Declining Medicaid Fees Translates To Fewer Available Primary Care Appointments

MedicalResearch.com Interview with:

Molly Candon, PhD Postdoctoral Fellow, Leonard Davis Institute of Health Economics Center for Mental Health Policy and Services Research University of Pennsylvania

Dr. Candon

Molly Candon, PhD
Postdoctoral Fellow
Leonard Davis Institute of Health Economics
Center for Mental Health Policy and Services Research
University of Pennsylvania

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

Response: We conducted a secret shopper study in 2012, 2014, and 2016 in which simulated Medicaid patients called primary care practices and attempted to schedule an appointment. When Medicaid fees were increased to Medicare levels in 2013 and 2014, primary care appointment availability increased. Once the federally-funded program ended in 2015, most states returned to lower fees. As expected, provider participation in Medicaid declined as well.

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Transplant Network Undercaptures Post-Transplant Skin Cancers

MedicalResearch.com Interview with:

Thuzar M.Shin MD, PhD Assistant Professor of Dermatology Hospital of the University of Pennsylvania

Dr. Shin

Thuzar M.Shin MD, PhD
Assistant Professor of Dermatology
Hospital of the University of Pennsylvania

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

Response: The Organ Procurement Transplant Network (OPTN) collects data on cancers that develop after organ transplantation. Previous studies have shown incomplete reporting to the OPTN for many cancers (including melanoma). Skin cancer is the most common malignancy in solid organ transplant recipients and the most common post-transplant skin cancer, cutaneous squamous cell carcinoma (cSCC), is not captured in standard cancer registries. We hypothesized that cSCC and melanoma are underreported to the OPTN. When compared to detailed medical record review obtained from the Transplant Skin Cancer Network database (JAMA Dermatol. 2017 Mar 1;153(3):296-303), we found that the sensitivity of reporting to the OPTN was only 41% for cSCC and 22% for melanoma. The specificity (99% for cSCC and 100% for melanoma) and negative predictive values (93% for cSCC and 99% for melanoma) were high. As a result, the OPTN database is unable to robustly and reliably distinguish between organ transplant recipients with and without these two skin malignancies.

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Severe Psoriasis Linked To Increased Risk of Mortality

MedicalResearch.com Interview with:

Megan H. Noe MD, MPH Clinical Instructor and Post-Doctoral Research Fellow University of Pennsylvania, Department of Dermatology Perelman Center for Advanced Medicine Philadelphia, PA 19104

Dr. Megan Noe

Megan H. Noe MD, MPH
Clinical Instructor and Post-Doctoral Research Fellow
University of Pennsylvania, Department of Dermatology
Perelman Center for Advanced Medicine
Philadelphia, PA 19104

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

Response: Previous research has shown that patients with psoriasis have higher rates of hypertension, diabetes, cardiovascular disease and chronic kidney disease that may put them at an increased risk of death.

Our research found that patients with psoriasis covering more than 10% of their body had almost double the risk of death than people of the same age with similar medical conditions, but without psoriasis.

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Similar Signaling Pathways Trigger Anxiety In Variety of Species

MedicalResearch.com Interview with:

Yuanyuan Xie, PhD Postdoctoral Researcher Department of Neuroscience University of Pennsylvania Philadelphia, PA 19104

Dr.Yuanyuan Xie

Yuanyuan Xie, PhD
Postdoctoral Researcher
Department of Neuroscience
University of Pennsylvania
Philadelphia, PA 19104

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

Response: I joined Dr. Richard Dorsky’s lab in mid 2013 after a lab switch toward the end of the fourth year in my PhD. By then, the Dorsky lab at the University of Utah had published zebrafish lef1 mutants with a hypothalamic neurogenesis phenotype. I was asked to perform an RNA-sequencing (RNA-seq) experiment to identify Lef1-dependent genes. In doing so, I also characterized the cellular phenotype in the hypothalamus of our zebrafish mutants in a greater detail.

The first transition of this project happened when I proposed in late 2013 to test whether Lef1’s function was conserved in the mouse hypothalamus. Dr. Dorsky liked that idea, but told me that I could only pursue that idea if there was a Lef1-flox mouse strain available, because he did not want me to delay my graduation after a lab switch by making a new mouse line. Fortunately, a quick google search located the right mouse line published from the group of Dr. Hai-Hui Xue, who was generous enough to share some mice with us. Because the Dorsky lab was a zebrafish lab by then, we collaborated with Dr. Edward Levine to maintain our mice under his animal protocol. I was initially trained by Dr. Levine and his lab specialist Anna Clark for general mouse colony management. After Dr. Levine moved to Vanderbilt University in early 2016, we began to maintain our mice under Dr. Camille Fung’s animal protocol. Dr. Dorsky also supported me in attending a 3-week Cold Spring Harbor Laboratory Course on Mouse Development, Stem Cells & Cancer in mid 2015, which made me much more confident in handling mouse work afterwards.

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Diabetes Alters Oral Microbiome Leading to Periodontal Disease

MedicalResearch.com Interview with:

Dana T. Graves DDS Department of Periodontics School of Dental Medicine University of Pennsylvania Philadelphia, PA

Dr. Graves

Dana T. Graves DDS
Department of Periodontics
School of Dental Medicine
University of Pennsylvania
Philadelphia, PA

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

Response: It was previously thought that diabetes did not have a significant effect on oral bacteria. We found that diabetes caused a change in the composition of the oral bacteria. This change caused resulted in a bacterial composition that was more pathogenic and stimulated more inflammation in the gums and greater loss of bone around the teeth.

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Google Searches Valuable Source of Cancer Incidence and Mortality Data

MedicalResearch.com Interview with:

Mackenzie R. Wehner, MD, MPhil Department of Dermatology University of Pennsylvania Philadelphia, PA

Dr. Weher

Mackenzie R. Wehner, MD, MPhil
Department of Dermatology
University of Pennsylvania
Philadelphia, PA

MedicalResearch.com: What is the background for this study?

Response: For some diseases, we have national registries, in which information about every person with that disease is entered for research purposes. For other diseases, unfortunately, we do not have such registries. There are growing opportunities to use information like internet searches to better understand behaviors and diseases, however. Our study was a proof-of-concept: we aimed to find out whether internet searches for diseases correlated with known incidence (how many people are diagnosed with the disease) and mortality (how many people die of the disease) rates. E.g. does the number of people who searched ‘lung cancer’ online correlate with the number of people who we know were diagnosed with or who died of lung cancer during that same time period? This is important to know if researchers in the future want to use internet search data for diseases where we lack registry information.

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VR/AR May Help Physicians Overcome Cognitive Biases To Admitting Errors

MedicalResearch.com Interview with:

Jason Han, MD Resident, Cardiothoracic Surgery Hospital at the University of Pennsylvania

Dr. Han

Jason Han, MD
Resident, Cardiothoracic Surgery
Hospital at the University of Pennsylvania

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

Response: The inspiration for this study comes from my personal experience as a medical student on clinical rotations. Despite having been a victim of a medical error while growing up myself, I found it extraordinarily difficult to admit to even some of my smallest errors to my patients and team. Perplexed by the psychological barriers that impeded error disclosure, I began to discuss this subject with my advisory Dean and mentor, Dr. Neha Vapiwala. We wanted to analyze the topic more robustly through an academic lens and researched cognitive biases that must be overcome in order to facilitate effective disclosure of error, and began to think about potential ways to implement these strategies into the medical school curriculum with the help of the director of the Standardized Patient program at the Perelman School of Medicine, Denise LaMarra.

We ultimately contend that any educational strategy that aims to truly address and improve error disclosure must target the cognitive roots of this paradigm. And at this point in time, simulation-based learning seems to be the most direct way to do so, but also remain hopeful that emerging technologies such as virtual and augmented reality may offer ways for students as well as staff to rehearse difficult patient encounters and improve.

