Medical Research Journals

MedicalResearch.com Interview with: Donna Zulman MD MS Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park Division of General Medical Disciplines, Stanford University, Stanford California, USAMedicalResearch.com Interview with: Donna Zulman MD MS Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park Division of General Medical Disciplines, Stanford University, Stanford California, USA Medical Research: What is the background for this study? Dr. Zulman: Within the United States, a small number of individuals account for disproporationate health care spending. Many of these high-cost patients have complex chronic conditions such as heart failure and diabetes. Others have complicated mental health conditions. But the vast majority have multiple chronic conditions, which can create challenges when patients are navigating their health care. For this study, we examined patterns of chronic conditions among high-cost patients in the Veterans Affairs (VA) Health Care System, and studied the relationship between different chronic conditions patterns and health care utilization and costs. Medical Research: What are the main findings? Dr. Zulman: We found that within the VA, the 5% highest cost patients accounted for 47% of total VA health care costs. Approximately two-thirds of these patients had chronic conditions affecting 3 or more body systems (for example, cardiovascular disease, asthma, and depression). However, patients with severe, dominating diseases such as cancer and schizophrenia were less likely to have a lot of comorbid conditions. In addition, we found that even among these high-cost patients, having more conditions was associated with greater use of outpatient and inpatient services. However, as patients' multimorbidity across body systems increased, a greater share of their costs was generated in the outpatient setting and a smaller share of their costs was generated in the inpatient setting. This suggests that interventions focusing on high-cost patients should not only target costly hospitalizations, but should also coordinate and maximize efficiency of outpatient services across multiple conditions.

Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of MedicineMedicalResearch.com Interview with: Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Marlin: Oxytocin is a hormone that plays an important role in the expression of social and parental behaviors, but little is know about how it works in the brain to produce these behaviors. Virgin mice will usually ignore, and sometimes cannibalize newborn mouse pups. Our study has shown that oxytocin works in the auditory cortex of virgin mice to change both their neural responses, and eventually their behaviors, to mirror the maternal response.

Catherine L. Chen M.D., M.P.H. UCSF Dept of AnesthesiaMedicalResearch.com Interview with: Catherine L. Chen M.D., M.P.H. UCSF Dept of Anesthesia Medical Research: What is the background for this study? What are the main findings? Dr. Chen: Cataract surgery is a very common and safe surgery that most older adults have in their 70's or 80's. It usually happens as a same-day surgery and most patients only need eye drops to numb the eye with little or no intravenous sedation for a procedure that on average is only 18 minutes long. Given their age, these patients typically have other concurrent medical problems, so even though multiple research studies and professional societies have concluded that routine preoperative testing is not necessary before cataract surgery, we found that this testing still frequently occurs in these patients. More than half of the patients in our study had at least one preoperative test performed in the month before their surgery. We hypothesized prior to undertaking this study that the older and sicker patients were the ones who were most likely to get preoperative testing. Instead, what we found was that the most important factor that determined whether or not a patient got tested was the ophthalmologist who operated on the patient. This is an important finding because it shows that most patients are not getting extra testing, but the few that do are getting testing because that's the way their ophthalmologist typically prepares his patients for surgery. Most of the time, this testing is not needed and will not affect how well the patient does during and after surgery.

Josée Savard, Ph.D. School of Psychology, Laval University Cancer Research Center Quebec City, Quebec, CanadaMedicalResearch.com Interview with: Josée Savard, Ph.D. School of Psychology, Laval University Cancer Research Center Quebec City, Quebec, Canada MedicalResearch: What is the background for this study? What are the main findings? Dr. Savard: This paper reports on a secondary analysis of an 18-month longitudinal study initially conducted in 962 patients about to receive surgery for various types of cancer. The main results of this larger study indicated that insomnia is a significant problem in cancer patients. More precisely, it was found to affect up to 59% of patients at the peri-operative period. In addition, 32% of patients who were good sleepers developed insomnia symptoms at some point during the study (Savard et al., 2009; Savard et al., 2011). The goal of this particular analysis was to determine the role of cancer treatments and their side effects in triggering/aggravating insomnia symptoms during the 18-month follow-up. Study participants completed questionnaires assessing insomnia severity and somatic symptoms at baseline, as well as 2, 6, 10, 14 and 18 months later. This analysis was conducted separately in women treated for breast cancer (n=465) and men treated for prostate cancer (n=263). In breast cancer patients, chemotherapy and radiation therapy, but not hormone therapy, were found to be associated with increased insomnia severity. This deleterious effect appeared to be due to a number of side effects (e.g., nausea, night sweats, urinary symptoms). In prostate cancer patients, androgen-deprivation therapy was associated with aggravation of insomnia, an effect that was mainly due to the occurrence of night sweats.

