Medical research slideshare_may_6_2015

MedicalResearch.comExclusive Interviews with Medical Research and

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

Editor: Marie Benz, MD [email protected]

May 6 2015

For Informational Purposes Only: Not for Specific Medical Advice.

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Read more interviews on MedicalResearch.com

Selective Estrogen Receptor Degrader May Help Patients With Resistant ER+ Breast CancerMedicalResearch.com Interview with:Presented by Dr. Maura N. Dickler MDAssociate member of the Breast Medicine Service at Memorial

Sloan Kettering Cancer Center andWeill Medical College of Cornell University in New York

• Medical Research: What is the background for this study? • This year, breast cancer will claim the lives of nearly 40,000 women in the United States, and

up to half of these women will have a disease that is driven by the estrogen receptor.• Although medicines have been approved for the treatment of hormone receptor-positive

breast cancer for decades, more treatment options are needed.• Resistance to endocrine therapies causes morbidity and mortality for women with metastatic

estrogen receptor-positive (ER+) breast cancer as many patients relapse or develop resistance to available hormonal agents via estrogen-dependent and estrogen-independent mechanisms.

• Dual-acting investigational Selective Estrogen Receptor Degrader (SERDs) could potentially lead to a new treatment option for people with hormone receptor-positive breast cancer and may help overcome resistance to current anti-hormonal medicines.

• GDC-0810 is a dual-acting investigational next-generation oral SERD that works in a number of ways to prevent estrogen fueling tumor growth. It is not only designed to target the estrogen receptor (ER) as an antagonist, but also to cause degradation of the ER protein. In preclinical studies, GDC-0810 was shown to induce tumor regressions in both tamoxifen sensitive and tamoxifen resistant tumor models in vivo.

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

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
















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

MedicalResearch.com Interview with:George S. Stergiou, MD, FRCPProfessor of Medicine & Hypertension Hypertension Center STRIDE-7Third University Department of Medicine Sotiria Hospital Athens, Greece

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

Dr. Stergiou: This study explored the relationship among blood pressure measurements taken in the office, at home and with daytime ambulatory monitoring in 642 untreated subjects aged from 5 to 78 years referred to a university hospital hypertension clinic.

• The main finding is that the relationship between office and out-of-office blood pressure (home and ambulatory) differs across different age groups. More specifically, in children daytime ambulatory blood pressure is higher than both office and home blood pressure. The differences are progressively eliminated with increasing age and after the age of 30 years daytime ambulatory blood pressure is similar to home blood pressure and both are lower than office blood pressure. In individuals aged 60 years and older daytime ambulatory blood pressure may be lower than home blood pressure. Age, gender and hypertension status are the main predictors of the differences among blood pressure values obtained by different methods.


http://medicalresearch.com/author-interviews/blood-pressure-variability-by-setting-also-varies-by-age/13810/














http://medicalresearch.com/author-interviews/new-hypertension-guidelines-found-cost-effective/10978/







• Medical Research: What should clinicians and patients take away from your report?• Dr. Stergiou: It is known that the measured blood pressure values differ when obtained by

using different measurement methods, e.g. in the office, at home and with ambulatory monitoring. However, the differences among these measurements are not the same across all age groups.

• Current guidelines recommend that average home blood pressure levels are similar to average daytime ambulatory blood pressure levels, and both of them are by about 5 mmHg lower than the conventional office blood pressure measurements (systolic and diastolic). However, these differences appear to be present only in middle aged adults (older than 30 years) and not so in younger individuals, and are entirely different in children, adolescents and young adults.

• Because differences between office and out-of-office blood pressure measurements are common across all ages and unpredictable in the individual (due the white coat hypertension and the masked hypertension phenomena), the above information is particularly important in the management of such cases in clinical practice.
















http://medicalresearch.com/author-interviews/1-in-4-patients-with-controlled-hypertension-relapse/13420/







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

• Dr. Stergiou: Large prospective studies are needed providing direct comparisons of all the three blood pressure measurement methods in terms of blood pressure levels but also of prognostic ability across all the spectrum of age. In young individuals such data can only be obtained by setting endpoints of preclinical target organ damage. Future relevant research should include both general and selected populations, such as individuals referred for elevated blood pressure, because the latter are the most likely candidates for both office and out-of-office blood pressure evaluation in clinical practice.

• Citation:• Changing relationship among clinic, home and ambulatory blood pressure with increasing age• Stergiou, George S. et al.• Journal of the American Society of Hypertension

Published Online: April 24, 2015DOI: http://dx.doi.org/10.1016/j.jash.2015.04.002
















http://medicalresearch.com/heart-disease/blood-pressure-in-young-adults-increased-risk-cardiovascular-death/10993/

http://dx.doi.org/10.1016/j.jash.2015.04.002






Potassium May Play Larger Role Than Sodium in Adolescent Blood PressureMedicalResearch.com Interview with:Lynn L. Moore, DSc, MPHDepartment of MedicineBoston University School of Medicine Boston, Massachusetts

• Medical Research: What is the background for this study?

Dr. Moore: The USDA’s current Dietary Guidelines for sodium intake have become increasingly controversial. Current recommendations include restricting sodium intake after the age of 2 years to no more than 2300 mg per day. For African-American adults and children, intakes should be restricted to no more than 1500 mg per day. Actual intake levels are much higher, with most Americans consuming about 3500 mg per day. Our goal was to estimate the effects of dietary sodium and potassium intakes on the change in blood pressure throughout adolescence.

• We used data from the National Growth and Health Study, a prospective study of more than 2000 girls who were 9-10 years of age at the time of enrollment. Lifestyle factors were assessed repeatedly throughout the study, and blood pressure was measured annually. Dietary sodium and potassium were assessed using multiple sets of three-day diet records. We used longitudinal modeling to estimate the effects of dietary sodium and potassium on blood pressure change over 10 years.


http://medicalresearch.com/author-interviews/potassium-may-play-larger-role-than-sodium-in-adolescent-blood-pressure/13714/









http://medicalresearch.com/author-interviews/elevated-bmi-linked-to-higher-blood-pressure-in-healthy-teenagers/12338/







Medical Research: What are the main findings?

Dr. Moore: In this study, there was no evidence for a beneficial effect of reduced sodium intake on blood pressure change during adolescence. By 19-20 years of age, girls who consumed more than 4000 mg of sodium per day had systolic and diastolic blood pressure levels that were similar to those seen among girls with lower levels of sodium intake. Specifically, there was no beneficial effect on blood pressure associated with sodium intakes of less than 2500 mg per day. These results were similar for blacks and whites. In contrast, the repeated measures analyses showed that girls who consumed more than 2400 mg of potassium per day had lower blood pressures throughout adolescence compared with girls consuming less than 1800 mg per day of potassium.











http://medicalresearch.com/heart-disease/reduced_sodium_intake_may_improve_heart_failure_prognosis/9251/







• Medical Research: What should clinicians and patients take away from your report?• Dr. Moore: This study suggests that dietary potassium plays a much larger role in determining

the change in adolescent blood pressure than does sodium. In both blacks and whites, sodium restriction had essentially no impact on systolic or diastolic blood pressure. Well over 90% of Americans fail to meet the USDA Guidelines for potassium intake. It would be better to guide families to include more potassium-rich foods and snacks (e.g., bananas, raisins, dried apricots, spinach, dairy products, sweet potatoes, etc) than to focus on salt restriction.


• Dr. Moore: This study had no data on salt-sensitivity in these girls. It may be that lowering salt intake has a role in the subset of individuals who are salt-sensitive. Currently, there is no simple and accurate measure of salt-sensitivity but developing such a test would be valuable for use in large-scale observational studies as well as clinical settings.

• Citation:• Buendia JR, Bradlee M, Daniels SR, Singer MR, Moore LL. Longitudinal Effects of Dietary Sodiu

m and Potassium on Blood Pressure in Adolescent Girls. JAMA Pediatr. Published online April 27, 2015. doi:10.1001/jamapediatrics.2015.0411.











http://medicalresearch.com/author-interviews/dietary_potassium_associated_with_lower_risk_of_stroke_in_postmenopausal_women/7388/

http://archpedi.jamanetwork.com/article.aspx?articleid=2272973









Service To Others May Help Addicted Adolescents Overcome Fear Of Social HumiliationMedicalResearch.com Interview with:Maria Pagano, PhDCase Western Reserve University School of MedicineDepartment of Psychiatry, Division of Child

Psychiatry Cleveland, OH

• MedicalResearch: What is the background for this study?

Dr. Pagano: Socially anxious adolescents quickly figure out that alcohol and drugs can provide ease and comfort in social situations that are anxiety provoking. Reaching for a substance to change how you feel can quickly become a knee-jerk reaction, can develop into an addiction, and robs youths of learning how to tolerate interpersonal differences and uncomfortable feelings, developing emotional maturity, and cultivating self acceptance.

• Adolescents who fear being criticized by their peers are likely to not speak up in group therapies during treatment, which can limit their benefit from treatment. There is a lot of healing that comes sharing your insides with others. Socially anxious patients may not get this healing nor let others really get to know who they are and give input to their lives

• Higher peer helping in AA during treatment means getting active in low intensity tasks like putting away chairs, or making coffee at a 12-step meeting. It is less about needing peer assistance or expecting praise or recognition from giving service. It is more about adopting the attitude of “how can I be helpful?”


http://medicalresearch.com/addiction/service-to-others-may-help-addicted-adolescents-overcome-fear-of-social-humiliation/13716/
















• MedicalResearch: What is the background for this study?

Dr. Pagano: Socially anxious adolescents quickly figure out that alcohol and drugs can provide ease and comfort in social situations that are anxiety provoking. Reaching for a substance to change how you feel can quickly become a knee-jerk reaction, can develop into an addiction, and robs youths of learning how to tolerate interpersonal differences and uncomfortable feelings, developing emotional maturity, and cultivating self acceptance.

• Adolescents who fear being criticized by their peers are likely to not speak up in group therapies during treatment, which can limit their benefit from treatment. There is a lot of healing that comes sharing your insides with others. Socially anxious patients may not get this healing nor let others really get to know who they are and give input to their lives

• Higher peer helping in AA during treatment means getting active in low intensity tasks like putting away chairs, or making coffee at a 12-step meeting. It is less about needing peer assistance or expecting praise or recognition from giving service. It is more about adopting the attitude of “how can I be helpful?”


















• MedicalResearch: What are the main findings?• Dr. Pagano: Almost half of patients entering adolescent residential treatment suffer from a

persistent fear of social humiliation that began years before they started to experiment with alcohol and other drugs. Getting active in service in the 12-step program cuts of return to the drink-trouble cycle in half, and particularly benefits youths with social anxiety.


















• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Pagano: Professionals should encourage and help facilitate patients’ participation in service activities at the start of

treatment and monitor their engagement as one would exercise throughout treatment. We do a disservice by limiting their service participation or considering service as an activity for those who graduate from treatment.

• There are many real-world applications of the findings from this study. Adolescents would benefit from knowing that most people feel like they do not fit in and that it is a lifelong journal to get comfortable in your own skin. Parents, teachers, and other positive adults in the lives of adolescents can provide education about this and the role alcohol and other drugs can play in providing initial comfort and long-term cost. Using alcohol and drugs to fit in or be the life of the party can develop into a habit and ultimate an addiction. Learning to tolerate feeling different and letting other people have their opinions about you takes practice, but it gets easier. Play-role practicing with safe friends or adults who pretend to dismiss or view the adolescent negative is another real-world application that can help an adolescent develop this muscle.

• Citation:• Social Anxiety and Peer Helping in Adolescent Addiction Treatment

• Alcoholism: Clinical and Experimental Research

• Volume 39, Issue 5, May 2015, Pages: 887–895, Maria E. Pagano, Alexandra R. Wang, Brieana M. Rowles, Matthew T. Lee and Byron R. Johnson

• Article first published online : 14 APR 2015, DOI: 10.1111/acer.1269

• MedicalResearch.com Interview with: Maria Pagano, PhD (2015). Service To Others May Help Addicted Adolescents Overcome Fear Of Social Humiliation











http://onlinelibrary.wiley.com/doi/10.1111/acer.12691/abstract










Rapid Genome Sequencing Helps Pinpoint Diagnosis In Ill NewbornsMedicalResearch.com Interview with:Stephen F. Kingsmore MB ChB BAO DSc FRCPathDee Lyons/Missouri Endowed Chair in Genomic Medicine,Children’s Mercy – Kansas City


Response: The background to this study is that genetic diseases are the leading cause of death in infants and, especially, in infants in neonatal intensive care units. Making a molecular (etiologic) diagnosis of the specific genetic disease is critical for optimal care and decision making for acutely ill infants who are likely to have such diseases. However there are over 5000 known genetic diseases and their presentations overlap considerably in infants. Until now it has not been possible to make timely diagnoses in these infants.

