Author Interviews, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, MarylandMedicalResearch.com Interview with: Emmanuel S. Antonarakis, M.B.B.CH Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies. (more…)
ASCO, Author Interviews, Biomarkers, Cancer Research / 06.06.2015

MedicalResearch.com Interview with: Dr. Kirsten Timms, PhD Program Director VP Biomarker Discovery at Myriad Genetics Inc Medical Research: What is the background for this study? What are the main findings? Dr. Timms: The Homologous Recombination Deficiency (HRD) score is a tumor biomarker which quantitates genomic rearrangements associated with defects in DNA damage repair. It has been shown in multiple studies that HRD score can identify tumors sensitive to DNA damaging agents such as platinum salts or PARP inhibitors. Many tumors are spatially heterogeneous: different parts of a tumor show variation at both the genomic level, and in their appearance. This tumor heterogeneity has the potential to negatively impact the accuracy of biomarker tests. This study assessed the consistency of the HRD score in multiple biopsies obtained from the same cancer to understand the impact of tumor heterogeneity on the HRD score. The main finding of this study is that the HRD score is highly conserved between different biopsies of the same tumor. (more…)
Author Interviews, JAMA, Obstructive Sleep Apnea / 06.06.2015

Marie Marklund, DDS senior lecturer Department of Odontology, Faculty of Medicine Umeå University SwedenMedicalResearch.com Interview with: Marie Marklund, DDS senior lecturer Department of Odontology, Faculty of Medicine Umeå University Sweden MedicalResearch: What is the background for this study? What are the main findings? Response: Snoring and obstructive sleep apnea are common in the population and these disorders continuously increase because of the ongoing obesity epidemic in many countries. Today, 34% of men and 17% of women in the US suffer from obstructive sleep apnea of all severities. Symptoms include daytime sleepiness, poor sleep quality, headache, insomnia and restless legs. In the longer term, a more severe sleep apnea is associated with serious consequences, such as hypertension, stroke, cancer, traffic accidents and early death. Continuous positive airway pressure is a highly effective treatment for sleep apnea patients. Adherence problems, for instance from nasal stuffiness and claustrophobia reduces its effectiveness. An oral appliance holds the lower jaw forwards during sleep in order to reduce snoring and sleep apneas. This therapy has primarily been suggested for snorers and patients with mild and moderate sleep apnea. No previous placebo-controlled study has, however, evaluated this specific group of patients. Results from more severe sleep apnea patients have shown a good effect on sleep apneas. The effect of oral appliances on daytime symptoms is unclear. Symptomatic improvement is an important outcome for milder sleep apnea patients. The primary aims of the present study were to study the effects on daytime sleepiness and quality of life of a custom-made, adjustable oral appliance in patients with daytime sleepiness and snoring or mild to moderate sleep apnea, i.e. the primary target group for this type of therapy. Secondary aims included the effects on sleep apnea, snoring and various other symptoms of sleep disordered breathing such as headaches and restless legs. We found that oral appliance therapy was effective in reducing sleep apneas, snoring and symptoms of restless legs. The apnea-hypopnea index was normal (<5) in 49% of patients using the active appliance and in 11% using placebo, with a numbers needed to treat of three. Daytime sleepiness and quality of life did not differ during active treatment and the placebo intervention. The patients experienced reduced headaches with active treatment, but the results did not differ from placebo. It was concluded, that a custom-made, adjustable oral appliance reduces obstructive sleep apneas, snoring and possibly restless legs. The efficacy on daytime sleepiness and quality of life was weak and did not differ from placebo in this group of patients. (more…)
Author Interviews, BMJ, Heart Disease / 06.06.2015

MedicalResearch.com Interview with: Prachi Bhatnagar, MPH, DPhil Researcher University of Oxford British Heart Foundation Centre on Population Approaches for Non-Communicable Disease Prevention Nuffield Department of Population Health Oxford Medical Research: What is the background for this study? What are the main findings? Response: We know that cardiovascular disease presents a large burden to the UK. We aimed to bring together all the main data on cardiovascular disease mortality, morbidity, treatment and economic costs. We found that there are regional inequalities in cardiovascular disease mortality and prevalence in the UK. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, University of Michigan / 06.06.2015

