmissions were only associated with chronic illness burden and social determinants of health. (more…)
Author Interviews, Hepatitis - Liver Disease, NIH / 03.06.2015

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology University of Maryland, Baltimore Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels were clinically useful as on-therapy markers of treatment outcome. However, the standard-of-care for HCV treatment has recently evolved from interferon-based regimens to short-duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-making. We found that Hepatitis C viral loads on treatment and at end of treatment were not predictive of treatment success versus relapse with DAA therapy. Contrary to our experience with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment did not preclude treatment success. (more…)
Author Interviews, Cancer Research, JAMA, NYU, Surgical Research / 03.06.2015

Wiliam C. Huang, MD FACSAssociate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer InstituteMedicalResearch.com Interview with: Wiliam C. Huang, MD FACS Associate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved.  Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option. We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium.  We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians. (more…)
Author Interviews, Heart Disease, NIH, Radiology / 03.06.2015

David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator, NLBI, NIDDKMedicalResearch.com Interview with: David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator,  NLBI, NIDDK Medical Research: What is the background for this study? What are the main findings? Dr. Bluemke: Most knowledge about the extent of coronary disease is from high risk patients who have coronary angiograms. Yet most individuals are symptomatic and have lower cardiovascular risk, and would not undergo a coronary angiogram. Coronary CT angiography can be used to evaluate the extent of plaque in low or moderate risk individuals. The most concerning type of plaque is "soft plaque", which can increase or rupture over time. Using coronary CT, all coronary plaque throughout the entire heart was measured. Importantly, the amount of soft plaque was uniquely associated with risk factors such as LDL, diabetes, and hypertension. (more…)
Author Interviews, JAMA, Kaiser Permanente, Pain Research / 03.06.2015

Harley Goldberg, DO Physical Medicine and Rehabilitation Kaiser PermanenteMedicalResearch.com Interview with: Harley Goldberg, DO Physical Medicine and Rehabilitation Kaiser Permanente Medical Research: What is the background for this study? What are the main findings? Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with a herniated lumbar disk. Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common source of pain and disability for many adults. It is thought that inflammation from a disk herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory, such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has shown that lumbar diskectomy does not affect the one year outcome for most patients, and epidural steroid injections do not have strong support by clinical trials. If the use of epidural steroids injections is based on application of steroid anti-inflammatory to the affected nerve root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many physicians and have been included in some clinical guidelines, no large-scale clinical trials of oral steroids for sciatica have been conducted before. Our study found that among patients with acute radiculopathy associated with a herniated lumbar disk, a short course of oral steroids resulted in only modest improvement in function and no significant improvement in pain. (more…)
Author Interviews, Cost of Health Care, University of Pittsburgh / 03.06.2015

Julie M. Donohue, Ph.D. Associate professor and Vice Chair for Research Graduate School of Public Health Department of Health Policy and Management University of PittsburghMedicalResearch.com Interview with: Julie M. Donohue, Ph.D. Associate professor and Vice Chair for Research Graduate School of Public Health Department of Health Policy and Management University of Pittsburgh Medical Research: What is the background for this study? What are the main findings? Dr. Donohue: We looked at data on medication use from January through September 2014 on 1 million Affordable Care Act-established marketplace insurance plan enrollees. Our analysis found that among people who enrolled in individual marketplaces, those who enrolled earlier were older and used more medication than later enrollees. Marketplace enrollees, as a whole, had lower average drug spending per person and were less likely to use most medication classes than patients enrolled in employer-sponsored health insurance. However, marketplace enrollees were much more likely to use medicines for hepatitis C and for HIV, which is particularly important given the general concerns about the rising costs of these medications for consumers. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Transplantation / 03.06.2015

Paula Chatterjee, MD, MPH Department of Medicine, Brigham and Women’s Hospital Harvard Medical School Boston, MassachusettsMedicalResearch.com Interview with: Paula Chatterjee, MD, MPH Department of Medicine, Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Chatterjee: Thousands of patients die every year due to organ shortages. Finding ways to address this public health issue is critical. States have designed a variety of strategies to promote organ donation and transplantation, however we don’t know if any of these strategies have been successful. The goal of our study was to try to figure out which strategies have been most successful in terms of increasing organ donation and transplantation. We found that states have implemented a wide and creative set of strategies, but unfortunately, it seems that these strategies have had almost no effect on increasing organ donation and transplantation. In states that adopted these strategies compared to those that did not, the rates of donation and transplantation increased at nearly the same rate over the past two decades. The only strategy that seemed to have a small effect was when states created revenue pools dedicated toward organ donation activities. (more…)
Author Interviews, Diabetes, Diabetologia, Imperial College, Nutrition / 02.06.2015

