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, 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, 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…)
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.
(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…)
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, 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…)
Author Interviews, Endocrinology, Nature, NYU, Social Issues / 16.04.2015

Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of MedicineMedicalResearch.com Interview with: Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Marlin: Oxytocin is a hormone that plays an important role in the expression of social and parental behaviors, but little is know about how it works in the brain to produce these behaviors. Virgin mice will usually ignore, and sometimes cannibalize newborn mouse pups. Our study has shown that oxytocin works in the auditory cortex of virgin mice to change both their neural responses, and eventually their behaviors, to mirror the maternal response. (more…)
Author Interviews, Cost of Health Care, NEJM, Ophthalmology, UCSF / 16.04.2015

Catherine L. Chen M.D., M.P.H. UCSF Dept of AnesthesiaMedicalResearch.com Interview with: Catherine L. Chen M.D., M.P.H. UCSF Dept of Anesthesia Medical Research: What is the background for this study? What are the main findings? Dr. Chen: Cataract surgery is a very common and safe surgery that most older adults have in their 70's or 80's. It usually happens as a same-day surgery and most patients only need eye drops to numb the eye with little or no intravenous sedation for a procedure that on average is only 18 minutes long. Given their age, these patients typically have other concurrent medical problems, so even though multiple research studies and professional societies have concluded that routine preoperative testing is not necessary before cataract surgery, we found that this testing still frequently occurs in these patients. More than half of the patients in our study had at least one preoperative test performed in the month before their surgery. We hypothesized prior to undertaking this study that the older and sicker patients were the ones who were most likely to get preoperative testing. Instead, what we found was that the most important factor that determined whether or not a patient got tested was the ophthalmologist who operated on the patient. This is an important finding because it shows that most patients are not getting extra testing, but the few that do are getting testing because that's the way their ophthalmologist typically prepares his patients for surgery. Most of the time, this testing is not needed and will not affect how well the patient does during and after surgery. (more…)
Author Interviews, Cancer Research, Mayo Clinic / 15.04.2015

Michael B. Wallace, M.D., MPH, Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with: Michael B. Wallace, M.D., MPH Mayo Clinic Jacksonville, FL 32224   Medical Research: What is the background for this study? Dr. Wallace: Since its first consideration as an independent entity in 1996,1 intraductal papillary mucinous neoplasms (IPMN) of the pancreas have been diagnosed with increasing frequency. Detection and resection of IPMN offer a unique opportunity to cure and prevent adenocarcinoma of the pancreas, an otherwise highly lethal disease. The main clinical concern related to intraductal papillary mucinous neoplasms is its wide-ranging potential for malignancy from low-risk indolent lesions to those with high incidence of malignant degeneration. It is well-established that this malignant progression varies based on the morphological subtypes. The current methods of predicting malignant potential are limited to clinical, morphological, and cyst fluid cytology and biomarker data. Medical Research: What are the main findings? Dr. Wallace: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade dysplasia and were compared to the rest of the cohort. Multivariate logistic analysis showed no statistically significant association between cancer/high-grade dysplasia and gender, age or alcohol consumption. Smoking history and body mass index was significantly related with cancer/ high-grade dysplasia. Jaundice and steatorrhea were also associated with cancer/ high-grade dysplasia; however, weight loss was not. Univariate analysis showed no association between malignancy and the cyst number/location, although a strong association was shown for cyst size. The presence/size of nodules, and main duct involvement were strongly related with malignancy. (more…)
Author Interviews, Duke, Heart Disease, JACC, Women's Heart Health / 15.04.2015

