Author Interviews
26 May Unrecognized Carriers of Genetic Variants May Have Serious Medical Issues
MedicalResearch.com Interview with :
Prof. Alexandre Reymond
Director, Center for Integrative Genomics
University of Lausanne
Lausanne Switzerland
MedicalResearch : What is the background for this study?
Prof. Reymond: Though a subset of recurrent DNA copy number variants (differing numbers of copies of genetic sequence at locations in the genome; CNVs) with rare population prevalence are known to have strong impact on carrier’s health, up to now their association with phenotypes such as intellectual disability has been almost exclusively evaluated in clinical context using individuals ascertained for diagnostics of developmental disorders. Thus the contribution of these genetic variants to health, cognition and life quality in the general population remains unclear. We used a population biobank, that of Estonia (Estonian Genome Center, University of Tartu), which contains samples from 52,000 adult participants (representative 5% of the country’s adult population), a British birth cohort (The Avon Longitudinal Study of Parents and Children; ALSPAC) and two more population-based cohorts from the USA and Italy to explore the consequences of CNVs in presumptively healthy populations.
MedicalResearch : What are the main findings?
Prof. Reymond: Rare recurrent CNVs known to be causative for specific syndromes (termed genomic disorders) have a global population prevalence of around 1%. Contrary to popular assumption that carriers of these syndromic CNVs identified in unselected, but assumed to be healthy, adult population cohorts are asymptomatic, we found that they are associated with unrecognized, but serious clinical sequelae.
Additionally our results showed that individually rare (less than 1 in 2000 individuals) but collectively common (around 10% of population) intermediate-size CNVs are negatively associated with carriers’ educational attainment. Altogether our results suggest that the life quality of at least 1 of 40 people might be negatively affected by rare CNVs.
26 May Family History Alone Does Not Affect Breast Cancer Recurrence
MedicalResearch.com Interview with:
Professor Ramsey Cutress
Associate Professor in Breast Surgery
University of Southampton
Medical Research: What is the background for this study? What are the main findings?
Response: The main finding is that in young women with breast cancer, a breast cancer family history of breast cancer did not affect recurrence rates.
This work forms part of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study, which included 2850 women under age 41 years who were diagnosed with breast cancer and treated in the UK. The study, led by principal investigator Professor Diana Eccles, recorded patients’ personal characteristics, tumour characteristics, treatment, and family history of breast/ovarian cancer over a 15-year period.
24 May Number Of Infections Can Impact Cognitive Ability
MedicalResearch.com Interview with:
Dr. Michael Eriksen Benrós
Mental Health Centre Copenhagen
University of Copenhagen Faculty of Health Sciences
Copenhagen NV, Denmark,
National Centre for Register-based Research
Aarhus University Denmark
Medical Research: What is the background for this study?
Response: It is increasingly recognized that infections and immune responses can affect the brain and activate immunocompetent cells within the brain, influencing on neuronal signal transduction and possibly cognition. Impaired cognition has been observed in association with several infections and with elevated levels of CRP in smaller studies. Furthermore, experimental activation of inflammatory reactions in healthy volunteers has been shown to induce short-term reduced cognitive performance. Moreover, particularly patients with infection in the brain or sepsis have been shown to have affected cognition in long time periods after the infection has been cleared, thus infections might also have a longer lasting effect on cognition. However, large-scale longitudinal studies had been lacking on the association between infections and cognitive ability in the general population.
Medical Research: What are the main findings?
Response: Our study is the first large-scale study utilizing the extensive Danish registers to follow 190,000 males that had their IQ assessed at conscription, out of which 35% had a previous hospital contact with infection before the IQ testing was conducted. Our research shows a correlation between severe infections with a hospital contact and subsequent impaired cognition corresponding to an IQ score of 1.76 lower than the average. People with five or more hospital contacts with infections had an IQ score of 9.44 lower than the average. The study thus shows a clear dose-response relationship between the number of infections. Furthermore the effect on cognitive ability increased with the temporal proximity of the last infection and with the severity of the infection. Infections in the brain affected the cognitive ability the most, but many other types of infections severe enough to require a hospital contact where also associated with impairment of the cognitive ability.
24 May Elderly Hypertensive Patient With Declining Kidney Function Risk Cardiovascular Events
MedicalResearch.com Interview with:
Enayet Karim Chowdhury, Research Fellow
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University The Alfred Centre
Melbourne VIC 3004
Medical Research: What is the background for this study? What are the main findings?
Dr. Chowdhury: The study was conducted on elderly treated hypertensive population. Australia is currently undergoing a demographic transition towards having increasing number of older people. As age advances quality of life becomes increasingly affected by a variety of chronic diseases including poor renal function. Therefore early detection and management of the risk associated with these chronic diseases is crucial. Managing hypertension, even though challenging, can significantly improve quality of life of a person by reducing risk of having cardiovascular events. The main finding of the study is that in elderly treated hypertensive people, a rapid decline in renal function was associated with a higher risk of having cardiovascular events irrespective of having chronic kidney disease or not.
23 May Minimal Differences Between Young Adults Raised by Gay/Lesbian or Heterosexual Parents
MedicalResearch.com Interview with:
Dr. Simon Cheng PhD.
Department of Sociology
University of Connecticut, Storrs, CT
Medical Research: What is the background for this study? What are the main findings?
Dr. Cheng: Our research is an empirical response to the Regnerus study, one of the most visible and controversial articles ever published in the social sciences. His study concluded that individuals raised by a gay or lesbian parent display less favorable adulthood outcomes than those who grew up in intact biological families. There have been many debates about the study’s conclusion and analysis, but we (Cheng and Powell) are the first to reassess Regnerus’s findings by analyzing his own data. Our reanalysis seriously calls into question his conclusions. We find that a large number of the people studied in the Regnerus study likely were misclassified as living with gay/lesbian parents. The misclassifications took several forms:
- Of the 236 people Regnerus defined as being raised by a “lesbian mother” or “gay father’ 24 (10%) report that they actually never lived with that parent
- An additional 34 (14%) report that they lived with that parent for a year of less.