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Genetic Variants Tied To Kidney Disease in African Americans

MedicalResearch.com Interview with:

Katalin Susztak MD, PhD Associate Professor of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104

Dr. Susztak

Katalin Susztak MD, PhD
Associate Professor of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104

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

Response: Previous studies showed an association between genetic variants in the APOL1 gene and kidney disease development, but it has not been confidently shown that this genetic variant is actually causal for kidney disease. For this reason we developed a mouse model that recapitulates the human phenotype.

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Weight Shaming Can Cause Physical As Well As Mental Harm

MedicalResearch.com Interview with:
Rebecca L. Pearl PhD
Department of Psychiatry, Center for Weight and Eating Disorders
Perelman School of Medicine
University of Pennsylvania, Philadelphia, Pennsylvania

MedicalResearch.com: What is the background for this study? 

Response: Weight bias is a pervasive form of prejudice that leads to weight-based discrimination, bullying, and the overall stigmatization of obesity. Some individuals with obesity may internalize weight bias by applying negative weight stereotypes to themselves and “self-stigmatizing.” Exposure to weight bias and stigma increases risk for poor obesity-related health (in part by increasing physiological stress), but little is known about the relationship between weight bias internalization and risk for cardiovascular and metabolic diseases.

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More Gun Violence in PG-13 Than R-Rated Films

MedicalResearch.com Interview with:

Daniel Romer, PhD Annenberg Public Policy Center University of Pennsylvania Philadelphia, Pennsylvania

Dr. Daniel Romer

Daniel Romer, PhD
Annenberg Public Policy Center
University of Pennsylvania
Philadelphia, Pennsylvania

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

Response: We have been studying trends in health compromising behaviors in popular films that were released since 1950, and in 2013 we reported that films rated PG-13 had just passed the rate of portrayed gun violence shown in popular R-rated films in 2012. In this report, we updated the trends in gun violence through 2015 and found that the trend has continued. In addition, we noted the strong contribution to this trend of films with comic book heroes whose heavy use of guns omits the harmful and otherwise realistic consequences of blood and suffering.

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Bundled Payment For Joint Replacements Saved Hospitals and CMS Money

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: Amol Navathe, MD PhD University of Pennsylvania Staff Physician, CHERP, Philadelphia VA Medical Center Assistant Professor of Medicine and Health Policy, Perelman School of Medicine Senior Fellow, Leonard Davis Institute of Health Economics, The Wharton School Co-Editor-in-Chief, HealthCare: the Journal of Delivery Science and Innovatio

Dr. Amol Navathe


Amol Navathe, MD PhD

University of Pennsylvania
Staff Physician, CHERP,
Philadelphia VA Medical Center
Assistant Professor of Medicine and Health Policy, Perelman School of Medicine
Senior Fellow, Leonard Davis Institute of Health Economics, The Wharton School
Co-Editor-in-Chief, HealthCare: the Journal of Delivery Science and Innovation

MedicalResearch.com: What is the background for this study?

Response: Bundled payments pay a fixed price for an episode of services that starts at hospital admission (in this case for joint replacement surgery) and extends 30-90 days post discharge (30 days in this study). This includes physician fees, other provider services (e.g. physical therapy), and additional acute hospital care (hospital admissions) in that 30 day window.

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Child Abuse By Members of Military May Be Grossly Underreported

MedicalResearch.com Interview with:

Joanne N. Wood, MD, MSHP  Assistant Professor of Pediatrics Perelman School of Medicine at the University of Pennsylvania Research Director, SafePlace Faculty, PolicyLab The Children’s Hospital of Philadelphia

Dr. Joanne Wood

Joanne N. Wood, MD, MSHP
Assistant Professor of Pediatrics
Perelman School of Medicine at the University of Pennsylvania
Research Director, SafePlace
Faculty, PolicyLab
The Children’s Hospital of Philadelphia 

MedicalResearch.com: What is the background for this study?

Response: Each year the U.S. Army Family Advocacy program (FAP) investigates between 6000 to 9000 reports of alleged abuse or neglect involving children of Army service members.   In approximately 48% of reported cases FAP determines a child was a victim of maltreatment, substantiates the report, and collaborates with local civilian child protection service (CPS) agencies in providing services and ensuring safety. Thus, FAP plays a key role in supporting Army families and protecting children.  But FAP can only investigate and respond to cases of child abuse and neglect about which they are aware.

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Tocilizumab High Active For Refractory Graft vs Host Disease

MedicalResearch.com Interview with:

Dr. Alex Ganetsky

Dr. Alex Ganetsky

Alex Ganetsky, PharmD, BCOP
Clinical Pharmacy Specialist – Hematology/BMT
Hospital of the University of Pennsylvania

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

• Allogeneic hematopoietic cell transplant (HCT) recipients with steroid-refractory gastrointestinal acute graft-versus-host disease (GI-GVHD) have poor outcomes.
• There is no consensus for optimal treatment of these patients.
• We retrospectively evaluated the efficacy of tocilizumab, an interleukin-6 receptor monoclonal antibody, for the treatment of steroid-refractory GI-GVHD.
• 10/11 (91%) patients achieved a complete response after a median time of 11 days (range, 2 – 18) from tocilizumab initiation.
• The median time to response onset, defined as improvement in GVHD stage by at least 1, was 1 day (range, 1 – 6).
• At a median follow-up of 3 months (range, 1.1 – 12.8) from tocilizumab initiation, 8 of 11 patients are alive and free of the their underlying hematologic malignancy.
• No associations between serum levels of IL-6 and tocilizumab response could be identified.
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Penn Takes First Step in Development of Antibodies to HIV and Cure

MedicalResearch.com Interview with:

Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core

Dr. Katharine J Bar

Katharine J Bar, MD
Assistant Professor of Medicine
Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania
Physician, International Travel Medicine, Perelman Center for Advanced Medicine
Director, Penn CFAR Viral and Molecular Core

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

Response: The passive administration of monoclonal antibodies has revolutionized many fields of medicine. Anti-HIV monoclonal antibodies are being explored as components of novel therapeutic and curative strategies, as they can both neutralize free virus and kill virus-infected cells. We sought to determine whether passive administration of an anti-HIV monoclonal antibody, VRC01, to chronically HIV-infected individuals on antiretroviral medications (ART) would be safe and well tolerated and could delay virus rebound after discontinuation of their ART.

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Substituting Less Well Trained Assistants For Nurses Increased Hospital Mortality

MedicalResearch.com Interview with:

Dr Linda H Aiken PhD, FAAN, FRCN, RN Claire M. Fagin Leadership Professor in Nursing Professor of Sociology, School of Arts & Sciences Director, Center for Health Outcomes and Policy Research University of Pennsylvania School of Nursing Center for Health Outcomes and Policy Research Philadelphia, PA 19104

Dr Linda H Aiken

Dr Linda H Aiken PhD, FAAN, FRCN, RN
Claire M. Fagin Leadership Professor in Nursing
Professor of Sociology, School of Arts & Sciences
Director, Center for Health Outcomes and Policy Research
University of Pennsylvania School of Nursing
Center for Health Outcomes and Policy Research
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study?

Response: The idea that adding lower skilled and lower wage caregivers to hospitals instead of increasing the number of professional nurses could save money without adversely affecting care outcomes is intuitively appealing to mangers and policymakers but evidence is lacking on whether this strategy is safe or saves money.
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Bystander CPR Associated With Improved Outcomes in Pediatric Cardiac Arrest

MedicalResearch.com Interview with:

Maryam Y. Naim, MD Pediatric Cardiac Intensive Care Physician The Cardiac Center The Children’s Hospital of Philadelphia Perelman School of Medicine The University of Pennsylvania, Philadelphia

Dr. Maryam Y. Naim

Maryam Y. Naim, MD
Pediatric Cardiac Intensive Care Physician
The Cardiac Center
The Children’s Hospital of Philadelphia
Perelman School of Medicine
The University of Pennsylvania, Philadelphia

MedicalResearch.com: What is the background for this study? 

