MedicalResearch.com: Medical Research Exclusive Interviews April 28 2015

MedicalResearch.comExclusive Interviews with Medical Research and

Health Care Researchers from Major and Specialty Medical Research Journals and Meetings

Editor: Marie Benz, MD [email protected]

April 28 2015

For Informational Purposes Only: Not for Specific Medical Advice.

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Selective Estrogen Receptor Degrader May Help Patients With Resistant ER+ Breast CancerMedicalResearch.com Interview with:Presented by Dr. Maura N. Dickler MD

Associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center andWeill 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 tamoxifensensitive and tamoxifen resistant tumor models in vivo.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.

http://medicalresearch.com/cancer-_-oncology/breast-cancer/selective-estrogen-receptor-degrader-may-help-patients-with-resistant-er-breast-cancer/13639/

http://medicalresearch.com/menopause/should-the-ovaries-be-removed-at-time-of-hysterectomy-for-benign-disease/1236/




• 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.







• Medical Research: What should clinicians and patients take away from your report?• SERDs could potentially lead to a new treatment option for women with hormone receptor-positive

breast cancer and may help overcome resistance to current anti-hormonal medicines, such as tamoxifen, aromatase inhibitors, and fulvestrant.

• We believe these investigational next-generation oral SERDs could one day redefine the standard of care for hormone receptor-positive breast cancer.

• New therapies, like GDC-0810, that potentially have activity against treatment-resistant tumors are needed.

• When some women become resistant to anti-hormonal medicines and see their disease return or worsen, preclinical and clinical data suggest that the cancer continues to be driven by the actual estrogen receptor (not by natural hormones).

• We believe that when the SERDs bind to the estrogen receptor, they induce degradation and turnover of the estrogen receptor so that it is eliminated from the cell. So you could hypothesize that if the SERDs have the ability to eliminate the estrogen receptor from the cell altogether, this may circumvent the problem of resistance.

• These small molecules have been rationally designed to enter the cell, change the shape of the estrogen receptor, and mark it for elimination.

• Note: Philip Rosenberg from the NCI will present data at AACR reporting that the total number of breast cancer cases in the US is forecast to be 50% greater in 2030 than it was in 2011, when invasive and in-situ or screening-detected cancers are counted together, and this increase is driven mostly by a marked increase in cases of estrogen receptor (ER)–positive tumors and in women older than 70.







• Medical Research: What recommendations do you have for future research as a result of this study?

• In the Phase II portion of the study, we are evaluating GDC-0810 in patients previously treated with aromatase inhibitors and fulvestrant, including those with estrogen receptor mutations. We expect to enroll approximately 140 patients.

• Randomized studies are being planned to compare GDC-0810 against other standard of care therapies.

• Citation:

• Presented at the 2015 American Association of Cancer Research meetingApril 19 2015

• Abstract Number: 8953 Title: A first-in-human Phase I study to evaluate the oral selective estrogen receptor (ER) degrader GDC-0810

• (ARN-810) in postmenopausal women with ER+ HER2-, advanced/metastatic breast cancer (BC)

• Author Block: Maura Dickler1, Aditya Bardia2, Ingrid Mayer3, Eric Winer4, Peter Rix5, Jeff Hager5, Meng Chen6, Iris Chan6, Edna Chow-Maneval5, Carlos Arteaga3, Jose Baselga1. 1Memorial Sloan Kettering Cancer Center, New York, NY; 2Massachusetts General Hospital Cancer Center, Boston, MA; 3Vanderbilt-Ingram Cancer Center, Nashville, TN; 4Dana-Farber Cancer Institute, New York, NY; 5Seragon Pharmaceuticals, San Diego, CA; 6Genentech, Inc, South San Francisco, CA



http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=25#.VTWCAhcbraY



Osteoporosis May Increase Risk of Hearing LossMedicalResearch.com Interview with:

Dr. Kai-Jen Tien MDDivision 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.

• Medical Research: What should clinicians and patients take away from your report?

• Response: The prevalence of osteoporosis is increasing around the world, and it increases the risk of bone fracture, systemic disease, medical expenses, and mortality. Our study also shows the relationship between osteoporosis and the risk of sensorineural hearing loss. Osteoporotic patient should be aware to have an early intervention if they suffer from suspected hearing impairment.


http://medicalresearch.com/author-interviews/osteoporosis-may-increase-risk-of-hearing-loss/13643/

http://medicalresearch.com/author-interviews/hearing_loss_contributes_to_personality_changes_in_elderly/4655/

http://medicalresearch.com/author-interviews/hearing-loss-dietary-antioxidants/2677/



Osteoporosis May Increase Risk of Hearing LossMedicalResearch.com Interview with:

Dr. Kai-Jen Tien MDDivision of Endocrinology and Metabolism, Department of Internal Medicine

Chi Mei Medical Center, Tainan, Taiwan


• Response: Our study can not answer if early detection and treat osteoporotic patients with antiosteoporotic therapy can reduce the risk of sudden sensorineural hearing loss. Further prospective and intervention study containing detail information should be done to resolve the question.

• Citation:

• Increased Risk of Sudden Sensorineural Hearing Loss in Patients With Osteoporosis: A Population-based, Propensity Score-matched, Longitudinal Follow-up Study.Yeh MC1, Weng SF, Shen YC, Chou CW, Yang CY, Wang JJ, Tien KJ.J Clin Endocrinol Metab. 2015 Apr 16:jc20144316. [Epub ahead of print]





Decreased Medicare Payment Did Not Mean Increased Volume For Most Glaucoma ProceduresMedicalResearch.com Interview with: Dan Gong BA

Icahn School of Medicine at Mount Sinai 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


http://medicalresearch.com/ophthalmology/decreased-medicare-payment-did-not-mean-increased-volume-for-most-glaucoma-procedures/13647/







• 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, glaucomaprocedures 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.



http://medicalresearch.com/ophthalmology/detecting-glaucoma-before-it-blinds/248/







• Our research suggests that for many glaucoma procedures, decreased payment does not lead ophthalmologists to compensate by performing more procedures.

• More broadly speaking, it is incorrect to assume that one number can adequately and accurately describe how physicians respond to Medicare payment changes


• The relationship between Medicare payment and procedural volume is complex, requiring a more nuanced perspective that takes into account individual procedural and specialty variation.

• To more accurately project future Medicare spending, more research is necessary to study how physicians respond to changes in both Medicare payment rates and payment models.

• Citation:

• A Quantitative Analysis of the Relationship between Medicare Payment and Service Volume for Glaucoma Procedures from 2005 through 2009

• Gong D1, Jun L1, Tsai JC2.

• Ophthalmology. 2015 Jan 23. pii: S0161-6420(14)01146-4. doi: 10.1016/j.ophtha.2014.12.006. [Epub ahead of print]



http://medicalresearch.com/ophthalmology/high-blood-pressure-must-carefully-managed-glaucoma-patients/10570/

http://www.ncbi.nlm.nih.gov/pubmed/?term=A+Quantitative+Analysis+of+the+Relationship+between+Medicare+Payment+and+Service+Volume+for+Glaucoma+Procedures+from+2005+through+2009





Norovirus and Rotovirus May Be Resistant to Alcohol Based Hand DisinfectantsMedicalResearch.com Interview with:

Erwin Duizer, PhDHead 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 virucidalactivity 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.


http://medicalresearch.com/infections/norovirus-and-rotovirus-may-be-resistant-to-alcohol-based-hand-disinfectants/13649/

http://medicalresearch.com/infections/nanobody-may-make-noroviruses-self-destruct/12501/







• Dr. Duizer: With the quantitative carrier test we found that the virucidal effect of the ethanol and propanol based products against the non-enveloped noroviruses, enteroviruses, parechoviruses and adenoviruses was limited; after 3 min still 1% or more was left infectious. The propanol based product performed slightly better than the ethanol based product, with good activity, within 30 s, against rotavirus and influenzavirus.

• The average virus reduction from finger pads was close to 3log10 (ie from 100% to 0.1%) for the propanol based products, but a transferable quantity of virus could still be detected on 5 out of 12 fingers. After hand washing with water and soap, no virus was detected on any of the finger pads.



http://medicalresearch.com/author-interviews/hand-dermatitis-increases-in-health-care-workers-due-to-hand-washing-measures/11689/







• Dr. Duizer: Often, the use of alcohol based hand hygiene products will contribute to reduced spread of many pathogens, including bacteria, enveloped viruses and rotavirus. However, many non-enveloped viruses such as noroviruses and enteroviruses, are quite resistant to alcohols and may require strict hand washing to prevent transmission.

• Citation:

• Reducing viral contamination from finger pads: handwashing is more effective than alcohol-based hand disinfectants, by Tuladhar et al.Journal of Hospital Infection Published Online: April 09, 2015

• DOI: http://dx.doi.org/10.1016/j.jhin.2015.02.019



http://medicalresearch.com/pediatrics/childhood-outbreak-acute-flaccid-paralysis-linked-to-respiratory-virus/11198/

http://dx.doi.org/10.1016/j.jhin.2015.02.019



CPAP For Sleep Apnea May Decrease Atrial Fibrillation RecurrenceMedicalResearch.com Interview with:

Dr. Larry Chinitz MDProfessor 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.


http://medicalresearch.com/sleep-disorders/cpap-for-sleep-apnea-may-decrease-atrial-fibrillation-recurrence/13675/

http://medicalresearch.com/stroke/sleep-apnea-increases-stroke-risk-in-atrial-fibrillation-patients/11231/






• MedicalResearch: What should clinicians and patients take away from your report?

• Dr. Chinitz: Treatment of Obstructive sleep apnea with continuous positive airway pressure is a significant means to reduce atrial fibrillation recurrence. Thus, sleep apnea should be suspected in patients with atrial fibrillation and in patients with its confirmed diagnosis, use of continuous positive airway pressure should be strongly advocated with the intention to reduce recurrence of atrial fibrillation.



http://medicalresearch.com/general-medicine/women-with-atrial-fibrillation-at-greater-risk-of-stroke-than-men/11921/






• MedicalResearch: What recommendations do you have for future research as a result of this study?

• Dr. Chinitz: Randomized clinical trials are necessary to shed more light on the interaction between use of continuous positive airway pressure use and atrial fibrillation recurrence in patients with sleep apnea.

• Citation:

• Journal of the American College of Cardiology: Clinical Electrophysiology, news release, April 20, 2015





Targeted Melanoma Panel Identifies Genetic Subsets of MelanomaMedicalResearch.com Interview with:

Melissa Wilson, MD, PhDAssisstant Professor Perlmutter Cancer Center

NYU Langone Medical Center New York, NY


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 BRAFmutations. 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.


http://medicalresearch.com/genetic-research/targeted-melanoma-panel-identifies-genetic-subsets-of-melanoma/13422/







• Dr. Wilson: This study provides a comprehensive examination of melanoma genetics and provides novel insights in addition to the known, prevalent somatic mutations which identify melanoma tumors currently. Of course, functional studies are needed to confirm the biology of these genetic observations.









• Dr. Wilson: It will be important to evaluate these novel genetic subsets in tumor samples from melanoma patients. In addition, correlation of these novel genetic subsets with clinicopathologiccharacteristics and response to treatment is imperative. Identification of a genetic profile for melanoma tumors has potential implications for treatment decisions.

