AHA Journals, Author Interviews, Depression, Duke, Heart Disease, Race/Ethnic Diversity / 24.04.2015

Dr. Robert J. Mentz MD Assistant Professor of Medicine Director, Duke University Cooperative Cardiovascular Society Advanced Heart Failure and Cardiac Transplantation Duke University Medical Center Duke Clinical Research InstituteMedicalResearch.com Interview with: Dr. Robert J. Mentz MD Assistant Professor of Medicine Director, Duke University Cooperative Cardiovascular Society Advanced Heart Failure and Cardiac Transplantation Duke University Medical Center Duke Clinical Research Institute Medical Research: What is the background for this study? What are the main findings? Dr. Mentz: Previous studies have shown that depression is associated with worse outcomes in heart failure patients; however, most of these prior studies were conducted in primarily white patient populations. The impact of depressive symptoms on outcomes specifically in blacks with heart failure has not been well studied. We used data from the HF-ACTION trial of exercise training in heart failure patients, which collected data on depressive symptoms via the Beck Depression Inventory (BDI-II), to assess the association between depressive symptoms and outcomes in black patients as compared with white patients. We found that in blacks with heart failure, baseline symptoms of depression and worsening of symptoms over time were both associated with increased all-cause mortality/hospitalization. (more…)
Author Interviews, Dermatology, Genetic Research, Melanoma / 23.04.2015

Pedram Gerami, M.D.Associate Professor of Dermatology Director, Melanoma Research Northwestern Skin Cancer Institute Northwestern UniversityMedicalResearch.com Interview with: Pedram Gerami, M.D. Associate Professor of Dermatology Director, Melanoma Research Northwestern Skin Cancer Institute Northwestern University MedicalResearch: What is the basis and background for performing this study? Dr. Gerami: Most of the existing literature shows that Sentinel Lymph Node Biopsy (SLNB) will identify 25 to 35 percent of patients who will ultimately die of metastatic melanoma. Hence while SLNB is reported to be the strongest predictor of outcome for melanoma, the vast majority of patients who ultimately die of metastatic melanoma have a negative Sentinel Lymph Node Biopsy result. Hence in this study we aimed to determine whether a GEP assay developed by Castle bioscience could be used independently or in conjunction with SLNB to better detect those patients who are at high risk for developing metastatic disease and dying from melanoma. MedicalResearch: What are the findings of the study? Dr. Gerami: Our study, which examined the use of a Gene Expression Profile (GEP) assay developed by Castle Biosciences and Sentinel Lymph Node Biopsy alone and in combination in a multi-center cohort of 217 patients, demonstrated that the use of the GEP identified more than 80 percent of patients who develop melanoma Combining the two methods showed that patients predicted to be high risk based on the GEP test alone had similar rates of disease progression whether they were SLNB positive or negative. Patients who were SLNB negative and predicted to be low risk using the GEP test had lower rates of disease progression than the SLNB negative group as a whole. (more…)
AACR, Author Interviews, Cancer Research, NIH, Vaccine Studies / 22.04.2015

Daniel C. Beachler, PhD, Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) MedicalResearch.com Interview with: Daniel C. Beachler, PhD Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) Medical Research: What is the background for this study? What are the main findings? Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV. This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination. We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV. (more…)
Author Interviews, CDC, Cost of Health Care, Heart Disease, JACC, Stroke / 22.04.2015

Guijing Wang, PhD Senior health economist Division for Heart Disease and Stroke Prevention Centers for Disease Control and PreventionMedicalResearch.com Interview with: Guijing Wang, PhD Senior health economist Division for Heart Disease and Stroke Prevention Centers for Disease Control and Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Our study is one of the first to analyze the impact of hospital costs related to atrial fibrillation (or AFib) in a younger stroke population. To determine these findings, we examined more than 40,000 hospital admissions information involving adults between the ages of 18 and 64 with a primary diagnosis of ischemic stroke between 2010 and 2012. Although AFib is more common among those ages 65 and older, with strokes among younger adults on the rise in the U.S., we wanted to take a comprehensive look at AFib’s impact on hospital costs for these patients. AFib is associated with a 4- to 5-fold increased risk of ischemic stroke, which is the most common type of stroke. Overall, our research found that AFib substantially increased hospital costs for patients with ischemic stroke – and that was consistent across different age groups and genders of those aged 18-64. Of the 33,500 first-time stroke admissions, more than seven percent had AFib, and these admissions cost nearly $5,000 more than those without the condition. In addition, we found that both the costs of hospitalization, as well as the costs associated with AFib, were higher among younger adults (18-54) than those aged 55 to 64. (more…)
Author Interviews, Brigham & Women's - Harvard, Mental Health Research, Stroke, Toxin Research / 22.04.2015

