Medical Research Journals

MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands  Medical Research: What is the background for this study?   Dr. Poortmans:  Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.  Medical Research: What are the main findings?  Dr. Poortmans:  We found a decreased risk for development of distant metastases of 3% at 10 years, translated in a 3% overall improved overall disease free survival. Up to now, It leads to an improvement of 1.6% in overall survival at 10 years, which is, in contrast to the earlier 2 findings, just not statistically significant (borderline at p = 0.06). On the other hand, breast cancer related mortality is significantly improved and we did not see an increase in non breast cancer related causes of death. Overall toxicity was limited with only a significant increase in pulmonary toxicity, however to a low grade in the big majority of those patients. The benefit in overall survival is in a similar order of magnitude than adding for example taxanes to anthracycline-based adjuvant chemotherapy for a similar patient population as ours.  Medical Research: What should clinicians and patients take away from your report? Dr. Poortmans:     First, we should appreciated that the regional (lymph node) recurrence rate is a poor endpoint for evaluation of also locoregional treatment. This can be explained by the fact that once distant metastases are found, no further search for local (breast) or regional (lymph nodes) recurrences is performed any more, as this is not relevant anymore for treatment or prognosis. However, the spread of distant metastases might occur from cancer involvement of the lymph nodes, explaining why we saw the effect of the lymph node irradiation basically only on the rate of development of distant metastases.     As a second message, we can appreciate that the 3% decreased distant metastases rate did not yet fully translate into a survival benefit, which can be explained by the need for even longer follow-up than 10 years. The explanation lies simply in the fact that even after development of distant metastases, patients can live for quite some more years with, however, only very little chance for definitive cure.     Thirdly, we demonstrated with the quality assurance programme linked to this trial that radiation treatment as used those days (the accrual phase was from 1996 until January 2004) radiation therapy techniques should be nowadays considered as suboptimal with a lack of full coverage of the target volumes and delivery of a too high dose to the organs at risk. With modern techniques, we expect that the results will even be quite better.     And finally, that the overall outcome of breast cancer improved a lot: at the start of the trial, we estimated overall survival at 10 years being 50%, which we revised in 2000 to 75% and we ended up with more than 80%. Thereby, it becomes more of a challenge to demonstrate benefits of further improving treatment as the same relative improvement will be translated into a lower absolute improvement. Nevertheless, by more effectively preventing the development of distant metastases by improved systemic therapy (or even better by earlier detection with a lower basal rate of distant metastases) the importance of optimizing locoregional control becomes even higher.   Medical Research: What recommendations do you have for future research as a result of this study?  Dr. Poortmans:   o	First of all we have to improve our ability to define which patients will gain most from this treatment.  o	Secondly, we have to further investigate how to optimize the technical aspects of this loco regional treatment and … o	Thirdly how to optimally integrate all treatment aspects including locoregional ones and systemic ones.  o	Based on all this, we can develop and then provide the patients with shared decision making tools.    Citation: Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer Philip M. Poortmans, Ph.D., Sandra Collette, M.Sc., Carine Kirkove, Ph.D., Erik Van Limbergen, Ph.D., Volker Budach, Ph.D., Henk Struikmans, Ph.D., Laurence Collette, Ph.D., Alain Fourquet, Ph.D., Philippe Maingon, M.D., Mariacarla Valli, M.D., Karin De Winter, M.D., Simone Marnitz, M.D., Isabelle Barillot, Ph.D., Luciano Scandolaro, M.D., Ernest Vonk, M.D., Carla Rodenhuis, Ph.D., Hugo Marsiglia, Ph.D., Nicola Weidner, Ph.D., Geertjan van Tienhoven, Ph.D., Christoph Glanzmann, Ph.D., Abraham Kuten, M.D., Rodrigo Arriagada, M.D., Harry Bartelink, Ph.D., and Walter Van den Bogaert, Ph.D. for the EORTC Radiation Oncology and Breast Cancer Groups N Engl J Med 2015; 373:317-327 July 23, 2015 DOI: 10.1056/NEJMoa1415369       MedicalResearch.com is not a forum for the exchange of personal medical information, advice or the promotion of self-destructive behavior (e.g., eating disorders, suicide). While you may freely discuss your troubles, you should not look to the Website for information or advice on such topics. Instead, we recommend that you talk in person with a trusted medical professional. The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. Philip.Poortmans@radboudumc.nl MedicalResearch.com Interview with: Philip M.P. Poortmans PhD MD Head of Department, Radiation Oncology ESTRO President Radboud university medical center The Netherlands   Medical Research: What is the background for this study? Dr. Poortmans: Based on the former hypothesis that breast cancer sequentially spreads from breast to lymph nodes and from there to distant organs, up to the eighties it was very custom to perform extended radical surgery and to irradiate extensively locoregional for most patients. With the growing interest in systemic treatments to prevent development (= from already present undetectable cancer cells to really visible and threatening metastases) of distant metastases, new information about possible late side effects and our increasing knowledge about the biological behaviour of breast cancer in the eighties and the nineties, the extend of especially locoregional treatment was gradually reduced. For radiation therapy, often the irradiation of the internal mammary lymph nodes was left aside, as this was linked to the delivery of radiation dose to the heart, possibly or probably leading to late side effects. At the start of the study, about half of the radiation oncology departments did include irradiation of the internal mammary lymph nodes in patients with risk factors, while the other half did not. Hereby we had an ideal base for the investigation of the value of treating the non-operated part of the regional lymph nodes.

Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental MedicineMedicalResearch.com Interview with: Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Williams: Individuals with uncontrolled blood sugar levels frequently present with higher than normal rates of infection and protracted wound healing. The beta-defensin family of antimicrobial peptides responds to bacterial, fungal and viral invasion. As part of the innate immune system, these cationic peptides normally expressed by epithelial cells are important early responders that, together with other components of the innate immune response, act to inhibit microbial infection. Our initial observations led us to question whether glucose or a metabolite of glucose could contribute to antimicrobial peptide dysfunction, and thus compromise control of infection. Elevated levels of glucose result in increased production of dicarbonyls, a class of molecule that can selectively react with proteins having an unusually high content of cationic amino acids, such as arginine and lysine. We first investigated the effects of two well-characterized dicarbonyls, methylglyoxal (MGO) and glyoxal (GO) on recombinant beta-defensin 2 (rHBD-2) structure using MALDI TOF and LC/MS/MS mass spectral analysis of the recombinant peptide. We found MGO to be particularly reactive with the rHBD-2 peptide as it readily and irreversibly adducted to two arginine residues and the N-terminal glycine. Next we tested in vitro for the effects of adducted rHBD-2 on antimicrobial and chemotactic functions, both essential to an effective innate and adaptive immune response in vivo. Through radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, we found that both antimicrobial and chemotactic functions of rHBD-2 were significantly compromised by MGO.

Laura Ekblad, MD, researcher Turku PET CentreMedicalResearch.com Interview with: Laura Ekblad, MD, researcher Turku PET Centre Medical Research: What is the background for this study? What are the main findings? Dr. Ekblad: The background for our study is that the metabolic syndrome and diabetes have been shown to increase the risk for cognitive decline and dementia. Also, insulin resistance is thought to play a pivotal role in the pathophysiology of Alzheimer´s disease. In addition, intranasal insulin administration is being studied as a promising treatment for Alzheimer´s disease. Previous studies indicate that both gender and APOE epsilon 4 genotype modulate the effects of insulin on cognition. Our main findings are that insulin resistance is associated with poorer verbal fluency, but only in women. Our population-based study consisted of adults from 30-97 years of age and we had nearly 6000 participants. Age did not modulate the association of insulin resistance and cognition, which means that our results apply even to young adults. We also found that insulin resistance associated with poorer verbal fluency only in non-carriers of the APOE epsilon 4 genotype.

Thomas F. Imperiale, MD Indiana University Medical Center Regenstrief Institute Indianapolis, IN 46202 MedicalResearch.com Interview with: Thomas F. Imperiale, MD Indiana University Medical Center Regenstrief Institute Indianapolis, IN 46202   Medical Research: What is the background for this study? Dr. Imperiale: The background is that colorectal cancer (CRC) screening is effective and cost-effective, but it is underutilized (35% of eligible persons in the U.S. are not current with screening; 28% have never been screened) and inefficient (persons at low risk have colonoscopy; persons at high risk have stool blood testing or nothing). We know about several risk factors for colorectal cancer and advanced, precancerous polyps. We wanted to see how those factors perform together in stratifying (or separating) risk among the 85% of the U.S. population that is considered to be “average-risk”. Medical Research: What are the main findings? Dr. Imperiale: We found that age, sex, whether a first-degree relative has or had colorectal cancer, cigarette smoking, and waist circumference do a good job in separating risk into the 4 categories described in the paper.  When tested in the validation subgroup, the risk estimates reproduced themselves fairly well. 

Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center  Boston, MA 02114MedicalResearch.com Interview with: Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific. Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families.  Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family.

Vitaly A Kushnir MD The Center for Human Reproduction New York, NY 10021MedicalResearch.com Interview with: Vitaly A Kushnir MD The Center for Human Reproduction New York, NY 10021 Medical Research: What is the background for this study? What are the main findings? Dr. Kushnir: In January 2013, the American Society for Reproductive Medicine declared the technique of oocyte cryopreservation no longer experimental, although they body did call for further study. Vitaly A. Kushnir, M.D., of the Center for Human Reproduction, and colleagues used 2013 data from 380 U.S fertility centers to compare live birth and cycle cancellation rates using either fresh or cryopreserved donor oocytes. The study found roughly 20 percent of donor cycles used cryopreserved oocytes and 80 percent fresh oocytes. Of those embryos transferred, 56 percent that started as fresh oocytes resulted in live births compared to just 47 percent of those that started as cryopreserved oocytes.

