Age-Related Macular Degeneration: Lucentis Raises Stroke Risk

MedicalResearch.com Interview with:
Takashi Ueta, M.D., Ph.D.
Assistant Professor, Department of Ophthalmology
Graduate School and Faculty of Medicine
The University of Tokyo

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

Dr. Ueta: In 2009 we had reported an initial systematic review and meta-analysis which include pivotal RCTs but the number of the included studies were only 3 (MARINA, ANCHOR, FOCUS). During the following several years, more trials comparing different dosages and frequencies of ranibizumab treatment were conducted, which made us to update our meta-analysis.

Based on our updated meta-analysis, increase in several systemic vascular adverse events was observed: 86% increase in odds ratio (OR) for the risk of cerebrovascular accident (CVA) when 0,5 mg ranibizumab used. 89% increase in OR for the risk of CVA when monthly ranibizumab of any dosage is used. 57% increase in OR for the risk of non-ocular hemorrhage when ranibizumab of any dosage with any frequency is used. Continue reading

IV Melatonin Did Not Reduce Surgical Pain

Lars Peter Holst Andersen MD., Ph.d. Fellow / Læge, Ph.d. studerende Department of Surgery Herlev Hospital Gastroenheden, Herlev HospitaMedicalResearch.com Interview with:
Lars Peter Holst Andersen MD., Ph.d. Fellow / Læge, Ph.d. studerende
Department of Surgery Herlev Hospital
Gastroenheden, Herlev Hospital

Medical Research: What is the background for this study?

Dr. Andersen: The sleep hormone, melatonin is diverse molecule. Several experimental animal studies have documented significant antinociceptive effects in a wide range of pain models. In perioperative medicine, administration of melatonin has demonstrated anxiolytic, analgesic and anti-oxidant effects. Optimization of the analgesic treatment in surgical patients is required due to documented inadequate analgesia and the risk of adverse effects and complications caused by commonly used NSAIDs and opioids. Our goal was to investigate if melatonin was able to reduce pain scores or analgesic use in patients undergoing laparoscopic cholecystectomy.
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Higher Intake of Linoleic Acid Leads To Lower Coronary Heart Disease Risk

Prof. Frank B Hu Department of Nutrition Department of Epidemiology Harvard School of Public HealthMedicalResearch.com Interview with
Frank B. Hu, MD, PhD
Professor of Nutrition and Epidemiology
Harvard School of Public Health
Professor of Medicine Harvard Medical School
Boston, MA 02115


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

Dr. Hu: There has been much confusion and sensational headlines about the role of different types of fat in coronary heart disease.  A recent meta-analysis suggested that higher saturated fat intake was not associated with coronary heart disease (CHD), but people don’t consume saturated fat in isolation from other components of diet. Typically people swap for one type of fat for another. Therefore it is important to look at replacement nutrient when we talk about health effects of saturated fat. Randomized clinical trials have shown that replacing saturated fat with polyunsaturated fat reduces total and LDL cholesterol. Thus it is important to examine whether such replacement confers long-term beneficial effects on heart disease prevention. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the link between dietary intake of linoleic acid (the predominant type of polyunsaturated fat) and heart disease risk in generally healthy people. We identified 13 published and unpublished cohort studies with a total of 310,602 individuals and 12,479 total  coronary heart disease events including 5,882 CHD deaths. We found that dietary linoleic acid intake is inversely associated with  coronary heart disease risk in a dose-response manner—meaning, higher intake of linoleic acid resulted in a lower risk of CHD. Comparing the highest to the lowest level of consumption, dietary linoleic acid was associated with a 15% lower risk of  coronary heart disease events and a 21% lower risk of CHD deaths. These results were independent of common coronary heart disease risk factors such as smoking and other dietary factors such as fiber consumption.