Matthew E. Dupre, PhD Associate Professor of Medicine Department of Community and Family Medicine Department of Sociology Duke Clinical Research InstituteMedicalResearch.com Interview with: Matthew E. Dupre, PhD Associate Professor of Medicine Department of Community and Family Medicine Department of Sociology Duke Clinical Research Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Dupre: The negative health consequences of divorce have been known for some time. However, we showed that lifetime exposure to divorce can have a lasting impact on ones’ cardiovascular health, particularly in women. This is a good example of why people going through a divorce need a good divorce lawyer chicago in order to keep their stress levels down and help their cardiovascular health. Results from our study showed that risks for acute myocardial infarction (AMI) were significantly higher in women who had one divorce, two or more divorces, and among the remarried compared with continuously married women after adjusting for multiple risk factors. Risks for AMI were elevated only in men with a history of two or more divorces relative to continuously married men. We were especially surprised to find that women who remarried had risks for AMI that were nearly equivalent to that of divorced women. Men who remarried had no significant risk for acute myocardial infarction. The results of this study provide strong evidence that cumulative exposure to divorce increases the risk of acute myocardial infarction in older adults. Also somewhat unexpected was that the associations remained largely unchanged after accounting for a variety socioeconomic, psychosocial, behavioral, and physiological factors. However, we lacked information on several factors that we suspect may have contributed to the risks related to divorce – such as elevated stress, anxiety, and the loss of social support; as well as possible changes is medication adherence or other prophylactic behaviors. MedicalResearch: What should clinicians and patients take away from your report?

Mihaela S Stefan, MD FACP Research Scientist, Center for Quality of Care Research Director of Outpatient Perioperative Clinic and Medical Consultation Program Academic Hospitalist Baystate Medical Center Assistant Professor of Medicine, Tufts University School of Medicine Springfield MA 01199MedicalResearch.com Interview with: Mihaela S Stefan, MD FACP Research Scientist, Center for Quality of Care Research Director of Outpatient Perioperative Clinic and Medical Consultation Program Academic Hospitalist Baystate Medical Center Assistant Professor of Medicine, Tufts University School of Medicine Springfield MA 01199 MedicalResearch: What is the background for this study? Dr. Stefan : Mortality rates for patients with pneumonia are publicly reported and are used to evaluate hospital performance. The rates are calculated using Medicare administrative claims data which provide limited insight into severity of illness and comorbidities that may be associated with death. The mortality measure does not take into consideration advance directives or changes in goals of care preferences during hospitalization. MedicalResearch: What are the main findings? Dr. Stefan : In this retrospective chart review of 202 adults who died with a principal diagnosis of pneumonia between January 2008 and December 2012 in 3 hospitals in MA, we assessed the proportion of patients for whom pneumonia was determined to play a major or a minor role in the patient death. Pneumonia was considered a minor cause if the patient had advanced life threatening illnesses and this was found in 82% of the deaths. More than half of the patients were DNR at admission to the hospital. The majority of patients who died were frail elderly with life-threatening conditions who decided to forgo aggressive care at some point during their admission. Only a small fraction of deaths in the pneumonia mortality measure were the direct result of pneumonia.

MedicalResearch.com Interview with: Professor Hossam Haick Ph.D Department of Chemical Engineering and Russell Berrie Nanotechnology Institute Haifa, Israel Medical Research: What is the background for this study? What are the main findings? Dr. Haick: Our study is based on the hypothesis that timely detection of premalignant lesions (PMLs) may provide a tool to decrease either cancer mortality or incidence, thought, currently, there is no perfect non-invasive tool to screen for gastric cancer (GC) and the related premalignant lesions. Using 1002 samples collected from 501 volunteers, we show for the first time that premalignant lesions (PMLs) relevant to (gastric) cancer result in detectable differences in Volatile Organic Compound (VOC) signatures that can be detected and classified non-invasively through exhaled breath. We show additionally that these premalignant lesions can be well-discriminated from various stages of gastric cancer as well as other background stomach diseases.