• Medical Research: What are the main findings?• Response: Rapid whole genome sequencing is a new way of making a genetic disease

diagnosis in acutely ill newborns in neonatal intensive care units. It appears to be effective for diagnosis.


http://medicalresearch.com/genetic-research/rapid-genome-sequencing-helps-pinpoint-diagnosis-in-ill-newborns/13812/















Rapid Genome Sequencing Helps Pinpoint Diagnosis In Ill NewbornsMedicalResearch.com Interview with:Stephen F. Kingsmore MB ChB BAO DSc FRCPathDee Lyons/Missouri Endowed Chair in Genomic Medicine,Children’s Mercy – Kansas City

• Medical Research: What should clinicians and patients take away from your report?• Response: Rapid whole genome sequencing is a new way of making a genetic disease

diagnosis in acutely ill newborns in neonatal intensive care units. It appears to be effective for diagnosis.


• Response: As a result of this study, we have recently started a new randomized, blinded, prospective study of the clinical utility of rapid whole genome sequencing in acutely ill infants in neonatal intensive care units (NSIGHT, clinical trials.gov NCT02225522) which has been funded by NIH.

• Citation:• Whole-genome sequencing for identification of Mendelian disorders in critically ill infants:

a retrospective analysis of diagnostic and clinical findings • Laurel K Willig, Josh E Petrikin, Laurie D Smith, Carol J Saunders, Isabelle Thiffault, Neil A Mille

r, Sarah E Soden, Julie A Cakici, Suzanne M Herd, Greyson Twist, Aaron Noll, Mitchell Creed, Patria M Alba, Shannon L Carpenter, Mark A Clements, Ryan T Fischer, J Allyson Hays, Howard Kilbride, Ryan J McDonough, Jamie L Rosterman, Sarah L Tsai, Lee Zellmer, Emily G Farrow, Stephen F Kingsmore

• Published Online April 28, 2015 http://dx.doi.org/10.1016/ S2213-2600(15)00139-3












http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(15)00139-3/abstract















Aging: Vegetable Consumption and Exercise May Protect Against Muscle Mass LossMedicalResearch.com Interview with:Yunhwan Lee, MD, DrPH Director, Institute on AgingProfessor of Preventive Medicine & Public Health Ajou

University School of MedicineSuwon, South Korea


Dr. Lee: We have known for some time that there is a progressive loss of muscle mass with aging, where older people lose on average about 1% of their skeletal muscle mass per year. A decline in muscle mass is serious in that it increases the person’s risk of falls, frailty, disability, and death.

• Because there is currently no “cure” for muscle mass loss, prevention is the best strategy. Over the years, researchers have studied various lifestyle factors to identify potentially modifiable behaviors that may prevent or slow the loss of muscle mass. The majority of prior research so far have found that diet, in the form of protein supplementation, and exercise, especially resistance exercise, may confer some benefits.

• More recently, the scientific community have begun to pay attention to the positive role of vegetables and fruits intake on the muscle. The role of aerobic exercise on muscle mass is, however, less clear. Also, because people tend to adopt various lifestyles, we were interested in finding out whether those engaging in healthier patterns of diet and exercise retained higher muscle mass.

• Using data from a nationally representative sample of older adults, we investigated whether those who had healthier diet and participated in regular exercise, individually and in combination, maintained higher muscle mass. We looked at five healthy lifestyle factors that included dietary intake of three food groups (meat, fish, eggs, legumes; vegetables; and fruits) and participation in two types of exercise (aerobic and resistance).


http://medicalresearch.com/exercise-fitness/aging-vegetable-consumption-and-exercise-may-protect-against-muscle-mass-loss/13856/















http://medicalresearch.com/heart-disease/increase_fruits_vegetables_decrease_cv_mortality/6671/








• Medical Research: What are the main findings?

Dr. Lee: More women than men consumed the recommended level of three food groups, including meat products, vegetables, and fruits. In contrast, more men than women engaged in aerobic and resistance exercise. A higher percentage of women (18%) than men (11%) adhered to three or more of these healthy lifestyle factors.

• We found that older women who consumed a recommended level of 5 or more vegetables per day were 48% less likely to have low muscle mass than those who consumed less. Women who participated in aerobic exercise of moderate intensity for more than 150 minutes per week or vigorous intensity for more than 75 minutes per week were 38% less likely to experience low muscle mass, compared with those who exercised less.

• As to the combined lifestyle factors, those who adopted more number of healthy lifestyle factors were less likely to have low muscle mass. Particularly in women, those who adhered to three or more of the healthy lifestyle factors versus none had 55% lower odds of low muscle mass.

















http://medicalresearch.com/exercise-fitness/vigorous-exercise-linked-to-lower-all-cause-mortality/13325/








• Medical Research: What should clinicians and patients take away from your report?• Dr. Lee: For patients and older people in general, our findings point to the importance of

maintaining healthy diet and exercise in late life. It is important to keep in mind that vegetables consumption and aerobic exercise may protect against muscle mass loss.

• Clinical professionals need to assess the older person’s lifestyle behaviors to recommend behavior change that might be conducive to preventing decline in muscle mass. Monitoring the older patient for appropriate dietary consumption and encouraging regular exercise may help to lower the risk of muscle mass loss.

























• Dr. Lee: We have to be cautious in implying any causality from the study results, as these were based on a cross-sectional study. Longitudinal data with prospective study design would help to clarify the relationship between healthy lifestyle factors and low muscle mass.

• Clinical trials would help to identify individual lifestyle changes that prevent muscle mass loss. A multi-modal approach incorporating multiple healthy lifestyle factors may provide insight into developing effective health promotion programs. In addition, we need more intervention studies that are individually tailored, for example targeting those at high risk of and vulnerable to muscle mass loss, and community-based to be able to recommend preventive strategies to a wider population for higher impact.

• Citation:• Kim, J., Lee, Y., Kye, S., Chung, Y.-S. and Kim, K.-M. (2015), Association Between Healthy Diet a

nd Exercise and Greater Muscle Mass in Older Adults. Journal of the American Geriatrics Society. doi: 10.1111/jgs.13386

















http://medicalresearch.com/weight-research/high-fat-free-mass-linked-to-lower-mortality-in-men/11758/

http://onlinelibrary.wiley.com/doi/10.1111/jgs.13386/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=true








Poor Sleep Quality Increases Mood DisturbancesMedicalResearch.com Interview with: Jaime L. Tartar PhDBehavioral Neuroscience Major Chair Division of Social and Behavioral Sciences Nova Southeastern University

Fort Lauderdale, Florida

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

Dr. Tartar: We set out to understand how poor sleep quality can influence emotion processing. Our rationale for this study was that although sleep perturbations are known to impair cognitive performance, it is not currently clear how poor sleep alters emotion processes. However, given that poor sleep quality is closely associated with the development of mood disorders, it is important to understand how sleep quality affects emotional functioning. We specifically examined the possibility that poor sleep quality creates a cognitive bias in memory and interpretation for emotionally negative stimuli. This would result in maladaptive emotional experiences- for example, through enhanced memory for emotionally negative events (which is also a common characteristic of depression). The idea that negative cognitive bias occurs with poor sleep quality is also consistent with the finding that sleep loss increases sensitivity to emotional stimuli as well as increases undesirable mood states like irritability, anger, and hostility. It is particularly noteworthy that sleep perturbations result in increased emotionality since sleep perturbations are shown to result in a decrease in non-emotional cognitive processes (attention and memory). In order to clarify the role of sleep quality on emotion processing, we tested the relationship between sleep quality and a negative cognitive bias through the use of an emotional memory task. We also aimed to contrast these findings with performance on a non-emotional attention task since sleep impairments have previously been shown to cause impairments in (non-emotional) sustained attention. An interesting feature of the study was that we also accounted for potential confounding effects of stress sensitivity and chronotype (ones preferred time of day) since these are both factors known to be related to sleep quality. We found that, compared to those who reported good subjective sleep quality, participants who reported poor subjective sleep quality showed a negative cognitive bias towards emotionally negative stimuli. Also in agreement with previous work, we show that poor sleep quality has a negative effect on affective symptom measures- poor sleep quality relates to increased depressive symptoms, greater state and trait anxiety, and higher total mood disturbance (increased tension, fatigue, confusion and less vigor). Consistent with previous findings, we also found that subjective sleep quality was related to a decrease in performance on a sustained attention task. Although previous research suggests that stress sensitivity and chronotype would be important variables to consider in the impact of sleep perturbations on emotion processing, we did not find any stress, chronotype, or time of testing effects on these measures.


http://medicalresearch.com/sleep-disorders/poor-sleep-quality-increases-mood-disturbances/13852/











http://medicalresearch.com/sleep-disorders/menopause-poor-sleep-quality/3608/








• Medical Research: What should clinicians and patients take away from your report?• Dr. Tartar: The take away message is that good sleep quality is vital for both emotional and non-

emotional functioning. In particular, poor sleep quality is related to not only an increase in a negative cognitive bias in emotion processing, but also poor affective symptomatology outcomes (increased depressive symptoms, state and trait anxiety, total mood disturbances, tension, confusion, fatigue, and less vigor). A decrease in affective processing abilities is particularly problematic for medical professionals and patients who often suffer from reduced or poor quality sleep, but need to retain the ability to appropriately process and respond to emotionally-laden information and stimuli. Aside from these affect-related changes, it is also essential for clinicians and patients to recognize that there is a deficit in sustained attention to non-emotional stimuli with poor sleep quality which can adversely impact decision making and mental fluency- cognitive elements that are critical to both doctors and patients. These impairments in sustained attention to non-emotional stimuli can impact a wide range of activities, from driving to work related tasks. The nature of longer durations of work hours for many jobs, including emergency room physicians, or for jobs that require greater sustained attention, such as air traffic controllers, puts them at a greater risk for problems from poor sleep quality. As such, it is important to consider the implications of decreases in sustained attention, increases in negative cognitive bias, and poor affective symptomatology for individuals’ performance on the job. Additionally, clinicians should be aware that decrements in sustained attention that occur in a variety of psychological disorders, including depression, may be a result of poor sleep quality rather than a direct symptom of the disorder.













http://medicalresearch.com/sleep-disorders/sleep-quality-quantity-affects-cardimetabolic-markers-children/2705/









• Dr. Tartar: The effect of sleep impairments on emotion processing is an area that is grossly under investigated- even though emotional blunting can be detrimental to proper daytime functioning. Future research should aim to understand how different aspects of sleep hygiene (sleep deprivation vs. sleep quality vs. sleep duration etc..) uniquely, and in combination, affect various aspects of emotional and non-emotional cognitive processing. It is our expectation that each of these findings will contribute a missing, fundamental element to existing knowledge of how poor sleep health influences specific mental processing capabilities and leads to the development of mood disorders. Future work can also aim to understand how specific psychological health factors mediate the ability to maintain emotion processing with sleep loss.

• Citation:• Gobin, C. M., Banks, J. B., Fins, A. I. and Tartar, J. L. (2015), Poor sleep quality is associated wit

h a negative cognitive bias and decreased sustained attention. Journal of Sleep Research. doi: 10.1111/jsr.12302













http://medicalresearch.com/author-interviews/insomnia-major-contributor-fatal-falls-motor-vehicle-accidents/8701/

http://onlinelibrary.wiley.com/doi/10.1111/jsr.12302/abstract








Knowledge Of Gene Mutation For Hereditary Carcinoid May Allow Earlier DetectionMedicalResearch.com Interview with:Dr. Stephen Wank MDDigestive Diseases Branch, NIDDKNational Institutes of Health, Bethesda, Maryland

• MedicalResearch: What is the background for this study?• Dr. Wank: Small intestinal carcinoids are rare and difficult to diagnose because symptoms

may be absent or mistaken for more common diseases. Because carcinoids usually grow slowly over several years before spreading or causing symptoms, patients often seek medical attention late with advanced, incurable disease. However, when diagnosed at an early stage, carcinoid can be surgically cured. Presently, there are no long-term effective therapies for surgically non-resectable disease. Although carcinoids occur sporadically, there have been reports of family clusters (more than one blood relative with carcinoid). Hereditary small intestinal carcinoid has not been recognized as a disease and causative genetic factors have not been identified in either sporadic cases or families with multiple affected members.