- The 236 people include some questionable responses that lead us to doubt the seriousness of the person completing the survey. The most notable example is a 25 year-old man who reports that his father had a romantic relationship with another man, but also reports that he (the respondent) was 7-feet 8-inches tall, weighted 88 pounds, was married 8 times, and had 8 children. Another person claims to have been arrested at age 2.
- The 236 people also include responses that at best are inconsistent and illogical. For example, one person repots “having always live alone but also claims to have always lived with the mother, father, and two grandparents.”
23 May Early Life Exposure To Antibiotics May Impact Adult Health
MedicalResearch.com Interview with: Ms. Pajau Vangay Graduate Research Fellow Biomedical Informatics and Computational Biology Vice President of Grants, Council of Graduate Students University of Minnesota Medical Research: What is the background for this study? What are the main findings? Response: Previous studies showed links between antibiotic use and unbalanced gut bacteria, and others showed links between unbalanced gut bacteria and adult disease. Over the past year we synthesized hundreds of studies and found evidence of strong correlations between antibiotic use, changes in gut bacteria, and disease in adulthood.23 May Proximity To Liquor Stores Linked To Gun Violence, Especially In Distressed Neighborhoods
MedicalResearch.com Interview with:
Marie Crandall, MD, MPH, FACS
Associate Professor of Surgery
Northwestern University Feinberg School of Medicine
Chicago, IL 60611
Medical Research: What is the background for this study? What are the main findings?
Dr. Crandall: While the association between alcohol and interpersonal violence has been well established, research has been divided with respect to the direct effect of proximity to an establishment with a liquor license and violence. We used geographic regression analysis, which is a type of multivariate regression including geography as a variable, to examine the association between proximity to an establishment with a liquor license, such as a liquor store or tavern, and gun violence in Chicago.
We utilized our state trauma registry and geocoded 11,744 gunshot wounds that occurred between 1999-2009. On the assumption that different neighborhoods might experience risk differently, we used a combination of ordinary least squares and geographic regression analysis to identify homogenous areas with similar risk. We used sociodemographic variables as covariates in the analysis.
We found that the impact of proximity to an establishment with a liquor license and occurrence of gunshot wounds varied markedly by neighborhood. The areas of highest risk were found to have enormous associations, Odds Ratios (OR) greater than 500. These areas also tended to be more socioeconomically distressed areas of the city.
22 May Obesity Leads To Reversible Changes In Diabetes-Predisposition Genes
MedicalResearch.com interview Dorota Kaminska, MSc Department of Clinical Nutrition University of Eastern Finland MedicalResearch: What is the background for this study? What are the main findings? Response: The prevalence of obesity is increasing worldwide, making it one of the biggest health problems currently facing both developed and developing countries. Obesity is considered a primary risk factor for developing type 2 diabetes. While the majority of people with type 2 diabetes are obese, most of obese people do not develop diabetes, indicating that obesity is not the only risk factor for type 2 diabetes. Both obesity and type 2 diabetes are multifactorial complex diseases that are caused by a combination of genetic, environmental, and lifestyle factors. Results from twin studies suggest that genetic factors explain 50% to 90% of the variance in body mass index (BMI) and from 45% to 85% of the diabetes risk. However genetic variations identified by genome wide association studies (GWAS) explain only 2-4% of the obesity risk and 5-10% of the type 2 diabetes risk. Several options have been debated to be a source of so called “missing heritability”, including, among others, structural DNA variations, gene-gene and gene-environment interactions, epigenetic modifications and RNA splicing. We used adipose tissue samples from Kuopio Obesity Surgery (KOBS), very low calorie diet (VLCD), Metabolic Syndrome in Men (METSIM) and European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) studies to determine alternative splicing pattern of selected genes. The study focused on determining the effects of obesity and weight loss on alternative splicing of metabolically active genes (TCF7L2 and INSR). We showed that alternative splicing of both genes is dysregulated in obesity and type 2 diabetes, resulting in impaired insulin action in adipose tissue. Additionally we demonstrated, that obesity induced changes in splicing can be reversed by weight loss induced by gastric bypass surgery or very low calorie diet. Furthermore, the study identified alternatively spliced genes in the genomic regions associated with obesity risk, demonstrating that splicing of the MSH5 gene in subcutaneous fat is regulated by weight loss. The study also found that body mass index is a main determinant of TRA2B, BAG6 and MSH5 splicing in subcutaneous fat; however, the functional consequences of this finding require further investigation. These findings imply that the obesity-associated gene variants might act through regulation of splicing which in turn might underlie the pathogenesis of obesity in individuals carrying the risk variants.22 May Chemotherapy Before Ovarian Cancer Surgery May Benefit Some Patients
MedicalResearch.com Interview with: Mr Matthew Nankivell MRC Clinical Trials Unit at University College London Institute of Clinical Trials and Methodology Aviation House, London UK Medical Research: What is the background for this study? What are the main findings? Response: Ovarian cancer is diagnosed in over 7000 women each year in the UK. Over 75% of these already have advanced disease, for which the standard treatment is surgery followed by platinum based chemotherapy. The prognosis for these patients remains poor however, with less than 25% surviving for 5 years. There is consistent evidence that achieving optimal debulking (meaning less than 1cm of residual tumour after surgery) is key to increasing survival. The theory tested in Chorus is that giving the chemotherapy before surgery (neo-adjuvantly) would be as least as effective as giving it post-operatively, and may in fact increase the chance of achieving optimal debulking, and subsequently living for longer. In Chorus we randomised 552 women to receiving either the current standard of immediate surgery followed by chemotherapy, or chemotherapy followed by surgery. The trial met its primary aim of showing that neo-adjuvant chemotherapy was no worse than post-operative chemotherapy, with median survival times of 24.1 and 22.6 months respectively. The proportion of women achieving optimal debulking increased from 41% in the post-operative chemotherapy group to 73% in the neo-adjuvant chemotherapy group. Additionally we saw that fewer women experienced serious post-operative complications having had neo-adjuvant chemotherapy (14% vs 24%), and fewer women died within 28 days of surgery (<1% vs 6%). There is a planned meta-analysis, to combine the data from Chorus with those from a similar European trial, which will allow further investigations to take place, and may allow the identification of groups of women who are more likely to benefit from one or other of the approaches.22 May All-Cause Mortality Decreased In Post-Menopausal Women Who Reduce Sedentary Time