Addie Weaver PhD Research Investigator and LEO Adjunct Lecturer School of Social Work University of MichiganMedicalResearch.com Interview with: Addie Weaver PhD Research Investigator and LEO Adjunct Lecturer School of Social Work University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Weaver: The mental health of both African Americans and rural Americans has been understudied. Though depression is one of the most common, debilitating mental illnesses among women, very little is known about depression among African American women living in rural areas of the United States. In fact, much of what we know about rural women's depression in general is based on research conducted with community samples, as limited epidemiolgical research includes large enough samples of both African American respondents and rural respondents to assess potentially important subgroup differences by urbanicity (e.g., urban, suburban, rural) and race. Our study used the National Survey of American Life, the first and only nationally representative survey of African Americans, to examine the interaction of urbanicity and race/ethnicity on Major Depressive Disorder and mood disorder prevalence among African American and non-Hispanic white women residing in the South. We found that rural residence has a differential effect on depression and mood disorder for African American women and non-Hispanic white women. Overall, African American women living in rural areas experienced significantly lower odds of meeting criteria for lifetime and 12-month Major Depressive Disorder and lifetime and 12-month mood disorder than urban African American women. Conversely, non-Hispanic white women residing in rural areas had significantly higher odds of meeting criteria for lifetime and 12-month Major Depressive and lifetime and 12-month mood disorder when compared to rural African American women, and had significantly higher prevalence rates of 12-month Major Depressive Disorder and 12-month mood disorder than urban non-Hispanic white women. All analyses controlled for age, education level, household income, and marital status, suggesting that the urbanicity differences were not due to resource disparities often experienced by individuals residing in rural communities.

MedicalResearch.com Interview with: Arnon D. Cohen, MD, MPH, PhD Department of Quality Measurements and Research, Chief Physician's Office, Clalit Health Services, Tel Aviv Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel MedicalResearch: What is the background for this study? Dr. Cohen: Herpes zoster (HZ),...

Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute MedicalResearch.com Interview with: Gabriel Brooks, MD Gastrointestinal Cancer Center Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Brooks: The background for our study is that hospitalizations in patients with cancer are common, costly, and distressing to patients.  Acute hospital care is the single largest expenditure category in cancer care, accounting for substantially greater costs than even chemotherapy. However, patients generally wish to avoid hospitalization, and they certainly want to avoid complications of treatment that can lead to hospitalization. For these reasons, we sought to identify the extent to which hospitalizations are perceived as potentially avoidable by clinicians who are directly involved in patient care. We interviewed three physicians for each of 103 patients with cancer who experienced a hospitalization. For 24 patients (23%) two or more of the three physicians agreed that hospitalization had been potentially avoidable.

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with: Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT Southwestern MedicalResearch: What is the background for this study? Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts. MedicalResearch: What are the main findings? Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention.

Nancy E. Thomas, MD, PhD Department of Dermatology University of North CarolinaMedicalResearch.com Interview with: Nancy E. Thomas, MD, PhD Department of Dermatology University of North Carolina MedicalResearch: What is the background for this study? Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor initiation and maintenance. There are drugs that target BRAF mutations or the pathway that are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it remains unknown whether these mutations in primary melanoma are markers for melanomas with a worse prognosis. MedicalResearch: What are the main findings? Dr. Thomas:
  • In a large international population-based study, we found that of primary melanomas, 30% harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these mutations (wildtype).
  • In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an approximately 3-fold increased rate of death from melanoma compared to wildtype melanoma adjusted for other prognostic factors.
  • Primary melanomas with NRAS mutations were less likely to have tumor infiltrating lymphocytes (TILs) in the tumor microenvironment.