Dagfinn Aune, PhD student Norwegian University of Science and Technology and Imperial College LondonMedicalResearch.com Interview with: Dagfinn Aune, PhD student Norwegian University of Science and Technology and Imperial College London Medical Research: What is the background for this study? What are the main findings? Response: There are more than 360 million people worldwide that are affected by diabetes, and this number is projected to increase to more than 550 million by 2030, with serious consequences for the health and economy of both developed and developing countries. While previous research has found an association between increased dietary fibre intake and a reduced risk of developing type 2 diabetes, most of these data come from the United States, and amounts and sources of fiber intake differ substantially between countries. In this article the we evaluated the associations between total fiber as well as fiber from cereal, fruit, and vegetable sources, and new-onset type 2 diabetes in a large European cohort across eight countries, in the EPIC-InterAct Study (and included 12403 type 2 diabetes cases and 16835 sub-cohort members). We also conducted a meta-analysis where we combined the data from this study with those from 18 other independent studies from across the globe. We found that participants with the highest total fiber intake (more than 26 g/day) had an 18% lower risk of developing diabetes compared to those with the lowest total fiber intake (less than 19g/day), after adjusting for the effect of other lifestyle and dietary factors. When the results were adjusted for body mass index (BMI) as a marker of obesity, higher total fiber intake was found to be no longer associated with a lower risk of developing diabetes, suggesting that the beneficial association with fiber intake may be mediated at least in part by BMI. In other words, dietary fiber may help people maintain a healthy weight, which in turn reduces the chances of developing type 2 diabetes. In a meta-analysis of the EPIC-InterAct study and 18 other independent studies (>41000 type 2 diabetes cases) we found that the risk was reduced by 9% for each 10 g/day increase in total fiber intake and 25% for each 10 g/day increase in cereal fiber intake. There was no statistically significant association between fruit or vegetable fiber intake and diabetes. (more…)
ASCO, Author Interviews, Breast Cancer, Cancer Research, NEJM, Surgical Research, Yale / 31.05.2015

Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACSAssociate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT 06510MedicalResearch.com Interview with: Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven, Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT, Medical Research: What is the background for this study? What are the main findings? Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer -- the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease.  The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind.  No one likes to go back to the operating room -- so we asked the question, "How can we do better?".  Surgeons have debated various means of obtaining clear margins.  Some have advocated taking routine cavity shave margins -- a little bit more tissue all the way around the cavity after the tumor is removed at the first operation.  Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) -- i.e., selective margins.  We conducted a randomized controlled trial to answer this question.  We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit.  After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would ("NO SHAVE"), or take a bit more tissue all the way around the cavity ("SHAVE"). Patients in both groups were evenly matched in terms of baseline characteristics.  The key finding was that patients who were randomized to the "SHAVE" group half as likely to have positive final margins and require a re-operation than patients in the "NO SHAVE" group.  On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results.  While the volume of tissue excised in the "SHAVE" group was higher than in the "NO SHAVE" group, the distribution of patient-perceived cosmetic outcomes were identical in both groups.  Complication rate was also no different between the two groups.  We will be following patients for five years for long-term cosmetic and recurrence outcomes. (more…)
Author Interviews, Heart Disease, JACC, NIH, Race/Ethnic Diversity / 31.05.2015