Response: In adults bystander compression only CPR has similar outcomes to bystander conventional COR therefore the The American Heart Association recommends untrained lay rescuers perform compression only CPR in adults that have an out of hospital cardiac arrest. In children respiratory arrests are more common therefore conventional CPR with chest compressions and rescue breaths are recommended for out of hospital cardiac arrest.

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Biomarker NLR Found Not Predictive of Bladder Cancer Survival

MedicalResearch.com Interview with:

Eric Ojerholm, MD Resident, Radiation Oncology Hospital of the University of Pennsylvania

Dr. Eric Ojerholm

Eric Ojerholm, MD
Resident, Radiation Oncology
Hospital of the University of Pennsylvania

MedicalResearch.com: What is the background for this study?

Response: Multiple studies reported that a blood test —the neutrophil-to-lymphocyte ratio (NLR)—might be a helpful biomarker for bladder cancer patients. If this were true, NLR would be very appealing because it is inexpensive and readily available. However, previous studies had several methodological limitations.

MedicalResearch.com: What did you do in this study

Response: We therefore put NLR to the test by performing a rigorous “category B” biomarker study—this is a study that uses prospectively collected biomarker data from a clinical trial. We used data from SWOG 8710, which was a phase III randomized trial that assessed surgery with or without chemotherapy for patients with muscle-invasive bladder cancer. We tested two questions.

First, could NLR tell us how long a bladder cancer patient would live after curative treatment?

Second, could NLR predict which patients would benefit from chemotherapy before surgery?

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Androgen Deprivation For Prostate Cancer Linked to Dementia

MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil

Resident, Radiation Oncology
Perelman School of Medicine
Hospital of the University of Pennsylvania.

MedicalResearch.com: What is the background for this study?

Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function.

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Penn Reports Successful Pilot Study of Liquid Biopsy To Monitor Advanced Lung Cancer

MedicalResearch.com Interview with:

Erica L. Carpenter, MBA, PhD Research Assistant Professor, Department of Medicine Director, Circulating Tumor Material Laboratory Division of Hematology/Oncology Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania

Dr. Erica Carpenter

Erica L. Carpenter, MBA, PhD
Research Assistant Professor, Department of Medicine
Director, Circulating Tumor Material Laboratory
Division of Hematology/Oncology
Abramson Cancer Center
Perelman School of Medicine at the University of Pennsylvania

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

Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients’ tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy.

Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn’s Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.

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New Approach May Cure Autoimmune Diseases By Targeting Just Autoantibody Cells

MedicalResearch.com Interview with:

 credit Paul Foster, Penn Medicine for the photo.

from left to right:
Aimee Payne, MD, PhD – co-senior author
Christoph Ellebrecht, MD – first author
Michael Milone, MD, PhD – co-senior author

Aimee S. Payne, M.D., Ph.D.
Albert M. Kligman Associate Professor of Dermatology
University of Pennsylvania
Philadelphia, PA 19104

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

Dr. Payne: Autoimmunity occurs when the body’s immune system mistakenly attacks itself, instead of foreign viruses and bacteria. The most common way we treat autoimmunity is to suppress the immune system, but that can be dangerous, with risk of serious and even fatal infections. We have developed a method to use the body’s own immune system to specifically kill the disease-causing autoimmune cells, while sparing the “good” immune cells that protect from infection.

If you think about the way we used to treat cancer, we had no way of targeting the cancer cells specifically, so we just targeted all dividing cells, but this approach led to terrible side effects and even death from therapy. Over the last several decades, tremendous advances have been made identifying cell markers and signaling pathways that are specific to cancer cells, which has greatly reduced the toxicity of cancer treatments. Recently, researchers discovered that they could direct the body’s own immune cells to seek out and kill cancer cells, using a so-called “chimeric antigen receptor” or CAR, a breakthrough in medical technology that has cured previously incurable cancers.

We have re-engineered the CAR approach to specifically target the autoantibody-producing cells, by using the disease autoantigen in a “chimeric autoantibody receptor” or CAAR. We are hopeful that this approach might similarly prove to be a breakthrough in autoimmune disease therapy, since the concept can be extended to any autoantibody-mediated disease for which the autoantigen is known.

MedicalResearch.com: What should readers take away from your report?

Dr. Payne:  Ideally, the CAAR targeted therapy approach would be a one-time disease treatment that would cure autoantibody-mediated diseases, without the risks of generalized immune suppression. In contrast, our current therapies use chronic immune suppression for the goal of disease control, which can greatly reduce the quality of life for affected patients.

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

Dr. Payne: We are actively seeking to move this technology forward into human clinical trials. Our immediate focus is to use CAAR technology to cure pemphigus in dogs. Dogs are one of the only animals other than humans that naturally develop pemphigus. If we could safely treat and potentially cure pemphigus in dogs, that would be compelling evidence to encourage doctors and patients to enroll for clinical trials of CAAR therapy.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Pacemaker Type Device Is Option For Sleep Apnea Patients Who Don’t Tolerate CPAP

MedicalResearch.com Interview with:

Richard J. Schwab, MD Professor, Department of Medicine Division of Sleep Medicine Pulmonary, Allergy and Critical Care Division Co-Director, Penn Sleep Center University of Pennsylvania Medical Center Philadelphia, PA 19104

Dr. Richard Schwab

Richard J. Schwab, MD
Professor, Department of Medicine
Division of Sleep Medicine
Pulmonary, Allergy and Critical Care Division
Co-Director, Penn Sleep Center
University of Pennsylvania Medical Center
Philadelphia, PA 19104

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

Dr. Schwab: Hypoglossal nerve stimulation is a pacemaker (a tiny generator and a sensing lead) placed in the right side of the chest, but instead of using electrical pulses to control the heart, the device stimulates the hypoglossal nerve which is the nerve that controls the motion of the tongue. Patients use a remote control to turn on the device before going to sleep and turn it off upon waking up. Stimulation of the tongue moves the tongue forward which enlarges the upper airway. Continue reading

New HIV Infections Drop But Less Than Task Force Goals

MedicalResearch.com Interview with:

Robert Bonacci MPH, MD Candidate’16 University of Pennsylvania School of Medicine

Robert Bonacci

Robert Bonacci MPH, MD Candidate’16 
University of Pennsylvania School of Medicine

MedicalResearch.com: What is the background for this study?

Response: During the mid-2000’s, the HIV incidence rate stubbornly persisted around 50,000 infections per year. Responding to this trend, President Obama released the first comprehensive US National HIV/AIDS Strategy (NHAS) in 2010. The NHAS hoped to spur a more coordinated national response and set ambitious targets for reducing HIV incidence (25 percent) and the transmission rate (30 percent), among other goals, by 2015.

To evaluate whether the U.S. achieved the NHAS goals by 2015, we used mathematical models drawing on data from the U.S. Centers for Disease Control and Prevention (CDC) on HIV prevalence and mortality for 2007 to 2012, and our own previously published incidence estimates from 2008-2012. Changes seen from 2010 through 2012 were extrapolated for the time period 2013 through 2015.

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Females Tolerate Ischemia After Kidney Transplantion Better Than Males

MedicalResearch.com Interview with:

Matthew Levine, MD, PhD Associate professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania

Dr. Mathew Levine

Matthew Levine, MD, PhD
Assistant Professor of Transplant Surgery
Perelman School of Medicine
University of Pennsylvania

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

Dr. Levine: This work stemmed from a known finding that female mice tolerate kidney injury better than males and this is true of mice that share exactly the same genes.  Therefore, the gender difference was the driving factor.  My basic science laboratory works at the intersection between scientific discovery and clinical application and this led us to question whether the same phenomenon was true in humans and whether we could identify a way in which this could be used to improve injury tolerance above what is seen in untreated subjects.  What we found was that the hormonal environment seems to impact ischemia tolerance, with female environment being protective and the male environment worsening injury tolerance in ischemia models where blood flow is interrupted and then restored.  The kidneys seemed to adapt to take on the injury response of the host after transplantation, indicating that the differences were not forged into the kidney itself and therefore could be altered.  We then found that estrogen therapy improved kidney injury tolerance when given to female mice in advance of injury, but no effect was seen in male mice.  And most importantly, we found that in a large cohort of transplant recipients that female recipients had better injury tolerance after transplant than male recipients, as shown by ability to avoid dialysis in the first week after transplant, otherwise known as delayed graft function (DGF). This is a fairly major finding since it has not been observed in the literature despite several decades of transplant data being carefully studied.