• Citation:• Abstract presented at the 2015 AACR• 4668: Targeted, massively parallel sequencing identifies novel genetic subsets of cutaneous

melanomaTuesday, Apr 21, 2015Bradley Garman1, Clemens Krepler2, Katrin Sproesser2, Patrica Brafford2, Melissa Wilson3, Bradley Wubbenhorst1, Ravi Amaravadi4, Joseph Bennett5, Marilda Beqiri2, Michael Davies6, David Elder4, Keith Flaherty7, Dennie Frederick7, Tara C. Gangadhar4, Michael Guarino5, David Hoon8, GiorgosKarakousis4, Nandita Mitra1, Nicholas J. Petrelli5, Lynn Schuchter4, Batool Shannan2, Jennifer Wargo6, Min Xiao2, Wei Xu4, Xaiowei Xu4, Meenhard Herlyn2, Katherine Nathanson1. 1Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; 2The Wistar Institute, Melanoma Research Center, Philadelphia, PA; 3Perlmutter Cancer Center, NYU School of Medicine, NYU Langone Medical Center, New York, NY; 4University of Pennsylvania Abramson Cancer Center, Philadelphia, PA; 5Helen F. Graham Cancer Center, Newark, DE; 6MD Anderson Cancer Center, Houston, TX; 7Massachusetts General Hospital, Boston, MA; 8John Wayne Cancer Institute, Santa Monica, CA



http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=25#.VSWkVhcbq1t



Epigenetic Changes May Account For How Some Lymphoma Tumors Change Over TimeMedicalResearch.com Interview with:

Olivier Elemento, PhD Associate ProfessorHead, Laboratory of Cancer Systems Biology Department of Physiology and Biophysics

Institute for Computational Biomedicine Weill Cornell Medical College New York, NY, 10021


Dr. Elemento: In many cancer patients, initial treatment with chemotherapy or targeted therapy shrinks the tumor or makes it disappear; however the tumor eventually comes back in a form that is frequently resistant to treatment. This process is called relapse. In diffuse large B-cell lymphomas (an aggressive type of blood cancer), approximately 40% of patients eventually relapse. How relapse occurs and how these tumors adapt and become resistant to treatment is not well understood. Why 60% of patients do not relapse and are essentially cured of their disease while 40% relapse is not known. Many think the relapse process involves tumor cells acquiring DNA alterations that make them resistant to therapy. We have indeed previously identified such DNA mutations in diffuse large B-cell lymphomas (http://genomebiology.com/2014/15/8/432/abstract).

• However it became apparent to us and others that DNA mutations do not explain fully why these tumors become treatment-resistant and come back, sometimes years after initial diagnosis and therapy. We therefore turned to the epigenome to look for possible reasons. Specifically, we studied chemical modifications of DNA called DNA methylation. DNA methylation is transmitted faithfully from one cancer cell division to the next but can also be modified by specific enzymes. DNA methylation is thought to impact the way genes are expressed in tumors by modulating accessibility of DNA to proteins that regulate gene expression. DNA methylation is known to be altered in tumors. Could DNA methylation alterations also be at least partially responsible for relapse and resistance to treatment ?


http://medicalresearch.com/genetic-research/epigenetic-changes-may-account-for-how-some-lymphoma-tumors-change-over-time/13667/

http://genomebiology.com/2014/15/8/432/abstract






To address this question, we used a high-throughput DNA methylation profiling method to capture the DNA methylation landscape genome-wide. That is, we queried DNA methylation status at millions of locations in the tumor genome. We profiled B cell lymphoma biopsies from patients treated at Cornell and Torino. Since we were interested in how tumors change upon treatment, we profiled the initial tumor biopsy obtained at time of diagnosis (pre-treatment) then profiled the biopsy obtained at time of relapse in the same patients. The profiling produces enormous amounts of epigenomic data and we therefore had to use customized Big Data analytical algorithms together with supercomputers to interpret the methylation patterns.



http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-brain-metastasis-genomic-epigenomic-analysis/3884/






• Our main findings are as follows:

• 1) We found extensive changes in DNA methylation between diagnosis and relapse – many more epigenomic changes than DNA changes. The changes are partially random – every patient’s tumor changed in different ways. However, we observed many convergent changes. That is, near some genes, all or many patients undergo the same changes. Some of the genes are known to impact tumor biology, for example genes in the TGFbeta pathway. We also found significant epigenomic changes at genetic switches – the regions in the genome that control which genes are expressed. We think that DNA methylation changes occurring at relapse interfere with the function of these switches, and perturb expression of genes controlled by these switches.

• 2) Perhaps most interestingly, we found that the cell-to-cell methylation heterogeneity within tumors at time of diagnosis is highly predictive of relapse. Tumors with elevated cell-to-cell methylation heterogeneity, that is, tumors where every cell has a different methylation landscape, are more likely to relapse. The higher cell-to-cell methylation heterogeneity is, the faster tumors relapse.

• These are exciting findings that for the first time indicate a major role of the epigenome in supporting the evolution and adaptation of tumors in response to treatment.









• Dr. Elemento:

• 1) It is important to understand how tumors change in time, especially after treatment. This applies to all tumors, not only B cell lymphomas. A tumor found at relapse is not the same as the tumor found at initial diagnosis. Relapse tumors have evolved at the genomic level and even more so at the epigenomic level as our study shows. We cannot treat a relapse tumor as if it was the same tumor as the diagnosis one. The tumor changed – we need to understand what changed in order to tailor the treatment to the new tumor. This is important because for many patients, no biopsy is performed at time of relapse. This has to change.

• 2) The epigenome has potential clinical relevance. In our study we found that intra-tumor methylation heterogeneity early at diagnosis can predict which patients will eventually relapse and how fast they will relapse. The precise predictive power of the epigenome needs to be studied further but one may envision that eventually patients with elevated intra-tumor methylation heterogeneity will be monitored more aggressively for signs of relapse and/or given more aggressive treatment regimens since they may be at higher risk of relapse.









• Dr. Elemento: We need to better understand the role that the epigenome plays in tumor progression. What genes are affected and how? How does the tumor genome cooperate with the tumor epigenome ? Once we understand how the epigenome contributes to tumor progression, we may be able to find new ways to block or slow down such progression, maybe by modifying the epigenome. There are already FDA-approved drugs that can interfere with DNA methylation and other epigenetic mechanisms. Maybe such drugs will be used one day to limit the ability of tumors to evolve and adapt.

• At a time where precision medicine programs are put in place in hospitals across the country, we think it will be important to not only sequence the genome of patients but also characterize their epigenome. The epigenome may help understand the blueprint and alterations that led to disease (not only cancer) and provide a rich source of clinically actionable information.

• Citation:

• Olivier Elemento et al. Epigenomic evolution in diffuse large B-cell lymphomas. Nature Communications, April 2015 DOI: 10.1038/ncomms7921



http://medicalresearch.com/genetic-research/epigenetic-control-protein-allows-melanoma-cells-metatasize/10949/

http://dx.doi.org/10.1038/ncomms7921



PARP Inhibitor Combo For Cancer Patients With and Without BRCA MutationMedicalResearch.com Interview with:

Timothy Yap, MD, PhD, NIHR BRCThe Institute of Cancer Research and

The Royal Marsden NHS Foundation Trust London, United Kingdom.


Dr. Yap: This is a novel phase I trial assessing for the first time if the PARP inhibitor olaparibcan 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 olaparibwas 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.


http://medicalresearch.com/cancer-_-oncology/parp-inhibitor-combo-for-cancer-patients-with-and-without-brca-mutation/13562/







• Dr. Yap: The combination of olaparib and AZD5363 was well tolerated, with side effects including gastrointestinal symptoms, such as nausea, vomiting, diarrhea, as well as rash and fatigue. Out of 20 patients with advanced solid tumors, seven patients had either RECIST partial responses or prolonged disease stabilization. There were four confirmed RECIST partial responses, including in a patient with BRCA wild-type ovarian cancer, two patients with BRCA mutant breast cancer, and a patient with BRCA1-mutant ovarian cancer; two patients had ongoing prolonged RECIST disease stabilization, including a patient with BRCA unknown breast cancer at six months and a patient with peritoneal mesothelioma at one year, who had previously responded before progressing on treatment with a PI3K/mTORinhibitor. One patient with BRCA-mutant advanced prostate cancer also continues to have a sustained radiological response on MRI and by PSA tumor marker response criteria at 11 months.









• Dr. Yap: We have now established safe doses for this novel targeted combination and observed anticancer responses in patients with both BRCA positive and BRCA negative cancers. We are currently assessing this promising targeted combination of olaparib and AZD5363 in a larger cohort of patients with both BRCA and non-BRCA mutations. We believe that such PARP inhibitor based treatments have the potential to extend the use of PARP inhibitors to include patients with different types of non-BRCA positive cancers, such as breast, ovarian, prostate, small cell and pancreatic cancers. We also believe that other phase I trials of targeted combinations should incorporate the novel intrapatient dose escalation design assessed in this study to validate it independently.

• Citation:

• April 2015 AACR abstract:

• New PARP Inhibitor Combo Shows Early Promise for Cancer Patients With and Without BRCA Mutation

• MedicalResearch.com Interview with: Timothy Yap, MD, PhD, NIHR BRC (2015). PARP Inhibitor Combo For Cancer Patients With and Without BRCA Mutation



http://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=721#.VTePgRcbrEY



Opioid Tampering By Health Care Providers Can Lead To Hepatitis C TransmissionMedicalResearch.com Interview with:

Chong-Gee Teo, MD, PhDChief, Laboratory BranchDivision of Viral Hepatitis

CDC


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.


http://medicalresearch.com/hepatitis-liver-disease/opioid-tampering-by-health-care-providers-can-lead-to-hepatitis-c-transmission/13682/





CDC


• Dr. Teo: Disproportionately many cases of HCV infection from healthcare-associated hepatitis C outbreaks were attributable to provider tampering of anesthetic opioids. Thus, tampering was associated with 17% (8/46) of these outbreaks, but 53% (438/833) of cases.

• Of the eight tampering outbreaks studied, four (50%) were transmitted by anesthesiologists or nurse anesthetists, and the other four by allied health professionals. Six of the outbreaks (75%) involved fentanyl tampering. Spain hosted the largest outbreak (between 1988 and1997), involving 275 cases, and Australia the next largest (between 2006 and 2009), with 49 cases. Five outbreaks were reported from the United States, which generated 81 infected patients; the largest outbreak occurred in New Hampshire (between 2010 and 2012), involving 32 cases.

