News Article | February 15, 2017
A new investigational delivery method for localized vaginal estrogen therapy that utilizes an applicator free softgel to alleviate moderate-to-severe vaginal pain during intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), received high rates of patient satisfaction among post-menopausal women, according to post-trial survey results published in the journal Menopause. "These survey results show that something as simple as a change to a more elegant delivery system that is easier to use and not messy might empower more post-menopausal women to seek prescription treatment for VVA, and perhaps help them stay with the application guidelines for longer," said study first author Sheryl Kingsberg, PhD, Division Chief, OB/GYN Behavioral Medicine, UH Cleveland Medical Center; Professor of Obstetrics and Gynecology and Psychiatry, Case Western Reserve University School of Medicine; and first author of the survey analysis. "We still have to find better ways to educate the millions of women suffering with VVA about the symptoms, however, so that more of them know it is common, decide to discuss treatment with their healthcare professional, and seek symptom relief with appropriate treatment." The new results were part of a multi-center randomized, placebo-controlled phase 3 clinical trial for TX004HR, an investigational bio-identical 17β-estradiol applicator free vaginal softgel capsule. Previous publications have shown TX004HR to be safe and effective at alleviating symptoms of VVA. The survey, which included 731 respondents with a 96 percent response rate, sought to quantify participants' satisfaction with the application method and overall treatment delivery system. The majority of women taking either TX004HR or placebo (85.4 - 92.1 percent) found the product easy to use. VVA is a chronic condition associated with genitourinary syndrome of menopause (GSM). VVA affects 50 to 70 percent of post-menopausal women, and is characterized by pain with sexual activity, dryness, and discomfort. Current on-the-market treatments for VVA include both over-the-counter creams and moisturizers as well as several safe and effective prescription treatments in cream, tablet, ring or oral form. Previous survey research completed by Dr. Kingsberg and others has shown that while 32 million women may be experiencing symptomatic VVA and suffering from related impacts on sexual function, interpersonal relationships, self-esteem and overall quality of life, only 7 percent are currently using a prescription therapy to alleviate symptoms. Though they may suffer from physical and emotional pain as a result of VVA, women may not feel comfortable discussing these symptoms with a healthcare professional, may not recognize the symptoms as treatable, may not fully understand the treatment options available, or if they did receive treatment, found the current prescription treatment options inconvenient, messy, or uncomfortable to use. Financial disclosure: Dr. Kingsberg has served as a consultant for TherapeuticsMD, the manufacturer of TX004HR, as well as Acerus Pharmaceuticals, AMAG Pharmaceuticals, Bayer Healthcare, Emotional Brain, Materna, Novo Nordisk, Nuelle, Palatin Technologies, Pfizer, Sermonix Pharmaceuticals, Shionogi Inc. and Valeant Pharmaceuticals. Founded in 1866, University Hospitals serves the needs of over 1 million patients per year through an integrated network of 18 hospitals, more than 40 outpatient health centers and 200 physician offices in 15 counties throughout northern Ohio. The system's flagship academic medical center, University Hospitals Cleveland Medical Center, located on a 35-acre campus in Cleveland's University Circle, is affiliated with Case Western Reserve University School of Medicine. The main campus also includes University Hospitals Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; University Hospitals MacDonald Women's Hospital, Ohio's only hospital for women; and University Hospitals Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, including cancer, pediatrics, women's health, orthopedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, dermatology, transplantation and urology. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including "America's Best Hospitals" from U.S. News & World Report. UH is also home to Harrington Discovery Institute at University Hospitals - part of The Harrington Project for Discovery & Development. UH is the second largest employer in northern Ohio with 26,000 employees. For more information, go to UHhospitals.org.