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of MichiganMedicalResearch.com Interview with: Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Michigan Medical Research: What is the background for this study? Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes. Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma. Medical Research: What are the main findings? Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes. In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases. (more…)
AHA Journals, Author Interviews, Compliance, Duke, Heart Disease / 06.06.2015

Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NCMedicalResearch.com Interview with: Robin Mathews, MD Duke Clinical Research Institute Duke University Medical Center Durham, NC Medical Research: What is the background for this study? What are the main findings? Dr. Mathews: Though treatment for patients with an acute myocardial infarction with evidence based therapies has increased significantly over the years, adherence to these therapies after discharge remain sub optimal. We used a validated instrument, the Morisky scale, to assess patient medication adherence.  We found that in a contemporary population of 7,425 patients across 216 hospitals, about 30% of patients were not adherent to prescribed cardiovascular medications as early as 6 weeks after discharge. Patients with low adherence were more likely to report financial hardship as well as have signs of depression. In addition, we found that patients who had follow up arranged prior to discharge and those that received explanations from the provider on the specific medications, were more often adherent to therapies. There was a non significant increase in risk of death or readmission at 2 months (HR [95% CI]: 1.35 [0.98-1.87]) among low adherence patients. (more…)
Author Interviews, Outcomes & Safety, Surgical Research / 06.06.2015

Dr. Janet Martin PharmD, PhD Director, Medical Evidence, Decision Integrity & Clinical Impact (MEDICI) Assistant Professor, Department of Anesthesia & Perioperative Medicine and Department of Epidemiology & Biostatistics Schulich School of Medicine & Dentistry, Western University London, ON Canada MedicalResearch.com Interview with: Dr. Janet Martin PharmD, PhD Director, Medical Evidence, Decision Integrity & Clinical Impact (MEDICI) Assistant Professor, Department of Anesthesia & Perioperative Medicine and Department of Epidemiology & Biostatistics Schulich School of Medicine & Dentistry, Western University London, ON Canada Medical Research: What is the background for this study? What are the main findings? Response: There remains some scepticism regarding the effectiveness of the safe surgery checklist (SSCL) to tangibly improve patient safety in the real world setting, especially with respect to relative benefits in high-income versus lower-income settings. In general, push-back has been related to surgical teams doubting the power of a simple checklist to make significant impact for surgical settings. Despite their deceptive simplicity, checklists can be powerful tools to deal with the sheer volume of information that must be addressed in sequence in order to support safe surgery. The objective of our study was to determine, through meta-analysis, whether clinically-relevant outcomes after implementation of the WHO Safe Surgery Checklist (SSCL) in the clinical trial setting and in the real world setting are improved, and whether greater benefit occurs in low-middle income countries (LMICs) than in high income countries (HICs). A total of 13 studies (262,970 patients) met the inclusion criteria, including 12 cohort studies and 1 randomized trial. For SSCL versus control, the odds of death was significantly reduced by 21% (OR 0.79, 95%CI 0.67-0.93; p=0.003). The odds of surgical site infection was reduced by 28% (OR 0.72, 95%CI 0.62-0.84; p=0.001). Similarly, overall postoperative complications were significantly reduced by 30% (OR 0.70, 95%CI 0.59-0.82; p=0.009). While HIC and LMICs both experienced reductions in death, surgical site infections, and overall complications, the magnitude of reduction was generally greater for LMICs than in HICs. Sub-analysis by study design demonstrated generalizability between the clinical trial setting and the real world setting. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA, Johns Hopkins / 05.06.2015

MedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John HopkinsMedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John Hopkins Medical Research: What is the background for this study? Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status  recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies. We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies. Medical Research: What are the main findings? Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort. (more…)
Author Interviews, HIV, Sexual Health, UCSD / 05.06.2015

MedicalResearch.com Interview with: Dr. Martin Hoenigl Center for AIDS Research University of California, San Diego Medical Research: What is the background for this study? What are the main findings? Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP). By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu. (more…)
Author Interviews, Weight Research / 05.06.2015