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Sales Receipts May Lead to High Levels of BPA Absorption

Julia A. Taylor, Ph.D. Assistant Research Professor Division of Biological Sciences University of Missouri Columbia, MO 65211MedicalResarch.com Interview with:
Julia A. Taylor, Ph.D.
Assistant Research Professor

Division of Biological Sciences
University of Missouri Columbia, MO 65211


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

Dr. Taylor: Bisphenol A (BPA) is an industrial chemical present in a large number of consumer products, including polycarbonate plastics, food can linings, resins and thermal paper. A 2008 study of BPA levels in human urine concluded that over 90% of the U.S. population is exposed to BPA. BPA is an endocrine disrupter; its estrogenic properties were first described long before its commercial use, but today it is known that it not only acts like an estrogen but also interferes with thyroid hormone, androgen and insulin action. In population-based studies, higher urinary levels of BPA have been linked to a number of human health issues. For example, higher BPA concentrations have been associated with obesity and aggressive and hyperactive behaviors in children, and with cardiovascular disease and diabetes, altered liver and kidney function, and immune and reproductive disorders in adults.

It was at one time thought that almost all human exposure occurs via food and drink, but calculations of exposure from these sources do not adequately account for the sometimes high amounts measured in urine, and the fact that BPA concentrations in population-based studies are not lower with increasing fasting time suggests that some other form of ongoing exposure. Our interest here was in thermal paper. BPA has been used as a color developer in thermal paper for many years and can be present in milligram amounts in the paper coating. Because thermal printing is widely used for items such as sales and ATM receipts, airline tickets and luggage labels, thermal paper may represent an important high-concentration source of exposure.

We screened thermal paper receipts from 50 in-state vendors and found that 44% used BPA as the color developer, but 52% used another chemical called BPS (bisphenol S) which was present in similar quantities to BPA. Two receipts contained neither BPA nor BPS, and so presumably used an alternative (unidentified) chemical.

In preliminary work we measured the transfer of BPA from thermal paper to the hands, and found much higher transfer to hands that were pre-wet using hand sanitizer. We also determined that BPA transferred to hands could then be transferred to food. In our study we asked men and women to first wet their hands with sanitizer before holding the receipts for a few minutes, and then with the same hands pick up french fries and hold them briefly before eating them. We then cleaned one hand but allowed the other to remain “contaminated”. We took blood samples over the next 90 minutes, either from the arm linked to the clean hand or the arm linked to the dirty hand, and collected a urine sample at the end.

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Ebola: Infectiousness Greatly Increases With Disease Progression

Dr. Dan YasminMedicalResearch.com Interview with:
Dan Yamin PhD
Postdoctoral Associate
Yale School of Public Health
New Haven, CT 06520

 

Medical Research: What is the background for this study?

Dr. Yamin: With limited resources, West Africa is currently overwhelmed by the most devastating Ebola epidemic known to date. In our research, we seek to address two questions:

  • 1) who is mostly responsible for transmission? and
    2) what intervention programs should be applied to contain the current Ebola outbreak?

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Meditation May Improve Creative Thinking and Problem Solving

MedicalResearch.com Interview with:
Dr. Lorenza S. Colzato, Assistant Professor

and Dominque Lippelt, Research Master Student
Cognitive Neuroscience ResearchProgram
Leiden, The Netherlands

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

Response: Our study aimed to investigate whether prior meditation experience could modulate the effect of two types of meditation on two aspects of creative thought. Creativity can be thought of as consisting of two main ingredients: Convergent thinking (finding one solution to a defined problem) and divergent thinking (finding many possible solutions to a problem). In a previous study we found that Open Monitoring meditation and Focused Attention meditaton (FAM) have distinguishable effects on creativity. OMM induces a control state that promotes divergent thinking while Focused Attention meditaton does not improve convergent thinking. Our results confirm and extend these findings. Open Monitoring meditation improved performance on a divergent thinking task, while Focused Attention meditaton did not, and these effects were present in both experienced and novice practitioners, suggesting that one does not have to have many years of meditation experience to benefit from its effects. However, while solving convergent thinking problems experienced practitioners tended to solve more problems through insight as opposed to using an analytical strategy, a way of problem solving that bears similarities to divergent thinking.
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Pregestational Diabetes Mellitus: Preconception Care May Improve Outcomes and Save Billions

MedicalResearch.com: Interview with:
Dr. Cora Peterson PhD
Health Economist at Centers for Disease Control

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

Dr. Peterson: Women with pregestational diabetes mellitus (PGDM) have increased risk for adverse birth outcomes. Preconception care for women with  pregestational diabetes mellitus reduces the frequency of such outcomes, most likely by improving glycemic control before and during the critical first weeks of pregnancy.

