MedicalResearch.com: Interview Invitation S. Akoudad, MD Msc PhD candidate
Dep. Epidemiology, Radiology, Neurology
Erasmus MC, Rotterdam , the Netherlands
Medical Research: What are the main findings of the study?Dr. Vernooij: We found that compared to never users, coumarin users had a higher prevalence of deep or infratentorial microbleeds and probably also a higher incidence of any microbleeds. A higher maximum international normalized ratio (INR) was associated with deep or infratentorial microbleeds, and among coumarin users, a greater variability in INR was associated with a higher prevalence of microbleeds.
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MedicalResearch.com Interview with:Joanna Martin, PhD student
MRC Centre for Neuropsychiatric Genetics and Genomics
Institute of Psychological Medicine and Clinical Neurosciences,
Cardiff University School of Medicine, Cardiff
Medical Research: What are the main findings of the study?
Response: In this study, we found that genetic risks which are collectively important for ADHD diagnosis also predict higher levels of traits of hyperactivity/impulsiveness, inattention and pragmatic language difficulties in childhood in the general population.
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MedicalResearch.com Interview with:Sayaka Suzuki, MD
Department of Clinical Epidemiology and Health Economics, School of Public Health, Faculty of Medicine, Department of Otolaryngology–Head and Neck Surgery, University of Tokyo, Tokyo, Japan
Medical Research: What are the main findings of the study?Dr. Suzuki:We found a slight increase in the risk of severe bleeding requiring surgery for hemostasis in children who were administrated intravenous steroid on the day of tonsillectomy.
Physicians should carefully make a decision to use steroids, taking into account patients' choice under being well informed on the risks and benefits of steroid use.
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Medical Research.com Interview with:
Terrence Loftus, MD, MBA, FACS
Medical Director, Surgical Service & Clinical ResourcesBanner HealthPhoenix, Arizona 85006
Medical Research: What are the main findings of the study?Dr. Loftus: This study demonstrated that a standardized safe surgery program effectively and systematically implemented across a diverse healthcare system resulted in a significant reduction in serious reportable events (SREs), thereby improving the quality of patient care and leading to significant cost avoidance. For the purposes of the study, SREs were defined as any reported retained surgical item, wrong site, wrong patient or wrong procedure event. Following implementation of the Safe Surgery Program there was a 52% reduction in the SRE rate in the operating rooms and L&D areas in our system. The most dramatic change and greatest area of improvement was in wrong site events which demonstrated a 70% reduction for this type of serious reportable events.
This was achieved through a Safe Surgery Program which consisted of three main components.
The first component was patient focused procedures. These are steps designed to prevent wrong site, wrong patient or wrong procedure events.
The second component was sponge, sharp and instrument count procedures. These are steps designed to prevent retained surgical items.
The final component was monthly observational audits that were performed to assess program compliance. (more…)
MedicalResearch.com Interview with: Richard M. Costanzo, PhD.
Professor of Physiology and Biophysics and
Special Assistant to the Vice President for Research
Virginia Commonwealth University
Medical Research: What are the main findings of the study?Dr. Costanzo: In this study we found that individuals with varying degrees olfactory impairment have an increased risk of experiencing a hazardous event. Those with complete loss (anosmia) were three times more likely to experience an event than those with normal olfactory function. Factors such as age,sex, and race were found to affect an individual’s risk.
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MedicalResearch.com Interview with: Daniel A. Waxman, MD, PhD
Department of Emergency Medicine
David Geffen School of Medicine
University of California, Los Angeles
RAND Corporation Santa Monica, California
Medical Research: What are the main findings of the study?Dr. Waxman:About 10 years ago, three states (Texas, Georgia, and South Carolina) passed laws which made it much harder for doctors to be sued for malpractice related to emergency room care. The goal of our research was to determine whether the lower risk of being sued translated into less costly care by emergency physicians. To figure this out, we looked at the billing records of nearly 4 million Medicare patients and compared care before and after the laws took effect, and between states that passed reform and neighboring states that didn’t change their laws. We found that these substantial legal protections didn’t cause ER doctors to admit fewer patients to the hospital, to order fewer CT or MRI scans, or to spend less for the overall ER visit.