MedicalResearch.com Interview with: Jasmine Lee, M.Sc. and Chris I. Ardern, Ph.D. School of Kinesiology and Health Science York University Toronto, ON, Canada Medical Research: What is the background for this study? Response: Although the benefits of physical activity are well known, the health and mortality risks associated with sedentary time (activities <1.5 MET)—which can occur in long, continuous bouts, such as at the workplace, during motorized transportation and via screen time— have been less frequently explored, and may differ across subgroups of the population. Like physical activity, sedentary time may fluctuate with major life events and occupation (e.g. aging, retirement, etc.), which raises the question of the short-term relationship between changes in sitting time and mortality risk. Medical Research: What are the main findings? Response: Maintenance of minimal sedentary time, as well as short-term reduction in sedentary time, were found to reduce the risk of all-cause and cancer- mortality amongst a sample of middle-aged and older women (50-79 y) who are prone to high rates of physical inactivity and sedentary time.22 May Breastfeeding Rates Remain Low Among Minority Women
MedicalResearch.com Interview with:
Katherine Jones, M.A.
Research Associate, Department of Research
The American College of Obstetricians and Gynecologists
Department of Psychology, American University
Medical Research: What is the background for this study? What are the main findings?
Response: It is well evidenced that breastfeeding is highly advantageous for the mother, child, and society. Benefits to breastfeeding may be significantly larger for minority women as they are disproportionately affected by numerous adverse health outcomes. The benefits of breastfeeding may help mitigate some of these negative health consequences, and thus, also bridge larger gaps in racial and ethnic health disparities. This article aimed to review the literature on racial and ethnic disparities in breastfeeding rates and practices, conduct a systematic review of breastfeeding interventions, address barriers to breastfeeding among minority women, and provide obstetrician-gynecologists (ob-gyns) with recommendations on how they can help improve rates among minority women.
Overall, racial and ethnic minority women continue to have lower breastfeeding rates than white women in the United States, with African American women having the lowest rates of breastfeeding initiation and continuation among to all women. Minority women report several unique barriers to breastfeeding, including lack of access to information that promotes and supports breastfeeding, lack of work and cultural acceptance and support, language and literacy barriers, acculturation, and historical, sociopolitical, and economic challenges. Results from the systematic review of breastfeeding interventions among minority women indicated that breastfeeding-specific clinic appointments, enhanced breastfeeding programs, group prenatal education, peer counseling, and hospital policy changes significantly improve breastfeeding initiation, duration, and exclusivity.
22 May Circulating Colon Cancer DNA Mutations May Predict Metastases
MedicalResearch.com Interview with:
Dr. Jeanne Tie
Medical Oncologist | Royal Melbourne and Western Hospital
Research Fellow
Walter and Eliza Hall Institute of Medical Research
Parkville, VIC
Medical Research: What is the background for this study?
Dr. Tie: The increasing number of active agents available to treat metastatic colorectal cancer has resulted in an ever-improving life expectancy in this group of patients. However, the ability to expose patients with metastatic colorectal cancer to all effective anti-cancer treatment, particularly 3rd line treatment and beyond, is increasingly challenging in routine practice as some patients’ condition deteriorate too rapidly and do not live long enough to enjoy the benefit of these additional therapies. This is partly due to the current imaged-based method of assessing treatment response with the Response Evaluation Criteria in Solid Tumors (RECIST), which is usually performed every 8-12 weeks during the course of treatment. This means that for non-responders to treatment, several weeks to months will elapse before a switch to alternative therapy will be made. Conceptually, if a patient’s response to treatment could be made earlier, such as with a blood test, then an earlier switch to an alternative treatment can be made, minimizing the side-effects of the ineffective therapy and providing the opportunity for a more effective one. Currently, blood biomarkers add little to imaging-based assessment, with CEA lacking sensitivity and specificity.
Colorectal cancer is characterised by several recurrently mutated genes and advances in genomics and molecular technologies have now enabled rapid detection and quantification of these cancer-specific mutations in patient’s circulation (circulating tumor DNA - ctDNA). Previous studies have demonstrated that ctDNA can be detected in a high proportion of patients with advanced cancer. In this study, we describe the potential role of ctDNA as an early predictor of treatment response in patients with treatment naïve metastatic colorectal cancer (mCRC) undergoing chemotherapy and as a marker of disease bulk that could complement RECIST measurement.
22 May Black Young Gay Men From Poor Neighborhoods More Likely To Contract HIV
MedicalResearch.com Interview with:
Perry N Halkitis, Ph.D., M.S., MPH
Professor of Applied Psychology
Global Public Health, and Population Health/Medicine
New York University.
Medical Research: What is the background for this study?
Dr. Halkitis: The P18 Cohort Study is a prospective cohort study of gay, bisexual and other young men who have sex with men (YMSM) which seeks to examine the development of health behaviors as these young men transition from adolescent to adulthood. Officially named “Syndemic Production among Emergent Adult Men”, this study was funded by the National Institute on Drug Abuse from 2009-2014 and renewed on March 1, 2014 for an additional five years.
