Medical Research Journals

[caption id="attachment_20345" align="alignleft" width="177"]Dr. Marc LaRochelle MD MPH Dr. LaRochelle[/caption] MedicalResearch.com Interview with: Marc R. Larochelle, MD, MPH Assistant Professor of Medicine Boston Medical Center Boston, MA  Medical Research: What is the background for this study? What are the main findings? Dr. Larochelle: More than 16 thousand people in the United States die from prescription opioid overdose each year. However, morbidity extends well beyond fatal overdose - nearly half a million emergency department visits each year are related to prescription opioid-related harms. Emergency department visits for misuse of opioids represent an opportunity to identify and intervene on opioid use disorders, particularly for patients who receive prescriptions for opioids to treat pain. We examined a cohort of nearly 3000 commercially insured individuals prescribed opioids for chronic pain who were treated for a nonfatal opioid overdose in an emergency department or inpatient setting. We were interested in examining rates of continued prescribing after the overdose and the association of that prescribing with risk of repeated overdose. We found that 91% of individuals received another prescription for opioids after the overdose. Those continuing to receive opioids at high dosages were twice as likely as those whose opioids were discontinued to experience repeated overdose.

[caption id="attachment_20200" align="alignleft" width="175"]Oreofe O. Odejide, MD Instructor in Medicine, Harvard Medical School Dana-Farber Cancer Institute Dr. Odejide[/caption] MedicalResearch.com Interview with: Oreofe O. Odejide, MD Instructor in Medicine, Harvard Medical School Dana-Farber Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Odejide: The care that patients with hematologic cancers receive near the end of life is distinct from patients with solid tumors. For instance, previous research has shown that patients with blood cancers are more likely to receive intensive care at the end of life such as chemotherapy within 14 days of death, intensive care unit admission within 30 days of death, and they are less likely to enroll in hospice. My colleagues and I hypothesized that timing of discussions regarding end-of-life preferences with patients may contribute to these findings, and we wanted to examine hematologic oncologists’ perspectives regarding end-of-life discussions with this patient population. We conducted a survey of a national sample of hematologic oncologists obtained from the publicly available clinical directory of the American Society of Hematology. We received responses from 349 hematologic oncologists, giving us a response rate of 57.3%. In our survey, we asked hematologic oncologists about the typical timing of EOL discussions in general, and also about the timing of the first discussion regarding resuscitation status, hospice care, and preferred site of death for patients. Three main findings emerged:
  • First, the majority of hematologic oncologists (56%) reported that typical EOL discussions occur “too late.”
  • Second, hematologic oncologists practicing primarily in tertiary care settings were more likely to report late discussions compared to those in community settings.
  • Third, a substantial proportion of respondents reported that they typically conduct the initial discussions regarding resuscitation status, hospice care, and preferred site of death at less optimal times.

[caption id="attachment_20276" align="alignleft" width="100"]Tara F Carr, MD Assistant Professor, Medicine and Otolaryngology Allergy and Immunology Fellowship Training Program Director Director, Adult Allergy Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona Tucson, AZ 85724 Dr.  Carr[/caption] MedicalResearch.com Interview with: Tara F Carr, MD Assistant Professor, Medicine and Otolaryngology Allergy and Immunology Fellowship Training Program Director Director, Adult Allergy Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona Tucson, AZ 85724 Medical Research: What is the background for this study? What are the main findings? Dr. Carr: Some patients with chronic rhinosinusitis continue to suffer from symptoms despite aggressive medical and surgical treatments. For these individuals, therapy is generally chosen based on bacterial culture results, and often includes the use of topical antibacterial rinses with a medication called mupirocin.  We found that if patients are still having problems after this treatment, the bacteria identified from repeated sinus cultures are very different than those usually expected, and in general more difficult to treat.

MedicalResearch.com Interview with: Filippo Montemurro, M.D. Director, Investigative Clinical Oncology (INCO) Fondazione del Piemonte per l'Oncologia Candiolo Cancer Institute (IRCCS) Torino, Italy Medical Research: What is the background for this study? Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The "indirectness" of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended. Based on these premises, we designed a study to pursue two aims;
  • the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
  • the second was to compare doctors and patients reports of toxicities at corresponding time-points.
Medical Research: What are the main findings? Dr. Montemurro: We administered the 10-item questionnaire after the first and third cycle of adjuvant chemotherapy to 601 women who had undergone surgery for breast cancer. To develop this questionnaire, CTCAE definitions of severity for each item (nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea) were translated into Italian and rephrased into statements. Patients were asked to choose the statement that best represented the worst experience with that side effect after the reference cycle of chemotherapy. At the same time-points, research nurses extracted information from the medical charts and reported them in paired doctor questionnaires. A total of 99% and 97% of the patient returned filled in questionnaires. Pairwise comparisons showed that doctors systematically underestimated both incidence and severity for all the side effects. Interestingly, comparison of the two patient questionnaires revealed temporal changes that were possibly related to the effect of prophylactic measures taken after the first cycle (i.e. reduction in vomiting, diarrhea and pain) or to cumulative toxicties (i.e. worsening dysgeusia and dyspnea). No such changes except for worsening dyspnea were observed comparing the two doctors questionnaires. Finally, we found a direct relationship between number of patients and magnitude of discrepancy in side effects reporting was observed, suggesting that the workload could be a factor influencing this phenomenon.