MedicalResearch.com Interview with: Aidan Gribbon M.Sc., CSEP-CEP From the Healthy Active Living and Obesity Research Group Children’s Hospital of Eastern Ontario Research Institute Ottawa, Ontario, Canada Medical Research: What is the background for this study? Response: The background for the study is that sedentary pursuits, such as video games, are omni-present in the daily lives of adolescents. Manufacturers of active video games (AVG) have been marketing them as a ‘healthy’ alternative to seated video games, with the possibility of preventing/treating obesity in this age group. Although, active video games have been shown to acutely increase energy expenditure over their seated counterparts, no study has examined their compensatory adjustments in energy expenditure or energy intake. Medical Research: What are the main findings? Response: The main finding of this paper was that although active video games are not associated with an increased food intake, they are compensated for by a decrease in physical activity such that their benefit of a reduction in the energy gap underlying weight gain is offset within 24 hours. (more…)
Author Interviews, Weight Research / 05.06.2015

Nia S. Mitchell, MD, MPH Assistant Professor Division of General Internal Medicine Department of Medicine University of Colorado Anschutz Medical CampusMedicalResearch.com Interview with: Nia S. Mitchell, MD, MPH Assistant Professor Division of General Internal Medicine Department of Medicine University of Colorado Anschutz Medical Campus Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: Despite decades of obesity research two issues remain elusive in weight management: significant, long-term weight loss and weight loss maintenance and widely accessible programs. There are numerous weight loss programs out there, but there is little evidence of the long-term effectiveness of many programs. Furthermore, these programs may not be accessible to the general population because they are too expensive and may not be geographically available. I chose to evaluate the Take Off Pounds Sensibly (TOPS) program because I thought it had the potential to address these issues. TOPS is a nationally-available, nonprofit, low-cost, peer-led weight loss program. It costs only $92 per year--$32 is the annual fee plus local chapter dues that average about $5 per month--and any four people can start a TOPS chapter, so it can be implemented and disseminated widely. The main objective of this study was to determine the weight change for individuals who consecutively renewed their membership in TOPS. We looked at people who joined TOPS from 2005 to 2011, so they could have been followed for up to seven years. We found that people who join TOPS and consecutively renew their annual membership can lose a clinically significant amount of weight and maintain the weight loss for up to seven years. Clinically significant weight loss is defined as weight loss of at least 5% of initial weight, because with a 5% weight loss people with weight-related medical conditions, such as diabetes, can see an improvement in their conditions. Therefore, a diabetic who weighs 200 pounds may see an improvement in her blood sugar control if she loses 10 pounds. In our study, fifty percent of individuals had clinically significant weight loss in their first year in the program, and 62% of those renewed their annual membership consecutively for seven years had clinically significant weight loss at seven years. This was exciting because many people who lose weight tend to gain it back. I often say that the unfortunate natural history of weight loss tends to be weight re-gain. However, the majority of these individuals maintained a clinically significant weight loss. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Nutrition / 05.06.2015

MedicalResearch.com Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. Atlanta, Georgia Dr. Wang: Several epidemiologic studies and a recent large pooled analysis suggest that higher blood levels of carotenoids, a group of lipid-soluble pigments that are rich in colorful fruits and vegetables, are associated with lower breast cancer risk. What remains unclear is whether or not the effect of carotenoids on breast cancer differ by estrogen receptor status, tumor stage, BMI, and smoking status. We examined plasma carotenoids and breast cancer risk overall, and by aforementioned tumor and participant characteristics in a cohort of 992 postmenopausal women. We found that higher pre-diagnosis plasma α-carotene, but not other subtypes or total carotenoids, was significantly associated with lower invasive breast cancer risk. The inverse association of α-carotene with breast cancer risk seems stronger for estrogen receptor positive tumors than for estrogen receptor negative tumors. There is a suggestive inverse association of total plasma carotenoid levels and breast cancer among ever smokers but not among never smokers. (more…)
Author Interviews, Infections, Pulmonary Disease / 05.06.2015

