MedicalResearch.com Interview with:
Jennifer R. Rider, ScD, MPH
Assistant Professor of Medicine
Channing Division of Network Medicine
Brigham and Women's Hospital and Harvard Medical School
Department of Epidemiology
Harvard T.H. Chan School of Public Health
Boston, MA 02115
Medical Research: What is the background for this study? What are the main findings?
Dr. Rider: Numerous studies have investigated the potential role of sexual activity on the development of prostate cancer. However, most of these studies have been small and retrospective, making them more prone to bias. In addition, previous studies often relied on proxies of exposure for sexual activity (number of sexual partners, age at first marriage, etc.), which may not adequately measure the aspects of sexual activity that are most important for prostate health. The current study is the largest prospective study to date on ejaculation frequency and prostate cancer. It includes 18 years of follow up of almost 32,000 healthy men, 3839 of whom later were diagnosed with prostate cancer. We asked men about their average monthly frequency of ejaculation between the ages of 20-29, 40-49, and in the year prior to the questionnaire (1991). We find that frequency of ejaculation throughout life course is inversely associated with risk of prostate cancer at all three of these time points. For instance, men who have an average monthly ejaculation frequency of 21 or more times/moth at ages 40-49 have a statistically significant 22% reduction in risk of developing prostate cancer compared to men with a frequency of 4-7 times/month, adjusting for multiple dietary and lifestyle factors, and prostate cancer screening history.
MedicalResearch.com Interview with:
Ryan P. Terlecki, MD, FACS
Director, Men's Health Clinic
Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility
Director, Medical Student Education
Associate Professor of Urology
Wake Forest Baptist Health
Medical Research: What is the background for this study? What are the main findings?
Response: In recent years, the value of generalized screening for prostate cancer (PCa) in adult men has been questioned, with several national associations recommending against the practice in men without recognized risk factors. Screening, when performed, often consists of a blood test for prostate specific antigen (PSA) and a digital rectal exam (DRE). Once PSA was developed as a screening tool, we witnessed a stage migration such that observing a locally advanced cancer that would be initially found via DRE became a rarer event. In practice, we have noticed that some men will actually avoid a clinic visit because of the DRE. Additionally, the digital rectal exam has limitations and is often poorly reproducible among providers. We chose to review a large body of data to shed some light on the utility of the digital rectal exam exam. We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening trial, to determine the ability of the digital rectal exam to result in a diagnosis of clinically significant PCa in the setting of a normal PSA. We found that if PSA is normal and digital rectal exam is considered abnormal, the chance of detecting a clinically significant cancer is similar to a situation of normal DRE and normal PSA. Also, 1,372 men would need to undergo a digital rectal exam to identify a single case of clinically significant prostate cancer not detected by PSA.
MedicalResearch.com Interview with:
Jim Dupree, MD, MPH
Assistant Professor
Department of Urology, Division of Andrology
University of Michigan
Medical Research: What is the background for this study? What are the main findings?
Dr. Dupree: There are increasing discussions in the United States about testosterone therapy and men with clinical hypogonadism (or low testosterone). Yet, to date, there have not been any nationally-representative studies of the prevalence of low testosterone in the United States. Using a validated national health examination program from the CDC, we found that the national prevalence of low testosterone (serum testosterone ≤ 300 ng/dL) in adult males in the US was 28.9%. Among other factors, men who were older, had a higher body mass index (BMI), or had a larger waist circumference were at risk for having lower testosterone levels.
MedicalResearch.com Interview with: Michael Brawer, M.D. Vice president of Medical Affairs Myriad Genetic Laboratories Editor’s Note: Dr. Brawer spoke with MedicalResearch.com regarding two studies presented by Myriad Genetic Laboratories at the American Urological Association's 2015 Annual Meeting, May 15 2015 on the use of the Clinical Cell Cycle Risk (CCR) Score or Prolaris Test...
MedicalResearch.com Interview with:
Judith Hibbard, Ph.D.
Senior Researcher, Health Policy Research Group
University of Oregon
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Hibbard: Two important trends are happening in health care today:
1) Policies which move away from paying for volume and toward paying for value; and
2) The emphasis on patient engagement and the need for the patient to play a key part in the care process. Because so many quality outcomes are determined to a large extent by patient behaviors, there is an implied assumption that if you pay primary care clinicians (PCPs) more for better quality outcomes, they will also try to engage the patient as a necessary partner in reaching quality targets. That is, there is a tacit assumption that clinicians will naturally engage patients if you incentivize them on the quality metrics. We had an opportunity to examine the soundness of this assumption, when we conducted a study of primary care clinicians whose compensation was based 40% on their performance of quality metrics.
