Author Interviews, Erectile Dysfunction, Melanoma, PLoS / 16.06.2016
Erectile Dysfunction Drugs Unlikely to Cause Increase in Melanoma
MedicalResearch.com Interview with:
Anthony Matthews
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine
London, United Kingdom
MedicalResearch.com: What is the background for this study?
Dr. Mathews: :The drug Viagra, which is used to treat erectile dysfunction, is one of a class of drugs called PDE5 inhibitors. Laboratory studies of cells from the skin cancer, malignant melanoma, suggest that PDE5 inhibitors might promote their growth, so there have been some concerns that people using these drugs might have an increased risk of malignant melanoma. Two previous studies comparing melanoma rates in PDE5 inhibitor users and non-users came to differing conclusions so we wanted to look further into this. To carry out the study we used anonymised GP records from the UK identifying over 150,000 men with a PDE5 inhibitor prescription, and over 500,000 men of a similar age, and from the same areas, who didn’t have a PDE5 inhibitor prescription. We then looked for later diagnoses of malignant melanoma to see how people’s exposure to PDE5 inhibitors affected their future risk of being diagnosed with melanoma.
Dr Siddharth Singh[/caption]
Siddharth Singh, MD, MS
Postdoctoral Fellow, NLM/NIH Clinical Informatics Fellowship
Division of Biomedical Informatics
Clinical Assistant Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine,
University of California
San Diego, La Jolla
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Singh: Over the last 4 years, four new medications have been approved for long-term use for weight loss by the FDA. We sought to evaluate the comparative effectiveness and tolerability of these medications through a systematic review and network meta-analysis. Based on 28 trials in over 29,000 overweight or obese patients, we observed that magnitude of weight loss achieved with these agents is variable, ranging from 2.6kg with orlistat to 8.8kg with phentermine-topiramate. Over 44-75% of patients are estimated to lose at least 5% body weight, and 20-54% may lose more than 10% of body weight; phentermine-topiramate was the most efficacious, whereas lorcaserin was the best tolerated.
Ambika Satija[/caption]
Ambika Satija
Departments of Nutrition & Epidemiology
Harvard T. H. Chan School of Public Health
Boston, MA
MedicalResearch.com: What is the background for this study?
Response: In this study, we followed more than 200,000 male and female health professionals across the U.S. for more than 20 years who had regularly filled out questionnaires on their diet, lifestyle, medical history, and new disease diagnoses as part of three large long-term studies.
Dr. Petkov[/caption]
Valentina Petkov, MD, MPH
Health Scientist/Program Officer
NIH/NCI/DCCPS/Surveillance Research Program
MedicalResearch.com: What is the background for this study?
Dr. Petkov: The number of breast cancer diagnoses is increasing in older patients because of increasing life expectancy and changing population demographics. Despite high incidence, little is known about breast cancer biology and outcomes in patients older than 70, which are often under-represented in clinical trials. The 21-gene Oncotype DX Breast Recurrence Score assay has been used in clinical practice to predict distant recurrence risk and chemotherapy benefit in lymph node negative, hormonal receptor positive (estrogen and/or progesterone receptor positive) invasive breast cancer since 2004. The goal of our study was to evaluate the role of the 21 gene assay in older patients at population level.
We used Surveillance Epidemiology and End Results (SEER) data. We included in the analysis 40,134 patients who were diagnosed with invasive breast cancer between 2004 and 2011, had negative nodes and their tumors were hormonal receptor positive and HER2 negative. Breast Cancer Specific Mortality (BCSM) was assessed at 5 years after diagnosis in patients with low risk (Recurrence Score <18), intermediate risk (Recurrence Score 18-30) and high risk (Recurrence Score >30).
Dr. Duk Woo Park[/caption]
Division of Cardiology, Asan Medical Center
University of Ulsan College of Medicine and National Evidence-based Healthcare Collaborating Agency
Seoul, Republic of Korea
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Currently, less restrictive blood pressure (BP) target by the 2014 hypertension guidelines (JNC-8) and more intensive BP target of the SPRINT is now conflicting, which causes uncertainty and confusion among clinicians. In our study, the proportion of persons who would meet the SPRINT BP goals is substantially less than those who would meet the 2014 guideline blood pressure goals. There is a positive association between the risk of major cardiovascular events and increasing levels of BP control status under different 2014 guideline and SPRINT criteria. Our study reconfirmed the findings of the SPRINT trials in real-world population.