• If small intestinal carcinoid occurs in families on a hereditary basis, we hypothesized that asymptomatic relatives in families with carcinoid are at a high risk of harboring an undiscovered tumor. To test this, we established a clinical research protocol at the National Institutes of Health in Bethesda, Maryland to screen asymptomatic relatives in families with at least two cases of small intestinal carcinoid in the hope of detecting their tumors at an early surgically curable stage. If successful in our endeavor, we would improve the outcome of the disease in these asymptomatic relatives and position ourselves to discover the genetic basis for their disease. Understanding the gene mutations causing small intestinal carcinoid would allow us to screen for the disease with a blood test, help us understand what causes the disease, and treat the disease with specific targeted therapies.


http://medicalresearch.com/cancer-_-oncology/knowledge-of-gene-mutation-for-hereditary-carcinoid-may-allow-earlier-detection/13837/















• MedicalResearch: What are the main findings?• Dr. Wank: We found that small intestinal carcinoid tumors occur in families on a hereditary

basis.• This is a new finding and important for several reasons. Establishing a hereditary basis for the

disease means that asymptomatic relatives are at high risk (up to 50% chance) for either having a tumor or developing a tumor in the future. Thus it makes sense to screen asymptomatic relatives for the presence of occult tumor. In fact, we found tumors in one third of asymptomatic relatives over 50 years old. Importantly, we found disease at an early stage that could be surgically cleared in 87% of those people. Equally important, none of the 87% who were surgically cleared of their tumor has had a recurrence after an average follow-up period of 4 years and some nearly 6 years. This outcome was much better than their symptomatic relatives who were diagnosed on average with later stage disease. Patients with hereditary small intestinal carcinoid have a very similar disease compared to the sporadic (non familial) type of carcinoid except that the majority (67-83%) of patients with familial carcinoid had multiple primary intestinal tumors. If, as we believe, multiple primary small intestinal tumors are characteristic of familial disease, then familial disease might account for as much as 22-35% of what was previously considered sporadic disease.

















Studying families with a hereditary basis for their disease gave us a unique opportunity to use genetic analysis methods to determine the gene mutation associated with small intestinal carcinoid. In one large family with a sufficient number of affected members, we were able to perform linkage analysis and next generation whole exome sequencing to find the first mutated gene associated with small intestinal carcinoid tumor. Unfortunately, this gene mutation was specific to this one family, but the specificity of the gene tells us that small intestinal carcinoids in other families can be associated with mutations in other genes and thus the disease is heterogeneous in origin.

















• MedicalResearch: What should clinicians and patients take away from your report?• Dr. Wank: It is important for physicians and patients to know that small intestinal carcinoid

can run in families as a hereditary disease. As a result, patients should be aware of whether any relatives (past, present and distant) have been diagnosed with small intestinal carcinoid.

• Healthcare providers should take a careful family history to determine if any relatives of their patients may have been diagnosed with small intestinal carcinoid. If there is a family history of carcinoid, patients with carcinoid-like symptoms should be screened, especially if their relative had multiple primary small intestinal tumors. If there are two cases of small intestinal carcinoid in a family, blood-related relatives should be screened for the disease.

















• MedicalResearch: What recommendations do you have for future research as a result of this study?• Dr. Wank: With this knowledge, family members can be screened to determine if they carry the gene

mutation. Future research should also determine the most sensitive and cost-effective methods to screen asymptomatic relatives who carry this gene mutation to determine as early as possible if they have a tumor. It is also important to determine when would be the most appropriate age to begin screening at-risk asymptomatic relatives considering both the risks and benefits associated with the screening process. Consistent with this approach, future research should aim to develop a sensitive and specific blood test to detect early stage disease in those relatives who carry the gene mutation. Armed with the knowledge of the gene mutations, such as the gene we found in one family, future research should investigate how the protein products of these genes cause the disease. With this knowledge, further investigation can lead to targeted therapies to correct or interfere in the process leading to the development of small intestinal carcinoid tumor and treat existing disease.

• Citation:• Gastroenterology.

2015 Apr 9. pii: S0016-5085(15)00499-0. doi: 10.1053/j.gastro.2015.04.008. [Epub ahead of print]• A Hereditary Form of Small Intestinal Carcinoid Associated with a Germline Mutation in Inositol Polyph

osphate Multikinase.• Sei Y1, Zhao X1, Forbes J1, Szymczak S2, Li Q2, Trivedi A1, Voellinger M1, Joy G1, Feng J1, Whatley M3,

Jones MS4, Harper UL4, Marx SJ5, Venkatesan AM6, Chandrasekharappa SC7, Raffeld M8, Quezado MM8, Louie A6, Chen CC3, Lim RM1, Agarwala R9, Schäffer AA10, Hughes MS11, Bailey-Wilson JE2, Wank SA12.











http://www.ncbi.nlm.nih.gov/pubmed/25865046




















































































White Opioid Users Increasingly Hooked On HeroinMedicalResearch.com Interview withSilvia S. Martins, MD, PHDAssociate Professor of Epidemiology Department of EpidemiologyMailman School Of Public Health Columbia

University New York, NY 10032

• MedicalResearch: What is the background for this study? What are the main findings?• Dr. Martins: The background for this study is former studies showing links between

nonmedical use of prescription opioids and transition to heroin and other illegal substances, prescription opioid-related and heroin-related fatal overdoses . In addition, a particular public health concern is that the transition to heroin and further injecting heroin may increase the risk of bloodborne infections.

• We used data from the National Survey on Drug Use and Health, a large nationally representative household sample of 67,500 people, and self-reported heroin use within the last 12 months, the researchers examined the change in patterns of past-year non-prescription drug and heroin use between 2002-2005 and 2008-2011 across racial and ethnic groups. The most significant rise in heroin use was among Hispanics and non-Hispanic whites, where the rate of heroin use for the latter group increased by 75 percent in 2008-2011 compared to earlier years. Regarding frequency of use, for Hispanics, increases were significant only among those using opioids about 1-29 days in the past year. Among blacks and whites, significant increases in the rate of heroin use were observed among those using prescription opioids more frequently (100-365 days) in the past year.


http://medicalresearch.com/author-interviews/white-opioid-users-increasingly-hooked-on-heroin/13833/











http://medicalresearch.com/addiction/todays_heroin_users_mostly_white_suburban/5578/






White Opioid Users Increasingly Hooked On HeroinMedicalResearch.com Interview withSilvia S. Martins, MD, PHDAssociate Professor of Epidemiology Department of EpidemiologyMailman School Of Public Health Columbia

University New York, NY 10032

• MedicalResearch: What should clinicians and patients take away from your report? • Dr. Martins: Clinicians, particularly pain clinic clinicians, psychiatrists and general

practitioners, should always monitor prescription drug use patterns among their patients and alert them about the risks of nonmedical use.

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

• Dr. Martins: More research is needed to better understand why these drug use transitions are occurring and what prevention strategies can curb not only nonmedical use but also transition to heroin use (and all risks associated with it) without jeopardizing access to these drugs to those that need them for legitimate medical conditions.

• Citation:• Silvia S. Martins, Julian Santaella-Tenorio, Brandon D.L. Marshall, Adriana Maldonado,

Magdalena Cerd&#2013265921;. Racial/ethnic differences in trends in heroin use and heroin-related risk behaviors among nonmedical prescription opioid users. Drug and Alcohol Dependence, 2015; DOI: 10.1016/j.drugalcdep.2015.03.020













http://medicalresearch.com/author-interviews/abuse-deterrent-opioids-inadvertently-led-to-increased-heroin-use/12645/

http://dx.doi.org/10.1016/j.drugalcdep.2015.03.020






Replacing Sugary Drinks With Plain Coffee Or Tea May Reduce Diabetes RiskMedicalResearch.com Interview with:Dr Nita Forouhi, MRCP, PhD, FFPHMMRC Programme Leader and Consultant Public Health Physician MRC Epidemiology Unit

University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK


Dr. Forouhi: Consumption of soft drinks is known to cause obesity and may contribute to the development of type 2 diabetes. We had previously published findings from the EPIC-InterAct study in 8 European countries that habitual consumption of sugar sweetened beverages increases the risk of developing type 2 diabetes, and we now wanted to probe deeper to understand more about this relationship between sweet beverages and diabetes.

• We conducted research in the large EPIC-Norfolk study which included more than 25,000 men and women aged 40–79 years living in Norfolk, UK. Study participants recorded everything that they ate and drank for 7 consecutive days covering weekdays and weekend days, with particular attention to type, amount and frequency of consumption, and whether sugar was added by the participants. During approximately 11 years of follow-up, 847 study participants were diagnosed with new-onset type 2 diabetes.

• By using this detailed information on diet, we were able to study several different types of sugary beverages, including sugar-sweetened soft drinks, sweetened tea or coffee and sweetened milk drinks as well as artificially sweetened beverages (ASB) – such as diet soft drinks – and fruit juice, and to examine what would happen if plain water, unsweetened tea or coffee or artificially sweetened beverages were substituted for sugary drinks.


http://medicalresearch.com/diabetes/replacing-sugary-drinks-with-plain-coffee-or-tea-may-reduce-diabetes-risk/13863/

























• Our study provided three main findings:• First, there was an approximately 22% increased relative risk of developing type 2 diabetes per

extra serving per day habitually of each of soft drinks, sweetened milk beverages and ASB consumed, even after accounting for a range of important factors including other lifestyle and social factors and for total energy intake. However, after further accounting for body mass index and waist girth as markers of obesity, there remained a higher risk of diabetes associated with consumption of both soft drinks and sweetened milk drinks, but the link with ASB consumption no longer remained, possibly because artificially sweetened beverages was likely to be consumed by those who were already overweight or obese.

• Second, when we estimated the likely effects of replacing a habitual serving of soft drinks with a serving of water or unsweetened tea or coffee, we found that the risk of diabetes could have been cut by 14%; and by replacing a habitual serving of sweetened milk beverage with water or unsweetened tea or coffee, that reduction could have been 20%–25%. However, consuming ASB instead of any sugar-sweetened drink was not likely to reduce the risk of diabetes, when accounting for baseline obesity and total energy intake.

• Third, we found that each 5% of higher intake of energy (as a proportion of total daily energy intake) from total sweet beverages (soft drinks, sweetened tea or coffee, sweetened milk beverages, fruit juice) was associated with a 18% higher risk of diabetes. We estimated that if study participants had reduced the energy they obtained from sweet beverages to below 10%, 5% or 2% of total daily energy, 3%, 7% or 15% respectively of new-onset type 2 diabetes cases could have been potentially avoided.




















http://medicalresearch.com/weight-research/diet-sodas-adverse-effects-of-altered-metabolism-weight-gain/1110/








• Medical Research: What should clinicians and patients take away from your report?• Dr. Forouhi: Our findings apply to people in the general population for the prevention of type

2 diabetes, and as such apply to adult consumers regardless of whether they are in a setting with their doctors or not. All healthcare and allied professional as well as public health bodies can provide advice about reducing the consumption of free sugars in the diet, in keeping with the most recent guidance from the World Health Organization. Limiting or eliminating the consumption of sugary beverages and replacing them with healthier alternatives is one of the easiest ways to achieve that goal.

• In particular, replacing the habitual consumption of sugar sweetened beverages with healthier beverage options, like water or unsweetened tea or coffee, can play an important part in the prevention of type 2 diabetes.

• This is the first report of an association between the habitual daily consumption of sweetened milk beverages and risk of new-onset type 2 diabetes. Past research typically considered sugar sweetened beverages as soft drinks such as fizzy drinks, colas, squashes and juice drinks, but our study raises the possibility that the habitual daily consumption of sweetened milk drinks such as flavoured milk and milkshakes may also elevate the risk of new-onset diabetes. Though this finding should be replicated in other studies, it certainly sounds a note of caution that the past focus solely on non-milk sweetened drinks may miss out an important class of sweetened beverages that could be related with adverse health effects through the non-milk free sugars.



