• Modeling studies showed that the likelihood of HCV transmission to a patient from exposure to an opioid preparation tampered by a provider unknown to be an injecting drug user or HCV infected (0·004%) is about >100 higher than from exposure to surgery conducted by a surgeon unknown to be HCV-infected (0·0004%). This risk escalates >15,000 times when exposure is to an opioid preparation tampered by a provider who is an injector. To pose a 50% risk of transmission, a surgeon, even when HCV-infected, can take as long 30 years, but a provider who is an injector takes only weeks or months, depending on how successful the provider is with opioid tampering at the workplace.



http://medicalresearch.com/hepatitis-liver-disease/hepatitis_c/3981/





CDC


• Dr. Teo: Testing for and treatment of HCV infection in providers, regardless of whether or not they are injectors, have access to controlled substances, or conduct exposure prone procedures, are beneficial and can extend from care and management recommendations and guidelines already developed for providers infected by blood-borne viruses. In the era of highly efficacious anti-HCV therapy, providers should feel less helpless after being found HCV infected and be more willing to avail themselves to testing and curative treatment.



http://medicalresearch.com/general-medicine/chronic_hepatitis_c_clinical_outcome_tool/5218/





CDC


• Dr. Teo: To reduce the risk of harm to patients from providers who tamper with anesthetic opioids, the following measures are suggested:

• periodic opioid screening of providers

• raising greater awareness among healthcare staff about provider substance abuse and provider diversion of controlled drugs

• educating healthcare staff on how colleagues abusing narcotics might be identified

• adopting computerized dispensing and charting systems to monitor controlled drug access

• and enabling staff recruitment agencies and bodies that credential and license healthcare professionals to verify past criminal history and reports of adverse actions taken by regulatory authorities and employers.

• Citation:

• Nosocomial hepatitis C virus transmission from tampering with injectable anesthetic opioids.

• Hepatology. 2015 Mar 22. doi: 10.1002/hep.27800. [Epub ahead of print]

• Hatia RI1, Dimitrova Z, Skums P, Teo EY, Teo CG.



http://www.ncbi.nlm.nih.gov/pubmed/25808284





Parent-Training Improves Behavioral Problems In Children With AutismMedicalResearch.com Interview with:

Lawrence Scahill, MSN, PhD and Karen Bearss, PhDDepartment of Pediatrics, Marcus Autism Center

Children’s Healthcare of Atlanta and Emory University Atlanta, Georgia


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% .


http://medicalresearch.com/mental-health-research/autism/parent-training-improves-behavioral-problems-in-children-with-autism/13685/

http://medicalresearch.com/mental-health-research/autism/autism_gene_that_removes_defective_proteins_may_be_altered/7564/







• Response: Both treatments resulted in improvement – but parent training was clearly better.

• The parent training program consists of 11 core sessions, 2 optional sessions, 2 telephone boosters, and 2 home visits. Our parent training program is relatively brief and can be implemented in a wide range of settings. With training, it can delivered by a wide range of practitioners.

• Persistent disruptive behavior often promotes uncertainty for parents about how to deal with these behaviors.

• By providing practical tools, parent training fosters parental confidence and promotes success in everyday life for the child and family.









• Response: Over the past decade our multisite group has developed and now tested a structured parent training program designed to teach parents how to address behavioral problems in young children with ASD. The intervention is acceptable to parents and it can be reliably delivered by therapists trained in the manual.

• This multi-site randomized trial showed that parent training is effective in reducing behavioral problems in young children with Autism spectrum disorder. Parent training is ready for wider implementation.

• The study was conducted by the Research Units on Behavioral Intervention (RUBI) Autism Network (Emory University, Indiana University, Ohio State University, University of Pittsburgh, University of Rochester and Yale University).

• The study was funded by the National Institute of Mental Health with addition support from Marcus Foundation and the JB Whitehead Foundation.

• Citation:

• Bearss K, Johnson C, Smith T, et al. Effect of Parent Training vs Parent Education on Behavioral Problems in Children With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA. 2015;313(15):1524-1533. doi:10.1001/jama.2015.3150.



http://medicalresearch.com/mental-health-research/autism/rise_in_autism_rates_largely_due_to_changes_in_diagnostic_criteria/8678/

http://jama.jamanetwork.com/article.aspx?articleid=2275445



increased Air Pollution Linked To More Strokes, Smaller Brain VolumesMedicalResearch.com Interview with:

Elissa Hope Wilker, Sc.D.Beth Israel Deaconess Medical CenterCardiovascular 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.


http://medicalresearch.com/stroke/increased-air-pollution-linked-to-more-strokes-smaller-brain-volumes/13689/

http://medicalresearch.com/mental-health-research/anxiety-symptoms-raised-by-air-pollution/12903/

http://medicalresearch.com/stroke/air-pollution-linked-to-increased-risk-of-stroke/12937/







• Dr. Wilke: Our findings suggest that air pollution is associated with insidious effects on structural brain aging, even in dementia- and stroke-free individuals. This work aids in our understanding of what might be going on in terms of associations observed between particulate air pollution exposures and clinically observed outcomes like stroke and impaired cognitive function.



http://medicalresearch.com/heart-disease/air-pollution-may-raise-risk-of-carotid-artery-stenosis/12710/







• Dr. Wilke: These are findings that will need to be confirmed or refuted in future work. We believe it will be interesting to investigate the impact of air pollution over a longer period, its effect on more sensitive MRI measures, on brain shrinkage over time, and other risks including of stroke and dementia.

• Citation:

• Long-Term Exposure to Fine Particulate Matter and Residential Proximity to Major Roads and Measures of Brain Structure

• Elissa Wilker*, Beth Israel Deaconess Medical Center, United States, [email protected]; Sarah Preis, Boston University School of Medicine, United States, [email protected]; Alexa Beiser, Boston University School of Medicine, United States, [email protected]; Philip Wolf, Boston University School of Medicine, United States, [email protected]; Joel Schwartz, Harvard School of Public Health, United States, [email protected]; Petros Koutrakis, Harvard School of Public Health, United States, [email protected]; Rhoda Au, Boston University School of Medicine, United States, [email protected]; Sudha Seshadri, Boston University School of Medicine, United States, [email protected]; Murray Mittleman, Beth Israel Deaconess Medical Center, United States, [email protected];

• Environmental Health PerspectivesAbstract Number : 1641 | ID : O-024



http://ehp.niehs.nih.gov/isee/o-024/



AFib Increases Hospital Costs For Young and Older Stroke PatientsMedicalResearch.com Interview with:

Guijing Wang, PhD Senior health economistDivision for Heart Disease and Stroke Prevention

Centers for Disease Control and Prevention


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.


http://medicalresearch.com/stroke/afib-increases-hospital-costs-for-young-and-older-stroke-patients/13694/

http://medicalresearch.com/stroke/stent-thrombetomy-may-be-new-standard-of-care-for-ischemic-stroke/11281/

http://medicalresearch.com/heart-disease/afib-progression-after-failed-ablation-drug-therapy-vs-re-ablation/1776/







• Dr. Wang: Stroke is the fifth leading cause of death in the United States, killing nearly 130,000 Americans each year and costing an estimated $34 billion annually in health care and lost productivity. This study helps to identify future research areas, such as the need to separately examine the health and economic burden of initial and recurrent strokes, or evaluate the cost-effectiveness of interventions for AFib and stroke prevention and control. And these findings will help clinicians, patients and public health representatives focus efforts as needed.

• For example, although research and public health efforts have focused on stroke management and prevention among those over 65-years-old, stroke interventions among younger adults may have great potential from an economic perspective. In addition, the higher costs associated with AFib could suggest that strokes related to the disorder might be more severe than those not linked to it – or it may reflect the added costs of diagnosis and treatment of AFib. Prevention of ischemic stroke in patients with AFib is potentially effective in reducing the disability and economic burden associated with stroke.










• Dr. Wang: AFib-associated costs among the elder population are still unknown, so further research is necessary to better understand the total economic burden nationwide. In addition, more examination of the impact of AFib on hospital costs for repeat stroke admissions is recommended, as well as research into variations in hospital costs across geographic regions of the U.S.

• Citation:

• Hospital Costs Associated With Atrial Fibrillation for Patients With Ischemic Stroke Aged 18–64 Years in the United States

• Wang G1, Joo H2, Tong X2, George MG2.

• Stroke. 2015 Apr 7. pii: STROKEAHA.114.008563. [Epub ahead of print]

• http://www.ncbi.nlm.nih.gov/pubmed/25851767



http://medicalresearch.com/general-medicine/women-with-atrial-fibrillation-at-greater-risk-of-stroke-than-men/11921/







HPV Vaccine Provides Protection at Multiple SitesMedicalResearch.com Interview with:

Daniel C. Beachler, PhD Postdoctoral fellowInfections and Immunoepidemiology Branch of the

National Cancer Institute (NCI)


• 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


http://medicalresearch.com/cancer-_-oncology/hpv-vaccine-provides-protection-at-multiple-sites/13618/

http://medicalresearch.com/author-interviews/oral-transmission-hpv/8967/







• Dr. Beachler: This research supports current US guidelines for HPV vaccination from the CDC. They recommend routine vaccination in 11-12 year olds, who are the least likely to be previously exposed to HPV. In addition, vaccination is recommended through the age of 26 in females who were not vaccinated previously. This is important given that only half of US females under 18 have been HPV vaccinated.



http://medicalresearch.com/author-interviews/new-ninevalent-hpv-vaccine-gives-greater-protection-against-cervical-cancer-and-genital-warts/12147/







• Dr. Beachler: Further research into better understanding HPV infection occurring outside the cervix is necessary, particularly determining how often oral and anal HPV infections are acquired at older ages.

• Citation:

• Presented at the AACR Annual Meeting 2015 April 2014

• HPV Vaccine Provides Protection at Multiple Sites Even Among Some Previously Exposed



http://medicalresearch.com/infections/hpv-infections-race-may-influence-natural-history/1317/



Seizure Medication Reduced Optic Neuritis In Multiple SclerosisMedicalResearch.com Interview with:

Dr. Raj KapoorNational Hospital for Neurology and Neurosurgery

University College London Hospitals NHS Foundation Trust


Dr. Kapoor: Current treatments for Multiple Sclerosis do not prevent disability which accumulates from relapses, or which progresses between relapses. Experimental work suggests that the neurodegeneration which underlies disability could be prevented using agents which block voltage gated sodium channels. We have tested this possibility using treatment with the sodium channel blocker phenytoin in patients with acute optic neuritis. We tested whether phenytoin could prevent the degeneration seen in the retinal nerve fiber layer and macula after an attack of optic neuritis.


http://medicalresearch.com/ophthalmology/seizure-medication-reduced-optic-neuritis-in-multiple-sclerosis/13702/






Medical Research: What are the main findings?

Dr. Kapoor: The main findings are that the group of patients treated with phenytoin had less degeneration in the retinal nerve fiber layer (rnfl) and in the macula (mv) in the eye affected by optic neuritis than the group treated with placebo. Phenytoin treatment reduced the degeneration by 30 % (rnfl) – 34% (mv).









• Dr. Kapoor: This is a study designed to test the concept of neuroprotection, and it appears that the treatment was successful. Phenytoin did not lead to better vision after optic neuritis, but our trial was too small to determine whether phenytoin could achieve this. By providing proof of concept for the treatment target, however, and by demonstrating neuroprotectionso robustly, we hope to open a door to even better treatments to prevent disability in Multiple Sclerosis.









• Dr. Kapoor: The trial suggests that proof of neuroprotection using different treatment targets could be sought in similar trials in optic neuritis. Better treatment effects could be achieved by refining the trial design, for example by looking for drugs with more potent effects on the relevant sodium channels, by treating even earlier from the onset of optic neuritis, and by combining such neuroprotection with other treatments to promote remyelination and to suppress inflammation in Multiple Sclerosis.