MedicalResearch.com Interview with: Maria Nygren Division of Pediatrics Linköping University, Sweden MedicalResearch: What is the background for this study? What are the main findings? Response: What factors that cause type 1 diabetes is still unknown, but we know that environmental factors are involved besides the genetics. Since the incidence of type 1 diabetes among children have increased worldwide in recent decades, it is important to find out the reasons behind the disease to hopefully be able to prevent new cases. We have in a prospective study of over 10000 children and their parents in Sweden investigated if psychological stress can be a risk-factor, and found that childhood experience of serious life events (such as death/illness in family, divorce, new adult/child in the family) was associated with increased risk for diagnosis of type 1 diabetes up to 14 years of age.

Emily Finlayson, MD, MS Department of Surgery, Division of General Surgery Department of Medicine, Division of Geriatrics Philip R Lee Institute for Health Policy University of California, San Francisco Director, UCSF Center for Surgery in Older AdultsMedicalResearch.com Interview with: Emily Finlayson, MD, MS Department of Surgery, Division of General Surgery Department of Medicine, Division of Geriatrics Philip R Lee Institute for Health Policy University of California, San Francisco Director, UCSF Center for Surgery in Older Adults Medical Research: What is the background for this study? What are the main findings? Dr. Finlayson: In general, the goal of lower extremity revascularization is to preserve the leg so that patients can maintain the ability to ambulate and maintain functional independence.  We evaluated the results of this operation in older nursing home residents in the United States.  We found that over the 3 year study period, over 10,000 nursing home residents underwent this procedure.  Most of them were functionally dependent before surgery, 3/4 were unable to walk, and over half had dementia. After 1 year, half of the residents had died.  Among residents who could not walk before surgery, 89% were dead or non ambulatory 1 year after surgery.

Kimberly Gudzune, MD, MPH Assistant Professor; The Johns Hopkins University School of Medicine Core Faculty; Welch Center for Prevention, Epidemiology, and Clinical Research The Johns Hopkins Digestive Weight Loss CenterMedicalResearch.com Interview with: Kimberly Gudzune, MD, MPH Assistant Professor; The Johns Hopkins University School of Medicine Core Faculty; Welch Center for Prevention, Epidemiology, and Clinical Research The Johns Hopkins Digestive Weight Loss Center Medical Research: What is the background for this study? What are the main findings? Dr.Gudzune: Changes in healthcare policy may encourage healthcare providers to screen their patients for obesity, so it is critical to then have a weight management plan if obesity is identified. Recent guidelines recommend that clinicians consider referring patients to high intensity weight loss programs. Commercial weight loss programs may be one of the options available, so providers need to know which programs help people lose weight and keep it off. We found that only 11 out of 32 programs that we looked at had rigorous studies reporting on weight loss, which means that we do not know whether most programs work. Several well-known commercial programs have been scientifically tested and two programs, Weight Watchers and Jenny Craig, achieved significant weight loss that was sustained 12 months later.

Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of MichiganMedicalResearch.com Interview with: Dr. Reshma Jagsi MD, DPhil Associate Professor and Deputy Chair for Faculty and Financial Operations in the Department of Radiation Oncology at the University of Michigan Health System Research Investigator at the Center for Bioethics and Social Sciences in Medicine University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Jagsi: We surveyed women diagnosed with breast cancer and found that many women were concerned about the genetic risk of developing other cancers themselves or of a loved one developing cancer.  Overall, 35 percent of the women we studied expressed a strong desire for genetic testing, but 43 percent of those did not have a relevant discussion with a health care professional. In addition, minority patients with a strong desire for testing were less likely to discuss it with a professional, even though studies show that minority patients are not at lower risk for these mutations.