Dr. Samson Y. Gebreab, Ph.D., M.Sc. Lead Study Author and Research Scientist National Human Genome Research Institute Bethesda, MarylandMedicalResearch.com Interview with: Dr. Samson Y. Gebreab, Ph.D., M.Sc. Lead Study Author and Research Scientist National Human Genome Research Institute Bethesda, Maryland Medical Research: What is the background for this study? Dr. Gebreab: It is well known that African Americans hold a commanding lead in cardiovascular disease (CVD) mortality and morbidity compared to whites and other ethnic groups.  Furthermore, the risk for developing CVD begins early in life and extends over a lifecourse.  Previous studies have indicated the influence of both childhood and adult socioeconomic status (SES) on CVD risk. However, the impact of lifecourse socioeconomic status (both childhood and adulthood) on CVD risk in African American population is not fully understood.  The purpose of our study was to investigate the associations of different measures of lifecourse socioeconomic status with cardiovascular disease risk in African Americans and whether the associations were modified by sex and/ or age after controlling for known cardiovascular disease risk factors.  We analyzed 10-year follow-up data of African American adults who were participating in Jackson Heart Study, Jackson, MS. Medical Research: What are the main findings? Dr. Gebreab: Our findings highlights that among those of lower socioeconomic status,  women and younger (<=50 years old)  African Americans are at increased risk of CVD, including heart disease and stroke compared to their counterparts of higher socioeconomic status groups.          African American women in the lowest socioeconomic status, had more than twice the risk of developing cardiovascular disease than those in the highest socioeconomic status group.          African Americans of 50 years and younger in the lowest socioeconomic status group had more than three times higher risk of experiencing a cardiovascular disease event than those in the highest socioeconomic status group. (more…)
ASCO, Author Interviews, Journal Clinical Oncology, Mayo Clinic / 31.05.2015

Ruben A. Mesa, MD, FACP Consultant Hematologist Chair, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center Scottsdale, AZMedicalResearch.com Interview with: Ruben A. Mesa, MD, FACP Consultant Hematologist Chair, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center Scottsdale, AZ Medical Research: What is the background for this study? What are the main findings? Dr. Mesa: Myelofibrosis is a rare and chronic blood cancer associated with significantly reduced quality of life and shortened survival. In patients with this disease, spleen enlargement (splenomegaly) is a very common and debilitating symptom – and as the disease progresses, the body slows production of important blood cells. The results presented at ASCO were from the PERSIST-1 study, which is a Phase 3 registration-directed trial designed to compare pacritinib — an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3 – to best available therapy (exclusive of a JAK inhibitor) in patients with myelofibrosis — regardless of their platelet counts.  Data from this study showed that compared to best available therapy, pacritinib resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms, regardless of platelet levels at the time of enrollment. (more…)
Author Interviews, Kaiser Permanente, Thromboembolism / 29.05.2015

MedicalResearch.com Interview with: Nathan Clark, PharmD Clinical pharmacy supervisor, anticoagulation and anemia management services and Thomas Delate, PhD Clinical research scientist Kaiser Permanente Colorado MedicalResearch: What is the background for this study? What are the main findings? Response: Patients with a history of blood clots are commonly prescribed warfarin, an anticoagulant, to decrease the body’s ability to form additional clots. Clinicians typically stop the use of warfarin in patients to reduce the risk of serious bleeding when invasive procedures, such as colonoscopy or orthopedic surgery are scheduled. However, when warfarin interruptions occur, patients are exposed to an increased risk of blood clots three to five days before and five or more days after invasive procedures. Bridge therapy with another, faster acting anticoagulant is often initiated in an attempt to reduce the patients’ risk for developing blood clots during that gap. Bridging has been a part of standard therapy for venous thromboembolism (VTE) patients undergoing invasive procedures for many years. But only limited data outlining the rates of bleeding and VTE recurrence were available to help clinicians analyze the risks and benefits of bridge therapy. We examined the electronic medical records of 1,178 patients with VTE who underwent 1,812 invasive diagnostic or surgical procedures between January 2006 and March 2012 that required the interruption of warfarin therapy. Study patients were categorized into three groups based on their annual risk of VTE recurrence without anticoagulant therapy. Within those groups, a total of 555 patients – 28.7 percent of low-risk, 33.6 percent of moderate-risk and 63.2 percent of high-risk patients – received bridging anticoagulant therapy. The 1,257 patients who did not receive bridge therapy interrupted their warfarin use and received no other anticoagulants during the perioperative period. The use of bridge therapy resulted in a 17-fold higher risk of bleeding without a significant difference in the rate of blood clot formation compared to patients who didn’t receive bridge therapy. In addition, there were no significant differences in the rates of blood clot occurrence or death between the bridged and non-bridged patient groups. (more…)
Author Interviews, Dermatology, Infections, NYU / 29.05.2015