Misha A. Rosenbach, MD Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania Assistant Professor of Dermatology in MedicineMedicalResearch.com Interview with: Misha A. Rosenbach, MD Assistant Professor of Dermatology at the Hospital of the University of Pennsylvania Assistant Professor of Dermatology in Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Rosenbach: Sarcoidosis is an inflammatory disease of unknown etiology where genetically susceptible patients develop multi-organ granulomatous inflammation in response to an as-yet unidentified stimulus.  Patients with sarcoidosis typically have granulomatous inflammation in their lungs, but the second most commonly affected organ is the skin; the eyes, lymph nodes, liver, heart, brain, and other organs can be affected as well.  Patients with sarcoidosis can experience a few disease trajectories; some spontaneously recover, while others have persistent, active inflammation, whereas another group can experience inflammation which leads to scarring and fibrosis.  It can be challenging to distinguish these cohorts of patients based on their lungs alone. The skin is much easier to evaluate, as it is right there on the surface, and can be examined by physicians without resorting to invasive tests or radiography.  At Penn, we developed a novel cutaneous sarcoidosis assessment tool, called the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI), which is designed to accurately measure how inflamed skin sarcoid lesions are in a given patient, as well as describing which type of cutaneous lesion patients’ have.  The CSAMI has in previously studies been shown to be reliable when used by dermatologists, with excellent inter-rater and intra-rater reproducibility. In this study, we had a group of Pulmonologists, Rheumatologists, and Dermatologists (representing the groups of physicians who most commonly care for patients with sarcoidosis, especially if there is skin involvement) evaluate a group of patients with cutaneous sarcoidosis, using the CSAMI and another sarcoidosis activity instrument, the SASI, which has also previously been used to measure skin sarcoidosis activity in a number of settings.  We were able to demonstrate that these cutaneous scoring tools are reliable and reproducible and able to accurately measure cutaneous sarcoidosis disease activity in a variety of patients with a range of skin disease severity.  We also compared the physician scores to patients’ own evaluations of their disease, and showed that the CSAMI (physician impression of disease) correlated well with patients’ own perception of their disease activity and severity.

[caption id="attachment_16540" align="alignleft" width="238"]Prof. Der-Cherng Tarng, MD, PhD Division of Nephrology Taipei Veterans General Hospital, and National Yang-Ming University, Taiwan Prof. Der-Cherng Tarng[/caption] MedicalResearch.com Interview with: Prof. Der-Cherng Tarng, MD, PhD Division of Nephrology Taipei Veterans General Hospital, and National Yang-Ming University, Taiwan MedicalResearch: What is the background for this study? What are the main findings? Prof. Tarng: Metformin is generally recommended as a first-line therapy for type 2 diabetes mellitus, but the use of metformin has been limited in patients with impaired kidney function because of the perceived risk of lactic acidosis. More recently, available evidence supports the cautious expansion of metformin use in patients with mild to moderate chronic kidney disease (CKD). However, no studies have yet examined whether metformin can be prescribed more widely to patients with advanced CKD. We conducted a propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database to assess the safety of metformin in patients with type 2 diabetes and serum creatinine levels >6 mg/dL, enrolled between January 1, 2000 and June 30, 2009 and followed-up until December 31, 2009, before Taiwan’s prescribing guidelines for metformin contraindicated its use in patients with CKD. From a consecutive sample of 12350 patients, 1005 (8.1%) were metformin users. Of these, 813 were successfully matched 1:3 to 2439 metformin nonusers. After multivariate adjustment, metformin use remained was an independent risk factor for mortality (hazard ratio 1.35, 95% confidence interval 1.20–1.45; p<0.0001). The increased risk was dose-dependent and was consistent across all subgroup analyses. However, metformin users compared with non-users were associated with a higher but insignificant risk of metabolic acidosis (hazard ratio 1.30, 95% confidence interval 0.88–1.93; p=0.188).

James M. Shikany, DrPH Professor of Medicine Division of Preventive Medicine University of Alabama at Birmingham Birmingham, AL MedicalResearch.com Interview with: James M. Shikany, DrPH Professor of Medicine Division of Preventive Medicine University of Alabama at Birmingham Birmingham, AL   Medical Research: What is the background for this study? What are the main findings? Dr. Shikany: There is a growing interest in the field of nutritional epidemiology in relating overall dietary practices to various disease endpoints. For example, the assessment of dietary patterns in a population may be more meaningful than concentrating on isolated nutrients or foods because they more closely reflect how people eat in the real world. Previously, we looked at how the degree to which one adhered to 5 dietary patterns identified in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study was associated with the risk of stroke. In the current study, we investigated how the degree to which one adhered to these dietary patterns was related to the risk of incident acute coronary heart disease. The main finding was that a Southern dietary pattern (characterized by added fats, fried foods, eggs and egg dishes, organ meats, processed meats, and sugar-sweetened beverages) was associated with a significantly greater hazard of incident acute coronary heart disease in REGARDS participants. The association persisted following adjustment for sociodemographics, lifestyle factors, and energy intake. Specifically, following multivariable adjustment, participants in the highest quartile of consumption of the Southern pattern experienced a 56% greater hazard of incident coronary heart disease compared with those in the lowest quartile of consumption of this pattern. Another pattern we observed – the Plant-based pattern – characterized by vegetables, fruits, beans, yogurt, poultry, and fish was not associated with an increased risk of coronary heart disease.

MedicalResearch.com Interview with: Alisa Khan, MD Pediatric hospitalist Boston Children's Hospital and Instructor of Pediatrics Harvard Medical School Medical Research: What is the background for this study? Dr. Khan: Patients can be readmitted to the same hospital they were discharged from or to a different hospital.  In adults, readmissions to different hospitals make up about 20% of all readmissions.  We don’t know a lot about how often different-hospital readmissions happen in children. Insurance companies know hospitals’ true readmission rates (which include when a hospital’s patients are readmitted to the same hospital and when they are readmitted to a different hospital).  However, hospitals don’t know their true readmission rates since they don’t have access to the full information that insurance companies have. If hospitals don’t know their true rates, they may think they are doing better at preventing readmissions than they really (for instance, if all their discharged patients are simply being readmitted to a different hospital).  Hospitals may also draw incorrect conclusions when they compare themselves to one another (like through benchmarking), and may not be able to predict whether they will be subject to penalties by insurers for having excessively high readmission rates. Medical Research: What are the main findings? Dr. Khan: We found that about 1 in 7 pediatric readmissions in New York over a 5-year period were to a different hospital than the hospital the patient was discharged from.   The percentage of different-hospital readmissions varied by hospital and patient characteristics.  Patients who were admitted to non-children’s hospitals, lower-volume hospitals, or urban hospitals had a higher chance of being readmitted to a different hospital, as did patients who were younger, white, privately insured, or who had certain chronic conditions (like mental health, neurologic, and circulatory conditions). We also found a lot of variability in how much individual hospitals would underestimate their true readmission rates if they only used this incomplete same-hospital readmission info.  Some hospitals would underestimate their true readmission rates by only 0.6 relative percentage points while others would underestimate them by 68 points.