• Citation:

• 2015 AAN abstract :

• Phenytoin is Neuroprotective in Acute Optic Neuritis: Results of a Phase 2 Randomized Controlled Trial



https://www.aan.com/conferences/2015-annual-meeting/



Gene Expression Profile Improves Melanoma Risk AssessmentMedicalResearch.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.


http://medicalresearch.com/genetic-research/gene-expression-profile-improves-melanoma-risk-assessment/13707/

http://medicalresearch.com/author-interviews/sentinel-lymph-node-biopsy-should-be-considered-for-all-thick-melanomas/12016/






• 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.

• Primary tumor tissue from 217 Stage I, II, III, or IV cutaneous melanoma patients with documented sentinel lymph node biopsy (SLNB) results was analyzed using the DecisionDx-Melanoma GEP test, developed by Castle Biosciences, Inc., under a multicenter, prospectively-planned, archival tissue study protocol. DecisionDx-Melanoma is a noninvasive test developed to identify high risk disease independent of other staging methods, such as AJCC stage and SLNB status. Using tissue from the primary melanoma, the DecisionDx-Melanoma test measures the expression of 31 genes and stratifies patients as either low risk Class 1 or high risk Class 2

• The predictive accuracy of the DecisionDx-Melanoma and SLNB prognostic tools were evaluated individually and in combination to assess primary endpoints of disease-free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS). Independently, the Gene Expression Profile and SLNB tests were shown to stratify patients according to their risk (univariate analysis using Cox proportional hazards p<0.0001 for GEP for all endpoints, SLNB for DFS and DMFS; SLNB for OS p=0.0099).

• Multivariate analysis found GEP Class to be independent of SLNB status for all endpoints (p<0.0001) and SLNB status to be independent of GEP Class for DFS (p=0.008) and DMFS (p=0.001) but not OS (p=0.11).

• Combining the GEP and SLNB tests showed improvements in stratifying patients who were SLNB negative. The SLNB negative group as a whole had a DFS of 55 percent. Using the GEP test to further stratify those patients resulted in identification of a higher risk (Class 2) sub-group of SLNB negative patients who had a DFS of 35 percent. Likewise, SLNB negative patients who were predicted to be low risk (Class 1) using the GEP had a DFS of 83 percent.








• MedicalResearch: What are the conclusions of the study?

• Dr. Gerami: Use of the GEP test, both independently and in combination with SLNB will help clinicians identify high-risk SLNB-negative patients with aggressive disease and patients identified as high-risk by conventional parameters who are unlikely to have progression of their disease. Based on data from our study and a prior validation study (published earlier this year in Clinical Cancer Resrearch), this non-invasive GEP prognostic tool could be used to help clinicians more accurately stratify patients as higher versus lower risk. We believe that the use of GEP prognostic testing may identify the majority of patients who are at risk for metastasis.

• Citation:

• J Am Acad Dermatol. 2015 May;72(5):780-785.e3. doi: 10.1016/j.jaad.2015.01.009. Epub 2015 Mar 3.

• Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

• Gerami P1, Cook RW2, Russell MC3, Wilkinson J4, Amaria RN5, Gonzalez R6, Lyle S7, Jackson GL8, Greisinger AJ9, Johnson CE2, Oelschlager KM2, Stone JF4, Maetzold DJ2, Ferris LK10, Wayne JD11, Cooper C12, Obregon R12, Delman KA3, Lawson D3.








Leveraging Big Data to Accelerate Drug DiscoveryMedicalResearch.com Interview with:

Neel S. Madhukar Graduate student in the lab ofOlivier Elemento, PhD, Associate Professor

Head, Laboratory of Cancer Systems BiologyDepartment of Physiology and Biophysics Institute for Computational BiomedicineWeill Cornell Medical College

• findings?

• Response: It takes on average 2.6 billion dollars and 10-15 years to develop a single new drug. Despite massive investment in drug discovery by pharmaceutical companies, the number of drugs obtaining FDA approval each year has remained constant over the past decade. One of biggest bottlenecks in the process of developing a new drug is to understand precisely how a drug works, that is, what it binds to in cells, how it binds, and what it does when it is bound. This process is collectively called target identification and characterization of mechanisms of action. At present, target identification is a slow and failure-prone process, driven by laborious experimentation. Every time we seek to develop a new drug, such laborious experimentation needs to be redone from scratch. We are not learning from data acquired from our past successes and failures.

• In Dr Olivier Elemento’s research laboratory at Weill Cornell Medical College, we have embarked on a journey to reboot the drug discovery process by adopting a Big Data strategy leveraging the plethora of drug data available.

• In work presented at AACR’15 in Phildadelphia(http://meyercancer.weill.cornell.edu/news/2015-04-21/new-tool-predicts-drug-targets-and-ids-new-anticancer-compounds) (http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3682&sKey=260955b6-99db-46c5-afd1-d0f832af42b5&cKey=d9d0b004-de88-4d49-962d-214863b271ba&mKey=19573a54-ae8f-4e00-9c23-bd6d62268424),


http://medicalresearch.com/medication-research/leveraging-big-data-to-accelerate-drug-discovery/13724/

http://meyercancer.weill.cornell.edu/news/2015-04-21/new-tool-predicts-drug-targets-and-ids-new-anticancer-compounds

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3682&sKey=260955b6-99db-46c5-afd1-d0f832af42b5&cKey=d9d0b004-de88-4d49-962d-214863b271ba&mKey=19573a54-ae8f-4e00-9c23-bd6d62268424






we described a new Big Data technique for accelerating drug discovery called BANDIT –a Bayesian Approach to determine Novel Drug Interaction Targets. BANDIT takes in information from a variety of datasets – in vitro drug efficacy across hundreds of cell lines, change in gene expression of thousands of genes upon drug treatment, millions of bioassays, complex description of drug structure, and reported side effects – and combines them through a probabilistic approach to predict the targets of a given small molecule. Each of these datasets is independently quite large and, thus combining them produced an enormous database that we had to use Big Data analytical algorithms together with supercomputers to analyze.








• Here are the main findings of this study :• Through the creation of BANDIT we have put together the largest and most comprehensive

database of small molecule target and effect information. This database will be invaluable to future research on improving drug discovery.

• We created a Big Data driven method that predicts the targets of drugs in a rapid and comprehensive manner. Using drugs with known targets and a statistical procedure called cross-validation, we clearly demonstrated that when it comes to drug discovery, the more data the better. The more data describing small molecule activity we integrated into BANDIT the more accurately we recovered their targets across a test set of known drugs.

• We applied BANDIT to over 50,000 small molecules with no known target or mechanistic information to predict targets and identify a potential therapeutic role. We made predictions for over 40% of these small molecules. In some cases, these predictions point to a new role for known drugs. One example is that we predicted Vismodegib a drug used to treat forms of skin cancer, to also act as a tyrosine kinase inhibitor, indicating its potential to be utilized in other treatment avenues.

• We found a set of novel molecules that BANDIT predicted to disrupt microtubules. We focused on microtubules because they are important targets for cancer chemotherapy. Together with our colleagues Evi Giannakakou and Prashant Khade at Weill Cornell Medical College, we performed experiments that clearly validate BANDIT’s prediction that these small molecules inhibit microtubules.

• We also demonstrated that BANDIT not only predicts the target of small molecules with high accuracy, but it also predicts precise mechanisms of action of small molecules, for example whether a molecule that acts on microtubules works by perturbing microtubule polymerization or depolymerization or works through a completely novel mechanism.








• Medical Research: What should clinicians and patients take away from your report?• Using BANDIT, we predict that the time and cost of drug development will be significantly

alleviated, and will allow treatments to reach patients much quicker than current practices would allow. BANDIT will help not only by predicting individual targets, but also by helping researchers determine the most cost-effective way to proceed with their drug development efforts. That is, BANDIT can indicate which data-generating experiment is most informative about a small molecule’s mechanism of action.

• Some of the new molecules that we showed computationally and experimentally to target microtubules might end up being valuable novel chemotherapeutic agents. Microtubules play a key role in cell proliferation and inhibiting them has tremendous efficacy in killing cancer cells and targeting other proliferative diseases. A commonly used antimicrotubule drug such as Docetaxelrepresents more than a 3 billion dollars market. However many patients do not respond to approved antimicrotubule agents or develop resistance. Adding new antimicrotubule drugs to the oncologist’s arsenal would enable to better treat many patients and perhaps target certain cancers that are hard to treat with standard microtubule chemotherapy and/or provide additional options for patients who have become resistant to existing antimicrotubule drugs.

• More broadly, one of the major problems in cancer patient care is developed drug resistance. There are many drugs that work well for a short period of time but eventually patients develop resistance and their condition relapses. By finding new molecules that act upon clinically relevant targets, there is a potential to discover new drugs that could overcome resistance mechanisms. BANDIT has the potential to dramatically accelerate the discovery of such molecules.

• Additionally, many diseases – such as brain cancers – are difficult to treat because of the inability of drugs to permeate the brain barrier. But, by determining a set of molecules with varying structures that all have the same target there is the potential to find a new drug able to overcome this challenge.



http://medicalresearch.com/cancer-_-oncology/breast-cancer/improved-survival-combination-therapy-her2-positive-metastatic-breast-cancer/11713/







• Response: We think that Big Data analytics will play an increasingly important role in drug discovery. As discussed before, we are not developing drugs fast enough. On the other hand, we have accumulated tremendous amounts of data on small molecule’s clinical safety, efficacy, and toxicity. Technologies such as automation, next-generation sequencing, genome engineering (CRISPR) can now be used to generate ever more such data. Now is the time to integrate everything we know about small molecules to predict their activity. We can build predictive models of drug toxicity and Big Data-driven models that predict how to combine drugs to maximize efficacy, decrease the likelihood of acquired resistance and minimize toxicity.

• To complement the work presented at AACR15, in our laboratory at Weill Cornell, we are essentially adopting a “Moneyball” approach to drug discovery. Using machine learning, we are actively seeking features of small molecules that predict a drug’s lack of toxicity, efficacy and eventual FDA approval. For these analyses we are combing through large databases of successful and failed clinical trials in humans, seeking to combine these data with small molecule activity and target information. Our initial results look promising and indicate for example that one can predict with reasonably high accuracy which clinical trials will fail early due to toxicity reasons. Such Big Data models may speed up the drug discovery process by identifying early the drugs and targets that are most likely to fail to reach FDA approval.

• Presented at the April 2015 AACR Conference in Philadelphia



http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=25#.VTwS1RcbquU



Antibacterial Gloves May Reduce Cross Contamination In ICU SettingMedicalResearch.com Interview with:

Ojan Assadian, M.D., DTMHProfessor for Skin Integrity and Infection Prevention Institute for Skin Integrity and Infection Prevention

School of Human & Health Sciences University of Huddersfield Queensgate, Huddersfield UK


• Prof. Assadian: Although medical gloves serve as an important mechanical barrier to prevent healthcare workers’ hands from getting contaminated with potentially pathogenic microorganisms, their inappropriate and incorrect use may support microbial transmission, eventually resulting in indirect horizontal cross-contamination of other patients.

• We conducted a clinical study designed to determine the efficacy of a newly developed synthetic antibacterial nitrile medical glove coated with an antiseptic, polyhexamethylen-biguanid hydrochloride (PHMB), on its external surface, and compared this antibacterial glove to an identical non-antibacterial glove in reducing surface contamination after common patient care measures in an intensive care unit.