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MedicalResearch.com Interview with:Professor Robert Insall
CR-UK Beatson Institute for Cancer Research
Glasgow UK
Medical Research: What are the main findings of the study?Prof. Insall:The principal message is that melanoma cells make their own steering signals, and thus drive themselves out of the tumour and into the bloodstream. This comes in two parts:
(a) The principal steering signal when we assay melanoma spread in vitro is lysophosphatidic acid, LPA. LPA steers cells with really remarkable accuracy; blocking LPA receptors stops them from spreading without hurting their health or ability to move.
(b) Where does the LPA gradient come from? They make it themselves. There seems to be lots of LPA around; they break down the LPA near them, leading to a gradient that's low near the cells and high further away. This is the gradient that steers the tumour cells.
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MedicalResearch.com Interview with:Craig A Umscheid, MD, MSCE, FACP
Assistant Professor of Medicine and Epidemiology
Director, Center for Evidence-based Practice
Medical Director, Clinical Decision Support
Chair, Department of Medicine Quality Committee
Senior Associate Director, ECRI-Penn AHRQ Evidence-based Practice Center, University of Pennsylvania Philadelphia, PA 19104
Medical Research: What are the main findings of the study?Dr. Umscheid: We developed an automated early warning and response system for sepsis that has resulted in a marked increase in sepsis identification and care, transfer to the ICU, and an indication of fewer deaths due to sepsis.
Sepsis is a potentially life-threatening complication of an infection; it can severely impair the body’s organs, causing them to fail. There are as many as three million cases of severe sepsis and 750,000 resulting deaths in the United States annually. Early detection and treatment, typically with antibiotics and intravenous fluids, is critical for survival.
The Penn prediction tool, dubbed the “sepsis sniffer,” uses laboratory and vital-sign data (such as body temperature, heart rate, and blood pressure) in the electronic health record of hospital inpatients to identify those at risk for sepsis. When certain data thresholds are detected, the system automatically sends an electronic communication to physicians, nurses, and other members of a rapid response team who quickly perform a bedside evaluation and take action to stabilize or transfer the patient to the intensive care unit if warranted.
We developed the prediction tool using 4,575 patients admitted to the University of Pennsylvania Health System (UPHS) in October 2011. We then validated the tool during a pre-implementation period from June to September 2012, when data on admitted patients was evaluated and alerts triggered in a database, but no notifications were sent to providers on the ground. Outcomes in that control period were then compared to a post-implementation period from June to September 2013. The total number of patients included in the pre and post periods was 31,093.
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MedicalResearch.com Interview with: Cathryn Bock, PhD
Associate Professor, Oncology Department
Karmanos Cancer Institute
Wayne State University School of Medicine
Detroit, MI 48201
Medical Research: What are the main findings of the study?
Dr. Bock:This study examined the association between dietary antioxidant micronutrients and risk of renal cell carcinoma (RCC) among a cohort of 96,196 postmenopausal women from the Women’s Health Initiative (WHI). During follow-up (median follow-up time was 12 years), there were 240 cases of confirmed renal cell carcinoma in the cohort. Dietary lycopene intake, measured at baseline, was associated with a decreased risk of renal cell carcinoma (RCC). Women with the highest quartile of lycopene intake (>6427.7 mcg/day) had approximately 40% lower risk of RCC compared to those women in the lowest quartile of lycopene intake (<2727.6 mcg/day). There were no statistically significant associations observed between intake of beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein + xeazanthin, vitamin C, or vitamin E and renal cell carcinoma.
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MedicalResearch.com Interview with:Dr. Brian Rostron PhD, MPH
Center for Tobacco Products
US Food and Drug Administration
Silver Spring, Maryland
Medical Research: What are the main findings of the study?Dr. Rostron: We estimated that Americans in 2009 had had 14 million major medical conditions such as heart attack, stroke, lung cancer, and COPD that were attributable to smoking. COPD was the leading cause of smoking-attributable morbidity, with over 7.5 million cases of COPD attributable to smoking.
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MedicalResearch.com Interview with: Andre Kalil, M.D., M.P.H.