News Article | February 15, 2017
Researchers at Case Western Reserve University will use a $2 million grant from the National Institutes of Health to develop and test a small, portable blood-adhesion monitor for sickle cell disease patients. The engineers and doctors hope to make the device as useful as at-home insulin monitors diabetes patients use to manage their disease. Sickle cell patients suffer painful damage to joints and organs during events called vaso-occlusive crises. These random and unpredictable crises occur when the misshapen and abnormal sticky blood cells that are characteristic of the disease clog blood vessels. Although the proximate causes of vaso-occlusive crises are not well understood, hemoglobin molecules link into long chains inside red blood cells, stiffening the cells and changing cell shape from a donut without a hole to a crescent--thus the name of the disease. Simultaneously, adhesive proteins form on the surface of the cells. These changes hamper the flow of the cells in the bloodstream and increase the likelihood they will clog blood vessels. Early versions of the monitor have proved capable of determining whether cells are sticky and the level of stickiness, "but we don't know if this information will make a difference in patients' lives or in how the disease is managed," said Umut Gurkan, assistant professor of mechanical and aerospace engineering and project leader. Gurkan and colleagues believe the stickiness of a patient's blood cells reflects disease severity and may be used to predict vaso-occlusive crises. If a prodrome, or early symptom indicating the onset of crises, can be identified, strategies can be (and are being) developed to block the generation of the vaso-occlusive episode. The device may also be useful in monitoring new sickle cell drugs designed to either block adhesive proteins on blood-cell surfaces or resolve clogs that block blood vessels and starve joints and organs of oxygen. Currently, there are no easily applicable tests for either scenario, the researchers say. To look for trends associated with crises, a team of researchers will test prototype monitors with patients in Cleveland and New York City (the Bronx) starting this year. Sickle cell disease is actually a group of inherited red blood cell disorders. About 300,000 babies with severe forms are born worldwide annually, the World Health Organization estimates. Life expectancy for those with the disease in the United States has increased the last few decades to a range of 40 to 60 years, the Centers for Disease Control and Prevention says. But the disease remains costly. Hospitalizations and treatments for crises and other harmful affects can amount to $8 million for one patient over a lifetime. "We think that, with much better monitoring and anti-adhesion therapies, the physical and financial cost will be reduced," Gurkan said. "There will be less time spent out of work and in the hospital, reducing stress and suffering by the patient and family and benefitting the health-care system." In the prototype monitor, blood flows through channels as wide as three to four cells across, reproducing microvessel size inside the body. The channel lining mimics the properties of endothelial cells lining blood vessels. Under a microscope, researchers can see cells stick to channel walls and determine the stickiness and number per unit volume of blood. The scientists are working on a way to quickly identify proteins on the surface. About a dozen proteins contribute to adhesion, and different patients have different proteins on their cells, providing an opportunity to customize treatment. Gurkan and Jane Little, associate professor of hematology and oncology at the Case Western Reserve School of Medicine, and an adult hematologist at University Hospitals Cleveland Medical Center, are team leaders on the project. Other members include: Deepa G. Manwani, chief of the Division of Hematology at the Children's Hospital at Montefiore in the Bronx; Karen Ireland, clinical coordinator at Montefiore; Charlotte Yuan and Erina Quinn, research assistants at UH Cleveland Medical Center; Erdem Kucukal, doctoral student in mechanical and aerospace engineering; and Evren G. Cavusoglu, assistant professor of electrical engineering and computer science, specializing in bioinformatics, at Case Western Reserve. The monitors will be tested on adult patients at University Hospital in Cleveland and children at University Hospitals Rainbow Babies & Children's Hospital and Montefiore beginning next year. "The test can be run in a primary care doctor's office during a visit," Gurkan said. Ultimately, take-home versions of the monitor would enable patients or parents to use the test daily to manage their condition. If the monitor proves effective during testing, the researchers plan to commercialize the device, which Gurkan said could have applications in malaria, certain cancers, lead poisoning and other diseases and conditions that cause changes in red blood cell properties.
News Article | February 28, 2017
CLEVELAND, Feb. 28, 2017 /PRNewswire/ -- A mother and her 29-week-old unborn child are doing well after a team of physicians performed a successful in utero procedure at University Hospitals Rainbow Babies & Children's Hospital (UH Rainbow) last week. Known as fetal aortic...
News Article | February 15, 2017
The Institute for Pediatric Innovation (“IPI”) is proud to announce that they have been the recipient of a pre-seed grant from the New England Pediatric Device Consortium (“NEPDC”). The award will go to further refinement and development of a novel alcohol wipe, aimed at reducing central line-associated bloodstream infections ("CLABSIs"). Expressing NEPDC’s continued support of the project, Scott Holson, Project Leader in Business Development reported, “NEPDC is excited to work with the team and help move this innovation closer to market and clinical use.” The new wipe has been developed through IPI’s Clinical Innovation Catalyst Program(TM) (“catalyst program”), which is run collaboratively with four pediatric hospital partners: Lucile Packard Children’s Hospital Stanford, University Hospitals Rainbow Babies and Children’s Hospital, Texas Children’s Hospital, and Shriners Hospital for Children – Northern California. The wipe was one of four products developed in the 2015-2016 catalyst cycle aimed at reducing CLABSIs in hospital settings. When a patient requires regular intravenous treatment, such as for dialysis or administration of frequent or large doses of medication, a central line is often used. This is a catheter that is inserted into a vein and run into the superior vena cava, the main vein carrying blood from the body into the heart. One end of this tube extends outside the body with the hub, or access point, attached