Extra information: We acknowledge that studies such as ours that are observational in nature do have limitations including that they do not prove a cause and effect association, whilst randomised controlled trials, such as those used when evaluating new drugs, provide the best evidence of cause and effect. Realistically we are limited to observational studies as it is impractical to randomly recruit and retain people to follow particular diets or drinks for long periods of time until a health condition develops. So, observational studies such as the one we report now have an important role to play in providing a good evidence base. The current study has several strengths that contribute to its robustness of findings: it is based on a large sample size of people who did not initially have diabetes so we could capture new-onset cases, it assessed diet with the detailed 7-day food diary, and it accounted for several important factors such as lifestyles and social factors as well as energy intake and obesity, that could potentially influence the findings because they may be related to intake of sugary drinks and to diabetes risk. Thus overall, the findings from this study are robust, and contribute meaningfully to understanding the link between sugary beverages consumption and risk of type 2 diabetes.




















http://medicalresearch.com/author-interviews/caloried_posting_reduced_adolescent_sugary_drink_purchases/8344/









• Dr. Forouhi: More research is needed to get a better understanding of the relationship between regularly consuming artificially sweetened beverages (ASB) such as diet drinks and risk of type 2 diabetes. This is a complex area to tease out because people who are already overweight or obese tend to consume ASB in preference to the sugary options as part of weight control, with potential for so-called reverse causation. In our study, once obesity was accounted for there was no demonstrable relationship between ASB consumption and type 2 diabetes, but replacing ASB for sugary drinks was not associated with a significant reduction in diabetes risk. This deserves further research to unravel the complicated relationships between these drinks, obesity, weight change and disease outcomes.



























Extra information: The challenge is that observational studies are prone to alternative explanations for findings through confounding and bias, and though randomised clinical trials would provide better evidence, they are difficult and expensive to conduct for disease end points. Random recruitment and retention would be challenging as participants would need to consume specific foods/drinks and hold other factors “constant” over long periods of time till an endpoint develops; that would be more feasible for weight change than for a condition like type 2 diabetes or other “hard” endpoints. Trials of intermediate metabolic endpoints, such as glucose or insulin levels or lipid blood fats, that are risk markers of disease conditions can be an option. Further observational studies that can account for changes in diet and changes in weight over time could help too.




















http://medicalresearch.com/cancer-_-oncology/obesity-related-cancers-blood-glucose-levels/2037/








• Further research should also address the relationship between sweetened milk drinks such as milkshakes, flavoured milks etc, and the risk of diabetes in different age groups, as our study was the first to report such an association in a long-term study of middle aged and older adults that followed them up over time for the development of diabetes.

• Citation:• O’Connor, L et al. Prospective associations and population impact of sweet beverage intake

and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia; 30 April 2015

























Rosacea Improved With Modified Release Doxycycline 40 mg Plus Topical MetronidazoleMedicalResearch.com Interview with:Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAADDirector, Medical AffairsGalderma Laboratories, L.P. Fort Worth TX

• MedicalResearch.com: What is the background for this study? What are the main findings?• Dr. Winkelman: Rosacea is a common dermatologic facial disorder estimated to affect 16 million

Americans. Rosacea is a chronic condition of the central face, including the nose, chin, cheeks and forehead, and is often characterized by flare-ups and remissions. While the cause of rosacea is unknown and there is no cure, its signs and symptoms can become markedly worse in the absence of treatment. Rosacea can be managed with topical and oral medications, and physicians often resort to using these medications in combination for more severe or resistant cases. Doxycycline 40 mg modified release (MR) and metronidazole 1% gel are FDA-approved oral and topical therapies, respectively, indicated to treat the papules and pustules of rosacea. We conducted a phase 2 study to assess the relapse rate, efficacy, and safety of doxycycline 40 mg MR compared to placebo after an initial 12-week once-daily combination regimen of doxycycline 40 mg MR and metronidazole 1% gel in subjects with moderate to severe disease.

Of the 235 subjects enrolled in the study, 71% were women, 94% were white, and 75% had Fitzpatrick skin type I, II or III. The mean age was 47.4 years. The percentage of subjects who achieved a success score of 0 (clear) or 1 (near clear) improved from 0% at baseline to 51% at week 12. Clinician’s erythema assessment scores, inflammatory lesion counts, and quality of life scores also improved. Most subjects reported no or mild scaling, stinging/burning, and dryness. Five adverse events were reported that were considered probably or definitely related to treatment: fungal infection, vulvovaginal mycotic infection, pain in extremity, erythema, and skin exfoliation.



Rosacea Improved With Modified Release Doxycycline 40 mg Plus Topical MetronidazoleMedicalResearch.com Interview with:Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAADDirector, Medical AffairsGalderma Laboratories, L.P. Fort Worth TX

• MedicalResearch.com: What should clinicians and patients take away from your report?• Dr. Winkelman: A once-daily combination regimen of doxycycline 40 mg MR and

metronidazole 1% gel was observed to be efficacious, safe, and tolerable, and had a positive effect on quality of life in subjects with moderate to severe rosacea.

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

• Dr. Winkelman: Future research should include long-term approaches to managing signs and symptoms of rosacea. In addition, further examination of the pathophysiology of rosacea and the mechanism of action of factors that trigger the onset of signs and symptoms and exacerbate the condition will be vital in treating this chronic skin condition.

• Citation:• Berlin J and Winkelman W. Efficacy and tolerability of oral doxycycline 40 mg modified

released with topical metronidazole 1% gel in moderate to severe rosacea. Poster presented at 73rd Annual Meeting American Academy of Dermatology; March 20-24, 2015; San Francisco, CA.



Vigorous Physical Activity May Lower Risk of Non-Hodgkin LymphomaMedicalResearch.com Interview with:Terry Boyle, PhDCIHR Fellow, MSFHR Trainee, Honorary UBC Killam FellowCancer Control Research, BC Cancer Agency

School of Population and Public Health, The University of British Columbia


Dr. Boyle : Little is known about what causes non-Hodgkin lymphoma (NHL), so trying to identify risk factors is particularly important for the prevention and control of this cancer. There is really good evidence that people who are physically active have a lower risk of some cancers (such as colon and breast cancers), but not many studies have investigated whether being physical active is associated with the risk of non-Hodgkin lymphoma.

• The key finding of this case-control study was that study participants who were in the higher (second, third, and fourth) quartiles of vigorously intense physical activity performance in their lifetimes had about 25 percent to 30 percent lower risk for NHL, compared with those who were in the lowest (first) quartile of vigorously intense physical activity.


http://medicalresearch.com/cancer-_-oncology/vigorous-physical-activity-may-lower-risk-of-non-hodgkin-lymphoma/13873/










http://medicalresearch.com/cancer-_-oncology/burkitts-lymphoma-effectivenss-low-intensity-therapy/2785/








• Medical Research: What should clinicians and patients take away from your report?• Dr. Boyle : We know that being physically active reduces the risk of colon cancer and breast

cancer, and also leads to a wide range of other physical and mental health benefits. The findings of this study suggest that people who do vigorous physical activity may also have a lower risk for non-Hodgkin lymphoma.












http://medicalresearch.com/cancer-_-oncology/colon-cancer/racial-disparities-in-colon-cancer-survival-persist/10218/









• Dr. Boyle : Currently there isn’t enough research on this topic to be able to confidently say that being physically active reduces the risk of non-Hodgkin lymphoma, so I’m planning to pool data from several studies to investigate this topic further.

• There are several different types of non-Hodgkin lymphoma, and we know that different types may have different risk factors, so one thing I’m planning to investigate is whether physical activity influences the risk of different types of non-Hodgkin lymphoma in different ways.

• Citation• Lifetime Physical Activity and the Risk of Non-Hodgkin Lymphoma• Terry Boyle, Richard P. Gallagher, Randy D. Gascoyne, Joseph M. Connors, Nhu D. Le, and John

J. Spinelli• Cancer Epidemiol Biomarkers Prev

May 2015 24:873–877; doi:10.1158/1055-9965.EPI-14-1303












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

http://cebp.aacrjournals.org/citmgr?gca=cebp;24/5/873










Your Genes May Explain Mosquitoes’ Preference For Your OdorMedicalResearch.com Interview with:G. Mandela Fernández-Grandon PhDDepartment of Disease Control, London School of Hygiene and Tropical Medicine

London, United Kingdom


Response: People often wonder why, when they are out with their friends or family, one person seems to get ravaged by mosquitoes but others come away relatively bite free. Mosquito bites can be a nuisance to many of us but they are no trivial matter. Mosquitoes are one of the most serious threats to public health through the transmission of diseases such as malaria, dengue fever, yellow fever, chikungunya and others.

• We knew that mosquitoes rely on odour to find their hosts but until now the link between our body odour and genes had only been shown using human sniffers1. In a strictly controlled laboratory environment, we were able to present the odours of individuals in identical and non-identical twin pairs to mosquitoes allowing them following the odour stream of whichever they found to be more attractive.


http://medicalresearch.com/genetic-research/your-genes-may-explain-mosquitoes-preference-for-your-odor/13875/


















Response: Mosquitoes are equally attracted to identical twins in a pair but with non-identical twins they display a preference for one individual.

• The ability of mosquitoes to distinguish non-identical twins but not identical twins suggests a genetic basis for our odour profile, a genetic difference which plays a role in whether we get bitten more or less than others.



















• Medical Research: What should clinicians and patients take away from your report?• Response: This work is an interesting new discovery but, at this stage, offers no new

recommendations to clinicians or patients. It is important they continue to follow the existing advice on bite prevention such as those provided on the World Health Organisation website (www.WHO.int).




















• Response: This opens up many exciting avenues of research. The first thing to address is how specific compounds in our odour profile link to specific genes. Once the associated genes are identified, we could screen individuals in different populations allowing us to more rapidly map odour profiles for different regions. Understanding variance in the population could be important for creating more accurate mathematical models of disease spread, taking into account the fact that not everybody will be bitten equally. Once we have a better understanding of the linkage between our genes and the odours we produce, it may be possible to synthesise bespoke repellents, or develop a way to manipulate our body’s production of specific repellent compounds.

• It is also likely that this work will extend beyond the field of insect biology. Studies on human odour communication can now approach it with a more robust understanding of the link between our genes and our smell. It is possible that in some areas, people with an odour less attractive to mosquitoes may be more likely to escape mosquito-borne disease; if so, are we more attracted to these people as potential partners?

• 1Roberts, S. C., Gosling, L. M., Spector, T. D., Miller, P., Penn, D. J., & Petrie, M. (2005). Body odor similarity in noncohabiting twins. Chemical Senses, 30(8), 651-656.

• Citation:• Heritability of Attractiveness to Mosquitoes• Mandela Fernández-Grandon, Salvador A. Gezan, John A. L. Armour, John A. Pickett, James G. Logan• Published: April 22, 2015 DOI: 10.1371/journal.pone.0122716












http://medicalresearch.com/author-interviews/how-our-brain-makes-sense-of-odors/10081/

http://medicalresearch.com/genetic-research/your-genes-may-explain-mosquitoes-preference-for-your-odor/13875/mosquitoes

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122716








Protein Driver of Aging Process IdentifiedMedicalResearch.com Interview with:Juan Carlos Izpisua Belmonte PhDProfessor, Gene Expression Laboratory Roger Guillemin ChairSalk Institute For Biological Science

• MedicalResearch: What is the background for this study? What are the main findings?• Response: Werner protein (WRN) plays roles in DNA replication, transcription, repair as well

as telomere maintenance. Mutations in WRN are associated with Werner syndrome. In the current study we discovered that WRN was interacting with proteins implicated in heterochromatin maintenance. We observed that mutations in the WRN protein led to alterations in heterochromatin and those alterations are drivers of the aging process.

• MedicalResearch: What should clinicians and patients take away from your report?• Response: In our study we observed a downregulation of the WRN protein associated with

heterochromatin disorganization in cells that led to the changes in the conformation of DNA and these changes are the drivers of aging.


http://medicalresearch.com/author-interviews/protein-driver-of-aging-process-identified/13879/
















Protein Driver of Aging Process IdentifiedMedicalResearch.com Interview with:Juan Carlos Izpisua Belmonte PhDProfessor, Gene Expression Laboratory Roger Guillemin ChairSalk Institute For Biological Science


• Response: We are currently developing epigenetic editing technologies to reverse the changes in heterochromatin that are observed during aging. In addition, we are also developing strategies to restore normal levels of WRN protein in old cells. Both of these approaches may have the potential to slow down or even reverse the aging process. In addition, studies using animal models will be necessary to evaluate the role of epigenetic changes at the organismal level and see if we can reverse these changes.