The findings show that the vast majority of clinicians did not invest their efforts in patient engagement and activation, when trying to maximize their income under this model. They put their efforts in other areas. However, a year later they were very frustrated that their income was influenced by patient behaviors. This was their greatest frustration with the compensation model, and they indicated that “patient’s unwillingness to change their behavior” as the greatest barrier to achieving their quality goals.
MedicalResearch.com Interview with:
Michael Rebold, PhD, CSCS
Assistant Professor
Department of Exercise Science
Bloomsburg University
Bloomsburg, PA 17815
Medical Research: What is the background for this study? What are the main findings?
Dr. Rebold: We assessed how common smartphone uses (texting and talking) interfere with treadmill exercise.
We found that when individuals use their smartphones during exercise for texting or talking, it causes a reduction in exercise intensity.
MedicalResearch.com Interview with:
Amie W. Hsia, MD
Medical Director, Comprehensive Stroke Center
MedStar Washington Hospital Center
NIH Stroke Program at MWHC
Associate Professor, Neurology
Georgetown University Washington, DC 20010
Medical Research: What is the background for this study? What are the main findings?
Dr. Hsia: Acute stroke is a common presenting problem in the emergency department. We know that “time is brain” and that for patients experiencing an ischemic or “blockage” type of stroke, the most common type, the sooner we can administer tPA, a clot-busting medication and the only FDA-approved medication to treat acute stroke, the better chance for a good outcome. Therefore, there is a goal national benchmark time of administering the drug to appropriate acute stroke patients within 60 minutes of their arrival to the emergency department. There are many steps that are necessary in the evaluation of an acute stroke patient in the emergency department before tPA can be given. This includes a brain scan to make sure a patient is not having the less common bleeding type of stroke. A CT or “CAT” scan is the typical type of brain scan that is performed in emergency departments across the country and the world to screen a patient before giving tPA. The primary purpose of the CT scan is to exclude bleeding; it is difficult to visualize an early stroke on CT. Though an MRI can give more complete information including showing the stroke as it is happening in these first few hours and though most hospitals have an MRI scanner, an MRI takes longer to perform and has not traditionally been used in an emergency setting.
At the two hospitals included in this study, MedStar Washington Hospital Center in D.C. and Suburban Hospital in Maryland, we are fortunate to serve as the sites for the NINDS intramural stroke clinical research program and use MRI routinely to screen acute stroke patients to learn more about stroke and develop new treatments for stroke. It is upon this foundation that we performed independent hospital-wide quality improvement initiatives engaging multidisciplinary committees with leadership from all the departments involved in the care of the acute stroke patient in that critical first 60 minutes. Inspired by our colleagues at Washington University in St. Louis led by Dr. Andria Ford who used similar methods in reducing treatment times with CT screening, we used lean manufacturing principles to streamline our processes that include MRI screening and dramatically reduced our treatment times from a baseline of 93 minutes down to 55 minutes while still maintaining safety. Through these efficiency improvements, we were able to achieve a 4-fold increase in the percentage of stroke patients treated with tPA within 60 minutes.
MedicalResearch.com Interview with:
Dr. Christine McCusker MD
Associate Professor, Department Pediatrics
Meakins-Christie Laboratories
McGill University and the MUHCRI, Montreal
Quebec, Canada
Medical Research: What is the background for this study? What are the main findings?
Dr. McCusker: When the body is exposed to new substances, the immune system must evaluate the “threat” and choose the type of response that will best protect the host. Allergies and allergic asthma develop after the response to “allergens” follows the TH2-type inflammatory pathway instead of the non-inflammatory tolerant pathway. Evidence suggests that there is some plasticity in this “choice” and thus it may be possible to influence the immune response to preferentially choose the tolerant pathway when exposed to allergens. We therefore treated very young mice to a molecule designed to inhibit activation of the TH2 pathway.
We showed that this early treatment resulted in long-lasting protection from the development of allergies. Instead of allergic responses, vaccinated animals developed tolerant responses to allergens and did not show any signs of allergies or asthma. Importantly, while the influence of the treatment was long-lasting, the molecule itself is rapidly removed from the system.