The original aims of the study were as follows:
- 1) to develop and test theoretically informed measurement models of the covariance of illicit drug use, unprotected sexual behavior and mental health burden (multiple overlapping epidemics known as a syndemic) among emergent adult HIV-negative YMSM within and across time;
- 2) to delineate the risk and protective bases- physical factors (e.g., pubertal onset, HIV status, etc.), relational and structural factors (e.g., family history of psychopathology, current romantic relationships, peer support, neighborhood factors, etc.), and psychosocial factors (e.g., sexual identity, internalized homophobia, hyper-masculine conceptions, etc.) that predict the development of syndemics; and
- 3) to determine the extent to which the development of a syndemic varies by race/ethnicity, social class, and homelessness/housing instability.
- In this current five year continuation we also seek
- 1) to describe the social and sexual networks of YMSM, and to examine the relationship between social and sexual network-level structural characteristics, social support and normative influences on syndemic production (illicit drug use, unprotected sexual behaviors, and mental health burden) in YMSM, singly and in combination with the physical, psychosocial, and relational predictors, both within and across time;
- 2) to describe the acquisition of sexually transmitted infections (STIs) in YMSM, specifically, urethral and rectal gonorrhea and chlamydia, pharyngeal gonorrhea as well as syphilis serology; and to determine the extent to which physical, relational, and psychosocial factors explain STI acquisition as part of the syndemic model within and across time.
- A third exploratory aim was also added: 3) to describe HIV clinical treatment markers (i.e., HIV viral load, ART uptake and adherence, HIV care) among HIV+ YMSM, and to assess the extent to which physical, relational, and psychosocial factors are associated with differences in these clinical markers among HIV+ YMSM, both within and across time. The study is led by Drs. Perry N Halkitis and Farzana Kapadia at New York University’s Center for Health, Identity, Behavior & Prevention Studies.
21 May Black Overweight Women Have Increased Cardiovascular Risk Even Without Metabolic Syndrome
Posted at 12:23h
in AHA Journals, Author Interviews, Heart Disease, Metabolic Syndrome, Race/Ethnic Diversity, Weight Research
MedicalResearch.com Interview with:
Michelle Schmiegelow, MD, PhD-student
Hjertemedicinsk Forskning
Gentofte Universitetshospital
Hellerup
Medical Research: What is the background for this study?
Dr. Schmiegelow: Obesity has become a worldwide epidemic, but the excess cardiovascular risk observed in obese individuals may primarily be attributable to metabolic mediators, rather than obesity per se. Several studies conducted in primarily non-Hispanic white populations suggest that obese individuals without the metabolic syndrome, defined as metabolically healthy obese, have a cardiovascular risk similar to that of normal weight metabolically healthy individuals.
We used prospectively collected data from the Women’s Health Initiative studies to evaluate whether obesity unaccompanied by metabolic abnormalities was associated with increased risk of cardiovascular disease (CVD) across racial/ethnic subgroups in postmenopausal women. Additionally, we examined whether the use of the metabolic syndrome to define the metabolically healthy obese applied to the various racial/ethnic subgroups by quantifying the number and type of metabolic syndrome components.
All women were classified by obesity level and metabolic health status at baseline. The women were thus categorized according to body mass index (BMI, kg/m2) into normal weight (BMI 18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (30.0 kg/m2) women. Metabolic health status was first defined by presence of the metabolic syndrome (yes/no), and second by number of metabolic syndrome components. In accordance with the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute we defined the metabolic syndrome as any two of the following (criteria for women): increased waist circumference ≥80 cm; increased level of triglycerides ≥150 mg/dL (≥1.7 mM); decreased level of HDL-C <50 mg/dL (<1.3 mM); increased blood pressure with either systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or treatment with antihypertensive drugs; and impaired fasting serum glucose ≥100 mg/dL (6.1 mM).
Medical Research: What are the main findings?
Dr. Schmiegelow: The study population comprised 14,364 women without diabetes or prior cardiovascular disease. The women had a median age of 64 years (interquartile range 57–69), and 47% were white, 36% were black and 18% were Hispanic. Over a median follow-up of 13 years (interquartile range 12–14 years), 1,101 women (7.7%) had a first cardiovascular event.
The main findings of this study were that metabolic abnormalities appeared to confer more cardiovascular risk among black women than among white women. Consistent with other studies, among white women without the metabolic syndrome, obesity was not associated with increased cardiovascular risk compared with normal weight women. Conversely, black overweight and black obese women had increased cardiovascular risk compared with normal weight black women without the metabolic syndrome, even in absence of the metabolic syndrome.
According to number of metabolic syndrome components, black overweight or obese women with just two metabolic abnormalities had increased risk of cardiovascular disease, although they would be considered “metabolically healthy” based on the standard definition, particularly since one of these abnormalities were abdominal obesity for 79% of overweight and 98% of obese women, irrespective of race/ethnicity. White obese women with three metabolic abnormalities did not have a statistically significantly increased cardiovascular risk compared with normal weight metabolically healthy women. Thus, cardiovascular disease risk appeared to be elevated in black women by the presence of only two or three metabolic abnormalities to a degree that would require four or more metabolic abnormalities among white women. These findings did not appear to be driven by any particular combination of metabolic abnormalities.
21 May Male Sex, Age and Occupation Linked To Workplace Suicide
MedicalResearch.com Interview with:
Dr. Hope M. Tiesman MSPH, PhD
CDC, Atlanta
Medical Research: What is the background for this study? What are the main findings?