Matthew E. Dupre, PhD Associate Professor of Medicine Department of Community and Family Medicine Department of Sociology Duke Clinical Research InstituteMedicalResearch.com Interview with: Matthew E. Dupre, PhD Associate Professor of Medicine Department of Community and Family Medicine Department of Sociology Duke Clinical Research Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Dupre: The negative health consequences of divorce have been known for some time. However, we showed that lifetime exposure to divorce can have a lasting impact on ones’ cardiovascular health, particularly in women. This is a good example of why people going through a divorce need a good divorce lawyer chicago in order to keep their stress levels down and help their cardiovascular health. Results from our study showed that risks for acute myocardial infarction (AMI) were significantly higher in women who had one divorce, two or more divorces, and among the remarried compared with continuously married women after adjusting for multiple risk factors. Risks for AMI were elevated only in men with a history of two or more divorces relative to continuously married men. We were especially surprised to find that women who remarried had risks for AMI that were nearly equivalent to that of divorced women. Men who remarried had no significant risk for acute myocardial infarction. The results of this study provide strong evidence that cumulative exposure to divorce increases the risk of acute myocardial infarction in older adults. Also somewhat unexpected was that the associations remained largely unchanged after accounting for a variety socioeconomic, psychosocial, behavioral, and physiological factors. However, we lacked information on several factors that we suspect may have contributed to the risks related to divorce – such as elevated stress, anxiety, and the loss of social support; as well as possible changes is medication adherence or other prophylactic behaviors. MedicalResearch: What should clinicians and patients take away from your report? (more…)
Author Interviews, Emory, Neurological Disorders / 15.04.2015

Erwin G. Van Meir, PhD Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology Emory University School of Medicine Atlanta GA 30322MedicalResearch.com Interview with: Erwin G. Van Meir, PhD Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology Emory University School of Medicine Atlanta GA 30322 Medical Research: What is the background for this study? What are the main findings? Dr. Van Meir: In this study we queried the role of the BAI1 protein in normal physiology. To do this we generated a transgenic mouse, which lacks the expression of the Bai1 gene. The mice had no obvious anomalies and reproduced according to mendelian rules. Since BAI1 is strongly expressed in the brain, including in neurons, we wondered whether they might have some cognitive defect that would only be revealed under specific testing conditions. We had the mice perform in an experiment that tests their ability to orient themselves in space and memorize the location of a hidden platform in a water maze. This experiment clearly demonstrated that the Bai1 deficient mice had deficits in spatial learning and memory. We then further probed the electrophysiological, anatomical and biochemical basis of this abnormal physiologic behavior and showed that hippocampal neurons had abnormal synaptic plasticity, reduced thickness of the post synaptic density and that this was associated with an increased degradation of a key PSD protein called PSD-95. (more…)
Author Interviews, Depression, JAMA, Race/Ethnic Diversity, University of Michigan / 11.04.2015

Addie Weaver PhD Research Investigator and LEO Adjunct Lecturer School of Social Work University of MichiganMedicalResearch.com Interview with: Addie Weaver PhD Research Investigator and LEO Adjunct Lecturer School of Social Work University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Weaver: The mental health of both African Americans and rural Americans has been understudied. Though depression is one of the most common, debilitating mental illnesses among women, very little is known about depression among African American women living in rural areas of the United States. In fact, much of what we know about rural women's depression in general is based on research conducted with community samples, as limited epidemiolgical research includes large enough samples of both African American respondents and rural respondents to assess potentially important subgroup differences by urbanicity (e.g., urban, suburban, rural) and race. Our study used the National Survey of American Life, the first and only nationally representative survey of African Americans, to examine the interaction of urbanicity and race/ethnicity on Major Depressive Disorder and mood disorder prevalence among African American and non-Hispanic white women residing in the South. We found that rural residence has a differential effect on depression and mood disorder for African American women and non-Hispanic white women. Overall, African American women living in rural areas experienced significantly lower odds of meeting criteria for lifetime and 12-month Major Depressive Disorder and lifetime and 12-month mood disorder than urban African American women. Conversely, non-Hispanic white women residing in rural areas had significantly higher odds of meeting criteria for lifetime and 12-month Major Depressive and lifetime and 12-month mood disorder when compared to rural African American women, and had significantly higher prevalence rates of 12-month Major Depressive Disorder and 12-month mood disorder than urban non-Hispanic white women. All analyses controlled for age, education level, household income, and marital status, suggesting that the urbanicity differences were not due to resource disparities often experienced by individuals residing in rural communities. (more…)
Author Interviews, Genetic Research, Nature, Pancreatic, UT Southwestern / 10.04.2015