Anthony Delitto, PT, Ph.D, FAPTA Professor and Chair Department of Physical Therapy Associate Dean for Research, SHRS School of Health and Rehabilitation Sciences Pittsburgh,MedicalResearch.com Interview with: Anthony Delitto, PT, Ph.D, FAPTA Professor and Chair Department of Physical Therapy Associate Dean for Research, SHRS School of Health and Rehabilitation Sciences University of Pittsburgh Medical Research: What is the background for this study? What are the main findings? Dr. Delitto: I work with a team, many of whom were authors on the paper, and we see a lot of patients with lumbar spinal stenosis. Some of them did very well with Physical Therapy and avoided surgery. Some people didn’t do well and we ended up having surgery. We really wanted to do a study that compared, in a randomized format, doing surgery vs. a non-surgical approach to lumbar spinal stenosis. The idea we had was to really put the two approaches head to head – a randomized trial of surgery vs. physical therapy for people with lumbar spinal stenosis. We decided only to recruit patients after they had consented to surgery in order to avoid the pitfalls of previous studies where people crossed over after being assigned to a group, for example, being assigned to surgery and then deciding against having surgery. Medical Research: What should clinicians and patients take away from your report? Dr. Delitto: Probably the biggest point to put across to physicians, patients and practitioners, one of the things we realized was: patients don’t exhaust all of their non-surgical options before they consent to surgery. And physical therapy is one of the non-surgical options. The obvious finding is, when you compare the two groups, they seem to do the same. The results were equivalent at two years. Now, embedded in that, there are patients who did well in surgery, and patients who failed in surgery. There are patients who did well in Physical Therapy, and there are patients who failed with PT. But when we looked across the board at all of those groups, their success and failure rates were about the same. So it tells us that for the most part there were equivalent outcomes at two years.

Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine, Brigham and Women’s Hospital Boston, MAMedicalResearch.com Interview with: Holly Gooding, MD, MS Harvard T.H. Chan School of Public Health Instructor in Pediatrics at Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital Division of General Internal Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gooding: As an adolescent medicine physician, I primarily care for patients between the ages of 12 and 30, although I first trained in internal medicine.  One of the things I noticed when I started working with this age group is that pediatric and adult guidelines differ for many conditions.  Cholesterol treatment is one condition that comes up frequently, because the NHLBI and the AAP recommend screening youth ages 17 to 21 for cholesterol problems. The study team and I set out to discover the proportion of American youth ages 17 to 21 who would meet criteria for pharmacologic treatment of abnormal cholesterol levels if clinicians applied the pediatric versus the adult guidelines.  We found that 2.6% of young people ages 17 to 21 would qualify for pharmacologic treatment of abnormal LDL cholesterol levels under the pediatric guidelines, but less than 1% would qualify under the adult guidelines.  This translates to almost 500,000 youth qualifying for treatment under the pediatric guidelines, but only about 78,000 under the adult guidelines.  Those who met pediatric criteria had lower LDL levels but higher proportions of high blood pressure, smoking, and obesity.

MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans.

MedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, MarylandMedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, Maryland Medical Research: What is the background for this study? Dr. Arem: The 2008 Physical Activity Guidelines for Americans recommend a minimum of 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity activity per week for “substantial” health benefit, and suggest “additional” benefit with more than double the exercise minimum. However, the guidelines note that there is a lack of evidence for an upper limit of health benefit. We set out to define the dose-response relationship between leisure-time physical activity and mortality and to determine the upper limit of benefit associated with higher levels of aerobic exercise. Medical Research: What are the main findings? Dr. Arem: We found that study participants who met the recommended minimum level of leisure-time physical activity derived most of the mortality benefit, with a 31% lower risk of death compared to inactive individuals. Study participants who engaged in three to five times the recommended minimum level of leisure-time physical activity had a marginally increased mortality benefit, with a 39% lower risk of death compared to inactive individuals. Three to five times the recommended minimum is equivalent to a weekly minimum of walking 7 hours or running 2 hours 15 minutes.