MedicalResearch.com Interview with: Dr. Michael van Leeuwen PhD Department of Epidemiology Netherlands Cancer Institute Amsterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Over the last decades cure rates for Hodgkin’s lymphoma patients have increased dramatically. Cure and long-term survival may, however, come at a price, in the form of an increased risk of second cancers and other late effects. Since the late 1980’s treatment of Hodgkin’s lymphoma has been changed towards smaller radiation target volumes and more effective, generally less toxic chemotherapy. In a study which included 3905 Hodgkin’s lymphoma patients treated between 1965 and 2000 in the Netherlands, the impact of these treatment changes on second malignancy risk was evaluated. Hodgkin’s lymphoma patients were between the ages of 15 and 50 years and had survived at least 5 years after treatment. During follow-up, 1055 second cancers were diagnosed in 908 survivors, corresponding to a risk of 4.6 times as high as the occurrence of cancer in the general population. Up to at least 40 years after treatment for Hodgkin’s lymphoma, survivors remained at increased risk for second cancers. The cumulative incidence of a second cancer was 33.2% at 30 years, compared with 9.6% in the general population, and 48.5% at 40 years, compared with 19.0% in the general population. Breast cancer was the most common second cancer reported followed by lung and gastrointestinal cancers. Thirty-year cumulative incidence was 16.6% for breast cancer, 7.1% for lower respiratory tract cancers, 7.0% for gastrointestinal cancers, and 3.7% for non-Hodgkin’s lymphomas. The risk of solid cancer after treatment for Hodgkin’s lymphoma was not lower among more recently treated patients (patients treated between 1989 and 2000) than among those who were treated in earlier time periods, despite changes in treatment. Nonetheless, patients treated with smaller radiation fields (e.g., a supradiaphragmatic field radiotherapy not including the axilla) were at a 63% lower relative risk of breast cancer as a second malignancy than if they received complete mantle-field radiotherapy. The lack of change in the cumulative incidence of solid cancers could be due to an incomplete adoption of the more modern radiotherapy concepts but may also be explained on the basis of a change in the chemotherapy regimens used in the 1990s. Because in the 1970’s many women exposed to high doses of alkylating agents were experiencing premature menopause, doses of alkylating agents were lowered over time to preserve fertility. However, early menopause introduced with the alkylating regimens was likely responsible for decreasing the breast cancer incidence. With the lower doses of the alkylating agents, this protection was taken away. The cumulative incidence of non-Hodgkin’s lymphoma and of leukemia (and the myelodysplastic syndrome) was, however, much lower among patients who were treated in the period from 1989 through 2000 than among those who were treated in the period from 1965 through 1976. For leukemia, the decrease in cumulative incidence is likely due to the much lower doses of alkylating agents used in Hodgkin’s lymphoma treatment in the 1990’s compared to earlier decades. It is important to realize that current common practice in radiation oncology, including involved-node or involved-site radiotherapy, three-dimensional conformal radiation treatment planning, and radiation doses of less than 36 Gy, was not applied in our study population. It is hoped that these changes may reduce the risk of solid cancer among patients treated after 2000.

MedicalResearch.com Interview with: Prof. dr. D.L.P. Baeten MD Clinical Immunology and Rheumatology Academic Medical Center University of Amsterdam Amsterdam, The Netherlands Medical Research: What is the background for this study? What are the main findings? Prof. Baeten: Ankylosing spondylitis is a debilitating rheumatic condition which affects young adults and with NSAIDS and TNF inhibitors as only therapeutic option. Over the last years, we generated evidence that IL-17 is an important inflammatory mediator in this condition. In the two studies reported here in the NEJM, we demonstrate that IL-17 inhibition with secukinumab has a very profound and long-lasting effect on signs and symptoms as well as inflammation in ankylosing spondylitis patients, even in those patients that failed a TNF blocker before.

[caption id="attachment_11475" align="alignleft" width="150"]Kazem Rahimi | FRCP DM MSc FESC Associate Professor of Cardiovascular Medicine, University of Oxford Deputy Director, The George Institute for Global Health James Martin Fellow in Healthcare Innovation, Oxford Martin School Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust Prof. Kazem Rahimi[/caption] MedicalResearch.com Interview with: Kazem Rahimi | FRCP DM MSc FESC Associate Professor of Cardiovascular Medicine, University of Oxford Deputy Director, The George Institute for Global Health James Martin Fellow in Healthcare Innovation, Oxford Martin School Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust Medical Research: What is the background for this study? What are the main findings? Prof. Rahimi: Although the benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established, the extent to which these effects differ by baseline blood pressure, presence of co-morbidities (such as stroke or diabetes), or drug class is less clear. Medical Research: What should clinicians and patients take away from your report? Prof. Rahimi: Our study has several implications for clinical practice. Our findings suggest that blood pressure lowering to levels below those recommended in current guidelines (ie, systolic blood pressure of less than 140 mm Hg) will reduce the risk of cardiovascular disease. By showing no evidence for a threshold below which blood pressure lowering ceases to work, the findings call for blood pressure lowering based on an individual’s potential net benefit from treatment rather than treatment of the risk factor to a specific target. Furthermore, the differences we identified between classes of drugs support more targeted drug use for individuals at high risk of specific outcomes (eg, calcium channel blocker therapy for individuals at high risk of stroke or and diuretics are more eff ective for prevention of heart failure). Overall, our findings clearly show that treating blood pressure to a lower level than currently recommended could greatly reduce the incidence of cardiovascular disease and potentially save millions of lives if the treatment was widely implemented. The results provide strong support for reducing systolic blood pressure to less than 130 mmHg, and blood pressure-lowering drugs should be offered to all patients at high risk of having a heart attack or stroke, whatever their reason for being at risk. 