Dr. Alessandro Biffi[/caption]
Alessandro Biffi, MD
Behavioral Neurology and Neuropsychiatry
Departments of Neurology and Psychiatry
Massachusetts General Hospital / Harvard Medical School
MedicalResearch.com: What is the background for this study?
Dr. Biffi: Intracerebral Hemorrhage (ICH) is the most severe form of stroke. It is a form of hemorrhagic (i.e. bleeding) stroke that accounts for ~ 15% of all acute cerebrovascular conditions, affecting ~ 70,000 Americans every year. However, because of its severity it is responsible for almost half of all stroke-related disability worldwide. Survivors of ICH are at very high risk for cognitive impairment (up to and including dementia) following the acute cerebral bleeding event. However, we possess very limited understanding of the time dynamics and risk factors for post-ICH dementia. In particular, prior to our study it was unclear whether the acute cerebral injury due to ICH would be the only mechanism potentially responsible for subsequent development of dementia.
This question is motivated by prior observations suggesting that Intracerebral Hemorrhage represents the acute manifestation of cerebral small vessel disease, a progressive degenerative disorder of small caliber arteries of the central nervous system.
There exist two major subtypes of small vessel disease:
1) cerebral amyloid angiopathy, caused by the deposition of a toxic protein product, beta-amyloid, in the blood vessels (in a process similar to the formation of beta-amyloid plaques that cause Alzheimer's disease);
2) arteriolosclerosis, caused by long-standing elevated blood pressure. ICH survivors have been previously shown to harbor very severe small vessel disease, which has been linked to dementia in patients without cerebral bleeding.
Our hypothesis was that early-onset dementia (occurring in the first 6 months after ICH) is a manifestation of the acute neurological damage associated with cerebral bleeding, whereas delayed onset dementia (developing beyond 6 months from the acute ICH event) is associated with known markers of small vessel disease, including imaging findings on CT/MRI and genetic markers (such as the APOE gene).
Dr. Geng Zong[/caption]
Geng Zong, Ph.D.
Research fellow at Harvard T.H. Chan School of Public Health
Boston, Massachusetts.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The refining process of grains removes most of fiber, minerals, vitamins, polyphenols and alkyl resorcinols that mainly exist in the outer layer of a kernel, thus enriches grains with carbohydrate and energy. Whole grains, on the other hand, are cereal grains or processed cereal grains that contains bran and germ, in addition to the inner most endosperm, as their natural proportions in the kernel. Observational studies have repeatedly linked whole grain intake with major chronic diseases, including obesity, diabetes, cardiovascular diseases, and cancer, but findings regarding mortality are inconsistent and have not been quantitatively summarized. By meta-analyzing 14 existing or unpublished prospective cohort studies, our investigation found that whole grain intake is inversely associated with mortality risk from all-causes, CVD, and cancer. Among people with whole grain consumption, estimated all-cause mortality risk was 7% (for 10 grams/day), 16% (for 30 grams/day), 20% (for 50 grams/day), and 22% (for 70 grams/day) lower than people with no whole grain consumption. Similar dose-response relationship was observed for CVD and cancer mortality.
Dr. Katri Korpela[/caption]
Dr. Katri Korpela, PhD
University of Helsinki
Helsinki
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Korpela: Previous studies have shown that breastfeeding reduces the frequency of infections in the child and is associated with lower risk of childhood overweight. Conversely, antibiotic use in early life is associated with increased BMI. Both antibiotic use and breastfeeding are known to influence the infant's microbiota. However, these two factors have not been studied together and it was not known whether antibiotic use could modify the beneficial effects of breastfeeding. We collected data on lifetime antibiotic use, breastfeeding duration, and BMI in a group of daycare-attending children aged 2-6 years. We found that the beneficial effects on long breastfeeding, particularly as regards BMI development, were evident only in the children who did not get antibiotics in early life. Antibiotic use before or soon after weaning seemed to eliminate the protection against elevated BMI in preschool age and weaken the protection against infections after weaning.
Dr. Stefania Papatheodorou[/caption]
Stefania I. Papatheodorou, MD, PhD
Cyprus International Institute for Environmental and Public Health
Limassol, Cyprus
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Marijuana is the most commonly used illicit drug in the United States. Despite increasing use and acceptance of marijuana, both medically and recreationally, gaps remain in our knowledge regarding potential health effects.
In this study, we aimed to evaluate associations between recent marijuana use, exhaled Nitric Oxide (eNO) and pulmonary function. We performed a cross-sectional study of 10,327 US adults participating in the National Health and Nutrition Examination Survey (NHANES) in the years 2007 to 2012.