Professor of Medicine
Director, Transplant ID Program
University of Nebraska Nebraska Medical Center
Omaha, NE 68198-5400
Medical Research: What are the main findings of the study?Dr. Kalil: In recent years, physicians treating staph infections with vancomycin have seen an increase in the minimum inhibitory concentration (MIC), the lowest concentration of an antimicrobial agent that inhibits the growth of a microorganism. This condition is referred to as vancomycin “MIC creep.” It is an indicator that the bacteria might be developing a reduced susceptibility to vancomycin. There also have been reports suggesting that elevations in vancomycin MIC values may be associated with increased treatment failure and death.
To determine the effectiveness of vancomycin and other newer antibiotics used to treat Staphylococcus aureus, the UNMC team analyzed nearly 8,300 episodes of Staphylococcus aureus bloodstream infections from patients around the U.S. and in several other countries. The adjusted absolute risk of mortality among patients with Staphylococcus aureus bloodstream infections with high-vancomycin MIC was not statistically different from patients with Staphylococcus aureus bloodstream infections with low-vancomycin MIC.
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MedicalResearch.com Interview with:Phil Tully PhD
Early Career Research Fellow, Discipline of Medicine
University of Adelaide Australia and
Abteilung für Rehabilitationspsychologie und Psychotherapie
Institut für Psychologie, Universität Freiburg Freiburg Germany
Medical Research: What are the main findings of the study?Response: The systematic review indicated that anxiety disorders ascertained by clinical interview are highly prevalent in patients with verified coronary heart disease. Also, approximately 50% of anxiety disorders were comorbid with depression. There was however some uncertainty in prevalence estimates with high level heterogeneity observed between studies. It was also evident that studies measuring generalized anxiety disorder in outpatient samples reported an increased prognostic risk for major adverse cardiac events in the longer term, when adjusted for confounding factors, however there was limited data. There were no randomized controlled trials targeting anxiety disorders in this population.
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MedicalResearch.com Interview with:
Donna Tepper, M.D.
Henry Ford Hospital
Medical Research: What are the main findings of the study?Dr. Tepper:We looked at 94 patients who underwent bariatric surgery at Henry Ford from 2003 through 2013. Of those, 47 subsequently had body recontouring procedures, such as body lift, abdominoplasty (tummy tuck), arm lift, thigh lift, face lift. We recorded the patients’ body mass index prior to bariatric surgery, and then again at 6 months, 1, 2.5, 4, and 5 years. Of the patients who underwent contouring surgery, the average decrease in BMI was 18.24 at 2.5 years, compared to a statistically significant 12.45 at 2.5 years for those who did not have further surgery. This is statistically significant. This 3 point change in BMI is an 18-21 pound difference depending on patient height. Furthermore, the BMI in the body contouring group continues to be lower at 4 and 5 years from bariatric surgery compared to the bariatric surgery alone group. (more…)
MedicalResearch.com Interview with: Elvira Cicognani PhD
Department of Psychology
School of Psychology and Education, University of Bologna
Piazza Aldo Moro, 90 - Cesena, Italy -
Viale Berti Pichat, 5 - Bologna, Italy
Medical Research:What are the main findings of the study?Dr. Cicognani:The study is part of a larger project of the Italian National Transplant Center (Centro Nazionale Trapianti, CNT), started in 2008, in collaboration with Istituto Superiore di Sanità, Centro Studi Isokinetic, University of Bologna, Cimurri Impresa e Sport and Patients’ associations. The general aim is to encourage transplant patients to practice physical activity and even sport activity, in view of its benefits in enhancing recovery and quality of life after transplantation.
In this study we assessed Health-related quality of life on 118 active kidney transplant patients practicing different sports at low to moderate intensity and compared them with those of 79 sedentary kidney transplant patients and with 120 active healthy control subjects.
Active transplant patients reported higher levels of quality of life than sedentary patients on most dimensions of quality of life and similar to active healthy controls. In brief, practicing sports may allow patients to achieve a level of quality of life similar to the general population of active individuals.
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MedicalResearch.com Interview Invitation Sara N. Bleich, Ph.D.
Associate Professor
Department of Health Policy and Management
Johns Hopkins Bloomberg School of Public Health
Baltimore, MD 21205
Medical Research: What are the main findings of the study?Dr. Bleich: Large chain restaurants appear to be voluntarily reducing the calories in their newly introduced menu items which contain an average of 60 fewer calories than items only on the menu in the prior year. This decline is primarily driven by new lower calorie salads and sandwiches.