MedicalResearch.com Interview with: Carole Decker, RN, PhD, CPHQ, FAHA Director, Cardiovascular Outcomes Research Saint Luke's Mid America Heart Institute Kansas City, MO 64111 Medical Research: What is the background for this study? What are the main findings? Dr. Decker: Stroke is the leading cause of disability and the fifth leading cause of death. The utilization of thrombolytic therapy is the national standard of care for acute ischemic stroke (AIS) treatment resulting in improved outcomes at 90 days and yet only 7% of patients with AIS receive a thrombolytic. The American College of Emergency Physicians emphasizes the importance of using a shared medical decision-making model with AIS patients and their caregivers to discuss benefits and risks of treatment. The recommended door-to-needle (emergency door to thrombolytic administration) is 60 minutes to achieve the optimal patient outcomes which can be problematic in that conversation on benefits and risks occurs in a hurried emergency setting. Multiple risk models to identify individualized benefits and risks of thrombolytic therapy have been developed but few are used prospectively and are not used at the point of care. Our team created ePRISM (Personalized Risk Information Services Manager), a Web-based tool, to generate personalized documents with patient-specific outcomes based on validated risks models. To support knowledge transfer and creation of a shared decision-making tool, our multidisciplinary team conducted qualitative interviews to define the information needs and preferred presentation format for stroke survivors, caregivers, and clinicians considering thrombolytic treatment.

[caption id="attachment_20297" align="alignleft" width="110"]Philipp Schuetz, MD, MPH University Department of Medicine Clinic for Endocrinology/Metabolism/Clinical Nutrition, Kantonsspital Aarau, Aarau, Switzerland Medical Faculty of the University of Basel Basel, Switzerland Dr. Schuetz[/caption] MedicalResearch.com Interview with: Philipp Schuetz, MD, MPH University Department of Medicine Clinic for Endocrinology/Metabolism/Clinical Nutrition, Kantonsspital Aarau, Aarau, Switzerland Medical Faculty of the University of Basel Basel, Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Schuetz: Malnutrition is common in hospitalised patients and associated with detrimental metabolic consequences. The current clinical approach is to provide at risk patients nutritional support as a strategy to tackle malnutrition and its associated adverse outcomes. Yet, whether this strategy is effective and improves clinical outcomes in the medical inpatient population is unclear. In addition, recent trials from critical care have shown adverse outcomes when nutritional therapy was used too aggressively. Herein, our metaanalysis is the first to systematically investigate effects of nutritional support in medical inpatients. Our analysis shows that nutritional support is highly effective in increasing energy and protein intake and helps to stabilize weight loss. Also, risk for unplanned readmission after discharge from the hospital was reduced and length of stay was shorter in the patient population with established malnutrition. Yet, for other important clinical outcomes such as mortality and functional outcomes effects of nutritional support remained uncertain. Also, the quality of evidence was found to be moderate to low.

[caption id="attachment_20266" align="alignleft" width="120"]Dr. Marjanka Schmidt PhD Group Leader, Molecular Pathology Netherlands Cancer Institut Dr. Schmidt[/caption] MedicalResearch.com Interview with: Dr. Marjanka Schmidt PhD Group Leader, Molecular Pathology Netherlands Cancer Institute Medical Research: What is the background for this study? What are the main findings? Dr. Schmidt: BRCA1/2 mutation carriers who developed a primary breast cancer are thought to be at high risk to develop a contralateral breast cancer (breast cancer in the opposite breast). Our study is one of the first to provide unbiased risk estimates for young breast cancer patients with a pathogenic BRCA1/2 mutation. We also showed that age of onset of the first breast cancer is a predictor for the development of contralateral breast cancer in BRCA1/2 mutation carriers, but not in non-carriers.

[caption id="attachment_20294" align="alignleft" width="150"]Dr. Janet Rowan Obstetric Physician National Women's Health, Auckland Dr. Rowan[/caption] MedicalResearch.com Interview with: Dr. Janet Rowan Obstetric Physician National Women's Health, Auckland Medical Research: What is the background for this study? Dr. Rowan: Clinicians are interested in screening during early pregnancy to identify women with previously unrecognised diabetes, as these women have increased risks of adverse pregnancy outcomes. HbA1c is a simple and reproducible measure of glucose elevations, but its usefulness as an early pregnancy screening test is not clear. The aim of this study was to examine whether pregnant women with an HbA1c of 41-49mmol/mol (5.9-6.6%) are a high risk subgroup and whether treating these women from early pregnancy improves outcomes compared with identifying them during routine screening for gestational diabetes (GDM) from 24 weeks’ gestation. This observational study compared women referred to the diabetes clinic <24 weeks’ who had an early pregnancy HbA1c of 41-49mmol/mol (5.9-6.6%) with women who, at the time of diagnosis of GDM ≥24 weeks’ (typically by 75gOGTT), had an HbA1c of 41-49mmol/mol (5.9-6.6%). Both groups were compared with women diagnosed with GDM who had a lower HbA1c at diagnosis.