Preconception care for women with  pregestational diabetes mellitus includes the following activities:

  • medical or dietary blood sugar control, blood sugar monitoring, screening and treatment of complications due to diabetes,
  • counseling and education about the risks of diabetes in pregnancy, and
  • using effective birth control or contraceptives until appropriate levels of blood sugar are achieved.

In this study, CDC researchers estimated the number of preterm births, birth defects, and perinatal deaths (death between the time a baby is at least 20 weeks old in the mother’s womb to one week after the baby is born) that could be prevented and the money that could potentially be saved if preconception care was available to and used by all women with  pregestational diabetes mellitus before pregnancy.

Researchers estimated about 2.2% of births (88,081 births each year) in the United States are to women with pregestational diabetes mellitus, including women who know they have diabetes before they become pregnant and those who are unaware they have diabetes. Preconception care before pregnancy among women with known pregestational diabetes mellitus could potentially generate benefits of up to $4.3 billion by preventing preterm births, birth defects, and perinatal deaths. Up to an additional $1.2 billion in benefits could be produced if women who do not know they have diabetes were diagnosed and received preconception care.

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Prostate Cancer: Androgen Deprivation Therapy May Be Harmful For Some Men

David R. Ziehr B.S., MD Candidate Harvard Medical SchoolMedicalResearch.com Interview with:
David R. Ziehr B.S., MD Candidate
Harvard Medical School

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

Response: Androgen deprivation therapy (ADT), commonly achieved with gonadotropin-releasing hormone agonists or antagonists, is a mainstay of prostate cancer therapy. While randomized controlled trials demonstrate that ADT improves survival among men with unfavorable risk prostate cancer, retrospective studies have suggested that some men with comorbid illnesses such as heart disease may not derive a benefit from—or may even be harmed by—ADT. However, the nature of this harm has not been characterized. We studied over 5000 men with prostate cancer who were treated with brachytherapy (implanted radioactive seeds) with or without ADT. We analyzed the men based on pre-treatment cardiac comorbidity and examined the association between ADT and death from cardiac causes. We found that among men with congestive heart failure or a past myocardial infarction (MI), Androgen deprivation therapy was associated with a three-times greater risk of death from heart disease. However, Androgen deprivation therapy was not associated with greater risk of cardiac mortality in men without heart disease or with a risk factor for heart disease, such as diabetes, hypertension or hyperlipidemia.
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Screening Chemotherapies for Effectiveness On Cultures Of Breast Cancer Biopsy Cells

Melissa Skala, Ph.D. Assistant Professor of Biomedical Engineering Assistant Professor of Cancer Biology Vanderbilt University Nashville, TN 372MedicalResearch Interview with:
Melissa Skala, Ph.D.
Assistant Professor of Biomedical Engineering
Assistant Professor of Cancer Biology
Vanderbilt University Nashville, TN 37235

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

Dr. Skala: We developed a new metabolic imaging technique that is highly sensitive to tumor cell response to anti-cancer drug treatment. We coupled this imaging technique with new, three-dimensional cultures that can be grown from breast tumor biopsies. Together, our data indicate that this approach could be used to perform rapid, low-cost, and accurate drug screens for individualized treatment of cancer patients.
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Study Identifies Potential Target In Huntington’s Disease Pathway

Srinivasa Subramaniam, Ph.D., Assistant Professor Department of Neuroscience The Scripps Research Institute Jupiter, Florida 33458MedicalResearch.com Interview with:
Srinivasa Subramaniam,
Ph.D., Assistant Professor
Department of Neuroscience
The Scripps Research Institute Jupiter, Florida 33458

 

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

Dr.  Subramaniam: Huntington’s disease (HD) is a genetic disorder occurs due to a mutation in a protein called huntingtin (mHtt), which affects 5-10 people per 100000 populations worldwide. Our research revolves around the question— why mutant huntingtin despite its ubiquitous expression through out the body selectively affects brain regions such as striatum, a region that regulates voluntary movement. We now found that mHtt activates a protein kinase complex, mammalian target of rapamycin complex 1 (mTORC1), which is required for normal functions such as translation of genes into proteins and also organelle recycling. We found the mTORC1 activation is so robust and sustained in the striatum that lead to the severe motor disabilities and premature death of HD mice. Our study indicates a functional relationship between huntingtin and mTOR the developmentally important genes with implication in Huntington’s disease pathogenesis.