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MedicalResearch.comInterview with:Mary Malloy, M.D.
Co-director of the Adult Lipid Clinic and the director of the Pediatric Lipid Clinic
UCSF Medical Center
Medical Research: What are the main findings of the study?Dr. Malloy: We studied an individual whom we found to be homozygous for a rare loss of function mutation in apolipoprotein E.
Because apolipoprotein E is necessary for clearance of lipoproteins from plasma, he has very high levels of cholesterol and triglycerides in blood, and unusual and very severe xanthomas. He had no evidence of neurocognitive or retinal defects.
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MedicalResearch.com Interview with: F.E. (Erica) Witkamp RN MSc
Senior lecturer University of Applied Sciences
Erasmus MC and Erasmus MC Cancer Institute
Rotterdam, The Netherlands.
Medical Research: What are the main findings of the study?Response: We investigated the experiences of 249 bereaved relatives (response 51%) of patients who had died in the hospital, after a hospitalization of at least six hours. The main outcome measure was their global score of the quality of dying (QOD) on a 0-10 scale, with zero being “very poor” and ten “almost perfect”. Further, we assessed multiple experiences in the last days of life, such as symptom burden, preparedness for life closure, awareness of impending death, and care in the last days of life. We analyzed which of these factors was related to the quality of dying score, and subsequently whether the related factors represented specific domains of the dying phase.
Relatives rated the overall score of QOD on average at 6.3 (sd 2.7) with a range from 0-10.
During the last day(s) of life, 26% of the patients, and 49% of the relatives had been fully aware of imminent death. In the end 39% of the patients and 50% of the relatives had said goodbye; 77% of the patients had died in the presence of a relative.
According to relatives patients had suffered moderately to severely from on average 7 out of 22 symptoms.
In 53% relatives reported that in the last 24 hours symptoms had sufficiently been alleviated; efforts to control symptoms had been sufficient in 75%. In 64% relatives had been informed by the physician about the imminence of death, and in 70% they were satisfied about their involvement in decision making. In 55% relatives had experienced sufficient attention to individual preferences and wishes, and in 70% hospital facilities had been sufficient. Patients had been sufficiently affirmed as a person in 63%.
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MedicalResearch.com: Interview with:Dr. David HodsonPhD
Faculty of Medicine, Department of Medicine
Imperial College London
Medical Research: What is the background for this research?Dr. Hodson: Type 2 diabetes represents a huge socioeconomic challenge. As well as causing significant morbidity due to chronically elevated glucose levels, this disease is also a drain on healthcare budgets (~$20billion in the UK per year). While current treatments are effective, they are sometimes associated with side effects, usually due to off-target actions on organs such as the heart and brain. In addition, the ability to regulate blood glucose levels more tightly may decrease complications stemming from type diabetes (e.g. nerve, kidney and retina damage). As a proof-of-principle that the spatiotemporal precision of light can be harnessed to finely guide and control drug activity, we therefore decided to produce a light-activated anti-diabetic. (more…)
MedicalResearch.com Interview with: Jordi Salas-Salvadó Professor of Nutrition
Human Nutrition Unit Department of Biochemistry & Biotechnology
IISPV School of Medicine.
Rovira i Virgili University CIBERobn, Instituto Carlos III
Medical Research: What are the main findings of the study?Response: In this large, multicenter, randomized clinical trial conducted in Mediterranean individuals at high cardiovascular risk, Mediterranean-diet supplemented with extra-virgin olive oil was associated to a lower increase in the prevalence of metabolic syndrome compared to the advice on a control low-fat diet. However, no beneficial effect of Mediterranean-diet on the incidence of metabolic syndrome among participants free of this condition at baseline was observed. Therefore, the lower increase in prevalence was especially due to the reversion of metabolic syndrome in those individuals with metabolic syndrome at baseline.
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MedicalResearch.com Interview with Nils P. Johnson, M.D., M.S.
Assistant Professor - Cardiovascular Medicine
Department of Internal Medicine
University of Texas Health Science Center
Houston Texas
Medical Research: What are the main findings of the study?Dr. Johnson: Our study had 3 main findings.
First, the numeric fractional flow reserve (FFR) value related continuously to risk, such that clinical events increased as FFR decreased and revascularization showed larger net benefit for lower baseline FFR values.