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention. (more…)
Author Interviews, Circadian Rhythm, Ophthalmology, Sleep Disorders, UCSD / 09.04.2015

MedicalResearch.com Interview with: Carolina P B Gracitelli, M.D. Ophthalmology - PhD Candidate/ Research Fellow University of California San Diego - Hamilton Glaucoma Center Medical Research: What is the background for this study? What are the main findings? Dr. Gracitelli: Of all the diseases that can lead to blindness, glaucoma is one of the most important diseases; it affects more than 70 million people worldwide, of whom approximately 10 % are bilaterally blind. Different studies have reported that the damage caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of RGC. This subpopulation of RGC is clearly related with non-image-forming visual function such as photic synchronization of circadian rhythms and the pupillary light reflex. However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian rhythm was until nowadays controversial. The main clinical finding of our study was that glaucoma leads to RGC death, including ipRGC death. These cells are connected to several non-image-forming functions, including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming and non-image-forming visual systems are associated with glaucoma. Circadian function has not been well investigated in clinical daily practice, but it can interfere with the quality of life of these patients. Concerns about sleep disturbances in glaucoma patients should be incorporated into clinical evaluations. Medical Research: What should clinicians and patients take away from your report? Dr. Gracitelli: Our data support the concept that glaucoma is associated with a loss of ipRGCs that mediate the pupillary light response, particularly to the sustained component of the blue flash with a luminance of 250 cd/m2. Additionally, glaucoma patients had significant sleep disturbances that were inversely correlated with a measure of ipRGC function, the pupillary light reflex. These results suggest that the loss of ipRGCs in glaucoma may also lead to sleep disturbances. Both non-visual functions of ipRGCs are correlated, indicating that attention should be paid to the non-image forming visual functions in glaucoma patients. Medical Research: What recommendations do you have for future research as a result of this study? Dr. Gracitelli: Sleep disorders is a complex system, therefore, some conclusions in this study should be carefully evaluated. Further studies with larger cohorts could also help to elucidate the association between the pupillary reflex and the polysomnography parameters. And longitudinal studies can better explain the associations between sleep disorders and glaucoma progression. In addition, we know that there are several types of ipRGCs and they have specific functions (pupillary reflex or circadian rhythms), therefore, evaluations would also need to include a more thorough assessment to understand better the specific role of ipRGCs in sleep disturbances. However, it is true that these ipRGCs functions are impaired in glaucoma, affecting the quality of life of these patients. Citation: Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma Gracitelli, Carolina P.B. et al. Ophthalmology Published Online: April 06, 2015 DOI: http://dx.doi.org/10.1016/j.ophtha.2015.02.030MedicalResearch.com Interview with: Carolina P B Gracitelli, M.D. Ophthalmology - PhD Candidate/ Research Fellow University of California San Diego - Hamilton Glaucoma Center Medical Research: What is the background for this study? What are the main findings? Dr. Gracitelli: Of all the diseases that can lead to blindness, glaucoma is one of the most important diseases; it affects more than 70 million people worldwide, of whom approximately 10 % are bilaterally blind. Different studies have reported that the damage caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of retinal ganglion cell. This subpopulation of RGC is clearly related with non-image-forming visual function such as photic synchronization of circadian rhythms and the pupillary light reflex. However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian rhythm was until nowadays controversial. The main clinical finding of our study was that glaucoma leads to retinal ganglion cell death, including ipRGC death. These cells are connected to several non-image-forming functions, including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming and non-image-forming visual systems are associated with glaucoma. Circadian function has not been well investigated in clinical daily practice, but it can interfere with the quality of life of these patients. Concerns about sleep disturbances in glaucoma patients should be incorporated into clinical evaluations. (more…)
Author Interviews, Blood Pressure - Hypertension, Social Issues, University of Michigan / 08.04.2015