Klaus Gebel GradDipExRehab, MExSc, MAppSc, PhD Senior Research Fellow Centre for Chronic Disease Prevention College of Public Health, Medical & Veterinary Sciences James Cook University Cairns AUSTRALIAMedicalResearch.com Interview with: Klaus Gebel GradDipExRehab, MExSc, MAppSc, PhD Senior Research Fellow Centre for Chronic Disease Prevention College of Public Health, Medical & Veterinary Sciences James Cook University Cairns Australia Medical Research: What is the background for this study? Response: The physical activity guidelines in most countries recommend for adults to accumulate at least 150 minutes of moderate physical activity (e.g. brisk walking) or 75 minutes of vigorous activity (e.g. jogging or cycling) or an equivalent combination of moderate and vigorous activities where 2 minutes of moderate-intensity activity counts the same as 1 minute of vigorous-intensity activity. However, there have only been a few studies that examined the health benefits of different proportions of moderate and vigorous activity in the composition of total activity. The objective of this study was to examine whether the proportion of total moderate-to-vigorous activity that is achieved through vigorous activity is associated with all-cause mortality, independently of the total amount of moderate-to-vigorous activity. Data were used from the 45 and Up study from the state of New South Wales in Australia, the largest cohort study ever conducted in the Southern hemisphere. Medical Research: What are the main findings? Response: During 1,444,927 person-years of follow-up, 7,435 deaths were registered. Compared with those who reported no moderate-to-vigorous activity (crude death rate=8.34%), the adjusted hazard ratios for all-cause mortality were 0.66 (95% CI 0.61-0.71; crude death rate=4.81%), 0.53 (0.48-0.57; 3.17%), and 0.46 (0.43-0.49; 2.64%) for reporting 10-149, 150-299, and for ≥300 minutes of activity per week respectively. Among those participants who reported any moderate-to-vigorous physical activity, the proportion of vigorous activity showed a dose-response relationship with all-cause mortality: compared with those reporting no vigorous activity (crude death rate=3.84%) the fully-adjusted hazard ratio was 0.91 (95% CI=0.84-0.98; crude death rate=2.35%) in those who reported some vigorous activity (but <30% of total activity); and 0.87 (0.81-0.93; 2.08%) among those who reported ≥30% of activity as vigorous. These associations were consistent in men and women, across categories of body mass index and volume of moderate-to-vigorous physical activity, and in those with and without existing cardiovascular disease or diabetes mellitus.

Gustavo C Machado, PhD student The George Institute for Global Health, Sydney Medical School University of Sydney Sydney AustraliaMedicalResearch.com Interview with: Gustavo C Machado, PhD student The George Institute for Global Health, Sydney Medical School University of Sydney Sydney Australia (Editor’s note: Paracetamol isalso known as acetaminophen) MedicalResearch: What is the background for this study? What are the main findings? Response: Back pain and osteoarthritis are the two major musculoskeletal conditions affecting people worldwide, and paracetamol is the most used over the counter medicine to treat these conditions. Recent debates on the efficacy and safety of paracetamol prompted us to conduct a systematic review of literature on the efficacy of this medication. In our study we included all available clinical trials that compared paracetamol to placebo, and our conclusions are based on data from more than 5,300 patients with low back pain and hip or knee osteoarthritis. We found that paracetamol is ineffective for low back pain and provides small and not clinically important benefits to patients with osteoarthritis.

MedicalResearch.com Interview with: Ricardo Battaglino, Ph.D. Department of Mineralized Tissue Biology The Forsyth Institute, Cambridge, Massachusetts Department of Oral Medicine, Infection, and Immunity Harvard School of Dental Medicine, Boston, Massachusetts,MedicalResearch.com Interview with: Ricardo Battaglino, Ph.D. Department of Mineralized Tissue Biology The Forsyth Institute, Cambridge, Massachusetts Department of Oral Medicine, Infection, and Immunity Harvard School of Dental Medicine, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Battaglino: Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. We found that Snx10, a molecule expressed in osteoclasts, was also expressed in the stomach. Studies in tissue specific or global knock-down mice showed that Snx10 deficiency resulted in a phenotype that was a consequence of deficiencies in both osteoclasts and gastric zymogenic cells. Our studies add to a growing list of genes, including atp6i (Tcirg1), whose expression is required both in bone and stomach to maintain normal gastric acidification and calcium absorption. Medical Research: What should clinicians and patients take away from your report? Dr. Battaglino: Our work provides additional insight into the mechanisms governing the regulation of bone accrual by the gastrointestinal tract. Because osteopetrorickets has not been described clinically in Snx10-related osteopetrosis, these findings highlight the importance of considering impaired acidification in both stomach and bone in osteopetrotic patients with mutations in SNX10 and other genes with similar patterns of expression and activities. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. Because defects in gastric differentiation and/or gastric acidification may cause or contribute to hypocalcemia, bone insufficiency, and early death, our results suggest that dietary calcium supplementation could be a life-saving intervention in these patients.