Elissa Hope Wilker, Sc.D. Beth Israel Deaconess Medical Center Cardiovascular Epidemiology Research Harvard Medical SchoolMedicalResearch.com Interview with: Elissa Hope Wilker, Sc.D. Beth Israel Deaconess Medical Center Cardiovascular Epidemiology Research Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Wilke: Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but the impact on structural changes in the brain is not well understood. We studied older adults living in the greater Boston area and throughout New England and New York and we looked at the air pollution levels and how far they lived from major roads. We then linked this information to findings from MRI studies of structural brain images. Although air pollution levels in this area are fairly low compared to levels observed in other parts of the world, we found that people who lived in areas with higher levels of air pollution had smaller brain volumes, and higher risk of silent strokes. The magnitude of association that we observed for a 2 µg/m3 increase in fine particulate matter (PM2.5) (a range commonly observed across urban areas) was approximately equivalent to one year of brain aging. The association with silent strokes is of concern, because these are associated with increased risk of overt strokes, walking problems, and depression. (more…)
Author Interviews, Autism, Education, Emory, JAMA, Pediatrics / 22.04.2015

MedicalResearch.com Interview with: Lawrence Scahill, MSN, PhD and Karen Bearss, PhD Department of Pediatrics, Marcus Autism Center Children’s Healthcare of Atlanta and Emory University Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Response: Autism spectrum disorder (ASD) affects an estimated 0.6 to 1% of children worldwide. In young children with ASD (e.g. 3 to 7 years of age) up to 50% also have disruptive behaviors such as tantrums, aggression, self-injury and noncompliance. When present, these disruptive behaviors interfere with the child’s readiness to make use of educational and other supportive services. The presence of disruptive behaviors also hinders the acquisition of routine daily living skills. Parent Training has been shown to be effective for young children with disruptive behaviors who do not have Autism spectrum disorder – but it has not be well-studied in children with ASD. The current multisite study shows that parent training is effective in reducing serious behavioral problems in young children with ASD. This is the largest randomized trial of a behavioral intervention in children with ASD.  180 children were randomly assigned to parent training or parent education. Both treatments were delivered individually to parents over 24 weeks. Serious behavioral problems were reduced by almost 50% in the parent-training group compared to about 30% for parent education. A clinician who was blind to treatment assignment rated positive response in 69% of children in the parent training group compared to 40% for parent education. In addition, 79% of children who showed a positive response to parent training at the end of the 24-week trial maintained benefit at 6 months post treatment. Parent training provided parents with specific strategies on how to manage tantrums, aggression, self-injury and noncompliance in children with autism spectrum disorder. Parent education provided up-to-date and useful information about ASD, but no instruction on how to address behavioral problems. Parents were engaged in the study treatments as evidenced by the low drop-out rate of 10% . (more…)
Author Interviews, CDC, Hepatitis - Liver Disease, Outcomes & Safety / 22.04.2015

MedicalResearch.com Interview with: Chong-Gee Teo, MD, PhD Chief, Laboratory Branch Division of Viral Hepatitis CDC Medical Research: What is the background for this study? Dr. Teo: Hepatitis C outbreaks in the course of providing healthcare continue to occur. Some happen when hepatitis C virus (HCV) is transmitted to patients following breakdowns in safe injection and infection control practices, and mishaps during surgery. Another route of provider – to patient HCV transmission is diversion, self-injection and substitution of opioids intended for anesthetic use (collectively referred to as “tampering”). A patient acquires infection when an HCV-infected provider, who is an injecting drug user, self-injects from a syringe prefilled with opioid anesthetic, fills the syringe with a volume substitute (e.g., saline or water), and then administers the adulterated preparation to the patient. The study consisted of two parts: 1) to quantify the extent that anesthetic opioid tampering contributes to hepatitis C outbreaks by analyzing healthcare-associated outbreaks occurring between 1990 and 2012 in developed countries. 2) to estimate the probabilities of provider-to-patient transmission reflecting the “real-world” setting in which a patient presents for health care, unaware of risks posed by procedures conducted by a provider who may or may not be an injecting drug user or HCV infected. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research / 22.04.2015