Dr. Tiesman: The authors regularly monitor non-occupational injury trends, including the recent and significant increase in suicide rates. This finding led the authors to consider how these non-occupational trends impacted the workplace. We used data for two large national surveillance systems. We obtained data on workplace suicides from the Bureau of Labor Statistics' Census of Fatal Occupational Injury (CFOI) which compiles data on all fatal work-related injuries in the US. We obtained data on non-workplace suicides from the CDC's Web-Based Injury Statistics Query and Reporting System or WISQARS. WISQARS data are compiled using national death certificate data. From here we calculated suicide rates and compared trends across workplace and non-workplace suicides as well as examined the socio-demographics and occupational characteristics of those who chose suicide in the workplace.
Several important findings to highlight. Across the 8-yr timeframe, we found that workplace suicide rates remained relatively stable, even somewhat decreasing that it is until 2007 when a large and significant jump in rates was found. This was in contrast with non-workplace suicide rates which increased over the entire study period. Men had signifıcantly higher workplace suicide rates compared to women and generally, as age increased, so did workplace suicide rates. Those aged between 65 and 74 years had the highest suicide rate of all workers which was also a bit different from non-workplace suicide rates. Finally, we found that those in protective service occupations, such as police and firefighters, had the highest workplace suicide rates, followed closely by those in farming/fishing/and forestry occupations. These occupations have been associated with higher overall suicide rates in prior studies. A somewhat novel finding was that those in automotive maintenance and repair occupations also had significantly higher workplace suicide rates.
21 May Analysis Of Large Medical Datasets Can Be Both Informative and Misleading
MedicalResearch.com Interview with:
David F. Penson, MD, MPH
Hamilton and Howd Chair in Urologic Oncology
Professor and Chair, Department of Urologic Surgery
Director, Center for Surgical Quality and Outcomes Research
Vanderbilt University Medical Center
Nashville, TN 37232-2765
Medical Research: What is the background for this editorial? What are the main findings?
Response: This editorial discusses the implication of the recent removal of the PSA data from the seer-medicare dataset. It reviews the significance of the action: specifically what it means for prior publications that used this information to address clinical research questions in prostate cancer. It makes the point that, while these datasets are powerful, researchers have stretched the limits of what they can do too far. Simply put, we cant always guarantee that the clinical data collected in administrative datasets will necessarily be accurate so we need to be more selective in how we use these data and not simply run analyses on the data just because it is easy.
21 May Disability At End Of Life Linked To Number Of Acute Hospitalizations
Posted at 11:21h
in Aging, Author Interviews, BMJ, Disability Research, End of Life Care, Geriatrics, Yale
MedicalResearch.com Interview with:
Thomas M. Gill, M.D
Humana Foundation Professor of Medicine (Geriatrics)
Professor of Epidemiology and of Investigative Medicine
Director Yale Program on Aging and Yale Center for Disability and Disabling Disorders
Director, Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related Research
Medical Research: What is the background for this study? What are the main findings?h
Response: Understanding the disabling process at the end of life is essential for informed decision-making among older persons, their families, and their physicians.
We know from prior research that the course of disability at the end of life does not follow a predictable pattern for most older persons. This raises the question about what is driving the development and progression of disability at the end of life.
We identified six distinct trajectories of disability in the last year of life, ranging from the least disabled to most disabled. We found that the course of disability in the last year of life closely tracked the monthly prevalence of hospitalization for each of the six trajectories.
21 May Grandfather’s Age At Paternity May Affect Man’s Fertility
Medicalresearch.com Interview with: Ross Anderson M.D.,M.C.R. Allina Health clinics and Jim Hotaling M.D.,M.S.,F.E.C.S.M. Utah Center for Reproductive Medicine Salt Lake City, UT 84108 MedicalResearch: What is the background for this study? What are the main findings? Dr. Anderson: There is a growing trend of delayed marriage and childbearing, particularly into the third and fourth decade of life. Advanced maternal age is well recognized as a risk factor for chromosomal abnormalities and perinatal complications, but there is also growing interest in the impact of advanced paternal age. Multiple studies have demonstrated that as men age their sperm quality and ability to have children decreases. We were interested in how the age of the parents and the age of the grandparents at the time of conception can affect a man’s sperm quality. We hypothesized that men with older parents and grandparents at the time of conception would have a linear decrease in the quality of their sperm. We used Utah’s two largest andrology lab’s semen analyses and these men were linked to the Utah Population Database. The Utah Population Database allows us access to birth certificate data and pedigree data going back to the late 1800s. With this we can determine the age of the parents and grandparents at the time they had each subsequent generation. We found that the age of the parents did not influence a man’s semen concentration, motility, or total sperm count. Interestingly, the age of the paternal grandfather was associated with an increased risk of poor semen concentration. For instance, if a grandfather was older than 45 year of age at the time of conception of the father, there is a 39% chance a man’s semen concentration would be considered low according to the World Health Organization (less than 15 million per milliliter).20 May Do Our Genes Influence Our Work Ethic and Leadership Ability?
MedicalResearch.com Interview with:
Wendong Li, Ph.D.
Assistant professor of psychological sciences
Department of Psychological Sciences
Kansas State University
Manhattan, KS
Medical Research: What is the background for this study? What are the main findings?
Dr. Wen-Dong Li: There has been a "nature versus nurture" debate in leadership: Are leaders born or made? In academia, research on trait theories of leadership has shown that important individual characteristics such as personality traits are predictive of whether one is a leader or not (leadership role occupancy or emergence). One author of this paper, Dr. Arvey conducted twin studies showing that about 30% of the individual differences in leadership is attributable to individual differences in their genetic makeup. But so far, little research has examined whether specific genes are involved and no research has examined the pathways linking genes to leadership.
This is where this research came in. We found that a dopamine transporter gene, DAT1 was involved in genetic influences on leadership role occupancy, but through two opposing pathways. One pathway is through proactive personality: DAT1 10-repeat allele was negatively related to proactive personality, which in turn was positively associated with leadership role occupancy. The negative indirect effect was significant. On the other hand, DAT1 was positively related to (moderate) rule breaking, which was positively associated with leadership role occupancy. The overall relationship between DAT1 and leadership was not significant. Thus we call it a mixed blessing because the two opposing mechanisms offset each other.