• Citation:• Weiqi Zhang, Jingyi Li, Keiichiro Suzuki, Jing Qu, Ping Wang, Junzhi Zhou, Xiaomeng Liu,

Ruotong Ren, Xiuling Xu, Alejandro Ocampo, Tingting Yuan, Jiping Yang, Ying Li, Liang Shi, Dee Guan, Huize Pan, Shunlei Duan, Zhichao Ding, Mo Li, Fei Yi, Ruijun Bai, Yayu Wang, Chang Chen, Fuquan Yang, Xiaoyu Li, Zimei Wang, Emi Aizawa, April Goebl, Rupa Devi Soligalla, Pradeep Reddy, Concepcion Rodriguez Esteban, Fuchou Tang, Guang-Hui Liu, and Juan Carlos Izpisua Belmonte. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science, 30 April 2015 DOI: 10.1126/science.aaa1356













http://medicalresearch.com/genetic-research/epigenetics-not-just-genes-control-many-complex-traits/12610/

http://dx.doi.org/10.1126/science.aaa1356






Novel Strategy May Lead To Elimination Of AML Stem CellsMedicalResearch.com Interview with:Dr. Alec (Chengcheng) ZhangMichael L. Rosenberg Scholar in Medical Research

Associate Professor of Physiology and Developmental Biology, Member of the Harold C. Simmons Comprehensive Cancer CenterUT Southwestern Medical Center


Response: Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. Treatments for AML yield poor outcomes, especially for the typical senior patients. The medical need for new therapies for AML is underscored by the fact that no new therapies for AML have been approved in over 30 years. There are over 50 experimental agents in clinical trials for the treatment of AML today, although only a few agents have promising data to date. New molecular targets and therapeutic strategies are needed for AML treatment.

• In 2012, we published a paper showing that we cloned the human leukocyte immunoglobulin-like receptor B2 (LILRB2) as a receptor for several angiopoietin-like proteins (Angptls) (Zheng et al 2012 Nature 485:656-660). The LILRB family receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and are classified as inhibitory receptors because ITIM motifs can recruit phosphatases SHP-1, SHP-2, or SHIP to negatively regulate immune cell activation. Surprisingly, in that work, we showed that PirB, the mouse ortholog of LILRB2, is expressed by AML stem cells (AML-SCs) and supports AML development. Although counterintuitive, this result is consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system.


http://medicalresearch.com/cancer-_-oncology/novel-strategy-may-lead-to-elimination-of-aml-stem-cells/13884/

















In the current paper, we continued the research and report that a number of receptors containing the ITIMs are crucial for the development of AML. We mainly focus on studying the function and downstream signaling of LAIR1 as a representative ITIM-containing receptor. We found that the deletion of LAIR1 does not affect normal hematopoiesis but abolishes leukemia development in several different mouse leukemia models. We also identified a mechanism by which LAIR1 supports AML development, showing that the LAIR1/SHP-1/CAMK1/CREB pathway sustains the survival and self-renewal of AML cells. Importantly, our findings are well supported by bioinformatics analysis of AML patient databases and experimental results of human leukemia cells. Since certain ITIM-containing receptors are essential for AML cells but not critical for normal hematopoiesis, and blocking their signaling can boost immunity, these ITIM-containing receptors including LAIR1 represent ideal targets for treating AML.



















• Medical Research: What should clinicians and patients take away from your report?• Response: Our study suggests that, the current treatment options, including chemotherapy,

may not efficiently target cancer stem cells because these inhibitory receptors enable the leukemia stem cells to survive the conventional therapies, eventually resulting in tumor relapse. The blockade of ITIM-receptor signaling may prove to be a novel effective strategy for elimination of leukemia stem cells and lead to complete remission of patients. This novel strategy may be a perfect combination of direct tumor targeting and immune therapy.












http://medicalresearch.com/cancer-_-oncology/breast-cancer/increased-risk-of-leukemia-after-breast-cancer/10187/









• Response: The supportive role of LAIR1 in AML may not be an exceptional case. Our in silico analyses indicate that expression of a number of ITIM inhibitory receptors negatively correlates with AML patient survival. We speculate that these receptors may also activate the same or a similar downstream signaling pathway as LAIR1 in AML cells. Because there are numerous types of ITIM receptors, different ITIM-containing receptors may have different expression patterns in different types or subtypes of leukemia and other cancers. It will be important to investigate the mechanisms by which other ITIM-containing receptors support cancer progression. Because SHP-1 is likely a common signaling mediator of a number of ITIM-containing inhibitory receptors that may support AML development, the identification of the specific inhibitors of the phosphatase-independent SHP-1 activity for AML treatment may have significant benefits.



















In addition, future investigations will be necessary to develop a better understanding of the signaling and function of these inhibitory receptors in cancer. For example, because the signaling through ITIM-containing receptors may be divergent, SHP-1 and CAMK1 may have downstream effectors other than CREB. The identification of other downstream targets of CAMK1 in leukemia cells is an important task. In addition, while we demonstrated that LAIR1/SHP-1/CAMK1/CREB is a novel signaling pathway that is essential to the activity of AML cells and that lair1 deficiency has a similar effect to the N-Myc B-ALL model, it is unclear whether different cancer cells share the same signaling. It will thus be interesting to determine the extent to which LAIR1 signaling in AML cells can be generalized to other immune inhibitory receptors and other types of cancer. Moreover, it will be important to understand whether therapeutic modalities for ITIM receptors may include antibodies against the extracellular domains of these receptors or whether inhibition of the intracellular signaling of ITIM receptors will represent a more powerful means of blocking these novel targets. Overall, blockade of ITIM-receptor signaling as a monotherapy, or in combination with conventional therapies including chemotherapy and targeted therapy may become novel strategy for AML treatment.



















• Citation:• Xunlei Kang, Zhigang Lu, Changhao Cui, Mi Deng, Yuqi Fan, Baijun Dong, Xin Han, Fuchun Xie,

Jeffrey W. Tyner, John E. Coligan, Robert H. Collins, Xiangshu Xiao, M. James You, Cheng Cheng Zhang. The ITIM-containing receptor LAIR1 is essential for acute myeloid leukaemia development. Nature Cell Biology, 2015; 17 (5): 665 DOI: 10.1038/ncb3158












http://dx.doi.org/10.1038/ncb3158






Novel Combination Treatment May Help Some Patients With Ovarian and Triple-negative Breast CancersMedicalResearch.com interview withDr. Victoria L. Chiou, MDMedical Oncology Fellow Women’s Malignancies Branch National Cancer Institute

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

• Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers.

• We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population.


http://medicalresearch.com/cancer-_-oncology/breast-cancer/novel-combination-treatment-may-help-some-patients-with-ovarian-and-triple-negative-breast-cancers13888/13888/












http://medicalresearch.com/cancer-_-oncology/breast-cancer/assay-may-determine-which-triple-negative-breast-cancers-respond-to-platinum-chemotherapy/13598/







• MedicalResearch: In your opinion, what was the key, or most important, finding? • Dr. Chiou: • We identified a safe drug treatment schedule for the new olaparib tablet formulation in

combination with carboplatin chemotherapy. We showed preliminarily that it also had activity, known as tumor shrinkage, in women with triple negative breast cancer and ovarian cancer. The different sequence of the drugs did not significantly impact the side effects that patients felt.

• We found evidence that olaparib tablet formulation given for 7 days, in combination with carboplatin given on one day, every 21 days, demonstrated preliminary clinical activity in heavily pretreated patients with breast and ovarian cancer. Women carrying a germline BRCA mutation had a 66% overall response rate; many patients achieved tumor shrinkage of more than 30%, and one patient had complete disappearance of all of the tumor.














http://medicalresearch.com/cancer-_-oncology/breast-cancer/novel-compound-may-shut-pancreatic-triple-negative-breast-cancer-cells/10939/








• Dr. Chiou: We are continuing correlative science work, performing additional studies to see whether there are differences in the genes of patients who responded to the therapy, and learning more about the new olaparib tablet formulation. Our goal is to identify biomarkers that predict susceptibility to this treatment combination. Interested patients may contact 1-888-624-1937 for more information about our clinical trials.

• Citation:• Abstract presented at the 2014 AACR meeting in Philadelphia

Olaparib Carboplatin Combination Showed Early Signs of Clinical Activity Against Ovarian and Triple-negative Breast Cancers














http://media.ne.cision.com/l/lahwofso/mb.cision.com/Public/3069/9755937/9ef90a2198ef11ad.pdf

http://media.ne.cision.com/l/lahwofso/mb.cision.com/Public/3069/9755937/9ef90a2198ef11ad.pdf






Obesity, Inactivity and Smoking Predict Disability in DiabetesMedicalResearch.com Interview with: Marianna Virtanen PhDFinnish Institute of Occupational Health,Helsinki, Turku and Tampere, Finland


Dr. Virtanen: Diabetes is a common chronic condition among working-aged populations but few studies have investigated work disability associated with diabetes. In this study, we examined trajectories of register-based work disability days over a 5-year period and lifestyle-related factors predicting these trajectories.

• Five trajectories described work disability: ‘no/very low disability’ (41.1% among diabetes cases, 48.0% among controls); ‘low–steady’ (35.4%, 34.7%); ‘high–steady’ (13.6%, 12.1%); and two ‘high–increasing’ trajectories (10.0%, 5.2%). Diabetes was associated with ending up to the ’high-increasing disability trajectory’, however, this affected only 10% of the population with diabetes. Obesity and physical inactivity predicted an adverse trajectory similarly among people with diabetes and those without diabetes while smoking was a stronger risk factor for an adverse trajectory in diabetes.


http://medicalresearch.com/diabetes/obesity-inactivity-and-smoking-predict-disability-in-diabetes/13848/









http://medicalresearch.com/author-interviews/diabetes-physical-and-functional-disability/1347/






Obesity, Inactivity and Smoking Predict Disability in DiabetesMedicalResearch.com Interview with: Marianna Virtanen PhDFinnish Institute of Occupational Health,Helsinki, Turku and Tampere, Finland

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

• Dr. Virtanen: The majority of employees with diabetes have relatively low disability rates although 10% are on a high and increasing disability trajectory. Lifestyle-related risk factors have similar associations with disability among employees with and without diabetes, except smoking which is more strongly associated with poorer prognosis in diabetes.


• Dr. Virtanen: Future research is needed to examine which types of interventions help in preventing work disability in diabetes.

• Citation:• Lifestyle-related risk factors and trajectories of work disability over 5 years in employees wi

th diabetes: findings from two prospective cohort studies• Virtanen, M. Kivimäki, M. Zins, R. Dray-Spira, T. Oksanen, J. E. Ferrie, A. Okuloff, J. Pentti, J. He

ad, M. Goldberg and J. Vahtera• Diabetici Medicine Accepted manuscript online: 27 APR 2015 08:22AM EST | DOI: 10.1111/d

me.12787











http://medicalresearch.com/diabetes/sitting-watching-tv-increases-diabetes-in-high-risk-individuals/13191/

http://onlinelibrary.wiley.com/doi/10.1111/dme.12787/abstract











Majority of Myocardial Infarction Patients Did Not Achieve Risk Factor ControlMedicalResearch.com Interview with:Andre Paixao, MDDivision of Cardiology Emory UniversityAtlanta, GA, 30322.

Medical Research: What is the background for this study?

Dr. Paixao: Despite advances in cardiovascular prevention, coronary heart disease remains a major cause of morbidity and mortality. Understanding risk factor burden and control as well as perceived risk prior to acute myocardial infarction (MI) presentation may identify opportunities for system-based interventions to promote adherence to evidence based recommendations and improve overall cardiovascular health.


http://medicalresearch.com/heart-disease/majority-of-myocardial-infarction-patients-did-not-achieve-risk-factor-control/13904/

















• Medical Research: What are the main findings?• Dr. Paixao: Our study assessed predicted risk and risk factor control prior to Myocardial

Infarction (MI) presentation in 443,117 patients included in the NCDR ACTION Registry-GWTG. Only 36.1% of patients met all assessed risk factor control metrics (i.e. LDL cholesterol, non-HDL cholesterol, nonsmoking status and aspirin use among those with prior cardiovascular disease). Risk factor control was suboptimal in the primary and secondary prevention groups.