Dr. Nelson Lee MBBS(HK),MD(CUHK),FRCP(Lond),FRCP(Edin),FHKCP,FHKAM(Med) Daniel Yu Professor of Infectious Diseases Head, Division of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong. Hon. Consultant, Prince of Wales Hospital, Hong KongMedicalResearch.com Interview with: Dr. Nelson Lee BBS(HK),MD(CUHK),FRCP(Lond),FRCP(Edin),FHKCP,FHKAM(Med) Daniel Yu Professor of Infectious Diseases Head, Division of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong. Hon. Consultant, Prince of Wales Hospital, Hong Kong Medical Research: What is the background for this study? What are the main findings? Dr. Lee: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of severe respiratory-tract infections in older adults, resulting in excessive hospitalizations and deaths annually. At present, no established antiviral treatment is available. The slow progress in therapeutics development is limited by the poor understanding of the clinical manifestations, severity, virologic changes, and pathophysiology in adult RSV diseases. To address the knowledge gap, we conducted a prospective study to look at the lower-respiratory complications, progression to respiratory failure, and their relationships to genomic viral loads in adults hospitalized for confirmed RSV infections. We found that among 123 RSV patients, nearly 90% had lower respiratory tract complications (acute bronchitis/bronchiolitis, radiographic pneumonia, exacerbation of underlying airway diseases, or their combinations), 53% developed respiratory insufficiency requiring bronchodilators and supplemental oxygen, 16% required assisted ventilation, and 12% were admitted to ICU or died. High viral RNA concentration was detected in their respiratory samples, including in patients who had onset longer than 2 days (>7 log10copies/mL). Viral load was associated with disease severity and development of respiratory insufficiency (about 40% increase in risk per log RNA increase). (more…)
Author Interviews, Fertility, Genetic Research, NEJM, University of Pittsburgh / 04.06.2015

Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213MedicalResearch.com Interview with: Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213 Medical Research: What is the background for this study? What are the main findings? Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem. We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies. (more…)
Author Interviews, CDC, HIV / 04.06.2015

MedicalResearch.com Interview with: Sandra Schwarcz, MD Senior HIV epidemiologist San Francisco Department of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Schwarcz: AIDS opportunistic illnesses continue to occur despite effective antiretroviral therapy. Although previous studies examined survival following a diagnosis of an opportunistic illness, there are few recent reports that are population-based. The San Francisco Department of Public Health has the only population-level data on the occurrence of and survival following opportunistic illnesses and use of antiretroviral therapy among persons reported with HIV in the United States. By measuring survival following the occurrence of opportunistic illnesses, we were able to document that survival following opportunistic illnesses has improved with better HIV treatment. However, opportunistic illnesses continue to occur and carry substantial mortality risk. Even in this era of effective HIV therapy, we found that 35% of persons who developed an opportunistic illness died within five years of their diagnosis and some opportunistic illnesses such as brain lymphoma and  progressive multifocal leukoencephalopathy remain highly lethal. (more…)
Annals Internal Medicine, Author Interviews, Beth Israel Deaconess, Hospital Readmissions / 04.06.2015

MedicalResearch.com Interview with: Kelly L. Graham, MD, MPH Instructor in Medicine Harvard Medical School Division of General Medicine and Primary Care Beth Israel Deaconess Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Graham: 30-day readmissions have become a standard quality metric used to represent inpatient quality of care and unnecessary healthcare utilization.  Effective 10/1/2009, hospitals with excess 30-day readmissions have been faced with financial penalties.  Experts have questioned the validity of this metric, and have raised concerns about the potential unintended consequence of creating health disparities, as critical access hospitals caring for the most socioeconomically burdened patients have faced the highest penalties. We were interested to see if factors associated with readmissions in the early part of the 30 day window (0-7 days post-discharge) differed from those associated with the later window (8-30 days post-discharge), ultimately attempting to better understand the "pathophysiology" of a readmission. Our findings suggest that early readmissions are associated with many factors, including those related to the index admission (acute illness burden and suboptimal discharge timing), and factors that are not related to the index hospitalization, such as chronic illness burden and social determinants of health.  In contrast, late readmissions were only associated with chronic illness burden and social determinants of health. (more…)
Author Interviews, Diabetes, mBio, Microbiome / 04.06.2015

Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242MedicalResearch.com Interview with: Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242 Medical Research: What is the background for this study? Dr. Schlievert:
  1. As people become obese and enter pre-diabetes type II, there is a gut microbiome shift in bacteria from Bacteroidetes to Firmicutes. A dominant pathogenic Firmicute in humans is Staphylococcus aureus.
  2. As people become obese, their skin becomes wetter due to enhanced sweating upon exertion and the presence of more skin folds. These, plus mucous membranes have enhanced Staphylococcus aureus numbers, such that 100% of people become colonized and numbers of the bacterium rise to 1013 per person. This number of bacteria is like a cubic inch of margarine spread across the skin and mucous membranes.
  3. All pathogenic Staphylococcus aureus bacteria make and secrete a family of toxins called superantigens, including toxic shock syndrome toxin and staphylococcal enterotoxins. In high amounts (0.1 μg/human), these toxins can be lethal, causing toxic shock syndrome. At lower concentrations, the same superantigen toxins cause total body inflammation without lethality.
  4. In order to show that a microbes causes human disease, it is necessary to fulfill Koch’s postulates:
    1. Must associate human symptoms with a particular disease,
    2. Must isolate a potentially causative bacterium that is always present when the disease is present.
    3. Must produce the disease in an experimental animal.
    4. Must re-isolate the microbe from the experimental animal and re-cause the disease in another animal.
Medical Research: What are the main findings? Dr. Schlievert: We have fulfilled Koch’s postulates, showing that Staphylococcus aureus and its superantigen toxins cause type II diabetes. (more…)
Author Interviews, Nutrition, Weight Research / 04.06.2015

Catarina Rendeiro Ph.D. Post-doctoral Research Associate Rhodes lab University of Illinois Urbana, IllinoisMedicalResearch.com Interview with: Catarina Rendeiro Ph.D. Post-doctoral Research Associate Rhodes lab University of Illinois Urbana, Illinois Medical Research: What is the background for this study? What are the main findings? Dr. Rendeiro: The motivation for this study emerges in the context of understanding the link between sugar intake, particularly fructose, and the rising obesity epidemic that we are currently facing. Overeating and lack of physical activity certainly play major roles in obesity, but the sources of calories are also important. Fructose, a simple monosaccharide found in fruit and vegetables, and composing half of sucrose (i.e., table sugar), has been on the increase in Western diets. In our rodent study, 18% of dietary calories were derived from sugar, either fructose or glucose. This level is similar to typical American diets. However, the fructose diet resulted in increased weight gain and fat deposition and reduced physical activity even though food intake was similar between the two groups. It is also important to note that our animals were consuming their regular amount of calories, not overeating. Only the source of sugar was different between experimental groups, and still calorie-for-calorie, fructose caused greater weight gain and less physical activity than glucose. (more…)
Author Interviews, Hepatitis - Liver Disease, NIH / 03.06.2015

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology University of Maryland, Baltimore Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels were clinically useful as on-therapy markers of treatment outcome. However, the standard-of-care for HCV treatment has recently evolved from interferon-based regimens to short-duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-making. We found that Hepatitis C viral loads on treatment and at end of treatment were not predictive of treatment success versus relapse with DAA therapy. Contrary to our experience with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment did not preclude treatment success. (more…)
Author Interviews, BMJ, Depression, Pediatrics / 03.06.2015