Dr. Timothy Yap MD, PhD Timothy Yap, MD, PhD, NIHR BRC The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust London, United Kingdom.MedicalResearch.com Interview with: Timothy Yap, MD, PhD, NIHR BRC The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust London, United Kingdom. Medical Research: What is the background for this study? What are the main findings? Dr. Yap: This is a novel phase I trial assessing for the first time if the PARP inhibitor olaparib can be combined with the AKT inhibitor AZD5363. The study was undertaken at the Royal Marsden and The Institute of Cancer Research in London, England. This targeted combination was based on strong preclinical rationale demonstrating synergy between both drugs in BRCA positive tumors and also antitumor activity in non-BRCA positive tumors. Although olaparib was recently approved by the FDA for treating advanced ovarian cancer associated with defective BRCA genes, antitumor efficacy in different non-BRCA tumors is yet to be established. The key finding for this study was that it was indeed possible to combine both drugs safely, with multiple patients with different cancers responding, including patients with and without BRCA1/2 mutations. We also assessed a new intrapatient dose escalation phase I trial design in this study, and demonstrated that the novel design could be successfully implemented, with completion of the dose escalation phase in 2 schedules of the combination with just 20 patients in 7.5 months. (more…)
Author Interviews, Heart Disease, JACC, NYU, Obstructive Sleep Apnea, Sleep Disorders / 22.04.2015

Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical CenterMedicalResearch.com Interview with: Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical Center MedicalResearch: What is the background for this study? What are the main findings? Dr. Chinitz: The treatment algorithms proposed currently for maintenance of sinus rhythm in patients with atrial fibrillation focus on use of anti-arrhythmic drugs and catheter ablation. Data available to evaluate the effect of modification of known adverse clinical factors on atrial fibrillation recurrence is scant. Obstructive sleep apnea in a known factor associated with both new onset atrial fibrillation as well as its recurrence after catheter ablation. Through a meta-analysis of available data we found that use of continuous positive airway pressure in patients with sleep apnea was associated with a 42% relative risk reduction in recurrence of atrial fibrillation. This effect was similar across patient groups irrespective of whether they were medically managed or with catheter ablation. (more…)
AACR, Author Interviews, Genetic Research, Melanoma, NYU, Personalized Medicine, Wistar / 21.04.2015

Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NYMedicalResearch.com Interview with: Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer.  Traditionally, it has been characterized by clinicopathologic characteristics.  More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT.  In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis.  Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis.  A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking.  Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis.  We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated. Samples were clustered based on deleterious mutations.  Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1.  Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations.  TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway.  Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations.  Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples. (more…)
Author Interviews, Emergency Care / 21.04.2015

Dr Mayris P Webber Dr.PH. MPH Bureau of Health Services Fire Department of the City of New York Brooklyn, NY Professor of Clinical Epidemiology & Population Health Montefiore Medical Center NYMedicalResearch.com Interview with: Dr Mayris P Webber Dr.PH. MPH Bureau of Health Services Fire Department of the City of New York Brooklyn, NY Professor of Clinical Epidemiology & Population Health Montefiore Medical Center NY Medical Research: What is the background for this study? What are the main findings? Dr. Webber:
  • To date, we and others have found adverse health outcomes associated with World Trade Center (WTC)  exposure among New York City’s first responders such as firefighters, police officers, and other rescue and recovery workers. We conducted the first study to concentrate on the health impact of the disaster on emergency medical service (EMS) workers.
  • In keeping with previous research on WTC’s first responders, we found that the WTC attacks adversely affected the physical and mental health of approximately 2,000 New York City Fire Department (FDNY) EMS who performed rescue and recovery work at the site.
  • We analyzed selected physical and mental health conditions that have been certified as being linked to the aftermath of the WTC attacks under the James Zadroga 9/11 Health and Compensation Act of 2010.
  • Over a 12 year period, between September 11 2001 and December 31 2013, the proportion of newly diagnosed cases of gastroesophageal reflux disease (GERD) was 12.1%; obstructive airways disease (OAD) 11.8%; rhinosinusitis 10.6%; and cancer 3.1%.
  • In their most recent mental health survey, nearly 17% of EMS workers reported symptoms consistent with depression; 7% with post-traumatic stress disorder (PTSD); and 3% with harmful alcohol use.
  • Compared with EMS workers who did not work at the WTC site, EMS workers who worked at the WTC site in the morning of 9/11 (i.e., most intensely exposed) were at greatest risk for nearly all of the health conditions analyzed.
  • For example, they were almost four times as likely to have GERD and rhinosinusitis, seven times as likely to have probable PTSD, and twice as likely to have probable depression. (We use the term probable because we used screening questionnaires instead of professional diagnoses for these mental health conditions).
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Author Interviews, Hand Washing, Infections / 21.04.2015