Exhaled Nitric Oxide was lower among participants who used marijuana in the past 0 to 4 days and those who last used marijuana 5 to 30 days before the examination compared with the never users. FEV1 was higher among participants who used marijuana within 0 to 4 days before the examination compared with those who never used marijuana, while FVC was higher in both past and current marijuana users compared with never users. The FEV1/FVC ratio was significantly lower among those who used marijuana in the 0 to 4 days before the examination compared with never users.
Dr. Katya Rubia[/caption]
Katya Rubia, PhD
Department of Child and Adolescent Psychiatry
Institute of Psychiatry, Psychology, and Neuroscience
King’s College London
London, England
MedicalResearch.com: What are the main findings?
Dr. Rubia: ADHD and OCD patients both suffer from poor inhibitory control and in both disorders this has been associated with structural and functional deficits in fronto-striatal networks. However, it is not clear to what extent the two disorders differ in their underlying neural substrates. This study therefore conducted a meta-analysis of all published whole brain structural and functional MRI studies of inhibitory control in both disorders.
MedicalResearch.com: What are the main findings?
Dr. Rubia: The main findings are that ADHD and OCD patients differ quite fundamentally in their structural and functional brain abnormalities. OCD patients have enlarged volume in basal ganglia and insula, while ADHD patients have reduced volumes in these regions. In fMRI, in the left hemisphere this was also observed for the left insula and putamen, which were increased in OCD and reduced in ADHD. In addition both disorders have different frontal deficits. OCD patients have deficits in rostro-dorsal medial frontal regions that are important for top-down control of affect while ADHD patients had reduced activation in lateral inferior frontal cortex, a key area of attention and cognitive control. The findings fit into the notion of fronto-striatal dysregulation in OCD where basal ganglia are overactive and poorly controlled by medial frontal regions and a delayed fronto-striatal maturation in ADHD where both lateral frontal regions and the basal ganglia/insula are smaller, and presumably less developed in structure and in function in ADHD.
Dr. Andrea Cipriani[/caption]
Andrea Cipriani, MD PhD
Associate Professor
Department of Psychiatry
University of Oxford
Warneford Hospital
Oxford UK
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cipriani: Major depressive disorder is common in young people, with a prevalence of about 3% in school-age children (aged 6–12 years) and 6% in adolescents (aged 13–18 years). Compared with adults, children and adolescents with major depressive disorder are still underdiagnosed and undertreated, possibly because they tend to present with rather undifferentiated depressive symptoms—eg, irritability, aggressive behaviours, and school refusal. Consequences of depressive episodes in these patients include serious impairments in social functioning, and suicidal ideation and attempts. Our analysis represents the most comprehensive synthesis of data for currently available pharmacological treatments for children and adolescents with acute major depressive disorder (5620 participants, recruited in 34 trials).
Among all antidepressants, we found that only fluoxetine was significantly better than placebo. According to our results, fluoxetine should be considered the best evidence-based option among antidepressants when a pharmacological treatment is indicated for children and adolescents with moderate to severe depression. Other antidepressants do not seem to be suitable as routine treatment options.
Adam Glassman[/caption]
MedicalResearch.com Interview with:
Adam Glassman, M.S.
Director, DRCRnet Coordinating Center
Jaeb Center for Health Research
Tampa, FL 33647
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Diabetic macular edema (DME) is the most common cause of vision loss in patients with diabetes, impairing the vision of approximately 750,000 people in the United States. The most common treatment involves the injection into the eye of one of 3 drugs that inhibit vascular endothelial growth factor (VEGF). The Diabetic Retinopathy Clinical Research Network, funded by the National Institutes of Health, conducted a randomized clinical trial on the comparative effectiveness of the 3 anti-VEGF drugs EYLEA®, Avastin®, or Lucentis® for eyes with decreased vision from diabetic macular edema. There are substantial cost differences between the three drugs. In the United States, EYLEA® costs approximately $1850, repackaged (compounded) Avastin® $60, and Lucentis® $1170 per injection. In eyes with relatively good starting vision, there were no differences in vision outcomes; all three groups, on average, had improved vision. In eyes with starting vision of 20/50 or worse, EYLEA® had better vision outcomes at 1 year than either Avastin® or Lucentis®, and better vision outcomes at 2 years than Avastin®. However, given that, on average, eyes will receive 9 to 10 injections within the first year of treatment and 5 injections in the second year, neither EYLEA® nor Lucentis® would be considered cost effective by standard benchmarks compared with Avastin® unless their prices decrease substantially.