• We found significantly lower numbers of bacteria on surfaces after performing typical clinical activities such as intravenous fluid handling, oral toilet, or physiotherapy, if touched with antibacterial gloves.


http://medicalresearch.com/infections/hospital-acquired/antibacterial-gloves-may-reduce-cross-contamination-in-icu-setting/13727/







• Prof. Assadian: Hand hygiene is one of the most important measures to prevent infection in the health care setting. The concept of hand hygiene, however, does not start and end with using alcohol-based hand rubs before and after patient care, but includes also the correct use of medical gloves.

• In 1996, the US Hospital Infection Control Practices Advisory Committee (HICPAC) published its “Guideline for isolation precautions in hospitals”. This guideline adjusted the previous concept of isolation precautions and introduced the concept of “Standard Precautions”, which mandates that all health-care workers who come in contact with body fluids should wear gloves. However, in practice it is largely ignored that this recommendation does not advocate the use of gloves for all clinical procedures; instead, healthcare workers are advised to assess the risk for possible contamination of hands in each clinical situation. However, frequent and often incorrect usage of glove is increasing observed without adequate risk assessment.



http://medicalresearch.com/infections/hand-hygiene-global-strategy/2060/








• Prof. Assadian: Although our study demonstrated that the use of antibacterial medical gloves does support reduction of cross-contamination in the ICU setting, such technical solutions alone do not help in solving issues with compliance to hand hygiene. Certainly it would be wrong to advocate universal use of antibacterial gloves as a measure to reduce cross-contamination instead of following the principles of hand hygiene. We still have to understand reasons for non-compliance to hand hygiene better.

• Citation:

• Evaluation of the efficacy of an antibacterial medical glove in the ICU setting

• Kahar-Bador, V. Rai, M.Y. Yusof, W.K. Kwong, O. Assadian

• Journal of Hospital InfectionDOI: http://dx.doi.org/10.1016/j.jhin.2015.03.009

• Publication stage: In Press Accepted Manuscript Published online: April 22, 2015



http://medicalresearch.com/outcomes-safety/hand-hygiene-improvement-program-electronic-monitoring-and-compliance/776/

http://authors.elsevier.com/sd/article/S0195670115001553






Carotid Artery Stenting: Comparison Of Embolic-Prevention DevicesMedicalResearch.com Interview with

Jay Giri, MD MPHDirector, Peripheral Intervention

Assistant Professor of Clinical Medicine University of Pennsylvania

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to

decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery. When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke). In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain.

• Two types of EPD exist. The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD).

• The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement.

• Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices. We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting.

• Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices. These studies have shown mixed results. However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices.

• We found that overall uptake of proximal embolic protection devices utilization in America has not been robust. Less than 7% of all domestic CAS procedures are performed with this technology. Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).


http://medicalresearch.com/stroke/carotid-artery-stenting-comparison-of-embolic-prevention-devices/13734/

http://medicalresearch.com/stroke/stroke-risk-increased-risk-with-intraplaque-carotid-artery-hemorrhage/1856/







• Dr. Giri: Use of proximal EPD during CAS was associated with low rates of in-hospital stroke/death similar to those with distal filter embolic protection devices. We cannot rule out a small benefit of proximal embolic protection devices and it certainly did not appear harmful. As such, we believe operator discretion should be used to select between the devices in given circumstances.



http://medicalresearch.com/author-interviews/mortality-risks-high-in-elderly-patients-after-carotid-artery-stenting/10565/







• Dr. Giri: Given our results, we have concluded that it is unlikely that a large controlled trial randomizing patients to these 2 devices will be feasible. This is because population-wide differences between the devices are small, so the scope of such a trial would be have to be very large (greater than 6,000 patients all followed for at least 30 days after the procedure).

• Citation:

• Giri J, Parikh SA, Kennedy KF, et al. Proximal Versus Distal Embolic Protection for Carotid Artery Stenting: A National Cardiovascular Data Registry Analysis. J Am Coll Cardiol Intv. 2015;8(4):609-615. doi:10.1016/j.jcin.2015.02.001.



http://interventions.onlinejacc.org/article.aspx?articleid=2276874



Malaria Vaccine Has Potential To Contribute To Disease ControlDr. Mary Hamel MedicalResearch.com Interview with:

Mary J Hamel, M.D. Chief, Strategic and Applied Sciences Unit,And Deputy Branch Chief for Science, CDC Malaria Branch US Centers for Disease Control and Prevention

Atlanta GA 30333

• Medical Research: What is the background for this study? What are the main findings?• Dr. Hamel: Major progress has been made in malaria control during the past decade with the scale up of

proven interventions including insecticide treated nets (ITNs), indoor residual spraying, effective diagnosis and treatment for malaria, and intermittent preventive treatment of malaria in pregnancy. Nonetheless, malaria remains a major cause of morbidity and mortality, and a leading cause of pediatric death worldwide. An estimated 198 million cases of malaria and 580,000 deaths occurred in 2013 – most of these in African children.

• Now we face additional challenges in malaria control – the emergence of insecticide and drug resistance threatens some of our most effective interventions. New tools are needed to reach the goal of malaria elimination and eventual eradication. Vaccines are some of our most cost-effective interventions, and an effective malaria vaccine would be an important addition to our current malaria control tools.

• This week, the RTS,S Clinical Trials Partnership published the final vaccine efficacy and safety results from the RTS,S/AS01 malaria vaccine phase 3 trial in the Lancet (Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial, http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60721-8/abstract). This large randomized controlled double-blind phase 3 clinical trial was conducted in 11 sites in 7 African countries across a range of malaria transmission levels. In all, 15,460 children and young infants were enrolled in two age-categories, those first vaccinated at 5-17 months of age (referred to as children), and those first vaccinated at 6-12 weeks of age (referred to as young infants) who received the RTS,S/AS01 vaccine along with their routine childhood immunizations. Participants were randomized into 3 groups – the first group received three doses of the RTS,S/AS01 vaccine followed 18 months later by a booster dose; the second group received three doses of the RTS,S/AS01 vaccine without a booster; and the third group received a comparator vaccine. All participants received an ITN. Children were followed for an average of 48 months and infants for an average of 38 months.


http://medicalresearch.com/infections/malaria-vaccine-has-potential-to-contribute-to-disease-control/13738/

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60721-8/abstract)





Atlanta GA 30333

• We found that vaccine efficacy was modest. Vaccine efficacy against clinical malaria in children was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was 32% with a booster and non-significant without. Efficacy results in young infants were lower than those in children– vaccine efficacy against clinical malaria was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was non-significant.

• However, impact, defined as the number of cases averted per 1000 participants vaccinated, was substantial in both age-categories, and highest where malaria burden was greatest. In children who received the booster, during 4 years follow-up, 1700 cases of clinical malaria were averted per 1000 children vaccinated. In young infants, during 3 years follow-up, nearly 1000 cases were averted per 1000 young infants vaccinated.

• The safety findings were comparable overall in the different study arms, but two safety findings are notable. Meningitis occurred more frequently among children (but not young infants) who received RTS,S/AS01 than among those who received the comparator vaccines. There was no relationship between when the vaccine was administered and when meningitis occurred, most cases occurred in only two study sites, and the finding may be due to chance. If RTS,S/AS01 is licensed, post-licensing studies will be done to establish the significance of this finding. Both children and young infants experienced more episodes of fever and associated febrile convulsions during the 7 days following vaccination; convulsions occurred in 2.2 – 2.5/1000 vaccine doses.







Atlanta GA 30333


• Dr. Hamel: Malaria continues to be a major cause of morbidity and mortality, and a major cause of pediatric deaths in Africa. To date, there is no licensed vaccine against malaria. The RTS,S/AS01 malaria vaccine is the first malaria vaccine to show efficacy in a phase 3 clinical trial. Vaccine efficacy is modest, but impact is considerable. The vaccine has the potential to make a substantial contribution to malaria control when used with other effective malaria control interventions, especially in areas of high transmission.







Atlanta GA 30333


• Dr. Hamel: Should the RTS,S/AS01 be recommended for use, it will be the first vaccine against malaria, but it will not be the last. Early trials to improve the efficacy of RTS,S/AS01 have already begun, as have malaria vaccine trials using different platforms.

• Citation:

• RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. The Lancet, 2015 DOI: 10.1016/S0140-6736(15)60721-8



http://dx.doi.org/10.1016/S0140-6736(15)60721-8



Dashboard Metrics Improve Physician Compliance With GuidelinesMedicalResearch.com Interview with:

Henry J. Michtalik MD, MPH, MHSDepartment of Medicine, Johns Hopkins University

Armstrong Institute for Patient Safety and Quality Baltimore, Maryland


Dr. Michtalik: Current healthcare reform emphasizes providing high-value, evidence-based care. Compliance with practice guidelines and best-practices remains a challenge in the ever-changing healthcare environment. Multiple methods are typically used to enhance compliance with these guidelines, including physician education, computerized order entry systems with clinical decision support, provider feedback, and payment incentives. These strategies are used for many conditions, including heart failure and venous thromboembolism (VTE), blood clots.

• The purpose of this study was to examine the impact of an individualized physician dashboard and pay-for-performance program on improving VTE prophylaxis rates amongst hospitalists. We performed a retrospective analysis of over 3000 inpatient admissions to a hospitalist service. We examined the impact of a web-based hospitalist dashboard which provided VTE prophylaxis feedback, both alone and in combination with a pay-for performance program which provided a small financial payment for achieving compliance rates greater than 80%.

• We found that compliance significantly increased from 86% during baseline to 90% during the dashboard alone phase. Addition of the pay-for-performance program further increased compliance to 94%. The fastest improvement occurred during the dashboard only phase. Annual physician payments ranged from $53 to $1244, with 17 of the 19 payments under $1000.


http://medicalresearch.com/author-interviews/dashboard-metrics-improve-physician-compliance-with-guidelines/13749/



Dashboard Metrics Improve Physician Compliance With GuidelinesMedicalResearch.com Interview with:

Henry J. Michtalik MD, MPH, MHSDepartment of Medicine, Johns Hopkins University

Armstrong Institute for Patient Safety and Quality Baltimore, Maryland


• Dr. Michtalik: Feedback is critical for improving provider compliance with guidelines and can be done by using real-time dashboards. Payment incentives served primarily as a method to engage providers and the fastest improvement occurred during the dashboard only phase, emphasizing the importance of directed feedback.


• Dr. Michtalik: Physician dashboards can be tailored to the specific priorities of a hospital, such as readmissions and length of stay. Similarly, financial incentives can be adjusted based on institutional priorities and resources. Both dashboards and pay-for-performance can be used to enhance compliance with practice guidelines and achievement of quality metrics.