dr-erwin-duizer.pngMedicalResearch.com Interview with: Erwin Duizer, PhD Head of section Enteric Viruses Centre for Infectious Diseases Control National Institute for Public Health and the Environment The Netherlands Medical Research: What is the background for this study? Dr. Duizer: Hand hygiene is important for interrupting the transmission chain of viruses through hands. Alcohol-based hand disinfectants are widely used in hospitals and healthcare facilities, due to convenience, rapidity, and broad acceptance by healthcare personnel. The effectiveness of alcohol-based hand disinfectant has been shown for bacteria and enveloped viruses but their effectiveness in reducing transmission of non-enveloped viruses, such as norovirus, is less certain. Therefore we tested, in a joint project of the RIVM and Wageningen University, the virucidal activity of a propanol based product and an ethanol based product in quantitative carrier tests. Additionally, the virus reducing effect of hand washing (according to health care guidelines) and the use the propanol based product was tested in a quantitative finger pad test. (more…)
Author Interviews, Cost of Health Care, Medicare, Ophthalmology / 21.04.2015

MedicalResearch.com Interview with: Dan Gong BA Yale University School of MedicineMedicalResearch.com Interview with: Dan Gong BA Yale University School of Medicine ------------ James C. Tsai, M.D., M.B.A. President - New York Eye and Ear Infirmary of Mount Sinai Delafield-Rodgers Professor and Chair Department of Ophthalmology Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? What are the main findings?
  • Congress first introduced the Medicare Physician Fee Schedule built on the resource-based relative value scale (RBRVS) in the Omnibus Budget Reconciliation Act of 1989. Until recently, Medicare payments to physicians were adjusted annually based on the sustainable growth rate (SGR) formula.
  • When adjusting physician payments, one controversial belief by policymakers was the assumption that in response to fee reductions, physicians would recuperate one-half of lost revenue by increasing the volume and complexity of services.
  • This study questioned this assumption that this inverse relationship between Medicare payment and procedural volume is uniform across all procedures. In particular, glaucoma procedures have not been studied in the past.
  • Using a fixed effects regression model, we found that for six commonly performed glaucoma procedures, four did not have any significant Medicare payment and procedural volume relationship (laser trabeculoplasty, trabeculectomy with and without previous surgery, aqueous shunt to reservoir). Two procedures, laser iridotomy and scleral reinforcement with graft, did have significant and inverse associations between Medicare payment and procedural volume. (more…)
Author Interviews, Hearing Loss, JCEM, Mineral Metabolism / 21.04.2015

Dr. Kai-Jen Tien MD Division of Endocrinology and Metabolism, Department of Internal Medicine Chi Mei Medical Center, Tainan, TaiwanMedicalResearch.com Interview with: Dr. Kai-Jen Tien MD Division of Endocrinology and Metabolism, Department of Internal Medicine Chi Mei Medical Center, Tainan, Taiwan Medical Research: What is the background for this study? What are the main findings? Response: Previous studies investigating the relationship between osteoporosis and sudden sensorineural hearing loss were rare. Most of the studies were of small sample size, or cross-sectional designs and their results were inconclusive. Our population-based study found an approximately 1.76-fold increase in the incidence of sensorineural hearing loss for patients with osteoporosis compared with the comparison group.Patients with more severe osteoporosis may have a higher risk of SSNHL than patients with osteoporosis of milder severity. (more…)
AACR, Author Interviews, Breast Cancer, UCSD / 21.04.2015

Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New YorMedicalResearch.com Interview with: Presented by Dr. Maura N. Dickler MD Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New York Medical Research: What is the background for this study? This year, breast cancer will claim the lives of nearly 40,000 women in the United States, and up to half of these women will have a disease that is driven by the estrogen receptor.
  • Although medicines have been approved for the treatment of hormone receptor-positive breast cancer for decades, more treatment options are needed.
  • Resistance to endocrine therapies causes morbidity and mortality for women with metastatic estrogen receptor-positive (ER+) breast cancer as many patients relapse or develop resistance to available hormonal agents via estrogen-dependent and estrogen-independent mechanisms.
  • Dual-acting investigational Selective Estrogen Receptor Degrader (SERDs) could potentially lead to a new treatment option for people with hormone receptor-positive breast cancer and may help overcome resistance to current anti-hormonal medicines.
  • GDC-0810 is a dual-acting investigational next-generation oral SERD that works in a number of ways to prevent estrogen fueling tumor growth. It is not only designed to target the estrogen receptor (ER) as an antagonist, but also to cause degradation of the ER protein. In preclinical studies, GDC-0810 was shown to induce tumor regressions in both tamoxifen sensitive and tamoxifen resistant tumor models in vivo.
Medical Research: What are the main findings?
  • Clinical data from the dose-escalation portion of a Phase I/IIa study evaluating GDC-0810 appears to have an acceptable safety profile with encouraging anti-tumor activity in postmenopausal women with advanced breast cancer positive for the estrogen receptor (ER), all of whom were previously treated with standard endocrine therapy.
  • Promising anti-tumor activity was observed in 38% of patients on study for six months or longer. At all doses tested, there was robust engagement of the estrogen receptor by GDC-0810 as demonstrated by fluoroestradiol (FES) PET scans.  Overall, the most common adverse events of any grade related to GDC-0810 were diarrhea, nausea and fatigue.
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AACR, Author Interviews, Cancer Research / 20.04.2015

Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee.MedicalResearch.com Interview with: Presented by Dr. Jeffrey R. Infante, MD 2015 American Association for Cancer Research Director of the Drug Development Program Sarah Cannon Research Institute in Nashville, Tennessee. Medical Research: What is the background for this study?
  • Inhibition of Checkpoint Kinase 1 (Chk1) may be effective at enhancing the effects of chemotherapeutic agents in tumor cells that lack other key cell cycle checkpoint regulators, such as the tumor suppressor protein p53 (p53 mutant tumors).
  • In a broad range of pre-clinical models, GDC-0425, an oral, selective Chk1 inhibitor, enhanced the efficacy of the chemotherapy drug gemcitabine. Greater efficacy was also observed in cancer cell lines lacking p53 activity.
  • Based on its proposed mechanism of action in enhancing the cytotoxicity of DNA damaging chemotherapy, GDC-0425 was evaluated in combination with a standard dose of gemcitabine.
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Author Interviews, Cancer Research / 20.04.2015

Pan Pantziarka, PhD Member of the ReDO project and the Anticancer Fund Research from the Repurposing Drugs in Oncology (ReDO) projectMedicalResearch.com Interview with: Pan Pantziarka, PhD Member of the ReDO project and the Anticancer Fund Research from the Repurposing Drugs in Oncology (ReDO) project MedicalResearch: What is the background for this study? Dr. Pantziarka: This study is one of a number initiated by the Repurposing Drugs in Oncology (ReDO) project. ReDO is an international collaboration between the Belgian foundation the Anticancer Fund and the US not-for-profit GlobalCures. ReDO includes researchers based in the UK, Belgium and the US. The project aims to identify the most promising non-cancer drugs which have evidence that they may be effective additions to oncological treatments. Itraconazole, the subject of this study, is a well-characterised and commonly used anti-fungal agent that is available internationally and at relatively low cost. MedicalResearch: What are the main findings? Dr. Pantziarka: We have summarised a broad range of in vitro, in vivo and clinical evidence of anti-cancer activity in itraconazole. In particular there is strong evidence that itraconazole has activity against the Hedgehog signalling pathway, which is active in a variety of different cancer indications. Our study also includes details of a number of positive clinical trials which have reported, and includes details of some still in progress. The level of evidence is particularly striking in basal cell carcinoma, prostate and lung cancer. (more…)
AACR, Author Interviews, Melanoma, Wistar / 20.04.2015

Adina Vultur, Ph.D. Staff Scientist Meenhard Herlyn Laboratory Melanoma Research Center The Wistar Institute, PhiladelphiaMedicalResearch.com Interview with: Adina Vultur, Ph.D. Staff Scientist Meenhard Herlyn Laboratory Melanoma Research Center The Wistar Institute, Philadelphia Medical Research: What is the background for this study? What are the main findings? Dr. Vulture: Our goal was to identify new drugs with anti-melanoma activity but with minor effects on normal cells. We screened structurally distinct kinase inhibitors first, against multiple cell lines and normal cells, and identified the organometallic compound SM200 as being the most effective and selective molecule, capable of halting melanoma cell growth and invasion. Further characterization of SM200 indicated that PIM kinases are highly inhibited by this compound compared to other targets. We then confirmed the contribution of PIM kinases to melanoma pathobiology by knockdown studies and by using a clinically available PIM-inhibitor. Encouraging results with PIM kinase inhibition in multiple melanoma models including xenografts suggests that this could be a useful strategy against melanoma. (more…)
Author Interviews, Breast Cancer / 20.04.2015