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Is Pretreatment With Platelet Inhibitors Beneficial or Harmful For Acute Coronary Syndrome?

MedicalResearch.com Interview with:
Anne Bellemain-Appaix
Service de Cardiologie-La Fontonne Hospital, Antibes, France and

Gilles Montalescot Professor of  Cardiology
Institut de CardiologiePitié-Salpêtrière Hospital
Université Paris 6, France
ACTION Study Group, Paris, France

Medical Research: What is the background for this study?

Response: Pretreatment with P2Y12 inhibitors for Non-ST-Elevation Acute Coronary Syndrome (NSTE-ACS) patients, although advised in current guidelines, has been recently questioned in term of benefit/risk ratio (no ischemic benefit and increase in major bleeding). We wanted to answer this question by giving enough power to results in a complete meta-analysis of studies comparing P2Y12 inhibitors pretreatment (defined as its administration before the coronary angiogram) to no pretreatment in NSTE-ACS. Continue reading

Does Milk Increase Bone Fractures?

MedicalResearch.com Interview with: Professor Karl Michaëlsson Professor in Medical Epidemiology, Senior Consultant in Orthopaedic Surgery Uppsala Clinical Research Institute
MedicalResearch.com Interview with:
Professor Karl Michaëlsson
Professor in Medical Epidemiology, Senior Consultant in Orthopaedic Surgery
Uppsala Clinical Research Institute

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

Prof. Michaëlsson: A high milk intake is recommended for the prevention of osteoporotic fractures but milk is also the major dietary source of galactose intake. The addition of galactose by injection or in the diet is an established animal model of aging by induction of oxidative stress and inflammation. Previous research results regarding the importance of milk intake for the prevention of fractures and the influence on mortality rates are conflicting. High milk intake was in our study associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

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Reliability of East German Pharmaceutical Investigations Questioned

MedicalResearch.com Interview with: Dr. med. Rainer Erices Institut für Geschichte und Ethik der MedizinMedicalResearch.com Interview with:
Dr. med. Rainer Erices
Institut für Geschichte und Ethik der Medizin

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

Dr. Erices: The study presents the results of a first systematic investigation of clinical drug trials carried out by Western pharmaceutical firms in Eastern Germany in the 1980s. The scientific investigation of the East German Health system has only just started. The study shows that in that period of time, around 220 clinical trials were carried out. We now know how many patients took part and what remuneration the GDR received. It continues to be difficult to evaluate these tests. Despite intensive research efforts in different archives, we have been unable to find documentation on how detailed (and systematically) patients were informed about the trial they were taking part in. The responsible institutions repeatedly advised testers to stick to the law during the clinical trials. The law required that these trials should only be carried out on patients which had given their informed consent and had decided to participate voluntarily. However, so far there is no convincing proof that these legal requests were met.

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Community Interventions Improved Blood Pressure Control In Diverse Populations

Kevin L Thomas, MD Assistant Professor of Medicine Division of Clinical Cardiac Electrophysiology Duke Clinical Research InstituteMedicalResearch.com Interview with:
Kevin L Thomas, MD
Assistant Professor of Medicine
Division of Clinical Cardiac Electrophysiology
Duke Clinical Research Institute

 

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

Dr. Thomas: The number of participants with controlled blood pressure (readings of less than 140/90) increased by 12 percent in the six months between the first and last readings. Mean systolic blood pressure for the population decrease by 4.7mmHg. The number of participants who had high blood pressure in the range of 140-149/90-99 decreased systolic blood pressure by a mean of  8.8mmHg and those with readings in the higher range of 150/100 or above decreased systolic blood pressure by 23.7percent. The study concluded that a program that followed this type of approach was associated with improved blood pressures across a diverse  high-risk community.”
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Gut Bacteria Linked To Heart Failure and Mortality Risk