MedicalResearch.com Interview with:
Robert A. Meguid, MD MPH FACS
Assistant Professor Section of General Thoracic Surgery
Division of Cardiothoracic Surgery Department of Surgery
University of Colorado Denver | Anschutz Medical Campus
Aurora, CO 80045
Medical Research: What is the background for this study? What are the main findings?
Dr. Meguid: The surgical literature on adverse outcomes after surgery on pregnant patients is conflicting. We know that the majority of surgery performed on pregnant patients is not elective (and just over 50% of it in the database studied was emergency surgery). We expected to find an increased rate of adverse outcomes in those pregnant patients. However, when we matched the pregnant and non-pregnant women who underwent surgery in the database, with excellent matching on all available preoperative characteristics and on the actual operation performed, we found similar, low rates of 30-day postoperative death and complication. In this study, pregnant patients had undergone a broad spectrum of different types of operations, including general, vascular, thoracic, head and neck, non-obstetric gynecologic and urologic, orthopedic, reconstructive, and neuro-surgery. Given the concern that we as surgeons have over operating on pregnant patients, both for the well-being of the patient and her child, our findings are reassuring. This suggests that we as a medical profession are diligent in minimizing risk to pregnant women who need surgery that cannot be delayed until after the child's birth. Again, this study faces the limitations of being unable to assess any short term harm done to the fetus and the subsequent long term outcome of the child.
MedicalResearch.com Interview with:
Katherine Aird, Ph.D.
Gene Expression and Regulation Program
The Wistar Institute, Philadelphia, PA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Aird: Senescence is considered an important tumor suppressor mechanism. In normal cells, activation of certain oncogenes decreases the levels of dNTPs (the building blocks of DNA), leading to replication stress. We previously found that loss of the rate-limiting enzyme in dNTP synthesis, ribonucleotide reductase M2 (RRM2), is the cause of this replication stress. Restoration of RRM2 expression could rescue the loss of dNTPs and replication stress, which overcame the senescence-associated growth arrest. Indeed, RRM2 is highly expressed in many cancer types, including melanoma and ovarian cancer. Therefore, we found that increased dNTP levels can overcome senescence and potentially lead to transformation of cells and cancer.
We next wanted to further our understanding of replication stress in the context of senescence. In the current study, we suppressed nucleotide metabolism by decreasing RRM2 expression as a model for replication stress and then determined what proteins are necessary for the induction of senescence. We found that loss of ATM could overcome replication stress-induced senescence. This was due to increased dNTP levels. dNTPs were increased due to a coordinated inactivation of p53 and activation of c-MYC by loss of ATM. These changes at the molecular level correlate with reprogramming of cellular metabolism by generating dNTPs. Thus, loss of ATM in the context of replication stress can change cellular metabolism to a more cancer-like phenotype.
Melinda L. Telli, M.D.
MedicalResearch.com Interview with:
Humphrey Yao, Ph.D.
Lead Researcher
Reproductive and Developmental Biology Laboratory
National Institute of Environmental Health Sciences (NIEHS)
National Institutes of Health (NIH)
Research Triangle Park, North Carolina
Medical Research: What is the background for this study? What are the main findings?
Dr. Yao: We wanted to understand how an organ forms, and what basic cell types were needed to form an organ. So, we used a mouse ovary model system to understand the process. The functional unit of the ovary is called the follicle, and it is made up of three types of cells — the maturing egg, granulosa cells, and theca cells. Scientists knew where the egg and the granulosa cells came from, but no one knew where theca cells came from. Theca cells are important, because they allow females to produce the hormones that sustain follicle growth. Researchers also lacked information about how the egg, granulosa cells, and theca cells talked to each other to promote growth and maintain a healthy ovary.
We made two discoveries. First, we answered the long-standing question of theca cell origin by determining that they have two sources, both inside and outside of the ovary. We don’t yet know why theca cells have two sources.
Second, we uncovered the molecular signaling system that the egg, granulosa cells, and theca cells use to communicate. We didn’t expect to find this three-way cellular crosstalk, but now that we know how they signal each other, I believe we are closer to understanding how an ovary develops and what happens when something goes wrong. Ovarian disorders, such as premature ovarian failure and polycystic ovarian syndrome, may start when cellular communication is altered or if the various cells fail to develop properly.