Dr. Marie C. Leger, MD, PhD Assistant Professor Ronald O. Perelman Department of Dermatology NYU Langone Medical CenterMedicalResearch.com Interview with: Dr. Marie C. Leger, MD, PhD Assistant Professor Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What inspired this study? How did it come about? Dr. Leger: As a dermatologist at NYU, I have taken care of several patients with tattoo reactions--some of them mild (like longstanding itching for example) and some of them more severe (like long term reactions to a particular color that can severely disfigure the tattoo) and wondered how common it was for people to have adverse tattoo reactions or complications. There were lots of case reports in the literature but only a few larger studies examining how common these kinds of complaints were--and these were all European studies. We decided to do a quick survey to give us a better idea of how common it is for people to have problems with their tattoos. Medical Research: What do you think is the most important takeaway from this study for the consumer? Dr. Leger: Tattoos have risks associated with them--which is part of their appeal I'm sure--but I do think it's important for people to know that long term tattoo reactions (including for example, itching, scaling, swelling) may be more common than we realize.  A recent Danish study shows that these kinds of reactions can be quite distressing for people and significantly impact their quality of life. (more…)
Author Interviews, Baylor College of Medicine Houston, Cancer Research, Colon Cancer, Gender Differences / 29.05.2015

Dr. Aaron P. Thrift PhD Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle, WA.MedicalResearch.com Interview with: Aaron P. Thrift, Ph.D. Assistant Professor, Department of Medicine Dan L. Duncan Cancer Center Baylor College of Medicine Houston, TX 77030-3498 Medical Research: What is the background for this study? What are the main findings? Dr. Thrift: Greater attained adult height is associated with increased risk of all cancers combined; however, the association may differ by cancer site and between women and men. For colorectal cancer, epidemiological studies suggest that the association with height may be stronger for women than for men. We used data from over 10,000 patients with colorectal cancer and over 10,000 population-based controls and conducted multiple analyses, including using Mendelian randomization (which incorporates genomic data with traditional approaches) to overcome potential issues of confounding and bias in observational studies, to further examine the association between height and risk of colorectal cancer. Overall, we found that taller height was associated with increased risk of colorectal cancer (8% increased risk per 10cm increase in height). When we examined women and men separately, our results strongly suggest that height is causally associated with colorectal cancer risk for women, whereas there was weaker evidence for a causal association between height and colorectal cancer risk for men. (more…)
Author Interviews, Diabetes, Johns Hopkins, Macular Degeneration, Ophthalmology, PNAS / 29.05.2015

MedicalResearch.com Interview with: Akrit Sodhi, M.D., Ph.D. Assistant Professor of Ophthalmology Retina Division Wilmer Eye Institute Johns Hopkins Medical Institutions Medical Research: What is the background for this study? What are the main findings? Dr. Sodhi: Diabetic eye disease is the most common cause of severe vision loss in the working age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In proliferative diabetic retinopathy, retinal ischemia leads to the upregulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization, in some, but not all diabetic patients, implicating additional factor(s) in proliferative diabetic retinopathy pathogenesis. In our study, we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identified angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is upregulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from proliferative diabetic retinopathy patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of proliferative diabetic retinopathy and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease. (more…)
ALS, Author Interviews, Mayo Clinic, Science / 28.05.2015

Dr. Leonard Petrucelli Ph.D Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with: Dr. Leonard Petrucelli Ph.D Mayo Clinic Jacksonville, FL 32224 MedicalResearch: What is the background for this study? Dr. Petrucelli: According to the ALS Association, more than 30,000 Americans live with amyotrophic lateral sclerosis (ALS), a condition that destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing. After Alzheimer’s disease, frontotemporal dementia (FTD) is the most common form of early onset dementia. It is characterized by changes in personality, behavior, and language due to loss of neurons in the brain’s frontal lobe. Once considered rare, frontotemporal dementia is now thought to account for up to 10 to 15 percent of all dementia cases, according to the Alzheimer’s Association. In 2011, Mayo investigator Rosa Rademakers, Ph.D., identified the most common genetic mutation known to cause ALS and FTD, namely a repeat expansion in the gene C9ORF72. The C9ORF72 repeat expansion leads to the generation of toxic RNA species that form abnormal foci, as well as inclusions of c9RAN proteins in affected cells in the central nervous system. Prior to this research study lead by Leonard Petrucelli, Chair of the Department of Neuroscience at the Mayo Clinic Florida, no animal model existed that fully recapitulated the known clinicopathological features of what is now collectively referred to as c9FTD/ALS. Without such an animal it has remained difficult to identify important mechanisms by which the repeat expansion leads to neurodegeneration and putative therapeutic targets that may mitigate disease in patients where currently there are no curative treatments. (more…)