Prof. Dr. med. Christian F. Poets Neonatologie, Univ.-Klinikum Tübingen Tübingen GermanyMedicalResearch.com Interview with: Prof. Dr. med. Christian F. Poets Neonatologie, Univ.-Klinikum Tübingen Tübingen Germany Medical Research: What is the background for this study? Prof. Poets: Episodes of intermittent hypoxemia (lack of oxygen) and bradycardia (slow heart rate) are common in very preterm infants and often a subject of considerable concern. However, up to now there has been a lack of knowledge as to how often or how long such episodes may occur without increasing an infant’s risk for impaired development or even death. In this study, we utilized long-term recordings (lasting 8-12 weeks) of oxygen saturation and heart rate obtained as part of the Canadian Oxygen Trial (COT), a large study performed in extremely immature infants and comparing a higher with a lower oxygen saturation target range (85-89 vs. 91-95% oxygen saturation measured by pulse oximetry). For this secondary analysis, we wanted to test the hypotheses that spending a high proportion of time at an oxygen saturation below 80% or a pulse rate <80 beats per minute increases the risk of the following adverse outcomes:
  1. Death after reaching a post-menstrual age of 36 weeks (i.e. 4 weeks before their due date) or disability, determined at 18-22 months corrected age and defined as motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness;
  2. Motor impairment (determined at 18-22 months corrected age);
  3. Cognitive or language delay (determined at 18-22 months corrected age);
  4. Severe retinopathy of prematurity.
Medical Research: What are the main findings? Prof. Poets: Analyzable recordings and outcome data were available for 1019 infants, of which the least affected 10% spent 0.4%, and the most affected infants 13.5% of the time at an oxygen saturation <80%. We found that the risk to develop all of the adverse outcomes mentioned above increased with the percentage of time spent at an oxygen saturation below 80%, but this was true only for hypoxemic events lasting for at least 1 minute. Episodes with a low heart rate (in the absence of concomitant hypoxemia) were not associated with an increased risk of an adverse outcome. Interestingly, hypoxemic events occurring in infants originally randomized to the higher oxygen group in the original COT study were associated with a stronger increase in the risk of death or disability than such episodes occurring infants randomized to the lower oxygen saturation target range. 

MedicalResearch.com Interview with: Matthew Schrag MD Department of Neurology Yale University New Haven, Connecticut   Medical Research: What is the background for this study? What are the main findings? Dr. Schrag: Central retinal artery occlusion  (CRAO) is a relatively rare disorder that is caused by interruption of blood flow to the retina, usually by a clot or some other embolus.  Despite around 150 years of research, no compelling treatment has been found for this disease.  Treatment with fibrinolytics has been used experimentally for a long time and some of the results have been encouraging.  The point of the current study was to aggregate all of this observational data and compare how patients withCentral retinal artery occlusion do when treated with fibrinolytics versus when they are treated with other approaches or not treated at all. The biggest surprise in the data was the poor performance of conventional treatments at less than half the recovery rate of patients who were simply left alone.  The literature on treating central retinal artery occlusion with ocular massage, hemodilution or anterior chamber paracentesis has never been particularly compelling, but these treatments were thought to be harmless and are often practiced in the acute management of central retinal artery occlusion.  This new analysis strongly suggests that these interventions may be harmful.  While this data is not perfect (it is retrospective, non-randomized, acquired over long periods of time, etc), for me it raises enough doubt that I think ocular massage, anterior chamber paracentesis and hemodilution should be abandoned as treatments for acute CRAO.

MedicalResearch.com Interview with: Raymond Osarogiagbon MD, FACP Thoracic Oncology Research Group Baptist Cancer Center Memphis, Tennessee MedicalResearch.com Interview with: Raymond Osarogiagbon MD, FACP Thoracic Oncology Research Group Baptist Cancer Center Memphis, Tennessee

Medical Research: What is the background for this study? What are the main findings? Dr. Osarogiagbon: Lung cancer care is complicated, but can be broken down into 5 steps: x-ray detection, biopsy, x-ray tests of cancer spread (the ‘stage’), biopsy of suspicious areas where cancer may have spread, and treatment. Looking only at patients who had surgery for a suspected lung cancer, we worked backwards to see how their care went through the key steps and how long it took. We found that patients often skip some of the crucial steps. For example, 22% did not have a staging PET/CT scan, 88% did not have an invasive staging test. Only 10% had the recommended combination of 3 staging tests leading up to surgery: a CT scan, PET/CT scan, and invasive staging test. It took a month and a half to more than 6 months for the middle half of patients to go from first abnormal x-ray sign of possible lung cancer to surgery.