[caption id="attachment_20219" align="alignleft" width="176"]Christina Y. Weng, MD, MBA Assistant Professor-Vitreoretinal Diseases & Surgery Baylor College of Medicine-Cullen Eye Institute Dr. Christina Weng[/caption] MedicalResearch.com Interview with: Christina Y. Weng, MD, MBA Assistant Professor-Vitreoretinal Diseases & Surgery Baylor College of Medicine-Cullen Eye Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Weng: Telemedicine has been around for a long time, but only recently have technological advances solidified its utility as a reliable, effective, and cost-efficient method of healthcare provision.  The application of telemedicine in the field of ophthalmology has been propelled by the development of high-quality non-mydriatic cameras, HIPAA-compliant servers for the storage and transfer of patient data, and the growing demand for ophthalmological care despite the relatively stagnant supply of eye care specialists.  The global epidemic of diabetes mellitus has contributed significantly to this growing demand, as the majority of patients with diabetes will develop diabetic retinopathy in their lifetime. Today, there are over 29 million Americans with diabetes, and diabetic retinopathy is the leading cause of blindness in working age adults in the United States.  The American Academy of Ophthalmology’s and American Diabetes Association’s formal screening guidelines recommend that all diabetic patients receive an annual dilated funduscopic examination.  Unfortunately, the compliance rate with this recommendation is quite dismal at an estimated 50-65%.  It is even lower amongst minority populations which comprise the demographic majority of those served by the Harris Health System in Harris County, Texas, the third most populous county in the United States. In 2013, the Harris Health System initiated a teleretinal screening program housed by eight of the district’s primary care clinics.  In this system, patients with diabetes are identified by their primary care provider (PCP) during their appointments, immediately directed to receive funduscopic photographs by trained on-site personnel operating non-mydriatic cameras, and provided a follow-up recommendation (e.g., referral for in-clinic examination versus repeat imaging in 1 year) depending on the interpretation of their images.  The images included in our study were interpreted via two different ways—once by the IRISTM (Intelligent Retinal Imaging Systems) proprietary auto-reader and then again by a trained ophthalmic specialist from the IRISTM reading center.  The primary aim of this study was to evaluate the utility of the auto-reader by comparing its results to those of the reading center. Data for 15,015 screened diabetic patients (30,030 eyes) were included.  The sensitivity of the auto-reader in detecting severe non-proliferative diabetic retinopathy or worse, deemed sight threatening diabetic eye disease (STDED), compared to the reading center interpretation of the same images was 66.4% (95% confidence interval [CI] 62.8% - 69.9%) with a false negative rate of 2%.  In a population where 15.8% of diabetics have STDED, the negative predictive value of the auto-reader was 97.8% (CI 96.8% - 98.6%).

[caption id="attachment_20237" align="alignleft" width="125"]4/23/13 Studio head shot portrait of Christine Veenstra for Hem/Oncol. Dr. Veenstra[/caption] MedicalResearch.com Interview with: Christine Veenstra MD Clinical Lecturer, Internal Medicine Medical Oncology University of Michigan Ann Arbor, MI  48109-5343 MedicalResearch: What is the background for this study? What are the main findings? Dr. Veenstra: Patients with cancer face many costs and incur financial burden as they go through diagnosis and treatment. For working patients, cancer diagnosis and treatment may come with the additional burden of time away from work, lost income, and even long-term job loss. Although 40% of US workers do not have access to paid sick leave, we hypothesized that availability of paid sick leave could reduce the need to take unpaid time away from work during cancer treatment and might therefore be associated with job retention and reduced personal financial burden. In a survey of over 1300 patients with Stage III colorectal cancer, we found that only 55% of those who were employed at the time of their cancer diagnosis retained their jobs. Working patients with paid sick leave were nearly twice as likely to retain their jobs compared with working patients who did not have paid sick leave. This held true even when controlling for income, education and health insurance. Furthermore, working patients without paid sick reported significantly higher personal financial burden than those who had paid sick leave available.

[caption id="attachment_20177" align="alignleft" width="129"]Dr Najib Rahman D Phil MSc MRCP Consultant and Senior Lecturer Lead for Pleural Diseases Oxford Centre for Respiratory Medicine Clinical Director, Oxford Respiratory Trials Unit Tutor in Clinical Medicine University College, Oxford Dr. Najib Rahman[/caption] MedicalResearch.com Interview with: Dr Najib Rahman D Phil MSc MRCP Consultant and Senior Lecturer Lead for Pleural Diseases Oxford Centre for Respiratory Medicine Clinical Director, Oxford Respiratory Trials Unit Tutor in Clinical Medicine University College, Oxford Medical Research: What is the background for this study? Dr. Rahman : Up to TIME1, the evidence base behind optimal pleurodesis for malignant pleural effusion in terms of tube size and analgesia was poor. Optimal pleurodesis in this context is one which is successful (i.e. the patient needs no further pleural interventions for that malignant effusion), but occurs with the minimum discomfort. This is particularly important as the treatment intent in malignant effusion pleurodesis is palliative. This is the first adequately powered randomized trial to address two important issues in pleurodesis for malignant pleural effusion - that of whether NSAIDs reduce pleurodesis efficacy, and if smaller chest tubes (12F) are "as good as" larger chest tubes (24F) for pleurodesis success and in terms of pain. Medical Research: What are the main findings? Dr. Rahman : The main and somewhat surprising findings are that:
  1. NSAIDs given short term but at high dose do not impair pleurodesis - they are no better than morphine for pain control (in fact, they needed modestly more rescue medication), but can be freely used during malignant effusion pleurodesis with no fear of reducing pleurodesis success.
  1. Smaller tubes were marginally less painful than larger tubes - but this difference was not clinically very relevant
  1. Smaller tubes cannot now be said to be "as good as" larger tubes for malignant effusion pleurodesis. Our data shows that they failed in non-inferiority to larger tubes for pleurodesis success at 3 months. 
  1. Smaller tubes resulted in higher fall our rates, a higher incidence of not being able to administer talc and were associated with more complications during insertion .