• Citation:

• Michtalik, H. J., Carolan, H. T., Haut, E. R., Lau, B. D., Streiff, M. B., Finkelstein, J., Pronovost, P. J., Durkin, N. and Brotman, D. J. (2015), Use of provider-level dashboards and pay-for-performance in venous thromboembolism prophylaxis. J. Hosp. Med., 10: 172–178. doi: 10.1002/jhm.2303



http://onlinelibrary.wiley.com/doi/10.1002/jhm.2303/abstract



Single Pill Combination Therapy For Some Hepatitis C SubtypesMedicalResearch.com Interview with:

Stefan Zeuzem, MDProfessor of Medicine Chief Department of Medicine

Goethe University Hospital Frankfurt


Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C(without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299/316 achieved SVR12 (undetectable HCV 12 weeks after treatment), including 144/157 with genotype-1a, 129/131 with genotype-1b, 18/18 with genotype-4, 8/10 with genotype-6, 68/70 with cirrhosis, and 231/246 without cirrhosis. Virologicfailure occurred in 13 patients including 1 breakthrough and 12 relapses, and was associated with baseline NS5A-polymorphisms and emergent NS3- and/or NS5A-variants. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo arms, respectively; none were considered drug-related.


http://medicalresearch.com/hepatitis-liver-disease/single-pill-combination-therapy-for-some-hepatitis-c-subtypes/13742/

http://medicalresearch.com/general-medicine/chronic_hepatitis_c_clinical_outcome_tool/5218/







• Dr. Zeuzem: Various interferon-free regimen are available for patients with chronic hepatitis C. Grazoprevir and Elbasvir are co-formulated and will be the second available treatment regimen with a single pill per day. The new treatment is restricted to patients infected with HCV genotypes 1, 4, and 6. In previously untreated patient the addition of ribavirin to this regimen is not required









• Dr. Zeuzem: Future research should explore the higher virologic relapse rate in high-viraemic, HCV-1a infected patients with pre-existent resistance-associated variants against elbasvir. The requirement of molecular tests to test for these variants before initiation of theray should be carefully defined.

• Citation:

• Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic HCV Genotype 1, 4, or 6 Infection: A Randomized Trial

• Stefan Zeuzem, MD; Reem Ghalib, MD; K. Rajender Reddy, MD; Paul J. Pockros, MD; Ziv Ben Ari, MD; Yue Zhao, PhD; Deborah D. Brown, BS; Shuyan Wan, PhD; Mark J. DiNubile, MD; Bach-Yen Nguyen, MD; Michael N. Robertson, MD; Janice Wahl, MD; Eliav Barr, MD; and Joan R. Butterton, MD

• Ann Intern Med. Published online 24 April 2015 doi:10.7326/M15-0785



http://annals.org/article.aspx?articleid=2279766





Neuropeptide Level May Signal Neuroblastoma PrognosisMedicalResearch.com Interview with:

Joanna Kitlinska, PhD Assistant ProfessorGeorgetown University Medical Center

Department of Biochemistry and Molecular & Cellular Biology Washington, DC 20057


• Dr. Kitlinska: Neuroblastoma is a pediatric malignancy with extremely heterogeneous phenotypes, ranging from spontaneously regressing to aggressive, untreatable tumors. Consequently, treatment strategies vary significantly between patients, depending on the initial risk assessment. Given the severe late effects of anti-cancer treatment administered to infants and children, proper disease stratification is of utmost importance for neuroblastomapatients.

• Due to their neuronal origin, neuroblastomas secrete neuropeptide Y (NPY), a small protein normally released from mature nerves. This, in turn, may result in elevated NPY levels in blood of neuroblastoma patients. We have found that serum NPY is particularly high in patients with aggressive, metastatic disease. Consequently, patients with elevated NPY levels have significantly worse survival. This finding is in agreement with our previous data indicating crucial role for NPY in stimulation of neuroblastoma tumor growth.


http://medicalresearch.com/author-interviews/neuropeptide-level-may-signal-neuroblastoma-prognosis/13756/







• Dr. Kitlinska: Elevated NPY can serve as a prognostic factor for neuroblastoma patients. In contrast to complex genetic analyses currently utilized to assess risk of the disease, the measurement of NPY levels in blood can be converted to a readily available analytical test. Importantly, a test like this does not require access to the tumor tissue, which is often limited, particularly in relapsing tumors. Thus, measuring NPY levels in blood may also allow for minimally invasive longitudinal monitoring of the disease progression, which currently involves complex and harmful radioimaging.

• In addition to potential utility of NPY systemic levels in neuroblastoma stratification and monitoring, our findings implicate NPY pathway as potential therapeutic target. Associations of high NPY levels with metastatic disease and relapse strongly indicate that such therapies may target patients with the most aggressive form neuroblastoma.



http://medicalresearch.com/cancer-_-oncology/neuroblastoma-risk-may-be-increased-by-stress-during-pregnancy/13754/







• Dr. Kitlinska: Our results should be confirmed in large, prospective study that would include samples collected at diagnosis and post treatment. Such longitudinal study would validate our findings and assess a value of serum NPY measurement in disease monitoring.

• In addition to the proposed clinical studies, our findings warrant further translational research designed to determine if blocking NPY signaling prevents neuroblastomaprogression and dissemination.

• Citation:

• Presented at the American Association for Cancer Research 2015 Annual Meeting in Philadelphia

• Neuropeptide Y (NPY) and its receptor expression in neuroblastoma patients – associations with disease prognosis and patients’ survival. Susana Galli, Jason Tilan, Arlene Naranjo, Collin Van Ryn, Chao Yang, Jessica Tsuei, Emily Trinh, Joanna B. Kitlinska.



http://medicalresearch.com/cancer-_-oncology/higher-birthweight-linked-to-increased-childhood-cancer-risk/11259/



Neuroblastoma Risk May Be Increased by Stress During PregnancyMedicalResearch.com Interview with:




• Dr. Kitlinska: Neuroblastoma is a pediatric tumor which arises due to defects in normal fetal neuronal development. Although the disease is associated with genetic changes, there are also clinical and experimental data implicating non-genetic factors in its etiology. We hypothesized that maternal stress during pregnancy can be one such factor, as it leads to fetal hypoxia and elevated cortisol levels – the two factors known to alter normal neuronal development and increase aggressiveness of neuroblastoma. Indeed, using an animal model of neuroblastoma, we have found that offspring of mothers which have been subjected to stress during pregnancy develop tumors twice as frequently as those from intact pregnancies. Moreover, tumors developing in prenatally-stressed mice were spreading more often to distant organs.



http://medicalresearch.com/author-interviews/majority-of-women-experience-stressful-life-events-in-year-before-giving-birth/12655/







• Dr. Kitlinska: If the stimulatory effect of prenatal stress on neuroblastoma development is confirmed by further studies, this new paradigm will enhance our understanding of etiology of these childhood tumors. This, in turn, can result in designing novel therapies and the first-ever preventative approaches for neuroblastoma. The latter may include pharmacological treatments or non-invasive behavioral interventions that have been shown to decrease levels of stress hormones.



http://medicalresearch.com/cancer-_-oncology/higher-birthweight-linked-to-increased-childhood-cancer-risk/11259/







• Dr. Kitlinska: Further studies are required to confirm our findings using established stress models and identify pathways mediating effects of prenatal stress on neuroblastomadevelopment. Moreover, epidemiological research is needed to validate our results in human population.

• Citation:

• Presented at the American Association for Cancer Research 2015 Annual Meeting in Philadelphia

• Prenatal stress increases neuroblastoma tumorigenesis in TH-MYCN mice model. Sung-Hyeok Hong, David Christian, Emily Trinh, Susana Galli, Meredith Horton, Yichien Lee, Christopher Albanese, Olga Rodriguez, Jason U. Tilan, Joanna Kitlinska.





Polygenic Risk Score Improves Breast Cancer PredictionMedicalResearch.com Interview with:

Nasim Mavaddat M.B.B.S. MPhil PhD PhDCentre for Cancer Genetic Epidemiology

Department of Public Health and Primary Care University of Cambridge, Cambridge, UK

• MedicalResearch: What is the background for this study?What are the main findings?

•

• Dr. Mavaddat: Recent large-scale genome wide association analyses have led to the discovery of genetic variation- called single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Individually these variants confer risks that are too small to be useful for risk prediction. But when combined as a single score, called a polygenic risk score (PRS), this score may be used to stratify women according to their risk of developing breast cancer. This stratification could guide strategies for screening and prevention.

• Our study was a large international collaboration involving 41 research groups from many different countries and included 33,673 breast cancer patients and 33,381 controls. We found that the genetic variants act more or less independently, and that the more risk variants a woman has the higher her risk of breast cancer. When women were ranked according to their PRS, women with scores in the top 1% had a threefold increased risk of breast cancer. This translates into an absolute risk of breast cancer of 29% by age 80. By contrast, women with the lowest 1% scores had a risk of 3.5%.

• The PRS was effective in stratifying women with and without a family history of breast cancer, so that highest risk was for women with a family history and a high PRS. Finally, we showed that the PRS was better at predicting the risk of ER-positive breast cancer (potentially relevant to the application of risk stratification to chemoprevention for example, with tamoxifen, raloxifene or aromatase inhibitors).

• There has been much debate as to whether genomic profiles are useful for individual risk prediction, especially in the context of the preventative strategies available at the present time. The estimates provided in this study will help inform these debates.


http://medicalresearch.com/cancer-_-oncology/breast-cancer/polygenic-risk-score-improves-breast-cancer-prediction/13758/

http://medicalresearch.com/cancer-_-oncology/breast-cancer/new-mayo-model-better-predicts-breast-cancer-risk-after-benign-biopsy/11154/







• Dr. Mavaddat: These findings are likely to generate interest in women wanting to know their risk of breast cancer. In the medium term this should lead to a more rational approach to prevention and screening, in women with or without a family history. We also aim to put these factors together into a comprehensive risk prediction tool, building on our current risk prediction model, BOADICEA. However further research is needed, particularly in determining the best way to combine the results with other risk factors, the best approaches to delivering the test and its acceptability, before the risk prediction test can be made available in routine clinical practice.









• Dr. Mavaddat: The next research priority is to investigate how information from the Polygenic Risk Score Improves Breast Cancer Prediction can be combined with other risk factors, including lifestyle factors like hormone replacement therapy and BMI, breast density and previous breast benign breast disease. Studies are also underway gathering prospective data, in order to validate our findings in an independent, prospective cohort.

• Although this study was very large, we would like more precise estimates of risk for people at very high or very low risk, and for women at very young ages. We also need to determine better how to calculate the risks for different tumour subtypes (for example oestrogen-receptor negative disease, or high-grade disease) and how the PRS might affect the prognosis from breast cancer.

• Our results apply to women of European ancestry. We don’t yet know how the results apply to women in other populations, for example in African or Asian women.

• Citation:

• Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

• JNCI J Natl Cancer Inst (2015) 107(5): djv036 doi:10.1093/jnci/djv036

• First published online April 02, 2015



http://medicalresearch.com/weight-research/pre-pregnancy-bmi-and-gestational-weight-gain-linked-to-childhood-obesity/12594/







Cancer Risk Elevated In Patients With Hepatitis CMedicalResearch.com Interview with:

Lisa M. Nyberg, MD, MPHTransplant Hepatologist Director, Hepatology Research

Kaiser Permanente, Garfield Specialty Center San Diego, CA 92111


Dr. Nyberg: The overall cancer rates were higher in patients with Hepatitis C (HCV) vs those without HCV. Of note, though, the HCV cohort had higher rates of alcohol abuse, tobacco use, cirrhosis and diabetes mellitus (DM). However, even after stratification for the variables alcohol abuse, tobacco use, body mass index (BMI) and DM; the increased cancer rates remained significant for total cancer sites, liver cancer and NHL.