Dr. Mathew Jankowich[/caption]
Matthew D. Jankowich, MD
Assistant Professor of Medicine
Alpert Medical School of Brown University
Staff physician at the Providence VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Jankowich: For some time, endothelin-1 has been known to cause vasoconstriction in the pulmonary circulation, and elevated endothelin-1 levels have been noted in patients with pulmonary arterial hypertension and decompensated congestive heart failure, as well as other advanced disease states. However, endothelin-1 has not been well studied in members of the general population. In our study, we examined plasma endothelin-1 levels in participants in the Jackson Heart Study and the relationship of plasma endothelin-1 levels to pulmonary hypertension, mortality and heart failure. We found increased odds of having pulmonary hypertension, defined as an echocardiography estimation of the pulmonary artery systolic pressure>40mmHg, in those participants with higher plasma endothelin-1 levels. Having higher endothelin-1 levels was also associated with an increased risk of both mortality and heart failure. Those participant with both high endothelin-1 levels (a level in the top 25%) and pulmonary hypertension were at the highest risk of mortality.
Dr. Cynthia Ogden[/caption]
Cynthia L Ogden PhD, MRP
Public Health, Nutrition and Dietetics
CDC Atlanta
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ogden: Monitoring trends in obesity prevalence is important because of the health risks associated with obesity and because obesity often tracks from childhood to adulthood. The most recent data before this point showed no increases overall in youth, men or women over the previous decade.
We used the most recent nationally representative data with measured weights and heights from the National Health and Nutrition Examination Survey to look at trends in obesity prevalence.
Dr. Lena S. Sun[/caption]
Lena S. Sun, MD
E. M. Papper Professor of Pediatric Anesthesiology
Professor of Anesthesiology and Pediatrics
Executive Vice Chairman, Department of Anesthesiology
Chief, Division of Pediatric Anesthesiology
Columbia University Medical Center
New York, New York 10032
MedicalResearch.com: What is the background for this study?
Dr. Sun: The background for the study is as follow: There is robust evidence in both rodent and non-human primate studies that exposure of the developing brain leads to impairment in cognitive function and behavior later in life. The evidence from human studies derives mostly from retrospective studies and the results have been mixed. Some have demonstrated anesthesia in early childhood was associated with impaired neurocognitive function, while others have found no such association. Our study is the first to specifically designed to address the question of effects of general anesthesia exposure on cognitive function, comparing exposure with no exposure.
Dr. Laura Ferris[/caption]
MedicalResearch.com Interview with:
Laura Ferris, M.D., Ph.D.
Associate professor, Department of Dermatology
University of Pittsburgh School of Medicine and
Member of the Melanoma Program
University of Pittsburgh Cancer Institute
MedicalResearch.com: What is the background for this study?
Dr. Ferris: Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment. Typically, patients receive skin checks by setting up an appointment with a dermatologist. UPMC instituted a new screening initiative, which was modeled after a promising German program, the goal being to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their primary care physicians (PCPs). PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.
Marissa Hall[/caption]
Marissa G. Hall, MSPH
Doctoral Candidate, Department of Health Behavior
Gillings School of Global Public Health
University of North Carolina at Chapel Hill
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The US Food and Drug Administration (FDA) requires pictorial warnings on cigarette packs, but implementation was stalled by a 2012 lawsuit by the tobacco industry. The US Court of Appeals for the DC Circuit ruled against pictorial warnings, saying that FDA had “not provided a shred of evidence” that the pictorial warnings reduce smoking. To address this critique, our randomized trial examined the impact on smoking behavior of adding pictorial warnings to the front and back of cigarette packs. We found that smokers with pictorial warnings on their packs were more likely to attempt to quit and to successfully quit than those whose packs had text-only warnings.
Dr. Rozalina McCoy[/caption]
Rozalina McCoy, M.D
Assistant Professor of Medicine
Division of Primary Care Internal Medicine
Department of Medicine
Mayo Clinic Rochester
MedicalResearch.com: What is the background for this study?
Dr. McCoy: Hypoglycemia is a serious potential complication of diabetes treatment; it worsens quality of life and has been associated with cardiovascular events, dementia, and even death. Most professional societies recommend targeting HbA1C levels less than 6.5% or 7%, with individualized treatment targets based on patient age, other medical conditions, and risk of hypoglycemia with therapy. Treating patients to very low HbA1c levels is not likely to improve their health, especially not in the short-term, but can cause serious harms such as hypoglycemia. The goal of our study was to assess how frequently patients with type 2 diabetes are treated intensively, focusing specifically on patients who are elderly or have serious chronic conditions such as dementia, kidney disease including dialysis need, heart disease, stroke, lung disease, and cancer. Moreover, while prior studies have suggested that intensive treatment may be common, there was no strong evidence that intensive treatment does in fact increase risk of hypoglycemia. Our study was designed specifically to assess this risk.