CDC- sleepMedicalResearch.com Interview with: Nan Hee Kim M.D., Ph.D., Professor Korea University Ansan Hospital, Gojan1-dong, Danwon-gu, Gyunggi-do, Korea MedicalResearch: What is the background for this study? Dr. Nan Hee Kim: Many individuals in modern society experience a discrepancy between social and biological time. Especially during the work or school week, we are often forced to be awake against our preferred time. In addition, the increase of light, TV, computer and internet make people stay up late at night. However, night owls (evening persons) have been reported to have more health and behavioral problems than morning persons. Evening persons experience eating disorders, negative mood and insufficient sleep compared to morning persons. They initiate sleep later in the night but need to wake up earlier than their biologic morning due to social demands. There is abundant evidence that short sleep duration and insomnia are significant risk factors for obesity and diabetes. Therefore, we feel the necessity to reveal whether evening persons are associated with metabolic abnormalities in the general population. MedicalResearch: What are the main findings? Dr. Nan Hee Kim: In middle-aged adults, people who stayed up late had a 1.7-fold increased risk for type 2 diabetes and metabolic syndrome, and a 3.2-fold increase in risk for sarcopenia as compared with morning persons, independent of sleep duration and lifestyle. Evening persons were associated with reduced muscle mass in men and increased fat mass including visceral fat in women.

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD MedicalResearch.com Interview with: Dr Richard Forshee PhD Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD On behalf of the study authors Medical Research: What is the background for this study? What are the main findings? Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken.  The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group.  The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients. In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness.  This pathway reduces the time it takes for needed medical products to become available to the public.  Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease. As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease. A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older.  The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose. Additional background about this study: “Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis” is available at: http://dx.doi.org/10.1016/S1473-3099(14)71087-4 A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at: http://dx.doi.org/10.1016/S1473-3099(15)70020-4

MedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology NYU Langone Medical CenterMedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology Member of the Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Mansukhani: Osteosarcoma is a highly aggressive pediatric bone cancer that is almost always advanced at diagnosis. Treatment outcomes have not improved in three decades and 40% of patients eventually succumb to the disease. A few years ago we identified that normal bone stem cells relied on the function of a gene called Sox2 to remain immature an self-renew. We went on to find that osteosarcoma cancer stem cells, that arise from immature bone cells, express high levels of Sox2. Like their normal counterparts, these cancer cells also need Sox2. Sox2 maintains the stemness properties of the cancer cells as well as their ability to form tumors in mice. Depleting Sox2 resulted in cells that had reduced tumor-forming potential and instead, were able to become mature bone cells. In this new study we have identified the mechanism by which Sox2 maintains the properties of osteosarcoma cancer stem cells. Sox2 inactivates the growth restraining function of the well-known tumor suppressive hippo pathway. Hippo signaling restrains the activity of a potent oncogene, YAP. In the osteosarcoma stem cells, Sox2 directly represses two genes (Nf2 and WWC1) in the hippo pathway and thereby unleashes the growth promoting activity of YAP. Like Sox2, YAP is required to maintain the tumorigenic properties of osteosarcoma cells. Consistently, we found high YAP and low NF2 and WWC1 expression in human osteosarcoma tissues. Our study makes a direct connection between Sox2 and repression of hippo signaling to enable YAP activity in osteosarcomas. This mechanism also operates in glioblastoma, an aggressive brain tumor.