MedicalResearch.com Interview with:
Dr. Shang-Ming Zhou
Senior Lecturer in Statistical Modelling and Analytics for Epidemiology and Public Health,
Public Health Informatics Group,
Health Information Research Unit (HIRU),
UKCRC DECIPHer (Development and Evaluation of Complex Interventions for Public Health Improvement) Centre,
College of Medicine, Swansea University, Swansea, UK
Medical Research: What is the background for this study? What are the main findings?
Response: In medical and sport science research, body-worn accelerometers are widely used to provide objective measurements of physical activity. However, accelerometers collect data continuously even during periods of nonwear (i.e. periods when participants may not be wearing their monitor, such as during sleeping). It is important to distinguish time of sedentary behaviours (eg. watching television) from time of nonwear. The clinical consequence of misclassification of accelerometer wear and nonwear would overestimate or underestimate physical activity level, and mislead the interpretation of the relationship between physical activity and health outcomes. Automated estimation of accelerometer wear and nonwear time events is particularly desired by large cohort studies, but algorithms for this purpose are not yet standardized and their accuracy needs to be established. This study presents a robust method of classifying wear and nonwear time events under free living conditions for triaxial accelerometers which combines acceleration and surface skin temperature data.
The new findings are: Either acceleration data or skin temperature data alone is inadequate to accurately predict wear and nonwear events in some scenarios under a free living condition; This study provides a simple and efficient algorithm on use of short time periods of consecutive data blocks for accurately predicting triaxial accelerometer wear and nonwear events; Combining both types of acceleration and skin temperature data can significantly improve the accuracy of accelerometer wear and nonwear events classification in monitoring physical activity.
MedicalResearch.com Interview with:
Maria Blomberg
Virus, Lifestyle & Genes
Danish Cancer Society Research Centre
Copenhagen, Denmark
Medical Research: What is the background for this study? What are the main findings?
Response: Two vaccines against human papillomavirus (HPV) were licensed almost one decade ago. Since then multiple countries have implemented HPV vaccination programs to help reduce genital warts (one of the kinds of warts most harmful to people), but many struggle with low coverage rates. An important barrier to vaccination is the cost of the vaccines and less developed countries also face considerable logistical challenges. Both vaccines were administered as three dose schedules, but in early 2014 the WHO’s Strategic Advisory Group of Experts and the European Medicines Agency reviewed the evidence of reduced dose schedules of HPV vaccination, and subsequently recommended a two dose schedule for young girls. A reduction of the number of doses has obvious advantages; it would lower the costs, ease implementation of vaccination schedules and potentially increase coverage rates. Based on these recommendations, countries around the world have reduced the dosing schedule in their HPV vaccination programs for young girls to two doses. However, the current evidence is based primarily on immunological studies, and because the immune correlate of protection is not known, studies with disease endpoints are very important.
Using the biologically relevant endpoint of genital warts, this study aimed to assess the clinical effectiveness of a two dose schedule of quadrivalent HPV vaccine compared with the standard three-dose regimen administered at month 0, 2 and 6. We found that with the standard vaccination schedule, completion of the three dose regimen is important to gain maximal protection. However, the effectiveness of two doses increased significantly with increasing time between the doses, and with an interval of approximately 6 months between dose one and two, no differences could be found between two and three doses.
MedicalResearch.com Interview with:
J L Mehta, MD, PhD
Professor of Medicine and Physiology and Biophysics
Stebbins Chair in Cardiology
University of Arkansas for Medical Sciences
Little Rock, AR 72205
Medical Research: What is the background for this study? What are the main findings?
Dr. Mehta: In 2007, ACC/AHA published new guidelines regarding infective endocarditis (IE) prevention. This guideline drastically differed from the way we practiced and prescribed antibiotics to our patients when they undergo surgery or any other procedure like dental procedure, endoscopy, etc. to prevent infective endocarditis. As a result of these guideline, antibiotic use is now being restricted to only a small number of patients who have cardiac conditions that puts them at very high risk for adverse outcomes from IE. However, there is paucity of data on IE trends in the community following such a major change in practice. Therefore evaluated the trend in incidence of infective endocarditis and their outcomes before and after the advent of new guideline.
Our study has several important findings.
First, there has been a steady increase in the incidence of infective endocarditis hospitalizations over the last decade in the US. However, the incidence of IE pre- and post-inception of new antibiotic prophylaxis guidelines is not significantly different. In parallel to these findings, the rate of valve replacement for infective endocarditis did not change after the release of new guidelines in 2007.