We examined medical claims, pharmacy fill data, and laboratory results of 31,542 adults with stable and controlled type 2 diabetes who were included in the OptumLabs™ Data Warehouse between 2001 and 2013. None of the patients were treated with insulin or had prior episodes of severe hypoglycemia, both known risk factors for future hypoglycemic events. None of the patients had obvious indications for very tight glycemic control, such as pregnancy.
“Intensive treatment” was defined as being treated with more glucose-lowering medications than clinical guidelines consider to be necessary given their HbA1C level. Patients whose HbA1C was less than 5.6 percent (diabetes is defined by HbA1C 6.5 percent or higher) were considered intensively treated if they were taking any medications. Patients with HbA1C in the “pre-diabetes” range, 5.7-6.4 percent, were considered to be intensively treated if using two or more medications at the time of the test, or if started on additional medications after the test, because current guidelines consider patients with HbA1C less than 6.5 percent to already be optimally controlled. For patients with HbA1C of 6.5-6.9 percent the sole criteria for intensive treatment was treatment intensification with two or more drugs or insulin.
The patients were separated by whether they were considered clinically complex (based on the definition by the American Geriatrics Society)—75 years of age or older; or having end-stage kidney disease, dementia; or with three or more serious chronic conditions. This distinction has been made to help identify patients for whom adding glucose-lowering medications is more likely to lead to treatment-related adverse events, including hypoglycemia, while not providing substantial long-term benefit.
Dr. Ramon Estruch[/caption]
Dr Ramon Estruch, MD PhD
Senior Consultant in the Internal Medicine Department of the Hospital Clinic
Barcelona
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Estruch: Although weight stability requires a balance between calories consumed and calories expended, it seems that calories from vegetable fats have different effects that calories from animals on adiposity. Thus, an increase of dietary fat intake (mainly extra virgin olive oil or nuts) achieved naturally in the setting of Mediterranean diet does not promote weight gain or increase in adiposity parameters such as waist circumference.
Dr. Giovanni Esposito[/caption]
Giovanni Esposito MD, PhD
Associate Professor of Cardiology
Department of Advanced Biomedical Sciences
Federico II University, Naples
Napoli - Italy and
Giuseppe Gargiulo, MD
PhD Student
Federico II University of Naples, Italy
Dr. Vincent Chung[/caption]
Dr Vincent Chung
Assistant Professor, Jockey Club School of Public Health and Primary Care
Associate Director (Education), Hong Kong Institute of Integrative Medicine
Registered Chinese Medicine Practitioner
The Chinese University of Hong Kong
MedicalResearch.com: What is the background for this study?
Response: Primary carpal tunnel syndrome (CTS) is one of the most common forms of peripheral entrapment neuropathy. It is a major cause of disability on the upper extremity incurring considerable limitation on daily activities among patients. Currently, there is no consensus on appropriate treatment for patients with chronic (≥6 months) mild to moderate symptoms [Archives of physical medicine and rehabilitation. 2014;95(12):2253-63].
Electroacupuncture is a common technique for managing pain and neuropathy in Chinese medicine. Current CTS treatment guidelines from the UK National Institute for Health and Care Excellence (NICE), American Academy of Orthopaedic Surgeons (AAOS) and the American College of Occupational and Environmental Medicine (ACOEM) made no specific recommendations for or against electroacupuncture.
Dr. Andrew Anglemyer[/caption]
Andrew Anglemyer, PhD MPH
Operations Research Department
U.S. Naval Postgraduate School
Monterey, CA 93943
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Anglemyer: Suicide prevention programs in the military are ubiquitous. We aimed to identify the trends in suicide for each service specifically and explore any nonclinical factors that may be associated with the chosen methods of suicide. The trends in suicide are similar to what others have found.
The differences in those rates between services are striking, though. Not only are most suicides in the active duty military among the Army personnel, but the suicide rate among Army personnel is the highest and has been every year since 2006. Additionally, among Army personnel and Marines who committed suicide, those with an infantry or special operations job classification were significantly more likely to use a firearm to commit suicide than those without those job classifications.