Rachel Patzer, PhD, MPH Director of Health Services Research, Emory Transplant Center Assistant Professor Department of Surgery Division of Transplantation Emory University School of MedicineMedicalResearch.com Interview with: Rachel Patzer, PhD, MPH Director of Health Services Research, Emory Transplant Center Assistant Professor Department of Surgery Division of Transplantation Emory University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Patzer: There are two main treatments for patients with end stage kidney disease: dialysis or kidney transplantation.  Kidney transplantation offers the best survival and quality of life compared to dialysis.  However, there is a limited supply of organs in the U.S., so not all patients with end stage organ failure get a kidney transplant. Certain regions of the country have lower access to kidney transplantation than other regions.  The Southeastern United States (GA, NC, and SC) has the lowest rates of kidney transplantation in the nation, and Georgia (GA) is the state that ranks at the very bottom. Our research team and collaborators from the Southeastern Kidney Transplant Coalition sought to examine some of the reasons for why Georgia had the lowest rates of kidney transplantation in the nation.  The transplant centers in our Coalition collaborated to share data on patient referrals from dialysis facilities, where the majority of end stage renal disease patients receive treatment, to transplant centers in Georgia. Referral from a dialysis facility to a transplant center is required for patients to undergo the extensive medical evaluation that is required for a patient to either be placed on the national deceased donor waiting list, or to receive a living donor kidney transplant (e.g. from a friend or family member). There were several major findings: 1)    That overall, referral of patients from a dialysis facility to a kidney transplant center is low (only about 28% of patients with kidney failure are referred to a transplant center within a year of starting dialysis). 2)    There was much variation in referral for transplantation across dialysis facilities in GA, where some facilities referred no patients within a year, and others referred up to 75% of their patient population.

MedicalResearch.com Interview with: Simona F. Shaitelman, MD, EdM Assistant Professor Department of Radiation Oncology University of  Texas MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? Dr. Shaitelman: Our study compared two different radiation therapy regimens for women with early stage breast cancer and examined the acute and short term...

MedicalResearch.com Interview with: Dr. Keith Ahamad, a clinician scientist at the BC Centre for Excellence in HIV/AIDS and a Family Doctor trained and certified in Addiction Medicine.  He is Division Lead for Addiction Medicine in the department of Family and Community Medicine at Providence Health Care, and is also an addiction physician at the St. Paul’s Addiction Medicine Consult Service, the Immunodeficiency Clinic and Vancouver Detox. He is also Lead Study Clinician for CHOICES, a US National Institutes of Drug Abuse (NIDA) funded clinical trial looking at an opioid receptor blocker (Vivitrol) to treat opioid or alcohol addiction in HIV positive patients.Dr. Keith Ahamad, a clinician scientist at the BC Centre for Excellence in HIV/AIDS and a Family Doctor trained and certified in Addiction Medicine. He is Division Lead for Addiction Medicine in the department of Family and Community Medicine at Providence Health Care, and is also an addiction physician at the St. Paul’s Addiction Medicine Consult Service, the Immunodeficiency Clinic and Vancouver Detox. He is also Lead Study Clinician for CHOICES, a US National Institutes of Drug Abuse (NIDA) funded clinical trial looking at an opioid receptor blocker (Vivitrol) to treat opioid or alcohol addiction in HIV positive patients. MedicalResearch: What is the background for this study? Dr. Ahamad: Previous methadone research has mostly been done in restrictive settings, such as the USA, where methadone can only be dispensed through restrictive methadone programs and cannot be prescribed through primary care physician’s offices. Since a systematic review in 2012, randomised controlled trials have compared methadone treatment provided at restrictive specialty clinics with primary care clinics, which have shown the benefits of primary care models of methadone delivery on heroin treatment outcomes, but not on HIV incidence. MedicalResearch: What are the main findings? Dr. Ahamad: After adjusting for factors commonly associated with HIV, methadone remained independently associated in protecting against HIV in this group of injection drug users. Those study participants who were not prescribed methadone at baseline were almost four times more likely to contract HIV during study follow up. MedicalResearch: What should clinicians and patients take away from your report? Dr. Ahamad: Methadone is an effective medication in treating opioid addiction. Through international randomized control trials, we already know that when prescribed though primary care offices, access to this life-saving medication is increased, effective, and increases patient satisfaction. Now, through our study, we have evidence that when delivered in this manner, it also decreases the spread of HIV.

[caption id="attachment_16466" align="alignleft" width="224"]Erika Newton MD, MPH Erika Newton MD, MPH[/caption] MedicalResearch.com Interview with: Erika Newton MD, MPH Department of Emergency Medicine Stony Brook University Medical Center Stony Brook, NY and Brenda Sirovich MD, MS Staff Physician Co-Director Outcomes Group VA Medical Center White River Junction, VT Associate Professor of Medicine and of Community and Family Medicine Geisel School of Medicine at Dartmouth, and The Dartmouth Institute for Health Policy and Clinical Practice Division of Trauma Surgery, Department of Surgery Stony Brook University Medical Center Stony Brook, New York Medical Research: What is the background for this study? Response: Clinical performance measures – quality indicators used to evaluate and motivate health care providers' performance – play a central role right now in efforts to improve quality in U.S. health care. But their potential to influence care on a wide scale has some worried about unintended effects. In particular, there’s been growing concern that if performance measures focus disproportionately on underuse of care – that is, measuring whether enough care is being provided – they risk leading to unexpected consequences.   Specifically, if incentives tend to reward clinicians for doing more without attention to whether they do too much – this could inadvertently contribute to the problem of excessive care, or overuse. Medical Research: What are the main findings? Response: We thought it was important to look at what that balance is – between measures of underuse and measures of overuse – in outpatient practice.   We looked at 16 major national collections of performance measures and essentially counted measures targeting underuse (‘Did the clinician do enough?’) versus overuse (‘Did the clinician do too much?’). We found that over 90 percent of 521 outpatient measures targeted underuse, while a mere 7 percent of outpatient measures addressed overuse – in fact nearly half of the collections contained no overuse measures at all.