• Prior cardiovascular disease was present in 41.6% of patients presenting with an acute MI. Among those without prior cardiovascular disease or diabetes, only 13.4% were classified as high risk based on the Framingham Risk Score.



















• Medical Research: How did you define LDL and non-HDL cholesterol goals?

• Dr. Paixao: Since our study included patients presenting between January 1, 2007 and November 11, 2013, we used the risk stratification model and cholesterol goals of the then prevailing Third Adult Treatment Panel (ATPIII). As an exploratory analysis, we also assessed statin eligibility according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines on the Treatment of Blood Cholesterol.

• Medical Research: Have you compared statin eligibility according to ATPIII and the 2013 ACC/AHA guidelines?

• Dr. Paixao: Applying ATPIII recommendations, only 60.8% of patients would be eligible for treatment with a statin medication prior to MI presentation. On the other hand, 89.9% of patients would qualify for statin treatment according to the 2013 ACC/AHA guidelines. Interestingly, a similar number of patients (81.4%) would be statin eligible according to the ATPIII optional LDL cholesterol goals.













http://medicalresearch.com/author-interviews/surprising_number_of_patients_do_not_take_their_prescribed_statin_medication/6074/

http://medicalresearch.com/heart-disease/myocardial-infarction-survival-and-diet-quality/1709/







• Medical Research: What should clinicians and patients take away from your report?• Dr. Paixao: In a large multicenter registry with >400,000 acute MI patients, risk factor control

was deficient across the spectrum of cardiovascular risk. Our findings indicate the need for better strategies to improve adherence to preventive targets for both primary and secondary prevention. Nationwide system-based interventions will likely be necessary to improve risk factor control.

• According to ATPIII recommendations, few MI patients without diabetes or prior CVD would be classified as high risk (13.4%) prior to presentation. In this primary prevention group, many would not have met ATPIII statin eligibility criteria prior to MI presentation (62.1%). Even though our study includes only MI patients and was not designed to compare the old and new cholesterol guidelines, our findings support the adoption of more aggressive treatment recommendations such as the ATPIII optional LDL goals or the 2013 ACC/AHA guidelines.













http://medicalresearch.com/general-medicine/updated-cholesterol-guidelines/9141/







• I also think our study gives some perspective to the debate over the 2013 ACC/AHA guidelines. Even applying the less aggressive ATPIII treatment recommendations, the vast majority of MI patients did not meet all assessed risk factor control metrics. This large gap between guideline recommendations and achieved risk factor control among MI patients suggests that we should perhaps present an “united front” and heavily invest in promoting adherence to preventive measures.

• Citation:• Risk Factor Burden and Control at the Time of Admission in Patients with Acute Myocardial In

farction: Results from the National Cardiovascular Data Registry

Andre R.M. Paixao, MD ,Jonathan R. Enriquez, MD, Tracy Y. Wang, MD, MHS, MSc ,Shuang Li, MS, Jarett D. Berry, MD, MS ,Amit Khera, MD, MSc ,Sandeep R. Das, MD, MPH James A. de Lemos, MD,Michael C. Kontos, MD

• American Heart Journal Received: April 21, 2015; Accepted: April 21, 2015; Published Online: April 24, 2015

DOI: http://dx.doi.org/10.1016/j.ahj.2015.04.021













http://www.ahjonline.com/article/S0002-8703(15)00254-9/abstract













Combination Medication Effective Hepatitis C Recurrence After Liver TransplantationMedicalResearch.com Interview with:Dr. Audrey Coilly MDFellow at the Centre Hepato-BiliairePaul Brousse Hospital Villejuif, France


Dr. Coilly: Hepatitis C (HCV) recurrence used to be a major issue during two decades for patients transplanted with an active HCV infection at the time of transplantation impacting both patient and graft survival. The combination of sofosbuvir and daclatasvir has not been studied after liver transplantation. The main findings are a high efficacy profile with an overall SVR12 rate of 95%. The safety profile is also good . The most frequent adverse event is anemia, particularly when ribavirin is still used.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Coilly: This combination is a good option to treat HCV recurrence. The use of ribavirin

does not seem to be mandatory but the enrollment of more severe patients in the RBV group justify to be very cautious regarding RBV avoidance and treatment duration. A decrease in creatinine clearance has been observed during treatment without clear explanation. Physicians should monitor carefully renal impairment during treatment.


http://medicalresearch.com/hepatitis-liver-disease/combination-medication-effective-hepatitis-c-recurrence-after-liver-transplantation/13925/














http://medicalresearch.com/hepatitis-liver-disease/hepatitis_c_triple_daa_plus_ribavirin_highly_effective_for_genotype_1_infections/4899/

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






Combination Medication Effective Hepatitis C Recurrence After Liver TransplantationMedicalResearch.com Interview with:Dr. Audrey Coilly MDFellow at the Centre Hepato-BiliairePaul Brousse Hospital Villejuif, France


• Dr. Coilly: We recommend to precisely look what happens in term of drug-drug interactions. • Citation:• Presented at The International Liver Congress™ 2015• THE ASSOCIATION OF SOFOSBUVIR AND DACLATASVIR FOR TREATING SEVERE RECURRENCE

OF HCV INFECTION AFTER LIVER TRANSPLANTATION: RESULTS FROM A LARGE FRENCH PROSPECTIVE MULTICENTRIC ANRS CO23 CUPILT COHORT
















https://ilc-congress.eu/






Mixing Alcohol With Energy Drinks Linked To Binge Drinking In AdolescentsMedicalResearch.com Interview with:Jennifer A. Emond, M.Sc., PhDResearch InstructorDepartment of EpidemiologyGeisel School of Medicine at Dartmouth College Cancer

Control Research ProgramLebanon, NH 03756


Dr. Emond: Several studies have documented a link between consuming alcohol mixed with energy drinks and an increased risk of negative outcomes while drinking, including binge drinking. It is known that mixing energy drinks with alcohol increases the risk for binge drinking–the high caffeine intake consumed when mixing energy drinks with alcohol may cause individuals to feel what is been called “wide-awake drunk,” and they may underestimate their level of intoxication. However, most studies to date have been conducted among undergraduate college students, and we wanted to know if those same associations were also observed among adolescents. In our study of 3,342 adolescents and young adults between the ages of 15-23, we also found a positive link between a history of consuming alcohol mixed with energy drinks and abusive alcohol use. Specifically, 22.3% of participants had ever consumed an energy drink mixed with alcohol (including 9.7% of 15-17 year olds), and such a history of mixed use was associated with a more than 4-fold increased likelihood of engaging in binge drinking. Importantly, that association was just as strong among 15-17 year olds as it was among the older participants. One critical component of our study was that we also looked at a validated outcome for alcohol use disorder (i.e., the participants completed the Alcohol Use Disorders Identification Test [AUDIT]), and participants with a history of consuming alcohol mixed with energy drinks were also 4.2 times more likely to meet that clinically defined criteria for alcohol use disorder as defined for adolescents. Again, those associations were observed for all participants, regardless of age.


http://medicalresearch.com/pediatrics/mixing-alcohol-with-energy-drinks-linked-to-binge-drinking-in-adolescents/13917/















http://medicalresearch.com/addiction/alcohol/primary-care-residents-ill-equiped-to-screen-for-binge-alcohol/12112/








• Our study has limitations. It was cross-sectional, so we cannot prove that mixed use of alcohol and energy drinks causes abusive alcohol use behaviors. However, our study does support that mixed use of alcohol with energy drinks can identify adolescents at risk for alcohol abuse.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Emond: It can be difficult to openly discuss alcohol use with adolescents. However, it’s

possible that clinicians, parents, and educators might open dialogues about alcohol use with adolescents by starting the discussion on the topic of energy drinks.

























• Dr. Emond: It is important for future studies to disentangle the main effects of individual traits, environmental influences and the practice of mixing alcohol with energy drinks on the development of abusive alcohol use behaviors in longitudinal studies.

• Citation:Jennifer A. Emond, Diane Gilbert-Diamond, Susanne E. Tanski, James D. Sargent. Energy Drink Consumption and the Risk of Alcohol Use Disorder among a National Sample of Adolescents and Young Adults. The Journal of Pediatrics, 2014; 165 (6): 1194 DOI: 10.1016/j.jpeds.2014.08.050

















http://dx.doi.org/10.1016/j.jpeds.2014.08.050






Many Patients With Disseminated Cancer Still Get SurgeryMedicalResearch.com Interview with:Robert J Canter MDAssociate Professor of Clinical SurgeryDivision of Surgical OncologyUniversity of California at Davis


Dr. Canter: Our data suggest that surgeons are improving in their ability to select patients for surgical intervention in cancer patients near their end of life. Our research suggests that surgeons may be operating on healthier patients who are anticipated to have a better recover from a palliative operation. These are patients who can perform activities of daily living without assistance, for example.

• Our interest in the appropriate surgical care of people with late-stage cancer grew from observing terminally ill patients whose acute problems were addressed through surgery, and who then suffered complications resulting in lengthy stays in intensive care units, and even in death.

• Unfortunately, it is quite common that this group of disseminated malignancy patients end up dying in the intensive care unit instead of being managed with less invasive interventions with hopes of returning home with their families, including with hospice care.


http://medicalresearch.com/cancer-_-oncology/many-patients-with-disseminated-cancer-still-get-surgery/13922/















Dr. Canter: For the study, we used the American College of Surgeons National Surgical Quality Improvement Program between 2006 and 2010 to identify 21,755 patients with stage IV cancer. Over the five years in the study period, surgical interventions declined just slightly, from 1.9 percent to 1.6 percent of all procedures. The most frequent operations were procedures to alleviate bowel obstructions among cancer patients with metastatic disease. Also over time, the patients undergoing surgery were more independent and fewer had experienced dramatic weight loss or sepsis. These characteristics are generally associated with poorer surgical outcomes.

• The patients’ rate of morbidity significantly decreased, from 33.7 percent in 2006 to 26.6 percent in 2010. Mortality declined as well, although more modestly, from 10. 4 percent to 9.3 percent over the study period.
















• Medical Research: What should clinicians and patients take away from your report?• Dr. Canter: Why surgeons continue to operate on patients at such high risk for complications

and death is likely multifactorial. Some of it has to do with the patients and families, and what their expectations are. If the patient seems to be declining, the patient and the family may attribute this to an acute surgical process, when it is, in fact, related to their underlying cancer. When they see an acute process, they often think it can be fixed with an operation, when surgery may actually not fix the problem, or sometimes make it worse. In addition, in some cases, the surgeon as well as other members of the health care team also may be too optimistic about what the surgical outcome will be.

• An important finding of this study was that just 3 percent of the patients with terminal cancer had Do Not Resuscitate (DNR) directives in place at the time of their surgery. DNRs, part of advanced directives used in end-of-life planning, direct physicians to withhold advanced life support if the patient stops breathing or their heart stops beating. These results imply that patients, families, oncologists, and other care providers, including surgeons, are often delaying discussions about the goals of the care and the priorities at the end of life. This is of critical importance since delaying end-of-life discussions can have serious consequences. This can lead to delayed referrals for palliative care and hospice. In addition, the patient risks undergoing multiple invasive, uncomfortable procedures in an attempt to prolong life, despite being against the patient’s goals of care and how they wish to spend their final days of life.










http://medicalresearch.com/author-interviews/community-based-palliative-care-teams-reduce-unnecessary-acute-care-end-life/5826/








• Dr. Canter: We think it is especially important that physicians and the treating team have end-of-life, goals-of-care discussions prior to the time that the patient comes into the hospital with an acute illness. This includes early referral of patients to palliative care treatment and to have a comprehensive end-of-life discussion to ensure that their goals of care are identified and respected as soon as patients are diagnosed with cancer, especially disseminated cancer since acute surgical problems may occur at any time and have dramatic impact of the patient’s end-of-life care.