Dr. Lucy Bowes Ph.D Leverhulme Early Career Research Fellow Fellow of Magdalen College Department of Experimental Psychology University of Oxford OxfordMedicalResearch.com Interview with: Dr. Lucy Bowes Ph.D Leverhulme Early Career Research Fellow Fellow of Magdalen College Department of Experimental Psychology University of Oxford Oxford Medical Research: What is the background for this study? What are the main findings? Response: Major depression is a severe mental illness, and a leading contributor to the global burden of disease. Rates of depression begin to rise in the teenage years, though the reasons for this remain unclear. Peers become particularly important during this time, and victimisation by peers or “bullying” has been proposed as one potentially modifiable risk factor for depression. There are robust findings that peer victimisation in childhood is associated with short-term internalizing symptoms, however it remains unclear whether victimization in the teenage years is associated with major depression. Only a relatively small number of longitudinal studies have prospectively investigated victimisation in relation to depression meeting diagnostic criteria in late adolescence or adulthood. Limitations of these studies include poor measures of bullying, lack of adjustment for key confounders such as baseline emotional and behavioral difficulties and child maltreatment. Our prospective cohort observational study, published in The BMJ, used detailed self-report data on peer victimisation at 13 years from 6,719 participants of the ALSPAC or ‘Children of the 90s’ study. The outcome was depression at 18 years, measured using a self-administered computerised version of the Clinical Interview Schedule Revised, CIS-R (data available for 3,898 participants). We adjusted for a range of confounders including baseline emotional and behavioral problems, family background and other risk factors. Of the 683 children who reported frequent victimisation at 13 years, 101 (14.8%) were depressed at 18 years. Of the 1,446 children reporting some victimisation, 103 (7.1%) were depressed, and of the 1,769 children reporting no victimisation at 13 years, 98 (5.5%) were depressed. Children who were frequently victimized had over a two-fold increase in odds of depression compared with children who were not victimized by peers. This association was slightly reduced when adjusting for key confounders. The population attributable fraction suggested that 29% of depression at 18 could be explained by peer victimisation if this were a causal relationship. (more…)
ASCO, Author Interviews, Chemotherapy / 03.06.2015

Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, BelgiumMedicalResearch.com Interview with: Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, Belgium MedicalResearch: What are the key points of the study? Professor Schöffski: This is the first and only randomised controlled trial of a single agent systemic therapy to demonstrate an improvement in overall survival in people previously treated for advanced soft tissue sarcomas. The study met its primary objective for overall survival benefit (OS) for investigational use in patients treated with eribulin compared to dacarbazine. Median OS for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit, meaning that patients treated with eribulin may have a 23% reduction in the risk of death. Furthermore, an additional study endpoint included progression-free survival (PFS) at 12 weeks.  While there was a numerical difference between arms favouring eribulin versus dacarbazine (33% vs 29%) this was not statistically significant. Median PFS was 2.6 months in both arms. (more…)
Author Interviews, Cancer Research, JAMA, NYU, Surgical Research / 03.06.2015

Wiliam C. Huang, MD FACSAssociate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer InstituteMedicalResearch.com Interview with: Wiliam C. Huang, MD FACS Associate Professor of Urology Division of Urologic Oncology NYU Langone Medical Center/Perlmutter Cancer Center Medical Research: What is the background for this study? What are the main findings? Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved.  Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option. We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium.  We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians. (more…)
Author Interviews, Heart Disease, NIH, Radiology / 03.06.2015

David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator, NLBI, NIDDKMedicalResearch.com Interview with: David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator,  NLBI, NIDDK Medical Research: What is the background for this study? What are the main findings? Dr. Bluemke: Most knowledge about the extent of coronary disease is from high risk patients who have coronary angiograms. Yet most individuals are symptomatic and have lower cardiovascular risk, and would not undergo a coronary angiogram. Coronary CT angiography can be used to evaluate the extent of plaque in low or moderate risk individuals. The most concerning type of plaque is "soft plaque", which can increase or rupture over time. Using coronary CT, all coronary plaque throughout the entire heart was measured. Importantly, the amount of soft plaque was uniquely associated with risk factors such as LDL, diabetes, and hypertension. (more…)
Author Interviews, Exercise - Fitness, Parkinson's / 03.06.2015