20 May PET Scan Can Detect Amyloid In Alzheimer’s and Other Dementias
MedicalResearch.com Interview with:
Rik Ossenkoppele PhD.
Postdoctoral researcher
UCSF Memory and Aging Center
MedicalResearch: What is the background for this study?
Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database.
MedicalResearch: What are the main findings?
Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of
1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype),
2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and
3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”).
The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials.
In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect
1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or
2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.
20 May Prevalence of US Adults With Metabolic Syndrome Stabilizing But Still High
MedicalResearch.com Interview with:
Robert Wong, M.D., M.S.
Attending Physician, Gastroenterology & Hepatology
Director, GI Research
Highland Hospital I A member of Alameda Health System
Oakland, CA 94602
Medical Research: What is the background for this study? What are the main findings?
Dr. Wong: The main findings are that despite the stabilizing prevalence of metabolic syndrome, a large proportion of U.S. adults affected with metabolic still raises concern, especially given the significant health consequences associated with this syndrome. In additional to cardiovascular disease, metabolic syndrome also increases the risk of concurrent nonalcoholic fatty liver disease, often considered the hepatic manifestation of metabolic syndrome. Many studies, including work that our group has completed suggests that nonalcoholic fatty liver disease will soon become the leading etiology of chronic liver disease in the U.S. Furthermore, our finding that metabolic syndrome increases with increasing age, reflects the increased risk for metabolic syndrome associated diseases such as hypertension, diabetes, and dyslipidemia with older age. This is important to recognize given the aging population of the U.S.
20 May Higher Suicide Rates Among Black Than White Children
MedicalResearch.com Interview with:
Jeff Bridge, Ph.D
Center for Innovation in Pediatric Practice
Principal Investigator
The Research Institute at Nationwide Children's Hospital
Medical Research: What is the background for this study?
Dr. Bridge: Suicide is a leading cause of death among children younger than 12 years. Suicide rates in this age group have remained steady overall for the past 20 years, but this is the first national study to observe higher suicide rates among black children compared to white children. Little is known about the epidemiology of suicide in this age group, as prior research has typically excluded children younger than 10 years old and investigated trends only within specific older age groups.
Medical Research: What are the main findings?
Dr. Bridge: We found that suicide ranked 14th as a cause of death among 5- to 11-year old black children in 1993-97 but rose to 9th in 2008-12. For white children, suicide ranked 12th in 1993-97 and 11th in 2008-12. Rates have remained stable in Hispanic and non-Hispanic children. The findings in this study highlight an emerging racial disparity in the epidemiology of childhood suicide.
19 May Transcatheter Heart Valves Linked To Less Blood Breakdown
MedicalResearch.com Interview with:
Josep Rodés-Cabau MD
Quebec Heart and Lung Institute,
Quebec City, QC, Canada
Medical Research: What is the background for this study? What are the main findings?
Dr. Rodés-Cabau: Hemolysis is the breakdown of red blood cells (RBC) in the body. There are many different causes of hemolysis, however a common cause is when RBCs traverse foreign substances, such as inserted heart valve prostheses. The biological interaction between the RBC and a foreign substance may cause RBC lysis/destruction. Furthermore, in the setting of turbulent blood flow, such as when a prosthetic heart valve is starting to leak, the degree of hemolysis could reflect the severity and duration of this leak. In the absence of valve leaks, hemolysis rates and severity may simply reflect how biocompatible a foreign/prosthetic valve is within the body. The lower the hemolysis rate and severity, the more biocompatible the valve/foreign body.
There are many different brands and generations of prosthetic heart valves that have been implanted in humans during the prior decades. The early-generation surgically implanted valves caused quite severe hemolysis requiring re-operation when possible. Modern-day surgical heart valves now have superior designs and rarely cause significant hemolysis. Nevertheless the rates of sub-clinical (or biochemical) hemolysis are around 30% for modern-day mechanical heart valves.
Nowadays, certain patients are eligible to undergo transcatheter aortic valve implantation (TAVI), a revolutionary means of valve replacement without the need for open heart surgery. However to-date, the biocompatibility of these new transcatheter heart valves has not been tested in humans in vivo. We systematically evaluated hemolysis rates and its associated factors in a large consecutive series of patients undergoing TAVI at the Quebec Heart & Lung Institute, Quebec, Canada.
We found that the rate of transcatheter heart valve hemolysis was 15%, lower than that reported for modern-day mechanical surgically implanted valves. No patient demonstrated severe hemolysis. The presence of a size mismatch between the patient and transcatheter valve (termed prosthesis patient mismatch) significantly associated with the likelihood of hemolysis. Indirect measurements of wall shear stress also associated with hemolysis rates.
19 May Lipid-Lowering Drugs Substantially Reduced Stroke Risk In Elderly Population
MedicalResearch.com Interview with:
Christophe Tzourio, MD, PhD
Professor of Epidemiology
University of Bordeaux
Medical Research: What is the background for this study? What are the main findings?
Dr. Tzourio: The efficacy of lipid-lowering drugs (LLD) - which include statins and fibrates - to reduce the risk of coronary events and stroke has already been demonstrated in randomized trials. However, these trials were performed on highly selected patients, usually of middle-age (50-70 yrs) and with a history of cardiovascular disease or a high vascular profile. There is therefore currently no indication on the benefit of these drugs in elderly individuals of the general population without a past-history of cardiovascular disease and guidelines do not recommend the use of lipid-lowering drugs in elderly individuals without clinical atherosclerotic disease.
As there are not randomized trials in non-selected individuals in this age category, observational population-based cohorts are therefore the only alternative to study the impact of lipid-lowering drugs on the risk of cardiovascular diseases in the elderly.