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Complement Inhibitor Reverses Periodontitis

MedicalResearch.com Interview with:

George Hajishengallis, D.D.S., Ph.D., Thomas W. Evans Centennial Professor University of Pennsylvania Penn Dental Medicine - Microbiology Philadelphia, PA 19104-6030

Dr. George Hajishengallis

George Hajishengallis, D.D.S., Ph.D.,
Thomas W. Evans Centennial Professor
University of Pennsylvania
Penn Dental Medicine – Microbiology
Philadelphia, PA 19104-6030

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

Dr. Hajishengallis: The current study is the result of eight years of collaboration with my colleague at Penn Medicine, Dr. John D. Lambris. In our earlier mechanistic studies, we have shown that complement, a system of innate immunity and inflammation, is critically involved in the pathogenesis of periodontitis, an oral inflammatory disease that leads to the destruction of the tissues (gums and bone) that support the teeth. C3 is the central component of the complement system, where all activation pathways converge. Therefore, we reasoned that blocking C3 with an appropriate inhibitor could block the development of periodontitis. The results of this study confirmed our hypothesis. Indeed, by administering the C3 inhibitor Cp40 to the periodontal tissue just once a week reversed naturally occurring chronic periodontitis in a preclinical model. Specifically, Cp40 inhibited pre-existing gingival inflammation (as determined by both clinical and laboratory assessment) and the formation of osteoclasts, that is, the cells involved in the resorption of bone.

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

Dr. Hajishengallis: Although in this study Cp40 was successfully applied as a stand-alone treatment, it can be envisioned as an adjunctive therapy to the management of human chronic periodontitis. Cp40 has now been developed for human clinical applications (AMY-101; Amyndas Pharmaceuticals). Future clinical trials could investigate the potential of Cp40/AMY-101 to inhibit periodontal inflammation and bone loss compared to scaling and root planing, whereas in very severe cases of the disease, the drug could be combined with scaling and root planing and compared to periodontal surgery, in an effort to obviate the need for a surgical approach.

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

Dr. Hajishengallis: There are different candidate approaches for the treatment of periodontitis. Our current work shows that strategies that aim to control the host inflammatory response have a great therapeutic potential. Future research should focus on translating important findings from preclinical models to the clinic. Dissecting mechanisms of disease is very important but translating this type of research into new and effective therapies is even more significant.

MedicalResearch.com: Is there anything else you would like to add?

Dr. Hajishengallis: As I alluded to earlier, Cp40/AMY-101 has a great potential to find application as a novel anti-inflammatory treatment for periodontitis. Periodontitis has a serious public health impact and economic burden, therefore, we need innovative treatments adjunctive to existing therapies – such as mechanical removal of the tooth-associated biofilm – which are not always sufficient to control periodontitis. This drug would not necessarily be implemented in a therapeutic setting (as used in our study) but could also be provided on a preventive basis to high-risk individuals for periodontitis, such as cigarette smokers and diabetic patients. Since Cp40/AMY-101 is intended for local treatment of human periodontitis,potential safety considerations are unlikely to apply, although of course this will need to be verified.  It should be noted though that no adverse effects were observed in the preclinical studies. 

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.

Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.

Maekawa T1,2, Briones RA3, Resuello RR4, Tuplano JV4, Hajishengallis E5, Kajikawa T1, Koutsogiannaki S6, Garcia CA3, Ricklin D6, Lambris JD6,Hajishengallis G1.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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George Hajishengallis, D.D.S., Ph.D. (0). Complement Inhibitor Reverses Periodontitis MedicalResearch.com

With Appropriate Dose and Formulation, Niacin Can Be Lipid Lowering and Cardioprotective

MedicalResearch.com Interview with:

Dr. Richard L. Dunbar MD MS Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine

Dr. Richard Dunbar

Dr. Richard L. Dunbar MD MS
Assistant Professor of Medicine, Attending Physician, Preventive Cardiovascular Medicine Clinic, Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of MedicineMember, Institute for Diabetes, Obesity and Metabolism,
University of Pennsylvania School of Medicine and

Dr. Harsh Goel WellSpan Academic Hospitalists Department of Medicine, York Hospital, PA

Dr. Harsh Goel

Dr. Harsh Goel
WellSpan Academic Hospitalists
Department of Medicine, York Hospital, PA 

MedicalResearch.com: What is the background for this analysis?

Response: Niacin is the first cholesterol lowering treatment to prevent heart attacks and lower long term mortality. It thus provided the first proof that lowering cholesterol reduces cardiovascular risk. However, it is generally poorly tolerated due to almost universal flushing, limiting use. The better-tolerated statin drugs overshadowed niacin, rightly dominating hyperlipidemia therapy. Despite their advantages, statins are far from perfect, leaving important gaps. Firstly, at least 10% of patients simply don’t tolerate statins. Secondly, about 40% of patients have insufficient cholesterol lowering, leaving them far from their target LDL-cholesterol levels. Finally, even though statins lower cardiovascular risk, they by no means eliminate it and significant residual risk remains even in patients who respond to them.

The relatively poor tolerance of niacin motivated development of an extended-release alternative which was dosed very differently from the established cardioprotective regimen used in the Coronary Drug Project (CDP) and the Stockholm Ischemic Heart Disease Study (SIHDS), the two landmark trials that proved niacin’s benefits. These trailblazing trials used 3 grams of niacin divided throughout the fed portion of the day as 1 gram thrice daily with meals. In sharp contrast, the alternative regimen was severely handicapped by a profoundly lower dose of only 2 grams per day. Perhaps worse, the alternative regimen dosed all of the niacin at one sitting, at bedtime before the overnight fast, rather than three times a day before meals. We believe these were critical departures from the established cardioprotective niacin regimen, insofar as they severely undermined the alternative regimen’s efficacy. Accordingly, when added to statins, the alternative regimen failed to recapitulate the benefits seen with the established cardioprotective regimen in two recent large clinical trials, the AIM-HIGH trial and the HPS2-THRIVE trial. Besides the inherent flaws of the alternative regimen, there were also major issues with the trial designs which likely contributed to null results.

From a practice standpoint, this is worrisome, because clinicians may draw erroneous conclusions from the trials of the alternative regimen, and thereby deny a significant population of hyperlipidemic patients the benefits of a well-proven cardioprotective therapy, i.e. the population which does not tolerate or does not respond adequately to statins (almost 50% of at risk patients). Hence, we embarked on a critical analysis and review of the alternative regimen with a special focus on the AIM-HIGH and HPS2-THRIVE trials to bring to light the pitfalls of comparing radically different regimens of what is nominally the same drug.

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Women At Greater Risk of PAD

Dr. Grace Wang MD FACS Assistant Professor of Surgery Division of Vascular and Endovascular Surgery Hospital of the University of Pennsylvania

Dr. Grace Wang

MedicalResearch.com Interview with:
Dr. Grace Wang MD FACS
Assistant Professor of Surgery
Division of Vascular and Endovascular Surgery
Hospital of the University of Pennsylvania

Medical Research: What is the background for this study?