Professor of Medicine, Cleveland Clinic Lerner College of Medicine at CWRU Director, Cardiomyopathy Program, Kaufman Center for Heart Failure Research Director, Section of Heart Failure and Cardiac Transplantation Medicine Heart and Vascular Institute, Cleveland Clinic Cleveland, OH 44195MedicalResearch.com Interview with:
W. H. Wilson Tang, MD FACC FAHA

Professor of Medicine,
Cleveland Clinic Lerner College of Medicine at CWRU
Director, Cardiomyopathy Program, Kaufman Center for Heart Failure
Research Director, Section of Heart Failure and Cardiac Transplantation Medicine
Heart and Vascular Institute, Cleveland Clinic Cleveland, OH 44195

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

Dr. Tang: A chemical byproduct of gut bacteria-dependent digestion, TMAO (trimethylamine N-oxide), was previously shown to contribute to heart disease development. In this study, blood levels of TMAO for the first time are linked to heart failure development and mortality risk.
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Leftover US Hospital Supplies Can Have Lifesaving Impact Overseas

MedicalResearch.com Interview with:
Eric Wan BS and Miceile Barrett BS

Johns Hopkins University School of Medicine
Baltimore, MD

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

Answer: Access to surgery is limited in resource-poor settings and low-and-middle income countries (LMICs) due to a lack of human and material resources. In contrast, academic hospitals in high-income countries often generate significant amounts of unused and clean medical supplies that cannot be re-used in the operating rooms of high-income countries. Programs such as Supporting Hospitals Abroad with Resources and Equipment (SHARE) provide an avenue for recovery of these supplies and donation to resource-poor hospitals in LMICs. From data collected from SHARE supplies donated by Johns Hopkins, we found that the nationwide impact for these programs to be $15.4 million among US academic hospitals, which accounts for only 19 categories of commonly recovered supplies. When we tracked our donated supplies to hospitals in Ecuador serving the poor, we found that the cost-effectiveness of these donations was US $2.14 per disability-adjusted life-year prevented.
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Snoring During Twenties May Be Predictive of Sleep Apnea in Forties

MedicalResearch.com Interview with:
Dr. Swati Gulati, MD Internal Medicine
John H. Stroger Hospital of Cook County
Chicago, IL

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

Dr. Gulati: We conducted an observational study by providing questionnaire about the onset and progression of sleep apnea symptoms to patients seen in our sleep clinic for CPAP set up. In our cohort, mean age at the onset of snoring was 28 years and the mean age at diagnosis was 52 years. There was a lag of almost 23 years between the onset of snoring and the diagnosis of sleep apnea. The snoring started in mid twenties (Phase I) and patients noticed poor concentration and headaches in mid thirties (Phase II). Later, patients developed cardiopulmonary symptoms in mid forties to the time of diagnosis (Phase III).

The evolution of simple snoring into apneic episodes occurred around 40 years of age after which there was a rapid progression of disease marked by development of Excessive daytime sleepiness (EDS), dyspnea and morning headaches. We also found that patients who had started snoring earlier or at a very young age had a more severe disease as documented by apnea-hypopnea index (AHI).

In the literature, most of the natural history studies have looked at the progression of sleep apnea after diagnosis with a shorter follow up period ranging from 6 to 10 years.   Through our study, we have aimed to determine the natural history of disease progression from simple snoring until the time of diagnosis.

Medical Research: What was most surprising about the results?

Dr. Gulati: We were surprised to find out that the symptoms of snoring started in the mid twenties and progressed over 2 decades before diagnosis. It was also surprising that the duration of snoring and change in weight were better predictors of obstructive sleep apnea (OSA)  severity than the patient characteristics at the time of diagnosis, such as age and BMI. In our study, weight gain per year was the strongest predictor of severity of sleep apnea and it made the BMI at the time of diagnosis insignificant. Surprisingly, we found no association between gender and AHI.