We analyzed data from the Three-City study, a community-based cohort in 7484 elderly individuals (mean age 74 years), followed-up during 9 years, without known history of vascular disease at baseline. We observed a one third decrease in the risk of stroke in lipid lowering drug users (hazard ratio 0.66, 0.49 to 0.90) compared with non-users. Reduction in stroke risk was similar for the statin and fibrate groups. No protective effect was seen on the risk of coronary heart disease.
19 May Circulating Tumor DNA May Be Able To Predict Breast Cancer Metastases
MedicalResearch.com Interview with:
Lao Saal, M.D. Ph.D.
Head, Translational Oncogenomics Unit
Assistant Professor
Department of Oncology and Pathology
Lund University Cancer Center
Lund, Sweden
Medical Research: What is the background for this study?
Dr. Saal: About a quarter of women diagnosed with primary (non-metastatic) breast cancer will unfortunately progress and later be found to have metastatic spread, which can occur many years to even a decade or more after the first diagnosis. At this point, the prognosis after identification of metastatic breast cancer is very poor. Metastatic disease is typically diagnosed only after it has grown large enough to cause symptoms, be noticed on exam, or be detectable by imaging. It is thought that early detection of metastasis has the potential to lead to better outcomes because therapies could be modified when the metastasis is still very small. Moreover, a very sensitive and specific test that could identify patients who appear "cancer-free" could also be useful. Essentially all cancers have unstable genomes, where chromosomes physically break and are reassembled incorrectly and thus the normal sequence is altered. Importantly, DNA material from cancer cells can be found in the blood circulation and therefore this circulating tumor DNA has the potential to be a cancer biomarker.
Medical Research: What are the main findings?
Dr. Saal: Eleonor Olsson, a PhD student in my lab who defends her thesis next week, and Christof Winter, a postdoc bioinformatician in my group, were the first authors of the paper. In our study we tested whether periodic monitoring of circulating tumor DNA (ctDNA) in blood plasma samples, taken before surgery for primary breast cancer and at multiple timepoints after surgery, could identify the metastastic spread, and whether the quantity of ctDNA was associated to patient outcome. We analyzed a retrospective cohort of 20 patients, who had enrolled many years ago in a separate epidemiological study run by Helena Jernström in our department, wherein the appropriate blood plasma samples had been biobanked and tumor tissue was available and we had long-term clinical follow-up information.
As far as we are aware, our study is the first to show the potential for serial ctDNA monitoring in the context of primary breast cancer. We found that our ctDNA blood tests could discriminate patients with eventual metastasis from those with long‐term disease‐free survival with 93% sensitivity and 100% specificity. Furthermore, ctDNA‐based detection of metastatic disease preceded clinical detection for 86% of patients by an average 11 months and in some cases by 3 years. In all of the patients who had long-term disease-free survival, we did not detect any ctDNA in any timepoints after surgery. Lastly, the measured quantity of ctDNA was a significant predictor of outcome: for each doubling of the ctDNA level, the odds ratio for metastasis was 2.1 and the odds ratio for death was 1.3. An interesting anecdote -- one patient we studied had bilateral breast cancer and we found that it was the right-side tumor (which actually had more favorable clinical characteristics) that gave rise to the metastasis and not the left-side tumor.
19 May Reminders Can Increase Adherence To Home Blood Pressure Monitoring
MedicalResearch.com Interview with:
Dr. Linnea A. Polgreen, Ph.D.
Assistant Professor, Health Services Research
Department of Pharmacy Practice and Science
Iowa City, IA
Medical Research: What is the background for this study? What are the main findings?
Dr. Polgreen: Many patients with hypertension are unaware that they have hypertension. Furthermore, a substantial number of patients diagnosed with hypertension are poorly controlled. Unfortunately there is no point-of-care test to diagnose hypertension. For most patients with multiple to moderate hypertension, multiple measurements are needed over time to confirm the diagnosis. This need to obtain multiple measurement often delays the diagnosis of hypertension, and delays potential for changes in therapy for those who are diagnosed but poorly controlled. Patients are routinely reminded to check their blood pressure measurements at home. However, these measurements often do not occur or are not collected in a timely fashion. Recently electronic medical records (EMRs) have built portals for patients to enter data such as blood pressure measurements, but it is unclear how effective these portals will be for diagnosing and treating high blood pressure.We studied 121 patients with at least one high blood pressure measurement in the past year and randomized them to three groups.
- The first group received text messages to which they were told to reply with their blood pressure measurements.
- The second group was sent text messages reminding them to enter their blood pressures measurements in the hospital’s EMR portal.
- The third group was instructed to enter their blood pressure measurements in the EMR portal, but they were not given reminders. Automated messages were sent to each patient in the bi-directional text messaging and EMR+reminder groups twice daily for up to 15 days. For the EMR only group, only 47.8% of patients successfully recorded a total of 14 blood pressure measurements within 15 days. For the EMR + reminder group, this percentage was 81.2%, and for the bi-directional text messaging group, it was 97.7%.
19 May A Neuronal Protein Keeps Alcohol Binge Drinking In Check
MedicalResearch.com Interview with:
Interview of Candice Contet, Ph.D.
Assistant Professor
The Scripps Research Institute, La Jolla, CA
MedicalResearch: What is the background for this study?
Dr. Contet: Alcohol changes the activity of numerous proteins in the brain. One of them is an ion channel found in neurons, the G-protein activated inwardly rectifying potassium (GIRK) channel. It is however unknown whether the ability of alcohol to open GIRK channels matters for its effects in vivo, i.e. how tipsy we feel or how motivated we are to drink alcohol. To address this question, we studied mice that are lacking one of the components of GIRK channels, the GIRK3 subunit. These mice behave normally in the absence of alcohol, and we sought to determine whether they respond differently to alcohol.