[caption id="attachment_20259" align="alignleft" width="180"]Ekaterina Subbotina Dr. Subbotina[/caption] MedicalResearch.com Interview with: Ekaterina Subbotina, Ph.D. Postdoctoral Research Scholar University of Iowa Carver College of Medicine Iowa City, IA 52242  Medical Research: What is the background for this study? Dr. Subbotina: Exercises represent the most natural and effective way to maintain physical and metabolic well-being. Lack of physical activity can contribute to many preventable diseases such as cardiovascular disease, stroke, cancer, diabetes and obesity. It is known that moderate exercise is beneficial for health but the mechanism of this effect is only partially understood. It becomes more and more evident that skeletal muscles function as an organ that produces and secretes biologically active molecules called myokines. Studies of the biological role and mechanism of action of myokines are important for understanding of muscle function under sedentary and exercise conditions.

[caption id="attachment_20247" align="alignleft" width="135"]Dr. Amin Hanjani Dr. Amin Hanjani[/caption] MedicalResearch.com Interview with: Sepideh Amin-Hanjani, MD FAANS FACS FAHA Professor & Program Director Co-Director, Neurovascular Surgery Department of Neurosurgery University of Illinois at Chicago Past Chair, AANS/CNS Cerebrovascular Section  Medical Research: What is the background for this study? What are the main findings? Dr. Amin-Hanjani: Posterior circulation strokes account for up to 30% of all ischemic strokes, and atherosclerotic occlusive disease of the vertebrobasilar (VB) is responsible for approximately one third of these cases. Symptomatic atherosclerotic VB occlusive disease is associated with a high risk of recurrent stroke despite medical therapy, in the range of 10-15% within 2 years. There have been advances in treatment options, particularly endovascular angioplasty and stenting, aimed at reverting the blockage; however these procedures themselves carry risks, and are likely to benefit only selected patients who are at highest risk without intervention. Our study, VERiTAS, aimed to determine if measurement of blood flow in the posterior circulation vessels could identify the high risk patients. Flow measurements were performed using the technique of quantitative magnetic resonance angiography (QMRA) relying on standard MR sequences and  the commercial software NOVA. These flow measurements were used to designate patients presenting with symptomatic vertebrobasilar disease as flow compromised or not, and patients were then followed for a median of 23 months in a blinded fashion to determine the risk of subsequent strokes. We found that among 72 such patients, only one quarter (18 patients) demonstrated flow compromise on QMRA, but that this group had a significantly higher risk of subsequent stroke at one year, 22% vs only 4% in the other group. The hazard ratio for subsequent stroke was markedly elevated at 11.5 even after adjusting for age and other stroke risk factors.

[caption id="attachment_20180" align="alignleft" width="277"]Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK Dr. Sandra Wilks[/caption] MedicalResearch.com Interview with: Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK  Medical Research: What is the background for this study? What are the main findings? Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources. In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
  • (1) an initial foundation layer (conditioning film) formed by individual 'colonising' P. mirabilis cells, which occurred in less than 1 hour;
  • (2) this was rapidly followed by a sheet-like microcrystalline material (after 24 hours) that covers this conditioning film;
  • (3) after 4 days exposure, large amounts of crystalline material was seen to extend out from the surface with;
  • (4) defined struvite crystals embedded within the structure and P. mirabilis visible throughout. This pattern was the same on both materials.

MedicalResearch.com Interview with: Dr Gerry McCann MD Reader in Cardiovascular Imaging Department of Cardiovascular Sciences University of Leicester Leicester UK Medical Research: What is the background for this study? Dr. McCann:  Cardiologists increasingly treat patients who suffer a large heart attack with an emergency procedure performed under local anaesthetic. The blocked artery that causes the heart attack is opened by inserting a small metal stent at the blockage. Up to 50% of patients treated in this way also have other narrowed heart arteries. Two recent studies (PRAMI and CvLPRIT) in patients with heart attacks and multiple narrowed arteries have suggested that treating all of the narrowed arteries (complete revascularization) may be better than just treating the blocked artery. However, there is concern that the longer procedure, and putting in more stents, may cause more injury to the heart. Medical Research: What is the background for this study? What are the main findings Dr. McCann:  We studied 203 patients having a heart attack who were randomly assigned to have only the blocked artery opened (105 patients) or complete revascularization during the initial hospitalization (98 patients) in the CvLPRIT study. We assessed the size of the heart attack and any smaller areas of damage using MRI scanning. Patients who were treated with complete revascularization were more likely to have evidence of more than 1 heart attack on the MRI than if only the blocked artery was treated (22% vs. 11% of patients). However, these additional heart attacks were generally small and the total percentage of the heart that was damaged was not increased (12.6% vs. 13.5%). The pumping function of the heart measured 3 days and 9 months after treatment was also similar with both treatments.

[caption id="attachment_20158" align="alignleft" width="132"]Dr. Jochen Reinöhl Consultant and Head of the ISAH team (intervention for structural and congenital cardiovascular diseases) Department of Cardiology and Angiology I (Medical Director: Prof. Dr. Christoph Bode) University Heart Center Freiburg ∙ Bad Krozingen Dr. Jochen Reinöhl[/caption] MedicalResearch.com Interview with: Dr. Jochen Reinöhl Consultant and Head of the ISAH team (intervention for structural and congenital cardiovascular diseases) Department of Cardiology and Angiology I  (Medical Director: Prof. Dr. Christoph Bode) University Heart Center Freiburg ∙ Bad Krozingen Medical Research: What is the background for this study? What are the main findings? Dr. Reinöhl: Aortic valve stenosis is a medical condition with very high short-term mortality. Previously its only treatment – therefore the gold standard – consisted of surgical valve replacement. Since 2007 transcatheter aortic-valve replacement (TAVR) can be considered alternative. Its impact on clinical practice, however, is largely unknown. TAVR numbers rose from 144 in 2007 to 9,147 in 2013, whereas surgical aortic-valve replacement procedures only marginally decreased from 8,622 to 7,048. For both groups in-hospital mortality, as well as, the incidence of stroke, bleeding and pacemaker implantation (but not acute kidney injury) decreased.