• Citation:• J Surg Res. 2015 Mar 27. pii: S0022-4804(15)00326-1. doi: 10.1016/j.jss.2015.03.063. [Epub a

head of print]• Current perioperative outcomes for patients with disseminated cancer.• Bateni SB1, Meyers FJ2, Bold RJ1, Canter RJ3.










http://medicalresearch.com/cancer-_-oncology/adult_cancer_end_of_life_care_palliative_chemotherapy/4052/


















Pre-College Youth Sports Concussions Occur More Often During PracticeMedicalResearch.com Interview with:Thomas P. Dompier, PhD, ATC President and Injury EpidemiologistDatalys Center for Sports Injury Research and Prevention, Inc Indianapolis

, IN 46202Adjunct Faculty Appointments Ohio University Rocky Mountain University of Health Professions University of South Carolina


D: Dompler: Per the Institute of Medicine’s recent recommendations to better describe the incidence of concussion in sport across the entire spectrum of youth sports (5-23 years), this study is the first to provide an apples-to-apples comparison using epidemiologic data provided by healthcare providers (athletic trainers) who attended all practices and games and used the same methodology to report concussions and student-athlete exposure information.


http://medicalresearch.com/pediatrics/pre-college-youth-sports-concussions-occur-more-often-during-practice/13919/






















http://medicalresearch.com/author-interviews/law-brings-more-student-athletes-to-er-for-sports-related-concussions/12504/








• Medical Research: What are the main findings?• D: Dompler:

a. The main findings are that the risk (how many players out of 100 can expect to suffer at least one concussion during the season) is lowest in the youth, and increases with age.

• b. Game concussion rates (how many players out of 1000 exposed during a practice or game, includes multiple concussions to the same player) are highest in college but practice concussion rates are lowest in college during practice. This suggests more can be done during high school and youth practices to reduce concussion frequency (e.g. limiting how much time can be devoted to full contact, reducing player-to-player contact by teaching proper tackling without using full contact drills such as the Oklahoma drill and others).

• c. While the rate is higher, there is still a substantial number of concussions that occur during practice (because there are more practices), therefore sports medicine staff should be available at both if possible (this is difficult at the youth level because of cost, however).
























http://medicalresearch.com/author-interviews/concussions-young-female-soccer-players/3475/








• Medical Research: What should clinicians and patients take away from your report?• D: Dompler: We didn’t see any concussions in the 5-7 year olds despite over 7,000

exposures, but we are unsure if this is because there were none, or perhaps the 5-7 year olds do not know to report symptoms in absence of any observable symptoms such as unconsciousness. Clinicians should consider this when examining the youngest youth players.
































• D: Dompler:a. Future research should consider both boys and girls sports such as lacrosse, soccer, ice hockey, and many others. At the Datalys Center, we currently have a mirror study ongoing in boys and girls lacrosse in players 9-23 years old.

• b. Additionally, future research should consider strategies for lowering the rate of concussion during practices, particularly at the youth and high school level.

• Citation:• Dompier TP, Kerr ZY, Marshall SW, et al. Incidence of Concussion During Practice and Games i

n Youth, High School, and Collegiate American Football Players. JAMA Pediatr. Published online May 04, 2015. doi:10.1001/jamapediatrics.2015.0210.
























http://medicalresearch.com/general-medicine/lacrosse/6812/









More Powerful Gene Vector Aims To Restore Vision In Inherited BlindnessMedicalResearch.com Interview with:Professor James Bainbridge, MA, PhD, FRCOphthProfessor of Retinal Studies, UCL Institute of OphthalmologyNIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust

• Medical Research: What is the background for this study? What are the main findings?• Prof. Bainbridge : Leber Congenital Amaurosis (LCA) is one of the most common causes of

inherited, untreatable blindness in children. There are at least 14 different types of Leber Congenital Amaurosis of which LCA Type 2 (LCA2), caused by defects in the gene RPE65, affects around one in 100,000 people worldwide. Evidence from animal studies support that LCA2 may be amenable to treatment with RPE65 gene replacement therapy.

• The main findings of this phase I/II clinical trial confirm our preliminary findings (published in NEJM, 2008) that gene therapy can improve night vision. Improvements peak within the first 12 months after treatment but then decline during the three-year follow-up period which is consistent with the published results and interim findings from other studies of RPE65 gene therapy.


http://medicalresearch.com/genetic-research/more-powerful-gene-vector-aims-to-restore-vision-in-inherited-blindness/13892/
















• Medical Research: What should clinicians and patients take away from your report?• Prof. Bainbridge : This trial provides further evidence of benefit and safety for gene therapy

in inherited blindness. However our data, together with results of a parallel study in dogs, indicate that the demand for RPE65 is not fully met with the current generation of gene therapies. We have concluded that early intervention using a more potent gene therapy vector, expressing higher levels of RPE65 is likely to provide greater benefit and protection against progressive retinal degeneration.












http://medicalresearch.com/ophthalmology/reversing_blindness_with_a_wireless_nanotube_system/9554/








• Prof. Bainbridge : We recognise the obvious potential for gene therapy to treat Leber Congenital Amaurosis and have now developed a new, more powerful gene therapy vector and are aiming to test this in a second LCA2 clinical trial funded by The UK Medical Research Council.

• Citation• Bainbridge, JWB, Mehat MS, Sundaram V, et al. Long-term Effect of Gene Therapy on Leber C

ongenital Amaurosis. Will be published in New England Journal of Medicine. 2015; [Epub ahead of print – available as of May 4, 2015].












http://www.nejm.org/doi/full/10.1056/NEJMoa1414221?query=featured_home








Non-Toxic Spores May Prevent C. difficile infectionMedicalResearch.com Interview with:Dale N. Gerding, MDResearch Physician, Edward Hines, Jr., VA HospitalProfessor, Department of Medicine of Loyola University Chicago Stritch

School of Medicine


Dr. Gerding: Naturally occurring strains of C. difficile lack the genes for production of the toxins that cause C. difficile infection (CDI) and are known as non-toxigenic C. difficile (NTCD). These strains when ingested by patients whose normal microbiota is disrupted by antibiotic treatment will harmlessly colonize the colon and remain in the gut for weeks to months. Specific strains of NTCD found in patients were shown to colonize the gut and prevent C. difficile infection when challenged with toxigenic C. difficile strains in animal models. One such NTCD strain, NTCD-M3, was shown to be safe and well tolerated in human volunteer trials and was used in the present study to determine if it would prevent recurrence of C. difficile infection in patients who had just completed treatment with vancomycin or metronidazole of either their first CDI episode or first recurrence ofC. difficile infection. 168 patients were randomized to receive by mouth in a liquid form, either 10,000 spores/day of NTCD-M3 for 7 days, 10 million spores/day for 7 days, 10 million spores/day for 14 days, or an identical placebo for 14 days. Primary outcome was safety, and secondary outcomes were the percent who colonized the gut with NTCD-M3 in the time period from end of treatment to week 6, and the rate of recurrent CDI in the patients at week 6. The results showed that NTCD-M3 was safe and well tolerated, and colonized the gut of 69% of patients who received it. The C. difficile infection recurrence rate was 30% in the placebo patients and 11% in patients who received any of the NTCD-M3 doses (P<.006). The best dose tested was 10 million spores/day for 7 days which resulted in a recurrence rate of only 5% (p<.01 vs placebo). Colonization of the gut was not permanent, but lasted a maximum of 22 weeks. The summary conclusion is that NTCD-M3 is safe, colonized the gut, and when it colonized the gut, reduced recurrence of C. difficile infection to 2% (p<.001 vs patients who were not colonized).


http://medicalresearch.com/infections/c-difficile/non-toxic-spores-may-prevent-c-difficile-infection/13844/













http://medicalresearch.com/infections/c-difficile/c-diff-most-common-health-care-infection/12069/







School of Medicine

• Medical Research: What should clinicians and patients take away from your report?• Dr. Gerding: This is a promising safe and simple method to prevent recurrence of

C. difficile infection in patients treated with standard antibiotics, metronidazole or vancomycin (or both). It needs confirmation in a larger phase 3 trial using the best tested dose and duration.















http://medicalresearch.com/general-medicine/hospital_acquired_c_diff_infections_incresase_both_length_of_stay_and_mortality/8210/







School of Medicine


• Dr. Gerding: This is a phase 2 trial, so a phase 3 confirmatory trial in patients still needs to be done, but the method is a safe and simple addition to standard treatment and with use of the optimal dose in phase 3 should reduce C. difficile infection recurrence to approximately 5%. Other studies of NTCD-M3 in patients are needed to show that it can be used to prevent first episode of CDI by giving NTCD-M3 to patients taking antibiotics who are at high risk for CDI. This could provide a transient (not permanent) protection against CDI during high-risk periods of antibiotic use.

• Citation:• Dale N. Gerding, MD et al. Administration of Spores of Nontoxigenic Clostridium difficile

Strain M3 for Prevention of Recurrent C difficile InfectionA Randomized Clinical Trial. JAMA, May 2015 DOI: 10.1001/jama.2015.3725















http://medicalresearch.com/infections/c-difficile/clostridrium_difficile_infections_in_us_hospitals_doubled_over_decade/7959/

http://dx.doi.org/10.1001/jama.2015.3725






Tracer Improves PET/CT Detection of Recurrent Prostate CancerMedicalResearch.com Interview with:Matthias Eiber, MDDepartment of Nuclear Medicine Munich, Germany


Dr. Eiber: The background of the study is the investigation of a novel 68Ga-PSMA ligand using PET/CT in the workup of patients with recurrent prostate cancer after radical prostatectomy. Hereby, we found substantial higher detection rate compared to other methods. In total 222 (89.5%) patients showed pathological findings in 68Ga-PSMA-ligand PET/CT. Stratified by PSA-level the detection rates were 96.8%,93.0%,72.7% and 57.9% of ≥2,1-<2, 0.5-<1 and 0.2-<0.5ng/mL, respectively.


http://medicalresearch.com/cancer-_-oncology/prostate-cancer/tracer-improves-petct-detection-of-recurrent-prostate-cancer/13958/










http://medicalresearch.com/cancer-_-oncology/prostate-cancer/prostate-cancer-does-timing-of-radiation-therapy-affect-outcome/12926/







• Medical Research: What should clinicians and patients take away from your report?• Dr. Eiber: For clinicians and patients the main point includes that 68Ga-PSMA PET/CT enables

detection and localization of recurrent prostate cancer at a higher efficiency than reported for other tracers/imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA-values (<0.5ng/mL), which in many cases can substantially influence the further clinical management.



















• Dr. Eiber: Further research in that area should focus on the use of 68Ga-PSMA-ligand PET imaging in the area of primary prostate cancer. Here, a direct comparison between the imaging finding and postoperative histopathology allows a better determination of the potential of this tracer as well as its usefulness in primary staging. In the setting of increased PSA-value with prior negative biopsy the use of 68Ga-PSMA PET/MR imaging combining the excellent morphological detail, multiparametric functional information in MR and molecular information in PET could possible improve the detection of primary prostate cancer

• Citation:• Eiber, T. Maurer, M. Souvatzoglou, A. J. Beer, A. Ruffani, B. Haller, F.-P. Graner, H. Kubler, U.

Haberhorn, M. Eisenhut, H.-J. Wester, J. E. Gschwend, M. Schwaiger. Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. Journal of Nuclear Medicine, 2015; 56 (5): 668 DOI: 10.2967/jnumed.115.154153












http://medicalresearch.com/cancer-_-oncology/prostate-cancer/excellent-prognosis-for-low-grade-localized-prostate-cancer-in-elderly/12966/

http://dx.doi.org/10.2967/jnumed.115.154153






Polypill For Heart Disease May Improve Improve Compliance, Reduces CostsMedicalResearch.com Interview with:Hueiming Liu | BA (Hons), MBBS, MIPHResearch Fellow, Renal & Metabolic DivisionThe George Institute for Global Health NSW Australia

• Medical Research: What is the background for this study?• Dr. Liu: Cardiovascular disease is a major cause of mortality and morbidity worldwide and is

projected to be the leading cause of death in 2030. A major part of the problem is large treatment gaps globally. Cardiovascular polypills which are fixed dose combinations of frequently indicated cardiovascular medications for high risk primary prevention and secondary prevention have been trialled internationally to improve provider prescribing and patient medication use. Encouragingly, recent results from randomised controlled trials have shown effectiveness in improving adherence. This study is part of a process evaluation of a pragmatic randomised, controlled trial evaluating a polypill-based strategy for high-risk primary and secondary cardiovascular disease prevention in Australian primary health care. The trial results showed that “ After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26).” Ultimately, the trial was underpowered for clinical outcomes, but in a separate meta-analysis that included 2 other trials using a near identical protocol in other countries, the polypill strategy was associated with significant reductions in blood pressure and LDL cholesterol. A within-trial cost analysis of polypill-based care versus usual care with separate medications showed a statistically significantly lower mean pharmaceutical expenditure and thus potential cost savings to tax payers and the Australian government should the polypill strategy be introduced.


http://medicalresearch.com/medication-research/polypill-for-heart-disease-may-improve-improve-compliance-reduces-costs/13963/















http://medicalresearch.com/diabetes/only-13-high-risk-diabetic-patients-comply-with-medications/12719/







In this qualitative study, we explored health provider and patient attitudes towards the use of a cardiovascular polypill as a health service strategy to improve cardiovascular prevention in Australia through in-depth, semi-structured interviews with 47 health providers and 47 patients involved in the trial.
