Dr. Wang: PAD is a major source of morbidity and mortality resulting in functional impairment, limb loss, as well as death. Despite epidemiologic studies which have contributed to our understanding of PAD prevalence and its association with traditional atherosclerotic risk factors, there have been conflicting studies published on the incidence of PAD and differences in treatment outcomes in women versus men. Patients with chronic kidney disease (CKD) are at particularly high risk for PAD. We set out to to define how the incidence of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age.
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Young Women With CAD Need Repeat Procedures More Often Than Men

MedicalResearch.com Interview with:

Dr. Robert L. Wilensky MD Director, Interventional Cardiology Research Director, Interventional Cardiology Training Program Professor of Medicine Hospital of the University of Pennsylvania

Dr. Robert Wilensky

Dr. Robert L. Wilensky MD
Director, Interventional Cardiology Research
Director, Interventional Cardiology Training Program
Professor of Medicine Hospital of the University of Pennsylvania

Medical Research: What is the background for this study?

Dr. Wilensky: We wanted to evaluate whether young women, under the age of 50 years, had an increased risk for recurrent ischemic events after percutaneous coronary intervention (PCI) compared to young men or older women.

Medical Research: What are the main findings?

 Dr. Wilensky: Despite having less severe coronary artery disease,  had an increased risk of repeated events, generally need for repeat PCI in either the exact location of the original procedure or within the artery that underwent the procedure. This despite the finding that young women were treated with the same medications as young men.

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Single Gene Rearrangement Uses Three Paths To Cause Rare Brain Tumor

MedicalResearch.com Interview with:

Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia

Dr. Adam Resnick

Dr. Adam C. Resnick, Ph.D
Assistant Professor of Neurosurgery
Faculty, Abramson Cancer Center
Director of Children’s Brain Tumor Tissue Consortium
Division of Neurosurgery
Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery
Children’s Hospital of Philadelphia

 

Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania

Payal Jain

Payal Jain, PhD Candidate
Division of Neurosurgery, Children’s Hospital of Philadelphia
Department of Neurosurgery
Cell and Molecular Biology Graduate Group
Gene Therapy and Vaccines Program
Perelman School of Medicine
University of Pennsylvania Philadelphia, Pennsylvania

 

Medical Research: What is the background for this study? What are the main findings?

Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics.

Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.

  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.

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Better Nursing Environment Linked To Lower Hospital Mortality

More on Nursing Research on MedicalResearch.com
MedicalResearch.com Interview with:

Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Professor of Health Services Research The Children's Hospital of Philadelphia Professor of Pediatrics and Anesthesiology & Critical Care, The University of Pennsylvania Perelman School of Medicine Professor of Health Care Management, The Wharton School Director, Center for Outcomes Research The Children's Hospital of Philadelphia Philadelphia, PA 19104

Dr. Jeffrey Silber

Jeffrey H. Silber, M.D., Ph.D.
The Nancy Abramson Wolfson Professor of Health Services Research
Professor of Pediatrics and Anesthesiology & Critical Care,  The University of Pennsylvania Perelman School of Medicine
Professor of Health Care Management
The Wharton School
Director, Center for Outcomes Research
The Children’s Hospital of Philadelphia
Philadelphia, PA 19104 


Medical Research: What is the background for this study?

Response: We wanted to test whether hospitals with better nursing work environments displayed better outcomes and value than those with worse nursing environments, and to determine whether these results depended on how sick patients were when first admitted to the hospital.

Medical Research: What are the main findings?

Response: Hospitals with better nursing work environments (defined by Magnet status), and staffing that was above average (a nurse-to-bed ratio greater than or equal to 1), had lower mortality than those hospitals with worse nursing environments and below average staffing levels. The mortality rate in Medicare patients undergoing general surgery was 4.8% in the hospitals with the better nursing environments versus 5.8% in those hospitals with worse nursing environments. Furthermore, cost per patient was similar. We found that better nursing environments were also associated with lower need to use the Intensive Care Unit. The greatest mortality benefit occurred in patients in the highest risk groups.

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Androgen Deprivation Therapy May Raise Risk of Alzheimer’s Disease

Kevin T. Nead, MD, MPhil Dept. of Radiation Oncology Perelman School of Medicine University of Pennsylvania

Dr. Kevin Nead

MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil
Dept. of Radiation Oncology
Perelman School of Medicine
University of Pennsylvania

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

Dr. Nead: There are a growing number of studies suggesting that the use of  Androgen Deprivation Therapy (ADT)  may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT.

We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive  Androgen Deprivation Therapy. We also found that this risk increased with a longer duration of ADT. These results were consistent using multiple statistical approaches and separately at both Stanford and Mr. Sinai.

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Obesity Paradox Tied To Smoking and Illness-Induced Weight Loss

Dr. Samuel H. Preston Ph.D Professor, Department of Sociology and Population Studies Center University of Pennsylvania Philadelphia, Pennsylvania

Dr. Samuel Preston

MedicalResearch.com Interview with:
Dr. Samuel H. Preston Ph.D
Professor, Department of Sociology and Population Studies Center
University of Pennsylvania
Philadelphia, Pennsylvania 

Medical Research: What is meant by the Obesity Paradox? Is it reported more in some groups?

Dr. Preston: The obesity paradox is a term that is used when a study finds that obese people have lower mortality than non-obese people. The finding is considered paradoxical because the obese do not have lower mortality in cross-sections of the general population. The paradox is, however, commonly observed among people who suffer from a particular illness such as heart disease or diabetes

Medical Research: What are the main findings of your study? What is reverse causation and how does it affect obesity studies?

Dr. Preston: We find in a nationally representative sample that, among people suffering from cardiovascular disease, mortality is indeed lower for people who are overweight or obese than for people of normal weight. So the paradox appears among this group. However, when we study people’s mortality according to their maximum lifetime weight, the paradox disappears. We attribute its disappearance primarily to the fact that many  people who have lost weight from their maximum are doing so because they are ill. This phenomenon is referred to as “reverse causation” because illness is affecting weight rather than weight affecting illness and mortality.
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Genome Wide Testing May Make Transplantation More Personalized

MedicalResearch.com Interview with:
Brendan J. Keating, DPhil
Assistant professor of Transplant Surgery
Penn Medicine

Medical Research: What is the background for this study? What are the main findings?

Response: Genetic studies in transplantation have been plagued by small samples and very complex phenotypes/outcomes of patients. Transplanted individuals are typically on potent immunosuppression drugs for the rest of their lives, as they have 3.5 million to 10 million variants difference from an unrelated transplanted donor organ. Such populations would certainly benefit from large well-powered genetic studies but only 3 transplant genome-wide genotyping studies comprising a few hundred individuals have been published.

The papers outline the resources in hand for the International Genetics & Translational
Research in Transplantation Network, comprising 22 studies to date (since the publication it has now expanded to 25 studies and > 32,000 subjects with genome-wide genotyping data). We show significant statistical power in iGeneTRAiN to detect main effect association signals across regions such as the MHC region (which harbors the HLA Class I/II regions which are well established to associate with transplantation outcomes). We also show strong genome-wide power to detect transplant outcomes that span all solid organs including graft survival, acute rejection, new onset of diabetes after transplantation (fast becoming the most common comorbidity post-transplantation), and delayed graft function (to date we have looked at this in kidney transplant patients only). We show that iGeneTRAiN is statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies.

The transplant specific GWAS array that we designed (described in depth in the Genome Medicine paper) show that the coverage in key transplant associated regions is much higher than conventional arrays, and we describe the ‘imputation’ pipeline to expand the 780,000 or so variants examined in any given individual to > 15 millions of variants using whole genome sequencing reference datasets.

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Novel DNA Vaccine Provides Protection Against MERS Virus

David B. Weiner, Ph.D. Professor, Department of Pathology and Laboratory Medicine Chair, Gene Therapy and Vaccine Program, CAMB Co-Leader Tumor Virology Program, Abramson Cancer Program University of Pennsylvania, Perelman School of MedicineMedicalResearch.com Interview with:
David B. Weiner, Ph.D.