Steven Jay Isakoff, MD, PhDHematology/Oncology Department of Medicine Massachusetts General HospitalMedicalResearch.com Interview with: Steven Jay Isakoff, MD, PhD Hematology/Oncology Department of Medicine Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Isakoff: Metastatic triple negative breast cancer remains a challenging clinical problem with no specific therapies targeted validated for this population.  From a number of preclinical studies and because of a link between BRCA1 associated breast cancer and triple negative breast cancer, platinum chemotherapy has emerged as a potential chemotherapy with activity in triple negative breast cancer.  However, it is not yet clear how to predict which triple negative breast cancer patients are more likely to respond to platinum chemotherapy.  We set out to answer several questions.
  • First, what is the response rate to platinum chemotherapy in the first or second line for metastatic triple negative breast cancer?
  • Second, can we identify biomarkers to predict response to platinum agents?  The results of our study showed that among 86 patients treated with platinum chemotherapy (either cisplatin or carboplatin), the response rate was about 25%.  We identified 11 BRCA mutation carriers in our population and the response rate among carriers was about 55% compared to about 20% in the non-carriers.  In addition, we found that a new assay called the Hologous Recombination Deficiency assay, which may identify tumors with a BRCA-like phenotype, seemed to predict which cancers were more likely to respond, whereas other biomarkers we looked at were not able to do so.
  • Another exciting finding was that 6 patients who had major responses have become long term responders with no subsequent progression, some whom for over 5 years so far.  Surprisingly, none of the long term responders are BRCA mutation carriers.
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AACR, Author Interviews, Cancer Research, Dental Research, Microbiome / 20.04.2015

Xiaodan Mai MBBS University at Buffalo, The State University of New York Buffalo, NYMedicalResearch.com Interview with: Xiaodan Mai MBBS University at Buffalo, The State University of New York Buffalo, NY MedicalResearch: What is the background for this study? What are the main findings? Response: Periodontal disease is a condition that is highly prevalent amongst the elderly, and is characterized by chronic polymicrobial infection and inflammation of gum tissue. Periodontal disease has been associated with increased cancer risk, and these findings may be partially explained by extra-oral translocation of subgingival bacteria that subsequently modulates host cell environment and function. However, there is limited research on whether the presence of certain subgingival bacteria influences cancer risk. . Oral bacteria have been categorized into color-coded complexes by their timing of colonization and strength of association with periodontal disease. Using data from an ancillary study of the Women’s Health Initiative conducted in Buffalo, New York (a cohort of 1300 postmenopausal women), we therefore investigated the associations between the presence of three early-colonizing periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus, i.e., "orange complex" bacteria moderately associated with PD), the presence of two late-colonizing periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, i.e., "red complex" bacteria strongly associated with PD) in dental plaque and cancer risk. We found borderline associations between presence of any early-colonizing pathogens and increased risk of total cancer and lung cancer. Individual pathogens were not associated with total cancer or site-specific cancers when analyzed singly. Presence of any pathogens or presence of any late-colonizing pathogens was not associated with total or site-specific cancer. (more…)
AACR, Author Interviews, Breast Cancer, Nutrition, UCSD / 20.04.2015

Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093MedicalResearch.com Interview with: Catherine Marinac Doctoral Candidate UC San Diego/San Diego State University Joint-Doctoral Program in Public Health La Jolla, CA 92093 MedicalResearch: What is the background for this study? What are the main findings? Response: The dietary advice for cancer prevention usually focuses on limiting consumption of red meat, alcohol, and refined grains, and increasing consumption of plant foods. However, new evidence suggests that other fundamental aspects of diet, such when and how often people eat, can also play a role in cancer risk. For example, research in mice suggests that decreasing the number of hours we eat during the day, and increasing the length of time we fast overnight can improve metabolic parameters and reduce risk of developing a number of chronic diseases including cancer. Similar to the data from animal models, we found that women who fasted for longer periods of time overnight had significantly better control over blood glucose concentrations – and these effects were independent of how much women ate. This finding is relevant to cancer research because people who have poor glucose control are significantly more likely to develop certain types of cancer. It is hypothesized that high concentrations of circulating glucose may fuel cancer growth and progression. (more…)
Author Interviews, Breast Cancer, Cancer Research, Cognitive Issues, JNCI / 19.04.2015

Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of MunichMedicalResearch.com Interview with: Dr. Kerstin Hermelink Senior psychologist Dept. of Gynecology and Obstetrics Ludwig Maximilian University of Munich MedicalResearch: What is the background for this study? What are the main findings? Dr. Hermelink: Many breast cancer patients report problems of cognitive functioning that interfere considerably with their professional and private lives. In the last two decades, a number of studies have confirmed that subgroups of breast cancer patients show at least subtle cognitive impairment. Initially, the condition has entirely been attributed to chemotherapy effects and has therefore colloquially been named “chemobrain”. Meanwhile, however, cognitive impairment has also been found in patients who were managed without chemotherapy and, surprisingly, even in patients who had not yet received any systemic treatment at all. Several hypotheses on the causation of cognitive impairment that occurs already pretreatment have been put forward; for instance, biological effects of the cancer itself might affect cognitive functioning, or there might be shared genetic vulnerability for cancer and cognitive impairment. None of these hypotheses have been empirically confirmed; thus, pretreatment cognitive impairment is as yet unexplained. Our study was designed to investigate the effects of cancer-related post-traumatic stress on cognitive function in breast cancer patients before the start of treatment. Stress has a substantial influence on cognitive functioning, and post-traumatic stress disorder (PTSD) is associated with impairment of cognitive function. While the incidence of full diagnosis of stress disorder is low among breast cancer patients, many of these patients show symptoms of PTSD, with a peak shortly after diagnosis. We did not find an elevated risk of overall cognitive impairment in pretreatment breast cancer patients compared with matched non-cancer controls; however, the cancer patients scored worse than the controls on a small fraction of the cognitive indices that were used. Performance on these indices was indeed robustly associated with PTSD symptoms. Our results therefore indicate that pretreatment cognitive impairment in breast cancer patients may be largely caused by the stress of being diagnosed with cancer. (more…)
Author Interviews, BMJ, Cost of Health Care, Stanford / 18.04.2015

MedicalResearch.com Interview with: Donna Zulman MD MS Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park Division of General Medical Disciplines, Stanford University, Stanford California, USAMedicalResearch.com Interview with: Donna Zulman MD MS Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park Division of General Medical Disciplines, Stanford University, Stanford California, USA Medical Research: What is the background for this study? Dr. Zulman: Within the United States, a small number of individuals account for disproporationate health care spending. Many of these high-cost patients have complex chronic conditions such as heart failure and diabetes. Others have complicated mental health conditions. But the vast majority have multiple chronic conditions, which can create challenges when patients are navigating their health care. For this study, we examined patterns of chronic conditions among high-cost patients in the Veterans Affairs (VA) Health Care System, and studied the relationship between different chronic conditions patterns and health care utilization and costs. Medical Research: What are the main findings? Dr. Zulman: We found that within the VA, the 5% highest cost patients accounted for 47% of total VA health care costs. Approximately two-thirds of these patients had chronic conditions affecting 3 or more body systems (for example, cardiovascular disease, asthma, and depression). However, patients with severe, dominating diseases such as cancer and schizophrenia were less likely to have a lot of comorbid conditions. In addition, we found that even among these high-cost patients, having more conditions was associated with greater use of outpatient and inpatient services. However, as patients' multimorbidity across body systems increased, a greater share of their costs was generated in the outpatient setting and a smaller share of their costs was generated in the inpatient setting. This suggests that interventions focusing on high-cost patients should not only target costly hospitalizations, but should also coordinate and maximize efficiency of outpatient services across multiple conditions. (more…)
Aging, Author Interviews, Case Western, Nursing / 17.04.2015

kathy-wrightMedicalResearch.com Interview with: Kathy Wright, PhD, RN, GCNS-BC, PMHCNS-BC KL2 Postdoc, Clinical Instructor 2011-13 SAMHSA Scholar 2010-12 National Hartford Center of Gerontological Nursing Excellence Patricia G. Archbold Scholar Frances Payne Bolton School of Nursing Case Western Reserve University Cleveland, Ohio MedicalResearch: What is the background for this study? Dr. Wright: This study was a secondary analysis of baseline data from the After Discharge Care Management of Low Income Frail Elderly (Agency for Healthcare Research and Quality grant #1 R01 HS014539-01A1). The participants were aged 65 and older enrolled during an acute care hospitalization. Each participant had at least one deficit in activities of daily living (e.g., bathing, dressing) or two deficits in instrumental activities of daily living (e.g., transportation, paying bills). The purpose of the study was to test House’s Conceptual Framework for Understanding Social Inequalities in Health and Aging in Medicare-Medicaid enrollees in a group of low-income older adults to determine the relationships between socio-demographic factors (i.e., race, education, age, gender, income, and neighborhood poverty), health behaviors, and physical function and emotional well-being. As a part of the health behavior component, participants were interviewed and asked questions regarding the amount of physical activity they engaged in during the week. (more…)
ADHD, AHRQ, Author Interviews, CDC / 17.04.2015