Kira S. Birditt, Ph.D. Research Associate Professor Life Course Development Program The Institute for Social Research University of Michigan Ann Arbor, MI MedicalResearch.com Interview with: Kira S. Birditt, Ph.D. Research Associate Professor Life Course Development Program The Institute for Social Research University of Michigan Ann Arbor, MI Medical Research: What is the background for this study? What are the main findings? Dr. Birditt: We know that negative marital quality (e.g., conflict, irritation) has important implications for physical health but the mechanisms that account for these links are still unclear. This study explored links between negative marital quality (e.g., criticism, demands), stress (long term chronic stresses) and blood pressure among older married couples in  a large longitudinal nationally representative sample of couples in the U.S..  We found that husbands had higher blood pressure when wives reported greater stress and that this link was even greater when husbands felt more negative about the relationship.  In addition, negative marital quality experienced by only one member of the couple was not associated with blood pressure but when both members of the couple reported higher negative marital quality they had higher blood pressure.  (more…)
Author Interviews, Kidney Disease, UCLA / 07.04.2015

MedicalResearch.com Interview with: Bryan B. Shapiro Harold Simmons Center for Kidney Disease Research and Epidemiology and Division of Nephrology and Hypertension Los Angeles Biomedical Research Institute Harbor–UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Response: The inverse relationship between body mass index (BMI) and mortality rates is well-documented in maintenance hemodialysis (MHD) patients. Virtually everyone has assumed that this relationship reflects the effect of body weight, and especially fat mass, on mortality in these patients. However, height is also a component of the BMI equation (BMI = body weight (kg)/height (m²)) and may be independently associated  with mortality in MHD patients. The results of this study, which examined 117, 644 MHD patients and was controlled for many demographic and laboratory variables, indicate that height, adjusted for body weight, is directly associated with mortality in a manner that is opposite to the weight-mortality relationship. Moreover, we found that the contribution of height to the inverse BMI-mortality relationship in dialysis is essentially as great as the contribution of weight. (more…)
Author Interviews, JAMA, Surgical Research, UCSF / 07.04.2015

Emily Finlayson, MD, MS Department of Surgery, Division of General Surgery Department of Medicine, Division of Geriatrics Philip R Lee Institute for Health Policy University of California, San Francisco Director, UCSF Center for Surgery in Older AdultsMedicalResearch.com Interview with: Emily Finlayson, MD, MS Department of Surgery, Division of General Surgery Department of Medicine, Division of Geriatrics Philip R Lee Institute for Health Policy University of California, San Francisco Director, UCSF Center for Surgery in Older Adults Medical Research: What is the background for this study? What are the main findings? Dr. Finlayson: In general, the goal of lower extremity revascularization is to preserve the leg so that patients can maintain the ability to ambulate and maintain functional independence.  We evaluated the results of this operation in older nursing home residents in the United States.  We found that over the 3 year study period, over 10,000 nursing home residents underwent this procedure.  Most of them were functionally dependent before surgery, 3/4 were unable to walk, and over half had dementia. After 1 year, half of the residents had died.  Among residents who could not walk before surgery, 89% were dead or non ambulatory 1 year after surgery. (more…)
Annals Internal Medicine, Author Interviews, Johns Hopkins, Weight Research / 06.04.2015