for medication or dialysis administration. A CLABSI is a bloodstream infection resulting from pathogens entering the bloodstream through the central line two or more days after it is placed. Every time the catheter is accessed is a risk potential for CLABSIs, so the hub must be sanitized each time, usually with an alcohol wipe. Although every hospital has procedures for hub disinfection, it is up to the clinician to determine if it has been adequately cleaned. IPI’s novel alcohol wipes take the guesswork out of sanitizing the hub by indicating when it has been adequately disinfected. The CDC estimates about 41,000 CLABSIs strike patients each year, and a study by JAMA Internal Medicine found that each infection costs a hospital about $46,000, more than any other hospital-acquired condition (HAC). Pediatric patients are at higher risk for CLABSIs than adults because they have a hard time sitting still while their lines are accessed, they put things—including the central line—in their mouths, and they wear diapers, where the line may occasionally end up. Due to the prevalence of CLABSIs, the condition was the focus of IPI’s 2015-2016 catalyst program cycle. The catalyst program is a professional education experience for bedside clinicians in pediatric settings. Pediatric clinicians and caregivers often need to adapt and improvise medical devices, medicines and materials not designed for children but needed for day-to-day patient care. This is because most companies have not considered the pediatric market viable. The absence of medical devices and materials genuinely optimized for treating children limits clinicians’ ability to eliminate certain HACs. The catalyst program aims to address this gap. Over the course of four workshops, participants from the partner hospitals learn the skills for evaluating clinical problems and developing novel or innovative devices to counteract them. They deeply study a selected HAC, define novel product designs, and develop the case the IPI uses to align with medical device companies to bring them to fruition. As one former participant said, “IPI’s program encourages learners to challenge assumptions and to maintain a questioning attitude,” while another related that the program “encourages brainstorming and [the] development of new ideas.” Participants from each of the four hospitals played a tremendous role in the production of the four devices developed through the 2015-2016 catalyst cycle. Patent protection is being pursued to protect the ideas, and discussions are underway with potential commercial partners to bring the devices to market. The 2016-2017 catalyst program cycle’s focus is unplanned extubations. This is an instance when a patient has a tube inserted into their trachea for breathing assistance and the tube becomes dislodged before clinicians intend to remove it. We look forward to seeing what product ideas come from this focus. For more information on the Institute for Pediatric Innovation and the Clinical Innovation Catalyst Program, please visit pediatricinnovation.org.
News Article | February 17, 2017
When a child is conceived, he or she receives DNA from both parents. The child's own genome thus consists of a maternal and a paternal genome. However, some genes -- about 100 out of the 20,000 encoded genes-- are exclusively expressed either from the maternal or from the paternal genome, with the other copy of the gene remaining silent. We know that these imprinted genes are more likely to lead to serious genetic diseases, such as Prader-Willi or Angelman syndrome. Researchers at the University of Geneva (UNIGE), Switzerland, have devised a new technique, based on a combination of biology and bioinformatics, to quickly and accurately detect the imprinted genes expressed in each of the cell types that constitute the human organs. This major breakthrough will improve our understanding and diagnosis of genetic diseases. The study can be read in full in the American Journal of Human Genetics. The research team, led by Professor Stylianos Antonarakis from the Department of Genetic Medicine and Development in the Faculty of Medicine at UNIGE, focused on genomic imprinting. This is a set of genes exclusively expressed from the genetic code inherited either from the father (the paternal allele) or from the mother (maternal allele). Why is there so much interest in the identification of the imprinted genes? Because if a deleterious mutation affects the functional allele, it cannot be compensated by the expression of the second silent allele, likely causing a serious genetic disease. The goal, therefore, is to determine the imprinted genes in all cell types of human body tissues that are liable to cause these kind of diseases. Until recently, millions of cells were analysed together without distinction. «We have now developed a new technique with a better resolution, known as Human Single-Cell Allele-Specific Gene Expression," explains Christelle Borel, UNIGE researcher. "The process can be used to simultaneously examine the expression of the two alleles, paternal and maternal, of all known genes in each individual cell. The method is fast and can be carried out on thousands of single cells with the utmost precision using next-generation sequencing technology." The heterogeneity of each tissue of the body is thus analysed in detail while searching for imprinted genes in disease-relevant tissue. The individual's genome is sequenced, as is the genome of both parents, in order to identify the parental origin of the alleles transcribed in the person's single cell. Federico Santoni, first author of the study and researcher at UNIGE and HUG (Geneva University Hospitals) further explains, "We establish the profile of the allelic expression for thousands of genes in each single cell. We then process this data with a novel computational and statistical framework to identify the specific signature of each imprinted gene, enabling us to accurately record them." This new technique redefines the landscape of imprinted genes by examining all cell types, and can be applied to all tissues affected by diseases, such as cardiac and brain tissue. Moreover, the scientists have discovered novel imprinted genes and demonstrated that some were restricted to certain tissues or cell types. This technique focuses on the specific characteristics of each individual by treating each cell as a single entity. This concept, called Single-cell Genomics, is part of an emerging field that is assuming an all-important role at UNIGE, which sees it as the future of medicine that will be personalised rather than generalised. Thanks to the technique pioneered by UNIGE researchers, it will be possible to identify new disease causing genes and to adapt a specific and targeted treatment for individual patients.