Dr. Lori P. Altmann Department of Speech, Language, and Hearing Sciences Center for Movement Disorders and Neurorestoration University of Florida, Gainesville, FloridaMedicalResearch.com Interview with: Dr. Lori P. Altmann Department of Speech, Language, and Hearing Sciences Center for Movement Disorders and Neurorestoration University of Florida, Gainesville, Florida Medical Research: What is the background for this study? What are the main findings? Dr. Altmann: There are a multitude of studies from our labs and others examining the effects of doing a variety of different cognitive tasks while walking or while maintaining postural control, and the results across studies are consistent—motor performance usually declines.  These “dual task effects” are exaggerated in healthy older adults, and are even more pronounced in people with Parkinson disease (PD).  Our study investigated dual task effects during cycling in healthy older adults and people with Parkinson disease.  In contrast to most studies of this type which typically contrast dual task effects of two cognitive tasks, we used an array of 12 cognitive tasks of graded difficulty, from very very easy to extremely difficult.  One of our primary goals was to establish that the dual task effects were directly related to the difficulty of the cognitive task. Our primary findings were that, instead of cycling slower when doing various cognitive task, both groups of participants sped up, and the amount they sped up was directly related to the difficulty of cognitive tasks.  In the easiest task, cycling speed increased by an average of about 25%, With some participants actually doubling their single task speed. There was no evidence that this increase in cycling speed came as a result of prioritizing cycling over the cognitive tasks, as scores on the cognitive tasks either remained the same or got slightly better.  Interestingly, people with Parkinson disease still showed faster cycling during the easiest tasks, but did not benefit as much from the dual task as the healthy adults. We attribute our findings to arousal that is triggered by both the cycling and the cognitive tasks which increases attentional resources that can be used for both motor and cognitive processing.  We believe the findings haven’t been documented before because most studies use gait or balance as the motor tasks, and these are much more difficult tasks that demand more attentional resources, leading to the typical findings of dual task costs instead of dual task benefits. The decrease in dual task benefits experienced by people with Parkinson disease, we believe, is due to the effects of Parkinson disease on neurotransmitters.  Both cognitive and physiological arousal increase the production of dopamine and norepinephrine in the brain, and disease processes in Parkinson disease interfere with production of these neurotransmitters, thus limiting arousal-based increases in attentional resources. (more…)
Author Interviews, JAMA, Kaiser Permanente, Pain Research / 03.06.2015

Harley Goldberg, DO Physical Medicine and Rehabilitation Kaiser PermanenteMedicalResearch.com Interview with: Harley Goldberg, DO Physical Medicine and Rehabilitation Kaiser Permanente Medical Research: What is the background for this study? What are the main findings? Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with a herniated lumbar disk. Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common source of pain and disability for many adults. It is thought that inflammation from a disk herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory, such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has shown that lumbar diskectomy does not affect the one year outcome for most patients, and epidural steroid injections do not have strong support by clinical trials. If the use of epidural steroids injections is based on application of steroid anti-inflammatory to the affected nerve root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many physicians and have been included in some clinical guidelines, no large-scale clinical trials of oral steroids for sciatica have been conducted before. Our study found that among patients with acute radiculopathy associated with a herniated lumbar disk, a short course of oral steroids resulted in only modest improvement in function and no significant improvement in pain. (more…)
ASCO, Author Interviews, Cancer Research, Chemotherapy, Genetic Research / 03.06.2015

MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.MedicalResearch.com spoke with Dr. Johnathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training. MedicalResearch.com: Can you tell us a little more about your background? How did you come to work at Myriad? Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the University of Wales, and then came to Duke for a research fellowship and residency training in Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon. At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and genetic underpinnings of ovarian cancer development and progression. Our translation research attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to chemotherapeutic agents. I also have experience in the management and financial issues facing medicine and health care. While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-chief and director of the Center for Women's Oncology. The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical care, research and management, to contribute to a broader mission of cancer treatment and prevention. MedicalResearch.com: What studies are being presented at ASCO this year by Myriad associated researchers? Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a testament to the emphasis Myriad places on basic and translational research (Myriad reinvests $300-400 of the proceeds from every clinical test performed into research). The studies center around two main themes: 1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers. 2: The use of Homologous Recombination Deficiency (HRD) testing and score, called MyChoice, which helps clinicians determine which patients may respond best to some chemotherapeutic agents. MedicalResearch.com: What does the MyRisk panel offer over and above the information learned from BRAC1/2 testing? Why should a patient or clinician want this testing performed? Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of determining who may be at increased risk for certain malignancies even if they are BRAC1/2 negative. The typical patient is one who has a family history of cancer but may have been told she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know that up to 50% of these patients may carry other genes that make them more susceptible to cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who would have been missed with more traditional BRAC1/2 testing alone. (more…)