Secondly, the increase in IE incidence was seen across all types of pathogens- Staphylococcus, Streptococcus, gram negative bacteria and fungi. The major offender involved in IE in the United States is Staphylococcus.
Finally, the rate of Streptococcus infective endocarditis related hospitalization increased significantly following the release of new guideline in the US, while Staphylococcus IE hospitalizations although on rise, did not increase significantly following the 2007 ACC/AHA guideline update.
MedicalResearch.com Interview with:
Matthew Pearce
NHS Gloucestershire Clinical Commissioning Group
UK
Medical Research: What is the background for this study? What are the main findings?
Response: Despite evidence to suggest that the prevalence of childhood obesity in the UK has stabilized in recent years, we know that approximately one in five children start their school life either overweight or obese, increasing to one in three children by the last year in primary school. Our research was the first to undertake an in-depth analysis on the UK’s National Child Measurement Programme (NCMP) and retrospectively track the weights of individual children over a 7-year period. Our study included a sample of 1863 children in South Gloucestershire, Bristol in the UK.
Our results were found to be similar to cross sectional data with obesity prevalence approximately doubling between the first (4/5yrs old) and last year (10/11yrs old) of primary school. Our findings provide little reassurance that those children who are obese in early childhood ‘grow out of ’ excess adiposity. Including overweight, we found that 84% of obese children at Reception year went on to be either overweight or obese by Year 6. Although previous studies have failed to identify any significant differences in BMI change between boys and girls during mid-childhood, our research found that more boys than girls dropped a weight category (from overweight or obese) by the time they reached Year 6. We found that the odds ratios of being overweight (BMI ?85th percentile) or obese (?95th percentile) based on BMI at Reception were similar to published literature. Our data found children who are within the upper range of the healthy weight category (75th–85th percentile) at Reception had an increased risk of being overweight or obese by the time they reach year 6.
Photo: Ulf Sirborn[/caption]
MedicalResearch.com Interview with:
Kristina Bečanovič Ph.D.
Department of Clinical Neuroscience
Karolinska Institutet, Stockholm, Sweden
Medical Research: What is the background for this study?
Dr. Bečanović: While the symptoms normally debut in middle-age, there is wide individual variation in how Huntington disease manifests itself, and even though two people carry the exact same genetic mutation that codes for the huntingtin protein, there can be up to a 20-year difference in onset of motor symptoms. This suggests that genetic variants, transcription factors and environmental factors could contribute to the observed differences in disease expressivity. As the identification of regulatory factors of the huntingtin gene would be targets for therapeutic intervention, we set out to study the regulation of the huntingtin gene as it has not been well-known which factors regulate the expression levels. We were interested in identifying both genetic variants and transcription factors that are of importance for gene regulation. We therefore used DNA from Huntington disease patients to study the regulation of the huntingtin gene promoter in cells.
MedicalResearch.com Interview with:
William M. Sage MD JD
James R. Dougherty Chair for Faculty Excellence
School of Law
The University of Texas
Medical Research: What is the background for this study? What are the main findings?
Response: We reviewed settlement agreements in malpractice claims closed by The University of Texas System as part of a larger study on incorporating patient perspectives into safety improvement funded by the Agency for Health Care Research and Quality. Over the five years studied, we found that 88.7% of the 124 settlement agreements that met our study criteria contained non-disclosure provisions, but with little standardization or consistency. Restrictions on disclosure, which selectively burdened patients and their families, seemed broader than needed to protect health care providers from disparagement or to avoid attracting additional litigation. Medical malpractice could happen to anyone at any time during your visit to your hospital. If you or a member of your family have been the victim of medical palpractice you might want to look into getting help from someone like this Tate Law Offices Ft. Worth Personal Injury Law Firm or a law firm that is local to you that might be able to help with your case.
Nearly half of the agreements (46.4%) prohibited disclosure of the underlying facts, which may be inconsistent with emerging principles of patient safety and compassionate care, and 26.4% prohibited reporting to regulatory bodies, a restriction that the health system subsequently eliminated in response to our findings. Settlements reached after tort reform took full effect in Texas had stricter non-disclosure provisions than earlier settlements, suggesting greater leverage by defendants notwithstanding the reduced risk of additional litigation.