[caption id="attachment_20155" align="alignleft" width="180"]Dr. Li Ding PhD Director, Medical Genomics group McDonnell Genome Institute Department of Medicine Washington University in St. Louis St. Louis, Missour Dr. Li Ding[/caption] MedicalResearch.com Interview with: Dr. Li Ding PhD Director, Medical Genomics group McDonnell Genome Institute Department of Medicine Washington University in St. Louis St. Louis, Missouri Medical Research: What is the background for this study? What are the main findings? Dr. Li Ding:  Next-generation sequencing technologies have provided unprecedented opportunities for building a comprehensive catalog of point mutations, simple insertion and deletion mutations (indels) and structural variants in human cancers. Although significant progress has been made for documenting these common events through studies from individual research labs and large consortiums, there has been little progress in the discovery of complex indels after the transition from Sanger sequencing to NGS technologies.  It is well known in the scientific community that indel detection using short next generation sequencing reads is a challenging problem. Our study, for the first time, directly addresses complex indel detection that has been barely touched in the cancer field. More importantly, our analysis discovered 285 complex indels in cancer genes such as PIK3R1GATA3, and TP53, revealing an unexpected high prevalence of these events in human cancers.

[caption id="attachment_20140" align="alignleft" width="200"]Lorette A. Stammen, MD Department of Educational Development and Research Faculty of Health, Medicine, and Life Sciences Maastricht University, Maastricht The Netherlands Dr. Stammen[/caption] MedicalResearch.com Interview with: Lorette A. Stammen, MD Department of Educational Development and Research Faculty of Health, Medicine, and Life Sciences Maastricht University, Maastricht The Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Stammen: Research indicated that we can improve the quality of care and reduce the health care costs by eliminating health care waste. Health care waste are health care services that are not beneficial to patients. There are many ways to reduce health care waste, like through insurance and government policies modification,  but we were especially interested in how the medical expertise of physicians could improve high-value, cost-conscious care. We conducted a systematic review with the aim of understanding how training programs cause learning among physicians, residents and medical students. We analyzed 79 articles using realist review method and found three important factors that facilitate the learning of physicians (in training).
  • First, educational programs should focus on knowledge transmission. Knowledge that is essential entails knowledge regarding prices and general health economics, scientific evidence, and patient preferences.
  • Besides knowledge, the second factor of training for high-value, cost-conscious care is reflective practice. Reflective practice for example using feedback and asking reflective questions, by peers, colleagues and supervisors to reflect on decisions made in daily practice.
  • The third element of training programs should address an supportive environment in which physicians, residents and medical students learn. A supportive environment is important to cultivate the importance of high-value, cost-conscious care on multiple levels in the health care system. Since physicians are a part of a health care team their training programs should incorporate the training of health care professionals.
  • Furthermore, it is important that role models demonstrate high-value cost-conscious care.

[caption id="attachment_20113" align="alignleft" width="100"]Dr. Peter C. Minneci, M.D., MHSc Center for Innovation in Pediatric Practice Assistant Professor, Pediatric Surgery The Ohio State's Wexner Medical Center Dr. Minneci[/caption] MedicalResearch.com Interview with: Dr. Peter C. Minneci, M.D., MHSc Center for Innovation in Pediatric Practice Assistant Professor, Pediatric Surgery The Ohio State's Wexner Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Minneci: Non-operative management of uncomplicated appendicitis has been shown to safe and effective studied in several international adult trials. To be a reasonable treatment alternative to urgent appendectomy, non-operative management of appendicitis in children must have a clinically acceptable success rate with minimal harm in patients that fail and subsequently undergo appendectomy. We performed a prospective single-institution patient choice trial allowing the families of children with acute uncomplicated appendicitis to choose between urgent appendectomy or non-operative management with antibiotics alone. We enrolled 102 patients, with 65 choosing surgery and 37 choosing non-operative management with antibiotics alone. Non-operative management had an in-hospital success rate of 94%, a 30-day success rate of 89%, and a 1-year success rate of 76%. Compared to the surgery group, patients managed non-operatively reported higher quality of life scores at 30 days and had significantly fewer disability days and lower costs, with no differences in the rates of complicated appendicitis or treatment-related complications at 1 year of follow-up. With this being said, there are some cases that I have read about where doctors have failed to diagnose patients for Appendicitis even after they have complained about having a number of the symptoms associated with it. Following this, some patients have even contacted companies like Negligence Claimline to get back what they deserve. You go to doctors as they are the ones who can help you get your health back in order, but when something like this happens, it is understandable as to why some people lose faith in this system.

[caption id="attachment_20096" align="alignleft" width="180"]Dr. Rashmi Patel MA (Cantab) MA BM BCh PGDip (Oxon) MRCPsych Psychiatry King's College London, London Dr. Rashmi Patel[/caption] MedicalResearch.com Interview with: Dr. Rashmi Patel MA (Cantab) MA BM BCh PGDip (Oxon) MRCPsych Psychiatry King's College London, London  Medical Research: What is the background for this study? What are the main findings? Dr. Patel: Antidepressants are a safe and effective treatment for depression. However, in a minority of cases, people who take antidepressants can also develop symptoms of elevated mood and mania as part of a bipolar disorder. This is important because although bipolar disorder is uncommon, people who are affected often first present with symptoms of depression and, if left untreated, bipolar disorder can be very distressing and significantly affect social and occupational functioning. In our study we investigated the association of antidepressants with mania in people with depression receiving care from the South London and Maudsley NHS Foundation Trust, a large provider of specialist mental healthcare in South London (UK). We found that antidepressants were widely prescribed and associated with a small increased risk in developing mania. However, we did not demonstrate a causal association between antidepressants and mania. Instead, it is likely that people who developed symptoms of mania with antidepressants already had a propensity towards developing mania prior to antidepressant treatment.