• Note that this study does not establish a cause and effect relationship between Hepatitis C and cancer. A strength of this study is that it is an evaluation of a large patient population (n=35,712 with HCV and 5,297,191 without HCV). Limitations of the study are those inherent in epidemiological studies using large databases. For example, confounders may not be accurately recorded in automated databases (smoking and alcohol abuse may be under-recorded).


http://medicalresearch.com/hepatitis-liver-disease/cancer-risk-elevated-in-patients-with-hepatitis-c/13773/




Cancer Risk Elevated In Patients With Hepatitis CMedicalResearch.com Interview with:

Lisa M. Nyberg, MD, MPHTransplant Hepatologist Director, Hepatology Research

Kaiser Permanente, Garfield Specialty Center San Diego, CA 92111


• Dr. Nyberg: Clinicians should advise patients to abstain from smoking and alcohol abuse, and to exercise and maintain a healthy weight to avoid or control diabetes. These are long term goals. In the short term, however, the clinician can treat and cure Hepatitis C which, according to our findings, may result in an incremental reduction in the risk of cancer.


• Dr. Nyberg: Our findings should be confirmed by a prospective study designed to follow patients with HCV before and after Hepatitis C treatment with cure and to compare cancer rates in HCV patients with those without HCV.

• Citation: Abstract presented at the April 2015

• European Association for the Study of the Liver



http://medicalresearch.com/hepatitis-liver-disease/new-oral-hepatitis-c-virus-treatment-works-but-will-cost-billions/12661/

http://medicalresearch.com/hepatitis-liver-disease/liver-fibrosis-starts-early-after-hepatits-c-infection/11277/

http://www.easl.eu/research/our-contributions/international-liver-congress



HPV Vaccine Still Valuable For Women Who Were Not Fully Vaccinated As ChildrenMedicalResearch.com Interview with:

Jacqueline Hirth, PhD, MPHAssistant Professor and

Dr. Abbey B. Berenson MD, MMS, PhDThe University of Texas Medical Branch at Galveston Texas


Response: In this sample of young women, vaccination was effective at reducing prevalence of vaccine-type HPV (6,11,16,18) compared to women who were unvaccinated. We also found a dose response, with young women who received at least 2 doses of the 3 dose vaccine series having a lower rate of vaccine-type HPV compared to those who only received one dose (8.6% compared to 16.9%, respectively).


• Response: HPV vaccination is still valuable for young women who did not receive the vaccine at the recommended age of 11 to 12 years of age. Further, our results show that fully vaccinating young women with all 3 doses of the vaccine series is particularly important to reduce the prevalence of vaccine-type HPV in this group. Therefore, clinicians should continue to screen their patients for vaccination status. They should initiate vaccination in all age-eligible women, and work with their patients to ensure that they receive all 3 injections.


http://medicalresearch.com/author-interviews/hpv-vaccine-still-valuable-for-women-who-were-not-fully-vaccinated-as-children/13311/

http://medicalresearch.com/author-interviews/strong-evidence-hpv-vaccination-highly-effective-outside-trial-settings/12380/



HPV Vaccine Still Valuable For Women Who Were Not Fully Vaccinated As ChildrenMedicalResearch.com Interview with:

Jacqueline Hirth, PhD, MPHAssistant Professor and

Dr. Abbey B. Berenson MD, MMS, PhDThe University of Texas Medical Branch at Galveston Texas


• Response: More interventions are needed to assist patients with obtaining follow-up doses of the HPV vaccine. We have had great success in our patient populations of achieving high follow-up by approaching our patients who are due for further doses each time they have an appointment at one of our clinics. More research needs to be conducted on how to assist young women who may not be a patient of a large health system to receive all 3 doses of the HPV vaccine.

• Citation: Presented at the 2015 American Association of Cancer Research Meeting April 2015

• AACR abstract titled “Comparison of HPV prevalence between HPV-vaccinated and non-vaccinated young adult women (20-26 years)”:



http://medicalresearch.com/author-interviews/hpv-16-18-vaccine-provides-some-cross-protection-to-other-cancer-causing-subtypes/11990/

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3682&sKey=7f019f73-accb-484e-becc-5ecc405f8ec5&cKey=e2313b32-d6ac-4443-ab2d-49c368ea3b89&mKey=19573a54-ae8f-4e00-9c23-bd6d62268424



CPR Rate High In End Stage Dialysis Patients Despite Poor OutcomesMedicalResearch.com Interview with:

Susan P. Y. Wong, M.D.Acting Instructor & Senior Research Fellow Division of Nephrology

University of Washington


• Dr. Wong: There is a paucity of information on the use of cardiopulmonary resuscitation (CPR) and its outcomes among patients receiving maintenance dialysis. To address this knowledge gap, we performed a retrospective study to define contemporary trends in in-hospital CPR use and its outcomes among a nationally representative sample of 663,734 patients receiving maintenance dialysis between 2000 and 2011. We found that in-hospital CPR use among this cohort of patients was very high—nearly 20 times more common than that found in the general population. The rate of in-hospital CPR use has also been increasing among patients receiving maintenance dialysis despite evidence of poor long-term survival among these patients. Median survival after hospital discharge for members of this cohort was only 5 months, and this has not change substantially in the recent decade.

• We also found that a large proportion of dialysis patients who died in hospital settings had received CPR during their terminal hospitalization. This proportion has also been steadily increasing over time, and in 2011, 1 in 5 dialysis patients who died in hospital had received CPR during their terminal hospitalization.


http://medicalresearch.com/heart-disease/cpr-rate-high-in-end-stage-dialysis-patients-despite-poor-outcomes/13711/

http://medicalresearch.com/heart-disease/mechanical_chest_compressions_did_not_enhance_cpr_outcomes/9048/



CPR Rate High In End Stage Dialysis Patients Despite Poor OutcomesMedicalResearch.com Interview with:

Susan P. Y. Wong, M.D.Acting Instructor & Senior Research Fellow Division of Nephrology

University of Washington


• Dr. Wong: These findings raise concern about the aggressiveness in the care that patients receiving maintenance dialysis experience near the end-of-life. This information may be helpful to patients and providers in supporting advance care planning and informed decisions about potentially life-sustaining treatments.


• Dr. Wong: More research is needed on the forces driving trends in in-hospital CPR use and the degree to which CPR practices reflect patients’ treatment goals and preferences.

• Citation:

• Wong SY, Kreuter W, Curtis J, Hall YN, O’Hare AM. Trends in In-Hospital Cardiopulmonary Resuscitation and Survival in Adults Receiving Maintenance Dialysis. JAMA Intern Med. Published online April 27, 2015. doi:10.1001/jamainternmed.2015.0406.



http://medicalresearch.com/author-interviews/end-of-life-care-practices-vary-across-asia/10519/

http://medicalresearch.com/heart-disease/mechanical_chest_compressions_did_not_enhance_cpr_outcomes/9048/

http://archinte.jamanetwork.com/article.aspx?articleid=2278949&resultClick=1



Family Members Can Help Patients Understand Hospital Discharge InstructionsMedicalResearch.com Interview with:

Dennis Tsilimingras, M.D., M.P.H. Assistant Professor,Co-Director of Michigan AHEC (Area Health Education Center), Director of Patient Safety,

Department of Family Medicine and Public Health Sciences Wayne State University School of MedicineDetroit, Michigan


Dr. Tsilimingras: There has been little research to examine post-discharge adverse events (AEs) in rural patients discharged from community hospitals.


• Dr. Tsilimingras: Over 28 % of 684 patients experienced postdischarge AEs, most of which were either preventable or ameliorable. There was no difference in the incidence of post-discharge AEs in urban versus rural patients, but post-discharge adverse events were associated with hypertension, type 2 diabetes mellitus, and number of secondary discharge diagnoses only in urban patients.


http://medicalresearch.com/general-medicine/family-members-can-help-patients-understand-hospital-discharge-instructions/13789/



Family Members Can Help Patients Understand Hospital Discharge InstructionsMedicalResearch.com Interview with:

Dennis Tsilimingras, M.D., M.P.H. Assistant Professor,Co-Director of Michigan AHEC (Area Health Education Center), Director of Patient Safety,

Department of Family Medicine and Public Health Sciences Wayne State University School of MedicineDetroit, Michigan


• Dr. Tsilimingras: Post-discharge adverse events were common in both urban and rural patients and many were preventable or ameliorable. Potentially different risk factors for AEs in urban versus rural patients suggests the need for further research into the underlying causes. Patients should be accompanied by family members at the time of discharge to better understand post-discharge instructions. Patients and family members should not be afraid to ask as many questions as possible regarding follow-up care in their community.


• Dr. Tsilimingras: Potentially different risk factors for adverse events in urban versus rural patients suggests the need for further research into

• the underlying causes. Different interventions may be required in urban versus rural patients to improve patient safety during transitions in care.

• Citation:

• Post-Discharge Adverse Events Among Urban and Rural Patients of an Urban Community Hospital: A Prospective Cohort Study.

• Tsilimingras D1, Schnipper J, Duke A, Agens J, Quintero S, Bellamy G, Janisse J, Helmkamp L, Bates DW.

• J Gen Intern Med. 2015 Mar 31. [Epub ahead of print]



http://medicalresearch.com/medication-research/adverse-events/3384/






Both Diabetes and Depression Raise Risk of DementiaMedicalResearch.com Interview with:

Dimitry S. Davydow, MD, MPH Associate ProfessorDepartment of Psychiatry and Behavioral Sciences

University of Washington School of Medicine Seattle, WA 98195


• Dr. Davydow: The medical and public health communities have known for quite a while that diabetes and depression are both potential risk factors for developing dementia later in life. Dr. Wayne Katon previously published two articles detailing the results of two studies of relatively large groups of patients (one with nearly 4,000 patients and the other with 29,000 patients) with diabetes showing that those with diabetes and co-existing depression had a greater risk of developing dementia later in life than those patients with just diabetes. These initial studies were important since patients with diabetes are 3 to 4-times more likely to suffer from depression compared to the general population.

• However, it remained unclear when comparing to a population without either diabetes or depression, to what extent each independently raised the risk of developing dementia, and then to what extent having both conditions increased an individual’s subsequent risk of dementia. We sought to answer these questions with this study.

• In addition, with the growing obesity epidemic, which carries with it higher burdens of both diabetes and depression, there is reason to be concerned that the risk of dementia could be higher at even younger ages. To address this issue, we also wanted to see if there was a differential impact of the combination of diabetes and co-existing depression on dementia risk among those younger than 65 compared to individuals 65 or older.

• We were fortunate to be able to examine health data from all Danish citizens 50 or older over a 6 year period, a population numbering nearly 2.5 million people to be able to answer these questions.


http://medicalresearch.com/mental-health-research/alzheimers-dementia/both-diabetes-and-depression-raise-risk-of-dementia/13544/

http://medicalresearch.com/general-medicine/obesity-in-us-aggravated-by-agricultural-policy-that-encourages-high-fatsugar-foods/1382/







• Dr. Davydow: We found that compared to individuals without diabetes or depression, those with diabetes alone had about a 15% greater risk of developing dementia, those with depression alone had about an 83% greater risk of developing dementia, and those with both diabetes and co-existing depression had a 107% greater risk of developing dementia compared to those without either condition.