Second, fractional flow reserve measured immediately after stenting also showed an inverse relationship with prognosis, likely due to its relationship with diffuse disease.
Third, an fractional flow reserve-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.
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MedicalResearch.com Interview with:Jaime Hart, ScD
Instructor in Medicine
Channing Division of Network Medicine
Medical Research: What are the main findings of the study?Response: The main findings are, that among 107,130 women in the Nurses' Health Study, even after adjusting for a number of traditional cardiovascular risk factors, those women living within 50 meters of a major roadway had a 38% increased risk of sudden cardiac death and 24% increased risk of fatal coronary heart disease, compared to women living 500 meters or more away.
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MedicalResearch.com Interview with: Dr Jelena Kornej
Department of Electrophysiology
Heart Center Leipzig Leipzig Germany;
Medical Research: What are the main findings of the study?Dr. Komej: Both atrial fibrillation (AF) and renal impairment are known to coexist and associated with increased morbidity and mortality. However, there is only limited data on changes of renal function after AF catheter ablation and predictors thereof. This is the largest study analyzing the effects of atrial fibrillation catheter ablation on renal function and changes thereof in a contemporary population during mid-term follow-up. We found that lower baseline eGFR was associated with higher CHADS2and CHA2DS2-VASc scores and that both scores were independently associated with eGFR changes after atrial fibrillation catheter ablation as were atrial fibrillation recurrences.
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MedicalResearch.com Interview with:Adam Spanier, MD, PhD, MPH, FAAP
Associate Professor of Pediatrics
Division Head, General Pediatrics & Developmental and Behavioral Pediatrics
Medical Director, Pediatrics at Midtown Department of Pediatrics
University of Maryland Midtown Campus Baltimore, MD 21201
Medical Research: What are the main findings of the study?Dr. Spanier: Bisphenol A (BPA) is a chemical that is present in many consumer products (lining of canned foods, some plastics, some receipt paper, etc).
We found that higher maternal Bisphenol A levels during pregnancy were associated with increased odds of persistent wheezing in children and a decrease in lung function at age four. Child BPA levels were not associated with these poor lung health outcomes.
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MedicalResearch.com Interview with: Zainab Samad, M.D., M.H.S.
Assistant Professor of Medicine
Duke University Medical Center
Durham, North Carolina
Medical Research: What are the main findings of the study?Dr. Samad: This was a sub study of REMIT, an NHLBI funded study. Our research team headed by Dr. Wei Jiang conducted the REMIT study between 2006-2011 at the Duke Heart Center. We found that women and men differ significantly in their physiological and psychological responses to mental stress. We explored sex differences across various domains felt to have implications towards cardiovascular disease pathophysiology and prognosis. We found that women had greater negative emotion, less positive emotion, while men had greater blood pressure increases in response to mental stress. On the contrary, women showed greater platelet reactivity compared to men in response to mental stress. A greater frequency of women had cardiac ischemia in response to mental stress compared to men.
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MedicalResearch.com Interview with: Emma H. Allott PhD
Division of Urology, Department of Surgery, Duke University School of Medicine
Cancer Prevention, Detection, and Control Program, Duke Cancer Institute Division of Urology
Veterans Affairs Medical Center Durham Durham, North Carolina.
Medical Research: What are the main findings of the study?Dr. Allott: Relative to normal triglyceride levels, high triglycerides (≥150 mg/dl) were associated with 35% increased risk of prostate cancer recurrence. In addition, we found that each 10 mg/dl increase in total serum cholesterol above the abnormal cut-off value of 200 mg/dl was associated with a 9% increased risk of prostate cancer recurrence, while each 10 mg/dl increase in HDL (high density lipoprotein; “good” cholesterol) below the abnormal cut-off value of 40 mg/dl was associated with a 39% increased risk of prostate cancer recurrence. These findings suggest that normalization, or even partial normalization, of serum lipid levels among men with dyslipidemia may reduce the risk of prostate cancer recurrence.
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MedicalResearch.com Interview with:Dr. Ilan Youngster, MD, MMSc
Division of Infectious Diseases, Massachusetts General Hospital,
Harvard Medical School,
Division of Infectious Diseases, Boston Children’s Hospital
Boston, Massachusetts
Medical Research: What are the main findings of the study?Dr. Youngster: The main finding is that oral administration seems to be as safe and effective as more traditional routes of delivery like colonoscopy or nasogastric tube. This is important as it allows Fecal microbiota transplantation (FMT) to be performed without the need of invasive procedures, making it safer, cheaper and more accessible to patients.