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

Dr. Gulati: Based on our study, snoring in these patients starts at an early age and not necessarily in the middle age. Evolution of simple snoring into sleep apnea and symptomatic manifestations takes at least a decade on average.

Significant symptoms of sleep apnea were ignored for at least 20 years by the patients or their physicians. This should provide ample time opportunity for physicians to screen patients for sleep disordered breathing. Timely screening and diagnosis of obstructive sleep apnea will lead to early initiation of treatment and will slow its progression.

 

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

Dr. Gulati: Since our study population consisted of patients with severe OSA, these findings should be tested on a sample of patient that includes mild to moderate OSA. Randomized controlled trials should be done to see if screening for snoring in young adults and initiation of early treatment can prevent the development of OSA and associated mortality.

 

CHEST abstract:

Progression of Symptoms of Obstructive Sleep Apnea  and Their Association With Its Severity at Diagnosis?
Swati Gulati; Aiman Tulaimat
Chest. 2014;146(4_MeetingAbstracts):946A. doi:10.1378/chest.1992430

 

 

 

 

“Bad Cholesterol” LDL-C Linked to Aortic Valve Disease

George Thanassoulis, MD MSc FRCP(C) Director, Preventive and Genomic Cardiology FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien Assistant Professor of Medicine, McGill University McGill University Health Center Montreal, QCMedicalResearch.com Interview with:
George Thanassoulis, MD MSc FRCP(C)

Director, Preventive and Genomic Cardiology
FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien
Assistant Professor of Medicine, McGill University
McGill University Health Center Montreal, QC

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

Dr. Thanassoulis: Although LDL-C (i.e. bad cholesterol) has been linked with aortic valve disease in several prior reports, randomized trials to lower cholesterol in aortic valve disease were not effective suggesting that cholesterol may not be important in valve disease.

To address this, we performed a Mendelian randomization study, that showed that a genetic predisposition to LDL-C, was associated with both calcium deposits on the aortic valve and aortic stenosis (I.e. Valve narrowing).  These results can be viewed as the effect of a life-long increase in LDL-C on the incidence of aortic valve disease and suggest that increases in LDL-C cause aortic stenosis.   Continue reading

Men With Sleep Disorders Have Greater Risk of Alzheimer’s Disease

Christian Benedict PhD Associate Professor of Neuroscience Uppsala University Dept. of NeuroscienceMedicalResearch.com Interview with:
Christian Benedict PhD
Associate Professor of Neuroscience
Uppsala University Dept. of Neuroscience

 

Medical Research: What is the background for this study?

Answer: Our study involved ~1500 men who were followed from 1970 to 2010. All participants were 50 years old at the start of study.

Medical Research: What are the main findings?

Answer: Men with reports of sleep disturbances had a 50%-higher risk to develop Alzheimer’s disease during the 40-year follow-up period, than men without reports of sleep disturbances.
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How To Quickly Disseminate Best Practices To Doctors

Luís A. Nunes Amaral PhD HHMI Early Career Scientist Professor of Chemical & Biological Eng. Professor of Medicine Howard Hughes Medical Institute Northwestern University, Evanston, IllinoisMedicalResearch.com Interview with:
Luís A. Nunes Amaral PhD
HHMI Early Career Scientist
Professor of Chemical & Biological Eng.
Professor of Medicine
Howard Hughes Medical Institute
Northwestern University, Evanston, Illinois

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

Dr. Amaral: There is a well known difficulty in promoting the rapid adoption of best practices by physicians.  Because of their work load and because of the inability to figure out when some result is a true advance or just hype, doctors tend to stick to what they believe works. Unfortunately, as a 15 year old Institute of Medicine study shows, this lack of adoption of best practices costs society hundreds of thousands of lives a year in the US alone.

The typical process for informing doctors of what best practices are (such as continual medical education and other broadcasting approaches) do not work well. We believe that a weakness of typical approaches is that they have a one talking to the many style, and they are out of a medical practice context.  Our hypothesis was that by seeding a few doctors with desired knowledge, one could have spread of the adoption through one-on-one contacts between physicians in the context of treating patients.  We found that this approach has the potential to be very effective.
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