• We also found that of all of the cases of dementia diagnosed in Denmark among individuals 50 or older between 2007 through 2013, 6% were potentially due to combination of having both diabetes and depression. This was also true for those 65 or older, where 6% of all diagnosed dementia was potentially attributable to the combination of both diabetes and depression. However, among individuals under age 65, we found that 25% of all cases of dementia may have been directly attributable to the combination of diabetes and co-existing depression.



http://medicalresearch.com/mental-health-research/alzheimers-dementia/twin-study-shows-physical-activity-may-decrease-dementia-mortality/11420/






• Dr. Davydow: Our findings are very important for both patients and their health care providers. Arguably, the best treatment available for dementia is to prevent it from developing. If it turns out through future research that what we have found in our study documents a true, causal link between diabetes, depression and dementia, then there is the potential that successfully treating these illnesses could prevent future cases of dementia and improve quality of life for millions of individuals world-wide. Diabetes and depression are both diagnosable, and treatable conditions, and both can improve significantly with the right treatments. However, we don’t do a very good job of diagnosing either diabetes or depression early. Too frequently, diabetes isn’t found until patients have already had complications, and depression isn’t addressed until it is interfering with care for medical conditions, causing problems with relationships and/or work/school, and/or resulting in suicide. Many studies have found that some interventions, based in primary care and other medical care settings, may lead to improved recognition and treatment of depression. One such study led by Dr. Wayne Katon, the TEAMcare study, which was published in the New England Journal of Medicine in 2010, found that a primary care-based intervention for patients with depression and either diabetes, high blood pressure, and/or elevated cholesterol not only reduced symptoms of depression but also improved blood pressure, cholesterol and blood glucose control. It remains to be seen whether interventions such as this one can prevent longer-term devastating consequences of these diseases, such as dementia.

• Our results focusing on the risks for individuals under age 65 with both diabetes and depression are particularly concerning in light of the rates of obesity and associated chronic illnesses in the United States, and further highlight the need to improve recognition and treatment of medical conditions and co-existing psychiatric conditions, such as depression, in order to help prevent a potential tsunami of dementia over the next several decades.



http://medicalresearch.com/sleep-disorders/night-owls-may-have-increased-risk-of-metabolic-syndrome-and-diabetes/13243/







• Dr. Davydow: Based on the results of our study, future research should seek to increase understanding of the biological mechanisms for how depression and diabetes may increase the risk of dementia, in order to develop potential treatments. For example, there is a fairly large body of research that has found that increased systemic inflammation may lead to cognitive impairment and decline, with elevated inflammation over time possibly increasing the risk of developing dementia. There have also been many studies that have found that during a depressive episode, patients have evidence of systemic inflammation, including elevated levels of cells regulating the body’s inflammatory response. One hypothesis is that increased inflammation could be a pathway by which depression, particularly repeated episodes of depression throughout life, may raise the risk of developing dementia later in life. We need additional research in this area.

• In addition, we need more research examining whether existing interventions, such as the TEAMcare interventions or other similar programs, could ultimately prevent dementia, as well as the continued development of new interventions that can prevent the development of dementia.

• Citation:• Katon W, Pedersen H, Ribe A, et al. Effect of Depression and Diabetes Mellitus on the Risk for

Dementia: A National Population-Based Cohort Study. JAMA Psychiatry. Published online April 15, 2015. doi:10.1001/jamapsychiatry.2015.0082.

•

• MedicalResearch.com Interview with: Dimitry S. Davydow, MD, MPH (2015). Both Diabetes and Depression Raise Risk of Dementia



http://medicalresearch.com/mental-health-research/depression/depression-remains-important-risk-factor-for-cardiovascular-disease/12449/

http://archpsyc.jamanetwork.com/article.aspx?articleid=2272732



Nurses and Nursing Assistants Face Occupational Injury and Workplace ViolenceMedicalResearch.com Interview with:

Ahmed Gomaa, MD, ScD, MSPHMedical Officer / Surveillance Branch

Division of Surveillance Hazard Evaluation and Health Studies National Institute for Occupational Safety and Health (NIOSH)Centers for Disease Control and Prevention (CDC)


Dr. Gomaa: In 2013, one in five reported nonfatal occupational injuries occurred among workers in the health care and social assistance industry, the highest number of such injuries reported for all private industries. In 2011, U.S. health care personnel experienced seven times the national rate of musculoskeletal disorders compared with all other private sector workers. To reduce the number of preventable injuries among health care personnel, CDC’s National Institute for Occupational Safety and Health (NIOSH), with collaborating partners, created the Occupational Health Safety Network (OHSN) to collect detailed injury data to help target prevention efforts. OHSN, a free, voluntary surveillance system for health care facilities, enables prompt and secure tracking of occupational injuries by type, occupation, location, and risk factors.


http://medicalresearch.com/author-interviews/nurses-and-nursing-assistants-face-occupational-injury-and-workplace-violence/13797/

http://medicalresearch.com/author-interviews/opioid-analgesics-prescribed-in-patients-with-skin-disorders-and-psychiatric-diagnoses/12893/






Medical Research: What are the main findings?

Dr. Gomaa: The Occupational Health Safety Network (OHSN) collects and reports near real-time, specific, standard benchmarking information on injuries to help target prevention measures toward workers, departments, and activities at highest risk. From January 1, 2012 to September 30, 2014, the highest incidence rates of the three categories of occupational injuries were among nurse assistants and nurses. Workplace violence injury incidence rates increased from 2012 to 2014; most of these injuries were physical in nature and caused by patients. In over half of patient handling injuries, lifting equipment was not used (51%).



http://medicalresearch.com/mental-health-research/mental-health-workers-frequently-risk-assault-at-work/11505/







• Dr. Gomaa: Injury prevention interventions mitigating high-risk aspects of nurse and nurse assistant duties are needed. Safety cultures that emphasize continuous improvement and support resources such as routine use of lifting equipment, as well as safe patient-handling training and lifting teams, might prevent many of the musculoskeletal disorders from patient handling and the associated costs of diagnosis, treatment, and disability.









• Dr. Gomaa: I recommend research to promote hospital safety which integrates patient safety, worker safety, and environmental safety which are highly interrelated. Research to promote culture of safety and the attitude that every single injury is an opportunity to find the risk factor for the injury and put in place an unceasing effort to prevent similar future injuries. Finally a research to document the benefits of culture of safety where the healthcare facility frontline workers up to top management believe that their facilities should offer best hospital safety and have daily huddle and strive to target prevention opportunities based on data driven information. OHSN is one of the tools that can be used to help the aforementioned effort.

• Citation:

• Occupational Traumatic Injuries Among Workers in Health Care Facilities — United States, 2012–2014

• MMWR Weekly

• April 24, 2015 / 64(15);405-410



http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6415a2.htm?s_cid=mm6415a2_w





Major Disease States Cause Slowdown in Red Blood Cell Production and DestructionMedicalResearch.com Interview with:

John M. Higgins, MDMGH Center for Systems Biology

Boston, MA


Dr. Higgins: Hundreds of studies over the past 8 years have shown that increased variation in the size of red blood cells (RBCs) is associated with increased risk for a very wide range of common diseases, like heart disease, many types of cancer, infection, many autoimmune diseases, and lots of other conditions. The size of red blood cells (RBCs) in the circulation of a healthy person usually varies by about 12-14%, meaning that if you took a sample of the cells, most of the bigger cells would be about 14% larger than the smaller cells. People whose red blood cells show more variation in size have a greater risk of developing a wide range of diseases. Also, among patients already diagnosed with many common diseases like heart disease or cancer, those with higher RBC size variation have worse outcomes. It is unknown how all of these different diseases could be connected to variation in the size of red blood cells. The study explains a major cause for this connection. We find that the human body seems to slow down the production and destruction of RBCs in just about every major disease very slightly. Since red blood cells gradually become smaller as they age, a delay in destruction will increase the fraction of small cells, and the overall variation in size increases. The study also describes a method to estimate a patient’s RBC clearance rate.


http://medicalresearch.com/author-interviews/major-disease-states-cause-slowdown-in-red-blood-cell-production-and-destruction/13799/





Boston, MA


• Dr. Higgins: Not much is known about how RBCs are removed from the bloodstream after their roughly 100-day lifespan. This study demonstrates that the removal process is extremely tightly regulated in healthy people and that it is often adjusted to be a bit slower in the earliest stages of a wide range of diseases. Clinicians should now suspect that patients with greater variation in RBC size likely have a slightly reduced rate of both RBC production and destruction. If we can accurately measure the production or destruction rate, we can screen patients for many common and important diseases in their early stages when they are most treatable. This paper shows how the destruction rate can be estimated using existing blood test measurements and a mathematical model.







Boston, MA


• Dr. Higgins: Future research will need to determine for which diseases healthy patients can be most effectively screened by estimating their RBC clearance rates. Future research will also help decide which chronic conditions can be best monitored by estimating patients’ RBC clearance rates.

• Citation:

• Patel, H. H., Patel, H. R. and Higgins, J. M. (2015), Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease. Am. J. Hematol., 90: 422–428. doi: 10.1002/ajh.23982



http://onlinelibrary.wiley.com/doi/10.1002/ajh.23982/abstract



ncreased Time Watching TV Linked To Childhood ObesityMedicalResearch.com Interview with:

Mark D. DeBoer, MD, MSc, MCRAssociate Professor of Pediatrics

Division of Pediatric Endocrinology, University of Virginia


Dr. DeBoer: The American Academy of Pediatrics recommends that children watch no more than 2 hours of TV daily. We wanted to see if children watching shorter amounts of TV were more likely to have higher weight status. We found that children in kindergarten who watched 1-2 hours a day were more than 40% more likely to be overweight and obese and gained more unhealthy weight over the next year.


• Dr. DeBoer: Even shorter amounts of TV are associated with unhealthy weight gain. Clinicians should encourage parents to restrict TV viewing and replace it with other healthy activities, including physical activity and learning opportunities.


• Dr. DeBoer: We would love to see evaluations into how reductions in TV viewing effect future weight gain and development.

• Citation:

• Viewing as Little as 1 Hour of Television Daily Is Associated with Higher Weight Status in Kindergarteners: The Early Childhood Longitudinal Study

• Presented April 26 at the Pediatric Academic Societies (PAS) annual meeting in San Diego – See more at: https://www.aap.org/en-us/about-the-aap/aap-press-room/Pages/Just-an-Hour-of-TV-a-Day-Linked-to-Unhealthy-Weight-in-Kindergartner


http://medicalresearch.com/pediatrics/increased-tv-watching-linked-to-childhood-obesity/13804/

http://medicalresearch.com/sleep-disorders/good-sleep-habits-children-early-consistent-bedtime-evening-tv/3854/

http://medicalresearch.com/sleep-disorders/good-sleep-habits-children-early-consistent-bedtime-evening-tv/3854/


http://medicalresearch.com/pediatrics/increased-tv-watching-linked-to-childhood-obesity/13804/



































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MedicalResearch.com: Medical Research Exclusive Interviews April 28 2015

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