Professor, Department of Pathology and Laboratory Medicine
Chair, Gene Therapy and Vaccine Program, CAMB
Co-Leader Tumor Virology Program, Abramson Cancer Program
University of Pennsylvania, Perelman School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Weiner: MERS, like the Severe Acute Respiratory Syndrome (SARS), is characterized by high fever and severe cough from pneumonia. MERS is caused by an emerging human coronavirus, which is distinct from the SARS coronavirus. Since its identification in 2012, MERS has been linked to over 1,300 infections and close to 400 deaths. It has occurred in the Arabian Peninsula, Europe, and in the US and in Asia. It can be spread in a hospital setting.

Scientists now report that a novel synthetic DNA vaccine can, for the first time, induce protective immunity against the Middle EastRespiratory Syndrome (MERS) coronavirus in animal species.   Researchers from the Perelman School of Medicine at the University of Pennsylvania. The NIH, the Public Health agency of Canada, and from a leading company in the development of synthetic DNA vaccine technology, Inovio described the results in a paper  published their work in Science Translational Medicine (STM) this week.  The experimental, preventive vaccine, given six weeks before exposure to the MERS virus, fully protects rhesus macaques from disease. The vaccine also generated potentially protective antibodies in blood drawn from camels, the purported source of MERS transmission in the Middle East.

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Penn Developed Sarcoidosis Score Reliably Measures Disease Activity

Misha A. Rosenbach, MD Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania Assistant Professor of Dermatology in MedicineMedicalResearch.com Interview with:
Misha A. Rosenbach, MD
Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania
Assistant Professor of Dermatology in Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Rosenbach: Sarcoidosis is an inflammatory disease of unknown etiology where genetically susceptible patients develop multi-organ granulomatous inflammation in response to an as-yet unidentified stimulus.  Patients with sarcoidosis typically have granulomatous inflammation in their lungs, but the second most commonly affected organ is the skin; the eyes, lymph nodes, liver, heart, brain, and other organs can be affected as well.  Patients with sarcoidosis can experience a few disease trajectories; some spontaneously recover, while others have persistent, active inflammation, whereas another group can experience inflammation which leads to scarring and fibrosis.  It can be challenging to distinguish these cohorts of patients based on their lungs alone.

The skin is much easier to evaluate, as it is right there on the surface, and can be examined by physicians without resorting to invasive tests or radiography.  At Penn, we developed a novel cutaneous sarcoidosis assessment tool, called the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI), which is designed to accurately measure how inflamed skin sarcoid lesions are in a given patient, as well as describing which type of cutaneous lesion patients’ have.  The CSAMI has in previously studies been shown to be reliable when used by dermatologists, with excellent inter-rater and intra-rater reproducibility.

In this study, we had a group of Pulmonologists, Rheumatologists, and Dermatologists (representing the groups of physicians who most commonly care for patients with sarcoidosis, especially if there is skin involvement) evaluate a group of patients with cutaneous sarcoidosis, using the CSAMI and another sarcoidosis activity instrument, the SASI, which has also previously been used to measure skin sarcoidosis activity in a number of settings.  We were able to demonstrate that these cutaneous scoring tools are reliable and reproducible and able to accurately measure cutaneous sarcoidosis disease activity in a variety of patients with a range of skin disease severity.  We also compared the physician scores to patients’ own evaluations of their disease, and showed that the CSAMI (physician impression of disease) correlated well with patients’ own perception of their disease activity and severity.

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No Evidence of Anti-Inflammatory Mediator Increase From Fish Oil Ingestion

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with:
Carsten C. Skarke MD
Research Assistant Professor of Medicine
McNeil Fellow in Translational Medicine
Institute for Translational Medicine and Therapeutics
Perelman School of Medicine
University of Pennsylvania

Medical Research: What is the background for this study? What are the main findings?

Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators.

Several aspects of our study design set us apart from what was done in previous studies.

  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.

The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans.

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Study Finds Increased Hospitalizations Near Marcellus Shale Fracking Wells

Reynold A. Panettieri, Jr., M.D. Robert L. Mayock and David A. Cooper Professor of Medicine Pulmonary, Allergy & Critical Care Division Director, Airways Biology Initiative Deputy Director, Center of Excellence in Environmental Toxicology Adjunct Professor, Wistar Institute Philadelphia, PA  19104-3413MedicalResearch.com Interview with:
Reynold A. Panettieri, Jr., M.D.

Robert L. Mayock and David A. Cooper Professor of Medicine
Pulmonary, Allergy & Critical Care Division
Director, Airways Biology Initiative
Deputy Director, Center of Excellence in Environmental Toxicology
Adjunct Professor, Wistar Institute
Philadelphia, PA  19104-3413

Medical Research: What is the background for this study? What are the main findings?

Dr. Panettieri: Over the past ten years in the US, unconventional gas and oil drilling (hydraulic fracturing) to generate natural gas has markedly increased.  In areas with hydraulic fracturing, there is a large increase in truck traffic, noise and potential air and water pollution.  Accordingly, residents may experience health consequences from such exposures.  We questioned whether proximity to active wells increases hospitalization rates in residents.  To address this question, we reviewed all hospitalizations in two counties in Pennsylvania, namely, Bradford and Susquehanna Counties, that experienced a meteoric increase in active wells.  In comparison, Wayne County, where there is a moratorium on hydraulic fracturing, is demographically identical to Bradford and Susquehanna Counties and served as a control population.  Having examined the 25 most common reasons for admission to the hospital, we determined that cardiovascular hospitalizations as well as neurologic, dermatologic and cancer hospitalizations were associated with living closer to active wells.  These data represent some of the first studies to associate active well drilling with hospitalizations in the United States. Continue reading

Placenta-on-a-Chip Technology Enhances Study Of Fetal Circulation

Dan Dongeun Huh, Ph.D. Wilf Family Term Chair & Assistant Professor Department of Bioengineering University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with:
Dan Dongeun Huh, Ph.D.
Wilf Family Term Chair & Assistant Professor
Department of Bioengineering
University of Pennsylvania
Philadelphia, PA 19104

Medical Research: What is the background for this study? What are the main findings?

Response: The placenta is a temporary organ central to pregnancy and serves as a major interface that tightly regulates transport of various endogenous and exogenous materials between mother and fetus.  The placental barrier consisting of the closely apposed trophoblast epithelium and fetal capillary endothelium is responsible for maintaining this critical physiological function, and its dysfunction leads to adverse pregnancy outcomes.  Despite its importance, barrier function of the placenta has been extremely challenging to study due to a lack of surrogate models that faithfully recapitulate the key features of the placental barrier in humans.  Our study aims to directly address this long-standing technical challenge by providing a microengineered in vitro system that replicates architecture, microenvironment, and physiological function of the human placenta barrier.  This “placenta-on-a-chip” device consists of microfabricated upper and lower cell culture chambers separated by a thin semipermeable membrane, and the placental barrier is generated by culturing human trophoblasts and fetal endothelial cells on either side of the membrane with steady flows of culture media in both chambers.  This microfluidic cell culture condition allowed the cells to form confluent monolayers on the membrane surface and to create a bi-layer tissue that resembled the placental barrier in vivo.  Moreover, the microengineered barrier enabled transport of glucose from the maternal chamber to the fetal compartment at physiological rates.