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MedicalResearch.com Interview with:Jen-Hao Chen, Ph.D.
Assistant Professor, Department of Health Sciences
University of Missouri, Columbia, MO 65211
Medical Research: What are the main findings of the study?Dr. Chen: In this study, we mapped four commonly-reported insomnia symptoms (feeling rested when waking up, having trouble falling asleep, waking up during the night, waking up too early and not being able to fall asleep again) to direct assessment of sleep characteristics in the general population of U.S. older adults. While we know older adults frequently complain about their sleep, we know little about how these complain reflect older adults’ actual sleep outcomes.
Using innovative actigraphy data of 727 older adults aged 62-91 from the National Social Life, Health and Aging Project, we found that two of these four common report of insomnia symptoms did not match specific objective sleep characteristics as these questions intends to index. The question of feeling rested was not related to any objective sleep characteristic. The question of difficulty falling asleep was not related to the objective measure of time to fall sleep but was related to other objective sleep characteristics. For waking up during the night question, high frequency was associated with more wake time after sleep onset and numbers of wake bout (but was also related to other objective sleep characteristics). For waking up too earlier question, answer of this question was related to earlier wake up time. But again, other objective sleep characteristics also predicted frequency of waking up earlier.
In sum, many of the relationships and non-relationships found in this study were unexpected. Findings suggested that these widely used questions did not related to older adults’ sleep outcomes as exactly as the wording suggested. Thus, while older adults’ report of these questions are related to objective sleep characteristics in some ways, insomnia symptoms and objective sleep characteristics did not complete match each other as expected.
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MedicalResearch.com Interview with: Michael S. Calderwood, MD MPH
Division of Infectious Diseases
Brigham and Women's Hospital
Boston, MA
Medical Research: What are the main findings of the study?Dr. Calderwood:"In our study, we found that the risk of surgical site infection (SSI) following total hip arthroplasty and coronary artery bypass graft (CABG) surgery is higher for Medicare patients undergoing surgery in U.S. hospitals with lower surgical volume. This suggests that volume leads to experience, and experience leads to improved outcomes."
"We found a significantly higher risk of surgical site infection in U.S. hospitals performing <100 total hip arthroplasty procedures and <50 CABG procedures per year on Medicare patients. In the lowest volume hospitals, 1 out of 3 infections following total hip arthroplasty and 1 out of 4 infections following CABG were in excess of expected outcomes based on experience in the highest volume hospitals."
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MedicalResearch.com Interview with: Dr Daniel Bradshaw
Chelsea and Westminster Hospital, London
Medical Research: What are the main findings of the study?Dr. Bradshaw: Over 40% of men with hepatitis C (HCV) infection have HCV RNA in their semen, although the level of RNA was much lower than blood (usually 4 log less than blood).
Neither HIV nor acute hepatitis C led to increased shedding of HCV RNA in semen. Interestingly, however, in acute HCV, HIV-positive men with higher blood levels of HCV RNA were more likely to shed RNA in their semen.
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MedicalResearch.com Interview with:Sana Dastgheyb
National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MDDepartment of Orthopedic Surgery,
Thomas Jefferson University, Philadelphia, PA andDr. Noreen Hickok
Department of Orthopedic Surgery
Thomas Jefferson University, Philadelphia, PA
Medical Research:What are the main findings of the study?Response: Physicians have long been resigned to the fact that staphylococcal joint infections are among the most challenging to treat. Our study points towards a definitive mechanism whereby bacteria become insensitive to antibiotics in the human joint environment. We added MRSA to synovial fluid and observed dense, biofilm-like aggregates, as well as a relative insensitivity to antibiotics as compared to ideal medium. Our findings suggest that serum/extracellular matrix proteins within synovial fluid contribute greatly to staphylococcal antibiotic insensitivity in synovial fluid. Furthermore, pre-treatment of synovial fluid with the enzyme plasmin, which degrades extracellular matrix proteins, significantly inhibits aggregate formation, and restores normal antibiotic sensitivity to MRSA.
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