MedicalResearch: What are the main findings?
Dr. Contet: We found that the absence of GIRK3 did not impact how fast the mice clear alcohol from their body nor how sensitive they are to alcohol intoxication. Alcohol reduced their motor coordination, made them sleepy and lowered their body temperature to the same extent as in normal mice. GIRK3-deficient mice also drank as much alcohol as normal mice when they were given continuous access to alcohol, a situation in which mice sporadically drink throughout the day but rarely get intoxicated. By contrast, when mice are given access to alcohol only for a couple hours per day at a specific time of the day, they drink to the point of intoxication. Under these conditions, which emulate “binge drinking”, the GIRK3-deficient mice drank more than normal mice.
The next step was to locate the region of the brain responsible for the effect of GIRK3 on binge drinking. We turned our attention to the mesocorticolimbic dopaminergic pathway, a neural circuit that facilitates reward seeking. This pathway originates in an area of the midbrain called the ventral tegmental area (VTA) and releases the neurotransmitter dopamine in two forebrain areas: the ventral striatum and the prefrontal cortex. Alcohol, like other drugs of abuse, activates this pathway. When we reintroduced GIRK3 in the VTA of GIRK3-deficient mice, their alcohol intake dropped down to normal levels. Increasing the levels of GIRK3 in the VTA of normal mice reduced their alcohol consumption even further. We concluded that GIRK3 in the VTA keeps binge drinking in check: the more GIRK3, the less binge drinking.
We then wanted to understand how GIRK3 controls binge drinking: do the GIRK3-deficient mice drink more because alcohol is more rewarding to them, or because more alcohol is needed for them to experience the same level of reward? To answer this question, we measured the activity of VTA neurons in brain slices. Alcohol usually make VTA neurons fire more – but in the absence of GIRK3, these neurons were completely insensitive to alcohol, even at a very high concentration. We also measured the levels of dopamine in the ventral striatum. Injecting mice with a moderate dose of alcohol usually causes a rise in dopamine levels – but again, GIRK3-deficient mice were completely unresponsive.
These results may seem paradoxical. If the canonical “reward pathway” of the brain cannot be activated by alcohol, these mice should not have any motivation to drink alcohol. But the mesocorticolimbic dopaminergic pathway is not the only brain circuit responsible for the rewarding properties of alcohol, and we think that GIRK3-deficient mice end up drinking more alcohol to activate alternative circuits more strongly than normal mice would.
18 May NFL Players: Concussions With Loss Of Consciousness Linked To Later Memory Problems and Brain Changes
MedicalResearch.com Interview with:
C. Munro Cullum, PhD, ABPP
Professor of Psychiatry and Neurology & Neurotherapeutics
Pamela Blumenthal Distinguished Professor of Clinical Psychology
Chief of Psychology , Director of Neuropsychology
Univ. of Texas Southwestern Medical Center Dallas, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Cullum: My colleague and principal investigator of the study, Dr. John Hart and I have been interested in the acute and longer-term effects of traumatic brain injury for years, and because of my roles in the Alzheimer’s Disease Center and the Texas Institute for Brain Injury and Repair at the University of Texas Southwestern Medical Center, it seemed like a natural to begin studying older individuals with and without cognitive disorder who have a history of traumatic brain injury. Our main findings are two-fold:
First, we demonstrated that a history of concussion with loss of consciousness (which make up only about 10% of all concussions) was associated with smaller memory centers in the brain (the hippocampus) and lower memory results in our sample of retired professional football players. Concussions that did not result in loss of consciousness did not show that same strong association.
Second, our data suggest that patients with a clinical diagnosis of mild cognitive impairment (ie a memory disorder that does not grossly impair overall functioning but may lead to dementia) who also have a history of concussion with loss of consciousness show worse memory results and more brain atrophy than similar individuals diagnosed with mild cognitive impairment in the absence of a history of concussion.
18 May Diabetes Medication May Improve Cardiac Profile Of HIV Patients on Antiretroviral Therapy
MedicalResearch.com Interview with:
Kevin Yarasheski, PhD
Assistant Director, Biomedical Mass Spectrometry Research Facility
Professor of Medicine, Cell Biology & Physiology, Physical Therapy
Washington University School of Medicine
Medical Research: What is the background for this study?
Dr. Yarasheski: People living with HIV and taking combination antiretroviral therapy (cART) have successfully reduced the amount of HIV virus in their blood and have partially reconstituted their immune system (CD4+ T-cell count >250 cells/µL). Despite this, many still experience residual immune cell activation and inflammation that is believed to increase HIV morbidity (non-AIDS conditions e.g., CVD, T2DM, obesity, liver fat, bone loss, dementia) and mortality. Scientists are seeking safe and effective interventions for residual immune cell activation and inflammation, that have the potential to reduce non-AIDS complications that threaten quality and quantity of life among HIV infected adults.
We have been testing the safety and efficacy of sitagliptin in people living with HIV; a dipeptidyl peptidase 4 inhibitor that is FDA approved for treating T2DM, and appears to have favorable anti-inflammatory and immune modulatory properties that might specifically benefit people living with HIV and experiencing cardiometabolic complications associated with residual immune cell activation and inflammation.
Medical Research: What are the main findings?
Dr. Yarasheski: In a randomized, double-blinded, placebo controlled 8-wk trial, we found that sitagliptin had beneficial anti-inflammatory, immune regulatory, hematopoietic progenitor cell mobilizing, and glucose lowering effects in cART-treated virally suppressed HIV adults with impaired glucose tolerance. Sitagliptin improved glucose tolerance (a risk factor for CVD), reduced circulating and adipose-specific inflammatory markers (risk factors for obesity, T2DM, liver fat accumulation, and CVD), and increased the number of blood stem cells that can repair damage and inflammation in the vascular walls.