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Wide US Regional Variation In Organ Donation Rates

MedicalResearch.com Interview with:
Dr. David Goldberg MD, MSCE
Assistant Professor of Medicine
LDI Fellow, Leonard Davis Institute, University of Pennsylvania
Medical Director for Living Donor Liver Transplantation, Hospital of the University of Pennsylvania
Senior Scholar, Center for Clinical Epidemiology and Biostatistics

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

Dr. Goldberg: While there are data that demonstrate differences in authorization (consent) rates for deceased donation among racial and ethnic minorities, it is unknown how these differences contribute to geographic differences in the number of deceased organ donors.  It has been postulated that geographic differences in the distribution of racial and ethnic minorities may contribute to differences in the deceased organ supply, yet there have been no empiric data to support this.  Using data on “eligible deaths,” defined as potential brain-dead organ donors <=70 years of age, we demonstrated that even after accounting for differences in the racial/ethnic demographics of the potential donor population, there are dramatic differences in authorization (consent) rates across geographic areas that are not explained by demographics alone. If the source of these differences could be identified, then there could be large increases in the number of organ donors, and lifesaving transplants, in areas with lower authorization rates.

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Carotid Artery Stenting: Comparison Of Embolic-Prevention Devices

Jay Giri, MD MPH Director, Peripheral Intervention Assistant Professor of Clinical Medicine University of PennsylvaniaMedicalResearch.com Interview with
Jay Giri, MD MPH
Director, 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).

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Adolescents Risk Failing HIV Treatment If No Parent Attends Clinic Visits

Elizabeth Lowenthal, MD MSCE Assistant Professor of Pediatrics Children's Hospital of PhiladelphiaMedicalResearch.com Interview with:
Elizabeth Lowenthal, MD MSCE

Assistant Professor of Pediatrics
Children’s Hospital of Philadelphia

Medical Research: What is the background for this study? What are the main findings?

Dr. Lowenthal: Between 2005 and 2012, HIV related deaths declined by 30% worldwide. However, during the same time period, HIV related deaths increased 50% among adolescents. Over 90% of HIV-infected children and adolescents live in sub-Saharan Africa and HIV is the leading cause of death among adolescents in Africa. Treatment is available that can allow babies born with HIV to live to be healthy adults. However, strict adherence to these medicines is necessary and often becomes a great challenge during adolescence. In our study of 300 adolescents (ages 10-19) in Botswana, my team found that adolescents who come to clinic without a parent or guardian have a 4.5X greater odds of failing their HIV treatment.

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Study Highlights Benefits of Cognitive-Behavioral Therapy for Childhood Anxiety.

Courtney Benjamin Wolk, Ph.D. Postdoctoral Researcher Center for Mental Health Policy and Services Research Perelman School of Medicine Department of Psychiatry University of Pennsylvania Philadelphia, PA 19104MedicalResearch.com Interview with:
Courtney Benjamin Wolk, Ph.D.

Postdoctoral Researcher
Center for Mental Health Policy and Services Research
Perelman School of Medicine Department of Psychiatry
University of Pennsylvania Philadelphia, PA 19104

Medical Research: What is the background for this study? What are the main findings?

Response: Previous research investigating the relationship between anxiety and suicidality has been mixed. An ongoing question in the field has been whether anxiety disorders independently increase risk for suicidal ideation and behavior or if the high co-occurrence of anxiety and mood symptoms or other shared demographic factors are driving relationships that have been observed between anxiety and suicidality.

We examined the relationship between response to treatment for an anxiety disorder in childhood and suicidal ideation, plans, and attempts 7 to 19 years after treatment with cognitive-behavioral therapy, more commonly referred to as CBT. Our results indicated that participants who responded favorably to cognitive-behavioral therapy during childhood had lower rates of lifetime, past month, and past two-week suicidal ideation endorsement than treatment non-responders. This was the case across both self-report and interview-report of suicidal ideation. Treatment response was not significantly associated with suicide plans or attempts, though plans and attempts were infrequently endorsed in our sample, limiting the ability to detect findings.

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Research Aims To Understand Heart Failure In Women

Dawn Pedrotty, MD, PhD Cardiovascular Medicine Fellowship University of PennsylvaniaMedicalResearch.com Interview with:
Dawn Pedrotty, MD, PhD

Cardiovascular Medicine Fellowship
University of Pennsylvania

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

Dr. Pedrotty: Heart failure (HF) is the most common cause for hospitalization among patients 65 years and older, affecting approximately 6 million Americans; at 40 years of age, American males and females have a one in five lifetime risk of developing heart failure. There are two distinct heart failure phenotypes: a syndrome with normal or near-normal left ventricular ejection fraction (LVEF) referred to as HF with preserved ejection fraction (HFpEF), and the phenotype associated with poor cardiac contractility or heart failure with reduced ejection fraction (HFrEF). Risk factors associated with HFpEF include female gender, especially women with diabetes, higher body mass index, smoking, hypertension, concentric left ventricular hypertrophy (LVH), and atrial fibrillation (AF). There has been a growing interest in the development of criteria for specific subsets of HFpEF, a syndromal disease where multiple cardiac and vascular abnormalities exist. One approach is to implement phenomapping, identifying phenotypically distinct HFpEF categories and developing a classification system to group together pathophysiologically similar individuals who may respond in a more homogeneous, predictable way to intervention. Another option would be to focus on a known physiologic differences which might shed light on pathologic mechanisms e.g. gender and the influences of obesity and atrial fibrillation.
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New and Experienced Surgeons Have Similar Patient Mortality Rates

Samuel D. Pimentel Doctoral student Statistics Department Wharton School of the University of PennsylvaniaMedicalResearch.com Interview with:
Samuel D. Pimentel
Doctoral student Statistics Department
Wharton School of the University of Pennsylvania

 

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

Response: Surgical training has undergone major changes in recent years – including a reduction of six to twelve months of training time – and there is controversy about whether these changes have been good or bad for patient outcomes.   Our work partially addresses the issue by asking whether newly-trained surgeons perform better or worse than experienced surgeons.  We compared surgical patients treated by new surgeons to a similar group of patients treated by experienced surgeons using a new statistical technique called large, sparse optimal matching.  Our analysis found no significant differences in mortality rates between the two groups.
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MRSA Persistence Linked With Household Members and Pets

MedicalResearch.com Interview with:
Valerie Cluzet, MD
Hospital of the University of Pennsylvania
Division of Infectious Diseases
Philadelphia, PA 19104

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

Dr. Cluzet: MRSA is a major cause of skin and soft tissue infection (SSTI) in the community and we know that colonization is an important risk factor for subsequent infection. Past studies have calculated duration of colonization based on colonization at hospital admission or focused on populations not representative of the typical community-dwelling patient. We wanted to identify the factors associated with duration of colonization in a typical patient that clinicians would see (i.e. adults and children presenting to ambulatory setting with a MRSA SSTI), so that the findings would be generalizable and relevant to their practice. In addition, there has been an increasing focus on the role of the household in transmission of MRSA, so wanted to specifically examine that in a longitudinal, systematic way.

There are a few major points that emerged from our study.

1) The first is that the duration of colonization after treatment for a methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI) is relatively short, but there is a significant subset of patients (approximately 20%) who will have persistent colonization.

2) We also found that treatment of the MRSA SSTI with clindamycin was associated with shorter duration of colonization, an association we did not see with other MRSA-active agents.

3) Finally, this study highlights the potential role of MRSA colonization among household members as a contributing factor in duration of colonization in patients.
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Patient Demands Not A Significant Driver Of Health Care Costs

Ezekiel Jonathan Emanuel MD PhD Department of Medical Ethics and Health Policy Perelman School of Medicine and Department of Health Care Management The Wharton School University of Pennsylvania Philadelphia, PAMedicalResearch.com Interview with:
Ezekiel Jonathan Emanuel MD PhD
Department of Medical Ethics and Health Policy
Perelman School of Medicine and
Department of Health Care Management
The Wharton School University of Pennsylvania
Philadelphia, PA

Editor’s note: Dr. Emanuel is a medical oncologist as well as director of the department of Medical Ethics and Health Policy at the University of Pennsylvania. Dr. Emanuel was kind enough to answer several questions regarding his most recent study, published in the new JAMA Oncology journal, Patient Demands and Requests for Cancer Tests and Treatments.

Medical Research: What is the background for this study? What are the main findings?

Dr. Emanuel: The genesis for this study is twofold.