Kimberly Gudzune, MD, MPH Assistant Professor; The Johns Hopkins University School of Medicine Core Faculty; Welch Center for Prevention, Epidemiology, and Clinical Research The Johns Hopkins Digestive Weight Loss CenterMedicalResearch.com Interview with: Kimberly Gudzune, MD, MPH Assistant Professor; The Johns Hopkins University School of Medicine Core Faculty; Welch Center for Prevention, Epidemiology, and Clinical Research The Johns Hopkins Digestive Weight Loss Center Medical Research: What is the background for this study? What are the main findings? Dr.Gudzune: Changes in healthcare policy may encourage healthcare providers to screen their patients for obesity, so it is critical to then have a weight management plan if obesity is identified. Recent guidelines recommend that clinicians consider referring patients to high intensity weight loss programs. Commercial weight loss programs may be one of the options available, so providers need to know which programs help people lose weight and keep it off. We found that only 11 out of 32 programs that we looked at had rigorous studies reporting on weight loss, which means that we do not know whether most programs work. Several well-known commercial programs have been scientifically tested and two programs, Weight Watchers and Jenny Craig, achieved significant weight loss that was sustained 12 months later. (more…)
Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, University of Michigan / 06.04.2015

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer.  Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations. (more…)
Annals Internal Medicine, Author Interviews, Surgical Research, University of Pittsburgh / 06.04.2015

Anthony Delitto, PT, Ph.D, FAPTA Professor and Chair Department of Physical Therapy Associate Dean for Research, SHRS School of Health and Rehabilitation Sciences Pittsburgh,MedicalResearch.com Interview with: Anthony Delitto, PT, Ph.D, FAPTA Professor and Chair Department of Physical Therapy Associate Dean for Research, SHRS School of Health and Rehabilitation Sciences University of Pittsburgh Medical Research: What is the background for this study? What are the main findings? Dr. Delitto: I work with a team, many of whom were authors on the paper, and we see a lot of patients with lumbar spinal stenosis. Some of them did very well with Physical Therapy and avoided surgery. Some people didn’t do well and we ended up having surgery. We really wanted to do a study that compared, in a randomized format, doing surgery vs. a non-surgical approach to lumbar spinal stenosis. The idea we had was to really put the two approaches head to head – a randomized trial of surgery vs. physical therapy for people with lumbar spinal stenosis. We decided only to recruit patients after they had consented to surgery in order to avoid the pitfalls of previous studies where people crossed over after being assigned to a group, for example, being assigned to surgery and then deciding against having surgery. Medical Research: What should clinicians and patients take away from your report? Dr. Delitto: Probably the biggest point to put across to physicians, patients and practitioners, one of the things we realized was: patients don’t exhaust all of their non-surgical options before they consent to surgery. And physical therapy is one of the non-surgical options. The obvious finding is, when you compare the two groups, they seem to do the same. The results were equivalent at two years. Now, embedded in that, there are patients who did well in surgery, and patients who failed in surgery. There are patients who did well in Physical Therapy, and there are patients who failed with PT. But when we looked across the board at all of those groups, their success and failure rates were about the same. So it tells us that for the most part there were equivalent outcomes at two years. (more…)
Author Interviews, Brigham & Women's - Harvard, Cannabis, JAMA, Lipids, Pediatrics / 06.04.2015

Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine, Brigham and Women’s Hospital Boston, MAMedicalResearch.com Interview with: Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gooding: As an adolescent medicine physician, I primarily care for patients between the ages of 12 and 30, although I first trained in internal medicine.  One of the things I noticed when I started working with this age group is that pediatric and adult guidelines differ for many conditions.  Cholesterol treatment is one condition that comes up frequently, because the NHLBI and the AAP recommend screening youth ages 17 to 21 for cholesterol problems. The study team and I set out to discover the proportion of American youth ages 17 to 21 who would meet criteria for pharmacologic treatment of abnormal cholesterol levels if clinicians applied the pediatric versus the adult guidelines.  We found that 2.6% of young people ages 17 to 21 would qualify for pharmacologic treatment of abnormal LDL cholesterol levels under the pediatric guidelines, but less than 1% would qualify under the adult guidelines.  This translates to almost 500,000 youth qualifying for treatment under the pediatric guidelines, but only about 78,000 under the adult guidelines.  Those who met pediatric criteria had lower LDL levels but higher proportions of high blood pressure, smoking, and obesity. (more…)
Author Interviews, Biomarkers, Lancet, Lymphoma, NIH / 06.04.2015

MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans. (more…)
Author Interviews, Exercise - Fitness, JAMA, NIH / 06.04.2015

MedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, MarylandMedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, Maryland Medical Research: What is the background for this study? Dr. Arem: The 2008 Physical Activity Guidelines for Americans recommend a minimum of 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity activity per week for “substantial” health benefit, and suggest “additional” benefit with more than double the exercise minimum. However, the guidelines note that there is a lack of evidence for an upper limit of health benefit. We set out to define the dose-response relationship between leisure-time physical activity and mortality and to determine the upper limit of benefit associated with higher levels of aerobic exercise. Medical Research: What are the main findings? Dr. Arem: We found that study participants who met the recommended minimum level of leisure-time physical activity derived most of the mortality benefit, with a 31% lower risk of death compared to inactive individuals. Study participants who engaged in three to five times the recommended minimum level of leisure-time physical activity had a marginally increased mortality benefit, with a 39% lower risk of death compared to inactive individuals. Three to five times the recommended minimum is equivalent to a weekly minimum of walking 7 hours or running 2 hours 15 minutes. (more…)
Author Interviews, Compliance, HIV, NYU / 06.04.2015

Marya Viorst Gwadz, Ph.D Senior Research Scientist Director, Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing New York, NY 10010 MedicalResearch.com Interview with: Marya Viorst Gwadz, Ph.D Senior Research Scientist Director, Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing New York, NY 10010 Medical Research: What is the background for this study? Dr. Gwadz: HIV is a major success story in that the tolerability, convenience, and efficacy of antiretroviral medications have improved dramatically over the last decade. A number of years ago in the course of another research study with vulnerable individuals infected with HIV in New York City, and we noticed that a substantial proportion of study participants were medically eligible for HIV medications, and had access to medications, but had declined or stopped taking them. We then turned our attention to understanding why this is the case, that is, to identify the individual, social, and structural barriers that persons living with HIV/AIDS (PLHA) experience to antiretroviral therapy. We focused in particular on African American/Black and Latino/Hispanic PLHA, because the overall emphasis of our research group at the NYU College of Nursing is the development and evaluation of culturally targeted intervention approaches to address health disparities. Around 2011, studies of the “HIV cascade of care” began to emerge, which highlighted the problem of poor engagement in HIV care and antiretroviral therapy nationally. The ultimate goal of HIV treatment is viral suppression, but at present, the Centers for Disease Control and Prevention (CDC) estimates that we have achieved that goal with only 30% of PLHA. Medical Research: What kind of intervention approach that emerged from these background findings? Dr. Gwadz: We found that barriers to HIV medication are complex and multi-faceted for PLHA from African American/Black and Latino/Hispanic backgrounds. In particular, PLHA experience serious emotional barriers to the uptake of HIV medications, such as fear of side effects, stigma, and disclosure of HIV status. Further, high rates of substance use and mental health distress, and barriers to accessing services for these concerns, impede medication uptake. Moreover, PLHA who are wary of HIV medication tend to avoid HIV primary care, often because they do not want to feel pressured to take medications, or explain to their providers why they are not taking them. So poor engagement in HIV care, which is very common among PLHA, and low uptake of HIV medication are actually related problems. With funding from the National Institute of Mental Health (grant #R34MH093352), and in collaboration with Mount Sinai Beth Israel and Mount Sinai St. Luke’s-Roosevelt Hospital Center, we developed a multi-component culturally targeted intervention grounded in the Motivational Interviewing approach that included three individual sessions, 12-24 weeks of patient navigation (as needed), up to five support groups with other PLHA who had declined medication, which were co-led by a “successful” peer who was engaged in HIV care and were taking HIV medication with good adherence. One novel aspect of the intervention was its focus on emotional barriers to HIV medication, and the program’s “no pressure, no judgment” stance, congruent with the Motivational Interviewing approach, was key to engaging participants into the study to talk about these difficult issues. (more…)