Dr. Liu: We found that there was general acceptability for the strategy from both providers and patients. Polypill patients commented frequently on cost-savings, ease and convenience of a daily-dosing pill. Most providers considered a polypill strategy to facilitate improved patient medication use. Indigenous health service providers and Indigenous patients thought the strategy acceptable and beneficial for Indigenous patients given the high disease burden. Providers noted the inflexibility of the fixed dose regimen, with dosages sometimes inappropriate for patients with complex management considerations. Future polypill formulations with varied strengths and classes of medications may overcome this barrier. Many providers suggested the polypill strategy, in its current formulations, might be more suited to high-risk primary prevention patients.























• Medical Research: What should clinicians and patients take away from your report?• Dr. Liu: The cardiovascular polypill can be an effective and cost effective health service

strategy in changing prescribing behaviour and facilitating patient medication adherence. However, medication adherence is complex and requires clinicians to consider the polypill strategy alongside other strategies and cater to specific patient contextual factors such as health literacy, sense of well-being, financial considerations, establishing ongoing respectful clinician and patient relationship and improving accessibility to health care.
























• Dr. Liu: The cardiovascular polypill could be trialled with other evidence based strategies in cardiovascular prevention. Research of different combinations of cardiovascular polypills could increase clinicians’ flexibility in prescribing indicated CVD medications. Our experience with this process evaluation have highlighted that future qualitative research embedded into randomised controlled trials of complex behavioural change is valuable.

• Citation:• Patients’ and Providers’ Perspectives of a Polypill Strategy to Improve Cardiovascular Preventi

on in Australian Primary Health Care: A Qualitative Study Set Within a Pragmatic Randomized, Controlled Trial

• Hueiming Liu, Luciana Massi, Tracey-Lea Laba, David Peiris, Tim Usherwood, Anushka Patel, Alan Cass, Anne-Marie Eades, Julie Redfern, Noel Hayman, Kirsten Howard, Jo-anne Brien, and Stephen Jan

• Circ Cardiovasc Qual Outcomes. 2015;CIRCOUTCOMES.115.001483published online before print May 5 2015, doi:10.1161/CIRCOUTCOMES.115.001483

















http://circoutcomes.ahajournals.org/content/early/2015/05/05/CIRCOUTCOMES.115.001483.abstract













Low Health Literacy Linked To Increased MortalityMedicalResearch.com Interview with:Candace McNaughton, MD MPH Assistant ProfessorDepartment of Emergency MedicineVanderbilt University, Nashville, TN


Dr. McNaughton: Heart failure affects more than 5 million Americans, is a frequent cause of hospitalization, and by 2030 is project to cost as much $70 billion, so there is a lot of interest in helping patients with heart failure manage their condition. Health literacy, or the ability to use and understand healthcare information, is important for all patients, but the stakes are very high for patients with heart failure. Some people who are highly literate or highly educated in other areas may have difficulty reading and understanding healthcare information. Patients with lower health literacy skills may have difficulty communicating with healthcare providers, navigating the healthcare system, recognizing signs of health decline, and knowing when and who to contact when they do become ill.


http://medicalresearch.com/author-interviews/low-health-literacy-linked-to-increased-mortality/13819/










http://medicalresearch.com/author-interviews/negative-patient-doctor-communication-more-powerful-than-positive-communication/11104/








Dr. McNaughton: To our knowledge, this is the first study in which health literacy was measured by nurses when patients were admitted to the hospital for heart failure. Nurses asked patients three questions about whether they have problems learning about their medical condition, their confidence filling out medical forms, and how often they have someone help them read hospital materials. With these three questions, information about the health literacy level of individual patients can be made easily available their healthcare providers.

• We found that among 1,379 patients hospitalized for acute heart failure, those with low health literacy had 34% greater risk of death compared to patients with a literacy score of 10 or higher, even after adjusting age, sex, race, insurance status, education, other medical conditions, and how long they were in the hospital.












http://medicalresearch.com/cancer-_-oncology/breast-cancer/many-breast-cancer-patients-have-limited-understanding-of-their-own-disease/11084/







• Medical Research: What should clinicians and patients take away from your report?• Dr. McNaughton: The most important takeaway is that clear communication is very

important. It’s important that patients feel empower to let their healthcare providers know when they have questions or concerns. Healthcare providers often overestimate the health literacy levels of their patients, so they may not know there is a problem. It is important that patients talk with their healthcare providers and ask questions until they have a good understanding of how to take their medications, what the goals for salt and water intake, water weight, and how to balance all of this with other conditions such as diabetes.



















• Dr. McNaughton: We are learning more and more about how to make the most of communication between patients and healthcare providers. For many healthcare providers, it is often difficult to know which patients have low health literacy – for example, patients with graduate degrees can have difficulty understanding healthcare information because the information and language can be quite specialized. When we identify low health literacy levels, should we simplify medication regimens? Follow patients in the outpatient setting more frequently or sooner after discharge? Give them extra resources like home health care? We don’t know the answers to these questions yet.

• Citation:• Health Literacy and Mortality: A Cohort Study of Patients Hospitalized for Acute Heart Failure• Candace D. McNaughton, Courtney Cawthon, Sunil Kripalani, Dandan Liu, Alan B. Storrow, an

d Christianne L. Roumie• J Am Heart Assoc. 2015;4:e001799, originally published April 29, 2015, doi:10.1161/JAHA.115.

001799












http://jaha.ahajournals.org/citmgr?gca=ahaoa;4/5/e001799










Insulin Resistance Linked To Increased Risk of Cardiovascular DiseaseMedicalResearch.com Interview with:Michelle Schmiegelow MD, PhD StudentGentofte HospitalCopenhagen Area, Capital Region, Denmark


Dr. Schmiegelow: Use of cardiovascular risk stratification models is highly encouraged by U.S. and European guidelines in order to prevent cardiovascular disease (CVD). Individuals with insulin resistance are likely to progress to type 2 diabetes, but measures of insulin resistance are not included in current risk stratification models, although this might improve prediction of CVD in patients without diabetes. The aim of this study was to evaluate whether measures of insulin resistance would improve CVD risk predictions based solely on traditional CVD risk factors in postmenopausal women without existing CVD or diabetes. The main outcome was risk of developing CVD, defined as non-fatal and fatal coronary heart disease and ischemic stroke, within ten years, and the measures of insulin resistance considered were fasting serum glucose, fasting serum insulin, “homeostasis model assessment-insulin resistance“ (HOMA-IR) and the ratio of triglycerides and high-density lipoprotein-cholesterol (TG/HDL-C).

• From the Women’s Health Initiative Biomarkers studies we identified 15,288 postmenopausal women with no history of CVD, atrial fibrillation, or diabetes at baseline (included 1993–1998), who over a mean follow-up of 9.2 years (standard deviation 1.9 years) had 894 first CVD events (5.8%).


http://medicalresearch.com/diabetes/insulin-resistance-linked-to-increased-risk-of-cardiovascular-disease/13913/









http://medicalresearch.com/exercise-fitness/1678/1678/








Dr. Schmiegelow: The main findings of our study were that measures of insulin resistance were significantly associated with increased risk of CVD after adjusting for age and race/ethnicity, but measures of insulin resistance did not provide additional prognostic information beyond traditional cardiovascular risk factors. Particularly, measures of insulin resistance appeared to add little prognostic information once HDL-C levels were considered.

















• Medical Research: What should clinicians and patients take away from your report?• Dr. Schmiegelow: Insulin resistance is suggested as the pathophysiological link between

obesity and CVD risk, but the information insulin resistance measures provides regarding risk seems to be adequately captured by traditional cardiovascular risk factors, primarily HDL-cholesterol. Put differently, although measures of insulin resistance were associated with CVD risk when considered alone, these associations were greatly attenuated after adjusting for traditional risk factors, particularly HDL-C.

• Recent studies suggest that HDL-C per se may not be causally related to cardiovascular disease risk, but HDL-C is still a key risk factor because of its strong association with coronary heart disease. Several explanations for the associations between HDL-C and coronary heart disease has been suggested including confounding by apolipoprotein and atherogenic lipoprotein concentrations, modified by insulin resistance, or that HDL-C simply just be a reliable marker of a harmful risk profile











http://medicalresearch.com/heart-disease/carotid_atherosclerosis-predicted-by-cholesterol-overloaded-hdl-particles/10896/








• Dr. Schmiegelow: Due to the observational nature of our study, we can only explore associations, not causality. Other types of studies are thus needed to disentangle the effects of insulin resistance and factors correlated with it; for assessment of causality, Mendelian randomization studies could be useful, and it could be tested if interventions that directly target insulin resistance reduce the incidence of CVD.

• Citation:• Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A Cohort St

udy From the Women’s Health Initiative• Michelle D. Schmiegelow, Haley Hedlin, Marcia L. Stefanick, Rachel H. Mackey, Matthew Alliso

n, Lisa W. Martin, Jennifer G. Robinson, and Mark A. Hlatky• Circ Cardiovasc Qual Outcomes. 2015;CIRCOUTCOMES.114.001563published online before pri

nt May 5 2015, doi:10.1161/CIRCOUTCOMES.114.001563











http://circoutcomes.ahajournals.org/citmgr?gca=circcvoq;CIRCOUTCOMES.114.001563v1











Many Women Still Have Heavy Menstrual Bleeding Leading To AnemiaMedicalResearch.com Interview with:Anita L. Nelson, MDProfessor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical CenterLos Angeles BioMedical

Research Institute Harbor-UCLA Medical CenterTorrance, California


Dr. Nelson: The clinical impact heavy menstrual bleeding has often been expressed in terms of quality of life issues, but many women have heavy and prolonged bleeding that can lead to serious medical problems. The frequency with which women were treated at Harbor-UCLA Medical Center with profoundly low hemoglobin levels prompted us to do a comprehensive review of such women during a recent five year period to remind readers that even in the 21st century, this is not an uncommon problem. Overall 149 woman were treated 168 times for severe anemia (hemoglobin < 5.0 g/dL); 40% had previously been transfused (but not effectively treated). Over a quarter had reactive thrombocytosis which placed them at high risk for thrombosis (DVT, PE, and stroke). Over a third were discharged without therapy to prevent recurrence.


http://medicalresearch.com/author-interviews/many-women-still-have-heavy-menstrual-bleeding-leading-to-anemia/13955/



















• Medical Research: What should clinicians and patients take away from your report?• Dr. Nelson: Both clinicians and patients should recognize that excessive menstrual bleeding

may present as acute crisis, but it usually represents a chronic problem that also needs long term therapy. Clinicians should recognize that severe anemia from any source is associated with increased risk for thromboembolism. In this context, use of high dose estrogen therapy may not be the most prudent first line therapy. High dose progestin-only therapy has been shown in at least two perspective studies to be effective in rapidly controlled acute excessive uterine bleeding for a wide range of endometrial pathologies.






















• Dr. Nelson: The numbers of women who have been prospectively studied in clinical trials designed to arrest acute vaginal bleeding are embarrassingly small (< 150 women). More research is clearly needed. In particular, the efficacy of high dose progestin therapies should be studied in women with very low hemoglobin levels. Other agents, including selective progesterone receptor modulators, should be investigated both for acute and chronic excessive bleeding.

• Citation:• Severe Anemia From Heavy Menstrual Bleeding Requires Heighened Attention• Nelson, Anita L. et al.• American Journal of Obstetrics & Gynecology• DOI: http://dx.doi.org/10.1016/j.ajog.2015.04.023














http://dx.doi.org/10.1016/j.ajog.2015.04.023

http://dx.doi.org/10.1016/j.ajog.2015.04.023






























































































































































































































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