One, the first referenced article, by John Tilbert1 discussed how physicians explain US health care costs. In this study, physicians felt patients, insurance companies, drug companies, government regulations and malpractice lawyers…all were more to blame than doctors themselves for the high cost of US health care.

Secondly, I give lots of presentations to doctors who offer two explanations for escalating health care costs: fear of malpractice litigation, and demanding patients, who request extensive testing and drugs. We decided to see whether the impression doctors frequently held of patients’ demands driving up health care costs, had been previously investigated. We could find no article to substantiate this belief. In addition, demanding patients were not common in my medical experience.

In our study we included 5050 patient encounters. We asked the clinician coming out of the encounter, did the patient make a demand or request? (By asking immediately after the doctor left the examination room, there was little risk of inaccurate recall of the specifics of visit). In 8.7% there was a patient request and of these, over 70% were deemed clinically appropriate as determined by the physician (i.e. a request for pain medication, palliative care or imaging to address a new symptom or finding). In only 1% of all encounters (50/5050) was a clinically inappropriate request made as determined by the doctor, and the doctors hardly filled any of these inappropriate requests (total of 7 of 5050 encounters).

We concluded that it is pretty rare for patients to make demands or requests, at least in this oncology setting, and even less common for the demands to be complied with by the doctor. Therefore it seems unlikely to us that health care costs are significantly driven by inappropriate patient requests. It is possible that there are more or different patient demands in other health care settings but we were very surprised to find no difference in patient requests based on patient-income, i.e. wealthier, more educated patients made no more demands than patients of lesser means.

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Expired Medicaid Payment Bump Had Increased New Patient Appointment Availability

Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of PennsylvaniaMedicalResearch.com Interview with:
Daniel Polsky PhD
Executive Director, Leonard Davis Institute of Health Economics
Professor of Medicine and Health Care Management
Perelman School of Medicine and the Wharton School
University of Pennsylvania

Medical Research: What is the background for this study? What are the main findings?

Dr. Polsky: The Medicaid Fee bump, a provision of the Affordable Care Act (ACA), raised Medicaid payments to Medicare levels in 2013 and 2014 for selected services and providers expired on January 1, 2015 before policymakers had much empirical evidence about its effects.   The federally funded increase in reimbursements was aimed at expanding access to primary care for the growing number of Medicaid enrollees. The reimbursement increase expired at the end of 2014 in most states.  We found that this policy worked to increase the number of providers offering primary care appointments to Medicaid patients.  The Medicaid pay bump was associated with a 7.7 percentage points increase in new patient appointment availability without longer wait times.   This increase in availability was largest in the states where primary care physicians received the largest increase in their Medicaid reimbursements.

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Racial Disparities in Colon Cancer Survival Persist

Jeffrey H. Silber, M.D., Ph.D. The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research The Children's Hospital of Philadelphia Professor of Pediatrics, Anesthesiology & Critical Care The Perelman School of Medicine Professor of Health Care Management, The Wharton SchoolMedicalResearch.com Interview with:
Jeffrey H. Silber, M.D., Ph.D.

The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research
The Children’s Hospital of Philadelphia
Professor of Pediatrics, Anesthesiology & Critical Care
The Perelman School of Medicine
Professor of Health Care Management, The Wharton School
The University of Pennsylvania  Philadelphia, PA 19104

Medical Research: What is the background for this study? What are the main findings?

Response: Differences in colon cancer survival by race is a well recognized problem among Medicare beneficiaries. We wanted to determine to what extent the racial disparity in survival is due to a racial disparity in presentation characteristics at diagnosis (such as advanced stage and the presence of chronic diseases) versus a disparity in subsequent treatment by surgeons and oncologists.

To answer this question, we compared black colon cancer patients to three matched white groups:

(1) “Demographics” match controlling age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site;
(2) “Presentation” match controlling demographics plus comorbidities and tumor characteristics including stage and grade; and
(3) “Treatment” match including presentation variables plus details of surgery, radiation and chemotherapy.

We studied Medicare patients 65 years of age and older diagnosed between 1991-2005 in the SEER-Medicare database. There were 7,677 black patients and 3 sets of 7,677 matched white controls.

We found that difference in 5-year survival (black-white) was 9.9% in the demographics match. This disparity remained unchanged between 1991-2005. After matching on presentation characteristics, this difference fell to 4.9%. Finally, after additionally matching on treatment, this same difference hardly changed, moving to only 4.3%. So the disparity in survival attributed to treatment differences comprised only an absolute 0.6% of the overall 9.9% survival disparity.

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Sleep Deprivation: Specific Molecular Changes Lead To Memory Impairment

MedicalResearch.com Interview with:
Jennifer Choi Tudor, Ph.D. Postdoctoral Fellow
Ted Abel Lab Department of Biology 10-17
Smilow Center for Translational Research
Philadelphia, PA 19104

Medical Research: What is the background for this study? What are the main findings?

Dr. Tudor: We (Dr. Tudor, Dr. Abel, and colleagues) are interested in better understanding the molecular changes that occur with sleep deprivation.  Previously, we found that the expression of over 500 genes changes with sleep deprivation and that many of the genes were involved with protein synthesis.  Upon further investigation, we found that 5 hours of sleep deprivation impairs protein synthesis in the hippocampus, a brain region critical for memory.  This impairment is due to changes in mammalian target of rapamycin (mTOR) signaling and eukaryotic initiation factor 4E binding protein 2 (4EBP2) is critical to this process.  When we boosted levels of 4EBP2 in the hippocampus, mice that were sleep deprived were resistant to the detrimental effects of sleep deprivation on memory.
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Septic Shock Patients Often Require Hospital Readmission

Mark E Mikkelsen, MD, MSCE Assistant Professor of Medicine Hospital of the University of PennsylvaniaMedicalResearch.com Interview with:
Mark E Mikkelsen, MD, MSCE
Assistant Professor of Medicine
Hospital of the University of Pennsylvania

Medical Research: What is the background for this study? What are the main findings?

Dr. Mikkelsen: Sepsis is common, afflicting as many as 3 million Americans each year. It is also costly, both in terms of health care expenditures that exceed $20 billion for acute care and in terms of the impact it has on patients and their families. To date, studies have focused on what happens to septic shock patients during the initial hospitalization. However, because more patients are surviving sepsis than ever, we sought to examine the enduring impact of septic shock post-discharge. We focused on the first 30 days after discharge and asked several simple questions. First, how often did patients require re-hospitalization after septic shock? And second, why were patients re-hospitalized?

We found that 23% of septic shock survivors were re-hospitalized within 30 days, many of them within 2 weeks. A life-threatening condition such as recurrent infection was the reason for readmission and 16% of readmissions resulted in death or a transition to hospice.
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Shared Savings May Promote Lower Costs With Equally Effective Health Care

Dr. Harald Schmidt, MA, PhD Assistant Professor, Department of Medical Ethics and Health Policy Research Associate, Center for Health Incentives and Behavioral Economics Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104-3308MedicalResearch.com Interview with
Dr. Harald Schmidt, MA, PhD
Assistant Professor, Department of Medical Ethics and Health Policy , Research Associate, Center for Health Incentives and Behavioral Economics, Perelman School of Medicine
University of Pennsylvania Philadelphia, PA 19104-3308

Medical Research: What are the main findings of the study?

Dr. Schmidt: We reviewed currently available policies for aligning cost and quality of care. We focused on interventions are similar in their clinical effectiveness, have modest differences in convenience, but pose substantial cost differences to the healthcare system and patients. To control health care costs while ensuring patient convenience and physician burden, reference pricing would be the most desirable policy. But it is currently politically unfeasible. Alternatives therefore need to be explored. We propose the novel concept of Inclusive Shared Savings, in which physicians, the healthcare system, and, crucially, patients, benefit financially in moving more patients to lower cost but guideline concordant and therapeutically equivalent interventions.

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