Helle Søholm, MD, PhDDepartment of Cardiology Copenhagen University Hospital Rigshospitalet Denmark MedicalResearch.com Interview with: Helle Søholm, MD, PhD Department of Cardiology Copenhagen University Hospital Rigshospitalet Denmark Medical Research: What is the background for this study? Dr. Søholm: The background of the current study is that previous studies have found higher survival rates after out-of-hospital cardiac arrest and admission to tertiary heart centres for post-resuscitaton care compared with nontertiary hospitals, however the reasons for this difference has only been speculative. The aim of the study was to examine the level-of post-resuscitation care at tertiary heart centers compared with nontertiary hospitals and to associate this with outcome. Only patients without ST-segment elevation myocardial infarction was examined to avoid referral bias. Medical Research: What are the main findings? Dr. Søholm: The main findings of the study of 1.078 patients was that the survival in patients admitted to tertiary heart centers was significantly higher compared with survival in patients admitted to nontertiary hospitals even after adjustment for known risk markers including pre-arrest co-morbidity. We found that the adjusted odds of predefined markers of level-of-care differed in both the acute phase after admission, during the intensive care admission and in the workup prior to hospital discharge. The odds of admission to an intensive care unit was 1.8 for patients admitted to a tertiary heart centre. During the intensive care admission the odds of a temporay pacemaker was 6.4, use of vasoactive agents 1.5, acute and late coronary angiography was 10 and 3.8 respectively, neurophysiological examination 1.8, brain computed tomography 1.9, whereas no difference in the odds of therapeutic hypothermia was found. Prior to hospital discharge the odds of a consultation by a cardiologist was 8.6, having an echocardiography was 2.9, and survivors more often had an implantable cardioverter defibrillator implanted (odds 2.1) as compared with patients admitted to nontertiary hospitals.

Prof-Kate-JollyMedicalResearch.com Interview with: Prof. Kate Jolly Professor of Public Health and Primary Care Public Health Building School of Health & Population Sciences University of Birmingham Edgbaston Birmingham Medical Research: What is the background for this study? Response: The UK is amongst 32 countries worldwide with evidence of iodine deficiency. Severe iodine deficiency during pregnancy is associated with a lower intelligence quotient (IQ) and developmental abnormalities in the children; these are reversible by iodine supplementation during pregnancy. However, the effects of mild or moderate iodine deficiency during pregnancy are less clear as there are no high quality trials of supplementation that have reported the outcome of child IQ. However, in two studies in the UK and Australia, nine year old children of women who had a urinary iodine concentration suggestive of mild iodine deficiency during their pregnancy exhibited reduced educational outcomes and decreased IQ scores compared to children of iodine replete mothers. Recent research from the UK suggests that the country has become mildly iodine deficient. Many countries address their iodine deficiency by programmes of adding iodine to salt and some recommend that pregnant women take iodine supplements. Neither of these occur in the UK, although some commonly used pregnancy supplements already include iodine. Controversy about the need for supplementation in pregnancy, the ethics of undertaking a trial in which women would be randomly allocated to have iodine supplements, or not, and the high cost of following-up and assessing large numbers of children makes a trial unlikely.

Henning Kelbæk, MD Department of Cardiology Roskilde Hospital Roskilde, DenmarkMedicalResearch.com Interview with: Henning Kelbæk, MD Department of Cardiology Roskilde Hospital Roskilde, Denmark Medical Research: What is the background for this study? What are the main findings? Dr. Kelbæk: The background to conduct the DANAMI 3-Primulti trial is the uncertainty of which strategy is most favourable to the patient with ST-segment elevation myocardial infarction: to treat the culprit (resposible for the acute infarction) lesion only or to treat all visible lesions (complete revascularisation) The main findings of the PRIMULTI trial are that patients with ST-segment elevation myocardial infarction and multivessel disease, benefit from supplementary complete revascularisation of lesions in non-infarct related arteries when the second procedure is done during the index admission guided by measurement of the fractional flow reserve. This strategy results in a significant reduction in the combination of all-cause mortality, nonfatal reinfarction, and ischaemia-driven revascularisation.

Connie N. Hess, MD, MHS Duke Clinical Research Institute Duke University Durham, North CarolinaMedicalResearch.com Interview with: Connie N. Hess, MD, MHS Duke Clinical Research Institute Duke University Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Dr. Hess: Guidelines recommend the use of anticoagulation for thromboembolic prophylaxis in atrial fibrillation and also recommend use of dual antiplatelet therapy to reduce cardiovascular events after myocardial infarction and percutaneous coronary intervention.  The use of triple therapy in patients with indications for DAPT and anticoagulation is challenging due to the increased bleeding risk associated with this regimen.  The optimal antithrombotic regimen in this population has not yet been defined. This study specifically focused on older patients, a population that is at greater risk for Atrial Fibrillation-related stroke and recurrent events after MI but also higher risk for bleeding. Despite a growing population of older patients with indications for triple therapy, these patients have been underrepresented in clinical trials and are therefore understudied. We found that relative to DAPT, patients on triple therapy had a similar risk of 2-year major adverse cardiac events but a significantly increased risk of bleeding requiring hospitalization, including greater risk of intracranial hemorrhage.