Susanna N. Visser, DrPH Epidemiologist at the National Center on Birth Defects and Developmental Disabilities CDCMedicalResearch.com Interview with: Susanna N. Visser, DrPH Epidemiologist at the National Center on Birth Defects and Developmental Disabilities CDC   Medical Research: What is the background for this study? What are the main findings? Dr. Visser: Attention-Deficit/Hyperactivity Disorder, or ADHD is one of the most common chronic conditions of childhood. It often persists into adulthood. When children diagnosed with ADHD receive proper treatment, they have the best chance of thriving at home, doing well at school, and making and keeping friends. In 2011, the American Academy of Pediatrics (AAP) updated their guidelines for ADHD treatment. The new guidelines give this advice to healthcare providers, psychologists, educators, and parents of children with ADHD:
  • For preschoolers ages 4-5 with ADHD, use behavioral therapy before medication.
  • For older children and teens with ADHD, use behavioral therapy along with medication.
In order to learn more about ADHD treatment patterns, CDC researchers looked at data from a national sample of children with special health care needs, ages 4-17 years, collected in 2009-10 just before the release of the 2011 guidelines. We found that most children with ADHD received either medication treatment or behavioral therapy as well as some other form of ADHD therapy to help. However, we also found that many children were not receiving treatment in the way it was outlined in the 2011 best practice guidelines.
  • Less than 1 in 3 children with ADHD received both medication treatment and behavioral therapy, the preferred treatment approach for children ages 6 and older.
  • Only half of preschoolers (4-5 years of age) with ADHD received behavioral therapy, which is now the recommended first-line treatment for this group.
  • About half of preschoolers with ADHD were taking medication for ADHD, and about 1 in 4 were treated only with medication.
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Author Interviews, Nutrition / 17.04.2015

MedicalResearch.com Interview with: Professor Kylie Ball PhD Centre for Physical Activity and Nutrition Research, Deakin University, Australia. Medical Research: What is the background for this study? What are the main findings? Response: Most Australians (95% of adults) do not eat enough fruits or vegetables for good health. This is concerning as low fruit and vegetable intakes are linked with increased risk for a range of adverse health outcomes, including hypertension, coronary heart disease, stroke and certain cancers. One of the commonly cited barriers to fruit and vegetable consumption is the high cost of these foods. At Deakin University's Centre for Physical Activity and Nutrition Research (C-PAN), we undertook a randomised controlled trial study in a supermarket setting to test whether addressing this barrier would help people to consume more fruits and vegetables. We found that a fairly small price reduction (20%) was effective in prompting people to buy more fruits and vegetables – about 2-3 more serves of fruit per week, and about 3 more serves of vegetables per week. These findings are exciting, as even small increases in fruit and vegetable consumption across the population can substantially improve the health of Australians. (more…)
Author Interviews, Cognitive Issues, Nutrition / 16.04.2015

Dr. Fredrik Jernerén PhD Postdoctoral Research Fellow Department of Pharmacology University of Oxford Oxford, United KingdomMedicalResearch.com Interview with: Dr. Fredrik Jernerén PhD Postdoctoral Research Fellow Department of Pharmacology University of Oxford Oxford, United Kingdom Medical Research: What is the background for this study? What are the main findings? Dr. Jernerén: Development of dementia and Alzheimer’s disease is associated with an accelerated rate of brain shrinkage. Identifying ways to reduce the brain atrophy rate at an early stage may offer new strategies to prevent or delay the onset of dementia. In this study on elderly subjects diagnosed with Mild cognitive impairment (MCI), who are at increased risk of developing dementia, we investigated whether the effect of B vitamin supplementation on reducing the brain atrophy rate was influenced by circulating levels of omega-3 fatty acids. We have found that this indeed was the case. The higher the baseline concentration of the combined omega-3 fatty acids (DHA+EPA), the greater the protective effect of the B vitamin treatment. In subjects with high omega-3 concentrations who at the same time had elevated homocysteine levels (indicating a lack of B vitamins), B vitamin treatment reduced the brain atrophy rate by about 70% compared with the placebo group.  (more…)