MedicalResearch.com Interview with: Bonny Rockette-Wagner, Ph.D. Director of physical activity assessment, University of Pittsburgh Graduate School of Public Health and Andrea Kriska, Ph.D. Professor of epidemiology, University of Pittsburgh Graduate School of Public Health Researchers’ Note: Drs. Kriska and Rockette-Wagner: It should be noted that this study looked at adults at high risk for diabetes. Not everyone in the general population would be at high risk. We would hypothesis that the risk increase from TV watching may be lower in those not at high risk for diabetes, but obviously could not test that in our study population. MedicalResearch: What is the background for this study? Response: In this research effort focused on participants in the Diabetes Prevention Program (DPP) study (published in 2002 and funded by the National Institute of Digestive and Diabetes and Kidney Diseases [NIDDK] section of the US National Institutes of Health [NIH]). That study enrolled 3,234 overweight US adults (1996–1999) of at least 25 years of age with the goal of delaying or preventing type 2 diabetes in high risk individuals with either a metformin drug or lifestyle intervention. The DPP demonstrated that the lifestyle intervention was successful at reducing the incidence of diabetes and achieving its goals of 150 minutes per week of moderate intensity activity (such as brisk walking) and a 7% weight loss (New England Journal of Medicine, 2002). There was no goal to reduce sitting in the Diabetes Prevention Program. Results from other studies suggest that it is unclear if interventions focusing on increasing physical activity also reduce time spent sitting. This current investigation examined whether the Diabetes Prevention Program lifestyle intervention, which was shown to be effective at increasing physical activity, also decreased self-reported sitting time. The effect of sedentary behavior on diabetes development was also examined. MedicalResearch: What are the main findings? Response: For the lifestyle participants, a reduction in reported TV watching alone and the combination of TV watching and work sitting was observed. This reduction was significantly greater than any changes seen in the other two randomized groups, who did not receive the intervention. Because these reductions were accomplished without an explicit program goal to reduce sitting we feel optimistic that with better awareness of sitting behaviors and goal setting to reduce sitting it may be possible to have an even greater impact than what was achieved in this cohort. Additionally, our results showed that for every hour spent watching TV there was a 3.4% increased risk of developing diabetes during the 3 year follow-up period in individuals at high risk for diabetes. This finding means that reductions in sitting can translate into a positive health effect separate from improvements in moderate-vigorous activity.

Pamela S. Douglas, M.D. Duke University School of Medicine Duke University Medical Center Durham, NC 27715MedicalResearch.com Interview with: Pamela S. Douglas, M.D. Duke University School of Medicine Duke University Medical Center Durham, NC 27715 Medical Research: What is the background for this study? Dr. Douglas: The primary objective of the PROMISE study was to compare the health outcomes of people who went to the doctor with new symptoms such as shortness of breath and/or chest pain that were suggestive of coronary artery disease and that required additional evaluation. This was an important investigation because no large research trial has ever been conducted to help guide the care of such patients. Instead, the selection of tests for such patients—which constitutes at least 4 million patients in the United States each year—has been largely left up to physician and patient preference rather than proven results. Medical Research: What are the main findings? Dr. Douglas: 10,003 patients from 193 different medical facilities across the US and Canada agreed to be part of the PROMISE study and  were randomized to a functional stress test or an anatomic test Using CT angiography.  The study found that the clinical outcomes of participants with suspected coronary artery disease were excellent overall, and were similar in terms of death and major cardiac conditions regardless of whether patients had a functional stress test or a computed tomographic scan. However, the CT scan may be better at ruling out the need for subsequent tests and procedures in patients who are free of heart disease, and involved a lower radiation exposure relative to a stress nuclear study. We also found, in a separately reported study, that the costs of the two diagnostic strategies were similar.

MedicalResearch.com Interview with: Dr. H. Jaap Bonjer, PhD, FRCSC Professor of Surgery Chair Department of Surgery VU University Medical Center Amsterdam Amsterdam Medical Research: What is the background for this study? Dr. Bonjer: Laparoscopic surgery for colon cancer is widely used after sufficient evidence was collected in various trials demonstrating similar long term cancer outcomes as open...

Henri van Werkhoven PhD student | Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The NetherlandsMedicalResearch.com Interview with: Henri van Werkhoven PhD student and Douwe-PostmaDouwe Postma PhD student Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Community-acquired pneumonia is an important cause of hospitalization and death worldwide. Recommendations for antibiotic treatment in patients hospitalized to a non-ICU ward vary widely between guidelines, because the optimal antibiotic strategy is unknown. Interpretation of the available evidence from clinical studies is complicated by the heterogeneity in designs and findings. In our study, we hypothesized that the most conservative strategy, beta-lactam monotherapy, would be non-inferior to strategies with a broader range of antibiotic coverage. The latter strategies are potentially related to increased antibiotic resistance. For this purpose, we randomized hospitals to follow three different strategies of preferred antibiotic treatment in consecutive periods of four months. Physicians were allowed to deviate from the preferred antibiotic treatment for medical reasons. We found that a strategy with beta-lactam monotherapy (e.g. amoxicillin) as the preferred treatment was non-inferior to the strategies with beta-lactam/macrolide combination therapy or fluoroquinolone monotherapy for 30 and 90-day all-cause mortality. Also there was no difference in length of hospitalization and rate of complications.