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: Reshma Jagsi, MD, DPhil Associate Professor and Deputy Chair Department of Radiation Oncology University of Michigan Medical Research: What is the background for this study? What are the main findings? Response: In recent years, there has been accumulating evidence from clinical trials that have supported the long-term safety and effectiveness of shorter courses of radiation therapy—“hypofractionated radiation therapy”—for patients with breast cancer.  However, little has been known about the experiences of patients during treatment, especially when this new approach is administered outside the setting of closely controlled clinical trials.  Our study examined the side effects and patient-reported experiences during radiation treatment of over 2000 breast cancer patients in the state of Michigan.  It found that women who received hypofractionated treatment were less likely to report side effects (including skin reaction and fatigue) than patients treated with more traditional courses of radiation treatment, delivered daily over 5-6 weeks or longer.

Dr. Audrey J Gaskins Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MAMedicalResearch.com Interview with: Dr. Audrey J Gaskins Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gaskins: Previous studies have linked shift work, long working hours, and physical factors to an increased risk of menstrual cycle disturbances, spontaneous abortion, preterm birth, and low birth weight; however the association with fecundity is inconsistent. Several papers have also reviewed the occupational exposures of health care workers and concluded that reproductive health issues are a concern. Therefore we sought to determine the extent to which work schedules and physical factors were associated with fecundity in a large cohort of nurses. Women who work in an industry that requires them to work from a height or even lift heavy objects requires them to undertake training which guides them though the effective stages on how to work safely at heights. Without the right training, this sort of work can become very dangerous. Our main findings were that that working >40 hours per week and moving or lifting a heavy load >15 times per day (including repositioning or transferring patients) were associated with reduced fecundity in our cohort of female nurses planning pregnancy. However, all other factors such as frequency of night work, duration of rotating and non-rotating night shifts, and time spent walking or standing at work were not significantly associated with fecundity in this cohort.

Dr. Arthur Caplan Ph.D. Drs. William F and Virginia Connolly Mitty Professor Head of the Division of Medical Ethics New York University, Langone Medical Center, NYMedicalResearch.com Interview with: Dr. Arthur Caplan Ph.D. Drs. William F and Virginia Connolly Mitty Professor Head of the Division of Medical Ethics New York University, Langone Medical Center, NY Medical Research: What is the background of the Down Syndrome Prenatal Education Act? Dr. Caplan: For many years women who  receive a positive prenatal test for Down syndrome have been aborting their pregnancies.  Rates of pregnancy termination, while somewhat disputed, are very high.  In the USA, UK and Denmark they have consistently been over 80% for many years.   This has led some parents of children with Down to wonder if the counseling that women receive is biased negatively against a life with Down. They working with pro life legislators in many states have promoted legislation to insure that mothers carrying an infant with a diagnosis of Down Syndrome have access to positive information and helpful resources about life with a child with Down.  This legislation has been enacted in many states and there is a Federal law as well. Medical Research: How does Chloe's Law impact genetic testing? Dr. Caplan: These laws represent a seismic shift in counseling about genetic disorders and diseases.  Historically counselors aspired to be value-free—simply trying to provide objective information to their patients/clients.  With laws like Chloe’s the public is saying they do not trust the neutrality of counselors and counseling and want more positive messages sent about Down.  This is quite simply an ethical revolution in how counseling for Down will be done in the future.  It is also a direct Challenge to the legitimacy of value-neutrality as a counseling norm that certainly will be extended to other conditions and disabilities where abortion rates are high and where there is the belief that there is unjustified prejudice or bias against disabilities among those working in clinical genetics.

Timothy M. Pawlik, MD, MPH, MTS, PhD, FACS, FRACS (Hon.)Professor of Surgery and Oncology John L. Cameron M.D. Professor of Alimentary Tract Diseases Chief, Division of Surgical Oncology Program Director, Surgical Oncology Fellowship Director, Johns Hopkins Medicine Liver Tumor Center Multi-Disciplinary Clinic Johns Hopkins Hospital Baltimore, MD 21287MedicalResearch.com Interview with: Timothy M. Pawlik, MD, MPH, MTS, PhD, FACS, FRACS (Hon.) Professor of Surgery and Oncology John L. Cameron M.D. Professor of Alimentary Tract Diseases Chief, Division of Surgical Oncology Program Director, Surgical Oncology Fellowship Director, Johns Hopkins Medicine Liver Tumor Center Multi-Disciplinary Clinic Johns Hopkins Hospital Baltimore, MD 21287 MedicalResearch: What is the background for this study? What are the main findings? Dr. Pawlik: In 2012, the Centers for Medicare and Medicaid Services (CMS) introduced the Hospital Readmission Reduction Program (HRRP) whereby hospitals with higher than expected 30-day readmission incur financial penalties. Initially proposed to target readmissions following acute myocardial infarction, pneumonia and congestive heart failure, the program has since expanded to encompass knee and hip replacement surgery with the inclusion of additional surgical procedures anticipated in the near future. Although initial results from the Hospital Readmission Reduction Program have been promising, several concerns have been raised regarding potential limitations in methodological approach; specifically in the ability to adequately risk-adjust and account for variations in patient, provider and disease. As a consequence, many fear that the Hospital Readmission Reduction Program may disproportionately penalize safety-net hospitals as well as hospitals caring for “sicker” and more vulnerable populations. In the current study we sought to investigate factors associated with the variability in 30-day readmission among a cohort of 22,559 patients discharged following a major surgical procedure at the Johns Hopkins Hospital between 2009 and 2013. Overall, 30-day readmission was noted to be 13.2% varying from 2.1% to 24.8% by surgical specialty / procedure and from 2.1% to 32.9% by surgeon. Non-modifiable patient specific factors such as preoperative comorbidity, insurance status and race / ethnicity, were found to be most predictive of 30-day readmission as well as postoperative factors such as complications and length of stay both of which may also be influenced by preoperative comorbidity. Overall, we noted that 2.8% of the variation in 30-day readmission was attributed to provider-specific factors, 14.5% of the variability was due differences in surgical specialty / procedure while over 84% of the variability in 30-day readmission remained unaccounted for due to non-modifiable patient-specific factors.