Hoit B.D.,Case Western Reserve University |
Hoit B.D.,University Hospitals
Journal of the American College of Cardiology | Year: 2014
The author examines the ability of left atrial size and function to predict cardiovascular outcomes. Data are sufficient to recommend evaluation of left atrial volume in certain populations, and although analysis of atrial reservoir, conduit, and booster pump function trails in that regard, the gap is rapidly closing. In this state-of-the-art paper, the author reviews the methods used to assess left atrial size and function and discusses their role in predicting cardiovascular events in general and referral populations and in patients with atrial fibrillation, cardiomyopathy, ischemic heart disease, and valvular heart disease. © 2014 by the American College of Cardiology Foundation.
Van Gerven L.,University Hospitals
Rhinology | Year: 2012
Non-allergic rhinitis (NAR) is a common disorder, which can be defined as chronic nasal inflammation, independent of systemic IgE-mediated mechanisms. Symptoms of NAR patients mimic those of allergic rhinitis (AR) patients. However, AR patients can easily be diagnosed with skin prick test or allergen-specific IgE measurements in the serum, whereas NAR patients form a heterogeneous group and are difficult to diagnose because of an extensive list of different phenotypes, all varying in severity, underlying etiology and type of inflammation. Characterization of those phenotypes, mechanisms and management of NAR represents one of the major unmet needs in the field of allergic and non-allergic diseases. This review aims at providing a comprehensive overview of the state of the art in classifying the NAR patients and focuses on the neuro-immune mechanisms involved in allergic and non-allergic rhinitis, including reflections on the pathophysiology and the currently available treatment options.
Samama C.M.,University Hospitals
Seminars in Thrombosis and Hemostasis | Year: 2016
Surgical bleeding has been decreasing steadily for the last 20 years, but there are still some hemorrhagic procedures occurring in scheduled surgical settings and emergency procedures. The interest in potent hemostatic agents has recently focused on fibrinogen concentrates. A weak historical rationale based on the rapid decrease in fibrinogen concentration in the bleeding patient and several uncontrolled studies have prompted the use of fibrinogen concentrates in emergency units and in operating theaters. Very few positive randomized studies are available to confirm the usefulness of fibrinogen concentrates. The largest most recent double-blind studies are even negative. As recent guidelines recommend early and liberal use of fibrinogen concentrates in massive bleeding patients, this review reports the most important facts and studies on efficacy and raises some questions about safety. © 2016 by Thieme Medical Publishers, Inc.
Vergote I.,University Hospitals
Expert Opinion on Investigational Drugs | Year: 2014
Introduction: Despite primary cytoreductive surgery followed by standard-of-care treatment, at least 60% of patients with ovarian cancer ultimately develop recurrent disease. There is an urgent unmet medical need to develop more effective treatments for ovarian cancer. Areas covered: This article provides a summary of the novel targeted therapeutics currently in development for the treatment of ovarian cancer. Expert opinion: The goal of first-line therapy is to increase progression-free survival and overall survival in women with ovarian cancer. Women with advanced disease frequently experience disease relapse following standard cytotoxic therapy, so new treatments are being explored. Using a molecular approach, targeted drugs are now being tested in clinical trials. These studies have investigated angiogenesis inhibitors (that target VEGF and other tyrosine kinases), angiopoietin inhibitors, poly(ADP-ribose) polymerase inhibitors, folate receptor blockers, MEK inhibitors and a protein kinase Cβ inhibitor (enzastaurin) in ovarian cancer. Of these, antiangiogenic agents (bevacizumab, pazopanib, nintedanib and trebananib) are furthest in development, having positive Phase III data. It is hoped that more effective agents are on the horizon and that the use of these agents can eventually be combined and tailored to the individual with ovarian cancer. © 2014 Informa UK, Ltd.
University Hospitals | Date: 2015-01-28
An intrathecal delivery system for a pharmaceutical includes a reservoir containing a volume of the pharmaceutical agent, and a pump configured to deliver a portion of the pharmaceutical agent contained in the reservoir. A controller is configured to receive biological cycle information pertaining to a biological cycle (e.g., cardiac cycle), and configured, based on the received biological cycle information, to control the pump to deliver the pharmaceutical agent into a patients intrathecal space as a high-speed bolus at a time corresponding to a time determined based on Processing the biological cycle information. The high-speed bolus may be delivered at a rate of 10-100 L per second. The timing of such delivery corresponds to a time within the biological cycle when cerebrospinal fluid flow is optimal for intrathecal delivery of the pharmaceutical agent. Conditions for which treatment is enhanced by the intrathecal delivery system include refractory hypertension, spasticity and chronic pain management.