[caption id="attachment_20054" align="alignleft" width="125"]Dr. Chris J. Hawkey, DM, FRCP, FMedSci. University of Nottingham and Nottingham University Hospital England Dr. Chris Hawkey[/caption] MedicalResearch.com Interview with: Dr. Chris J. Hawkey, DM, FRCP, FMedSci. University of Nottingham and Nottingham University Hospital England Medical Research: What is the background for this study?  Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn's Disease) systematically investigated the effect of immunoablation and autologous haemopoietic stem cell transplantation (HSCT) on objective signs of disease, symptoms and need for treatment and is the only controlled trial to have done so. The body’s immune system normally protects us from infections but in Crohn’s disease it turns on itself.  The treatment involves wiping out the body’s immune system (immunoablation) and replacing it with the patient’s own (autologous haemopoietic stem cell transplantation) innocent stem cells, a sort of immunological spring clean. Patients were randomly assigned to undergo transplantation (n=23) or just continue on best conventional treatment (n=22). ASTIC was stimulated by reports which suggested that long-term regression of disease amounting to potential cure could be achieved. But the treatment is hazardous with major potentially lethal risks, so recruitment to the trial was cautious and only the most resistant cases were studied. And we used the most stringent criteria ever developed for the trial’s primary endpoint. Medical Research: What are the main findings?  Dr. Hawkey: In fact the criteria we used for success were so stringent (no symptoms, no signs of disease on total bowel examination and no need for treatment) that few patients achieved them. Nevertheless, there were improvements in the individual measures underlying this composite endpoint. Objective signs of disease disappeared so that the gut looked normal from mouth to anus in about a quarter of actively treated patients vs no controls. Eight vs two patients were adjudicated free of active disease on endoscopy and radiology at final assessment (p=0.054). Patients were able to come off drug treatments: by the end of a year 61% of HSCT patients off immunosuppressive drugs for >3 months vs 23% of controls (p=0.012). Ten vs two patients had lost symptoms of active disease, eight vs two for of them for > 3 months (p=0.052). But treatment was challenging: there were 76 serious adverse events in HSCT patients (particularly infections) vs 38 in controls. One HSCT patient died.

[caption id="attachment_20050" align="alignleft" width="165"]Roger Stupp, MD Professor & Chairman Department of Oncology & Cancer Center University of Zurich & University Hospital Zurich (USZ) Zürich / Switzerland Dr. Roger Stupp[/caption] MedicalResearch.com Interview with: Roger Stupp, MD Professor & Chairman Department of Oncology & Cancer Center University of Zurich & University Hospital Zurich (USZ) Zürich / Switzerland Medical Research: What is the background for this study? Dr. Stupp: Tumor Treating Fields are an entirely novel modality in cancer treatment. Over 10 years ago researchers demonstrated that alternating electrical fields will block cell growth, interfere with organelle assembly, in particular perturb the spindle apparatus and cell division, all leading to mitotic arrest and ultimately apoptosis. This was shown in vitro, but importantly also in vivo animal models including not only mice and rats, but also hamsters and rabbits with deep seated solid tumours. So the question was whether we can demonstrate such an effect also in the clinic. Glioblastoma are locally invasive and aggressive tumours in the brain. They usually do not metastasise however they grow diffusely within the CNS and despite the best possible surgery, radiation and chemotherapy virtually always recur. We thus applied alternating electrical fields therapy, so called Tumor Treating Fields to the scalp of patients with newly diagnosed glioblastoma. After the end of standard chemoradiotherapy (TMZ/RT), patients were randomized to receive either standard maintenance TMZ-chemotherapy alone or in combination with TTFields. Almost 700 patients were randomized, here we report on a preplanned interim analysis looking at the first 315 patients included once they were followed for at least 18 months. The data on the first 315 patients are mature and allowed the IDMC to conclude that the trial should be stopped and the results made available. Medical Research: What are the main findings? Dr. Stupp: The study demonstrated a consistent prolongation of both progression-free and also of overall survival for patients who have been treated with TTFields in addition to standard therapy. The median progression-free survival and overall survival were prolonged by 3 months, translating to an absolute increase in overall survival at 2 years of 14%, from 29% to 43%. Or a hazard ratio of 0.74 for overall survival and of 0.62 for progression-free survival.