Edward W. Cowen, MD, MHSc Dermatology Branch, Center for Cancer Research National Cancer Institute Bethesda, MarylandMedicalResearch.com Interview with: Edward W. Cowen, MD, MHSc Dermatology Branch, Center for Cancer Research National Cancer Institute Bethesda, Maryland Medical Research: What is the background for this study? Dr. Cowen: Cutaneous leiomyomas are benign smooth muscle proliferations that are associated with pain that is typically not well-controlled by topical remedies or systemic pain medication. Hereditary leiomyomatosis and renal cell cancer is a rare syndrome in which patients may have dozens or even hundreds of these painful tumors. We sought to determine if botulinum toxin injected directly into leiomyomas may ameliorate discomfort and improve quality of life in patients who experience significant pain from cutaneous leiomyomas. Medical Research: What are the main findings? Dr. Cowen: In a double-blinded placebo-controlled study, we found that injection of botulinum toxin was associated with improved skin-related quality of life (p = 0.007) and decreased skin-specific pain (p = 0.048) on the Dermatology Life Quality Index. A trend for decreased pain (p = 0.06) by visual analog score was reported in the botulinum toxin treated group compared to the placebo group.

MedicalResearch.com Interview with: Paul Little MBBS, BA, MD, DLSHTM, MRCP, FRCGP, FMedSci Professor of Primary Care Research University of Southampton

Medical Research: What is the background for this study? What are the main findings? Prof. Little: Hand washing has been recommended to help prevent respiratory infections (coughs, colds flu, sore throats) - this can be important in normal winters but might be especially important in pandemic flu years. However, there has been little evidence from randomised trials to date to show that handwashing works. [caption id="attachment_16369" align="alignleft" width="350"]A simple internet based intervention to support increasing handwashing behaviour reduced the numbers of infections caught and the number of infections given to family members, A simple internet based intervention to support increasing hand washing behavior reduced the numbers of infections caught and the number of infections given to family members,[/caption]

Dr. Salim Abdool Karim at CAPRISA Doris Duke Medical Research Institute South AfricaMedicalResearch.com Interview with: Dr. Salim Abdool Karim at CAPRISA Doris Duke Medical Research Institute South Africa Medical Research: What is the background for this study? What are the main findings? Response: Globally, Herpes simplex virus type-2 (HSV-2) is among the most common sexually transmitted infections and is the leading cause of genital ulcers. Available global estimates indicate that approximately 417 million sexually active adults between the ages of 15 and 49 years had an existing prevalent HSV-2 infection in 2012. Current interventions to prevent HSV-2 infection, including condoms, circumcision, and antiviral treatment among heterosexual, HSV-2-discordant couples, have demonstrated protection levels ranging from 6% to 48%. This study showed that peri-coital tenofovir gel reduced HSV-2 acquisition in women by 51%, rising to 71% in high gel-users.

MedicalResearch.com Interview with: Lu Qi, MD, PhD, FAHA Associate Professor of Medicine Harvard Medical School Associate Professor of Nutrition and Epidemiology Harvard T.H. Chan School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Lu Qi: There are accumulating evidence from mostly experimental research to show the benefit...

MedicalResearch.com Interview with: Karen E. Hansen, M.D., M.S. Associate Professor of Medicine University of Wisconsin School of Medicine and Public Health Madison, WI 53705-2281 Medical Research: What is the background for this study? Dr. Hansen: The USPTF says to older community dwelling adults, "don't bother taking vitamin D", the Endocrine Society says "take 2,000-4,000 IU daily" and the Institute of Medicine gave an RDA of 600-800 IU daily. The Endocrine Society argues that optimal vitamin D levels are 30 ng/mL and higher, while the Institute of Medicine concludes that 20 ng/mL and higher indicates optimal vitamin D status. The disagreement between experts prompted my study. Medical Research: What are the main findings? Dr. Hansen: Among postmenopausal women whose vitamin D level was ~21 ng/mL at baseline, there was no benefit of high-dose or low-dose vitamin D, compared to placebo, on spine/hip/total body bone mineral density, muscle fitness by 5 sit to stand test or Timed Up and Go, or falls. We did see a small 1% increase in calcium absorption in the high-dose vitamin arm, but this small increase did not translate into clinically meaningful changes in bone density or muscle tests.