[caption id="attachment_20124" align="alignleft" width="154"]Camron D. Bryant, Ph.D. Assistant Professor Laboratory of Addiction Genetics Department of Pharmacology and Experimental Therapeutics & Psychiatry Boston University School of Medicine Boston, MA 02118 Dr. Camron Bryant[/caption] MedicalResearch.com Interview with: Camron D. Bryant, Ph.D. Assistant Professor Laboratory of Addiction Genetics Department of Pharmacology and Experimental Therapeutics & Psychiatry Boston University School of Medicine Boston, MA 02118  Medical Research: What is the background for this study? What are the main findings? Dr. Bryant: The addictions, including addiction to psychostimulants such as methamphetamine and cocaine, are heritable neuropsychiatric disorders. However, the genetic factors underlying these disorders are almost completely unknown. We used an unbiased, discovery-based genetic approach to fine map a novel candidate genetic factor influencing the acute stimulant response to methamphetamine in mice. We then directly validated the causal genetic factor using a gene editing approach. The gene - Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) - codes for an RNA binding protein that is involved in alternative splicing of hundreds of genes in the brain. Based on a genome-wide transcriptome analysis of differentially expressed genes within the striatum -  a crucial brain region involved in the stimulant properties of amphetamines - we predict that Hnrnph1 is essential for proper neural development of the dopamine circuitry in the brain. These findings could have implications for understanding not only the addictions but also other neuropsychiatric disordersthat involve perturbations in the dopaminergic circuitry. (e.g., ADHD and schizophrenia) as well as neurodegenerative disorders such as Parkinson's disease.

[caption id="attachment_20108" align="alignleft" width="180"]Meri K Tulic PhD Université de Nice Sophia-Antipolis Immune Tolerance Nice, France The International Inflammation 'in-FLAME' Network Worldwide Universities Network Dr. Meri Tulic[/caption] MedicalResearch.com Interview with: Meri K Tulic PhD Université de Nice Sophia-Antipolis Immune Tolerance Nice, France The International Inflammation 'in-FLAME' Network Worldwide Universities Network  Medical Research: What is the background for this study? What are the main findings? Dr. Tulic: We know that damaged epithelial gut barrier is a hallmark of gut inflammatory diseases including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). It has been long known that respiratory allergens such as house-dust mites (HDM) are the main causes of epithelial destruction in the lungs and initiation of allergic airway disease such as asthma. We set out to test whether  house-dust mites may also be present in the human gut and may contribute to intestinal barrier dysfunction. In this paper, we have shown that  house-dust mites is found in the gastrointestinal system of ~50% of all healthy subjects tested and it has detrimental effect on gut barrier function. The mechanisms include its direct destruction of tight-junction proteins which normally hold adjoining epithelial cells together, resulting in increased gut permeability. This process is driven by cysteine-proteases contained within the mite. In healthy individuals this effect is likely to be regulated by increased production of regulatory IL-10 (an anti-inflammatory mediator); our preliminary data indicate that a defect in regulatory responses may exist in IBS patients.

[caption id="attachment_20086" align="alignleft" width="120"]Erik K. Alexander, MD FACP Chief, Thyroid Section, Division of Endocrinology Brigham & Women's Hospital Associate Professor of Medicine, Harvard Medical School Dr. Erik Alexander[/caption] MedicalResearch.com Interview with: Dr. Erik K. Alexander, MD FACP Chief, Thyroid Section, Division of Endocrinology Brigham & Women's Hospital Associate Professor of Medicine, Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Alexander: Thyroid nodular disease has become an increasingly common medical illness, with prevalence reported to range between 26-67% in the adult.  Though advancing age is known to influence the formation of thyroid nodules, their precise relationship remains unclear.  Furthermore, it is uncertain whether age influences the risk that any thyroid nodule may prove cancerous.  Thus we conducted a study to determine the impact of patient age on nodule formation, the number of thyroid nodules, and risk of thyroid malignancy. Medical Research:  What are the main findings? Dr. Alexander: Our study is a prospective cohort analysis of consecutive adults who presented for evaluation of nodular disease from 1995-2011 at Brigham and Women’s Hospital, Boston, MA.  6,391 patients underwent thyroid ultrasound and fine needle aspiration that resulted in 12,115 thyroid nodules ≥1 cm.  Patients were stratified into six age groups and compared using sonographic, cytologic, and histologic endpoints. We found that the prevalence of thyroid nodular disease increases with advancing age.  The mean number of nodules at presentation increased from 1.5 in the youngest cohort (ages 20–30) to 2.2 in the oldest cohort (>70 years).  In contrast, the risk for malignancy in a newly identified nodule declined with advancing age.  Thyroid cancer incidence per patient was 22.9% in the youngest cohort, but 12.6% in the oldest cohort.  Despite a lower likelihood of malignancy, identified cancers in older patients demonstrated a more aggressive cancer subtype.  While nearly all malignancies in younger patients were well-differentiated, older patients were more likely to have higher risk papillary thyroid cancer variants, poorly differentiated cancer, or anaplastic carcinoma.

[caption id="attachment_20071" align="alignleft" width="120"]Francesco Zaccardi, MD Diabetes Research Centre Leicester General Hospital, Leicester, United Kingdom Dr. Zaccardi[/caption] MedicalResearch.com Interview with: Francesco Zaccardi, MD Diabetes Research Centre Leicester General Hospital, Leicester, United Kingdom Medical Research: What is the background for this study? Dr. Zaccardi: Nowadays there are different classes of drugs for the treatment of hyperglycaemia in patients with type 2 diabetes and, within the same class, multiple drugs are available.Glucagon-like peptide-1 receptors (GLP-1RAs) are a relatively new class of treatments that improve glucose control and reduce body weight, without an increased risk for hypoglycaemia. To date, however, no direct comparisons between once-weekly GLP-1RAs have been reported. In this view, the aim was to assess the comparative efficacy and safety profile of GLP-1RAs using a network meta-analysis, a methodology that allows the estimation of the comparative effectiveness of multiple treatments in the absence of direct evidence. Medical Research: What are the main findings? Dr. Zaccardi: There are several differences in the efficacy and safety profiles of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs). Some of these drugs evidenced a better glucose control or body weight reduction, while other had an increased risk of side effects, such as nausea. Compared to other once-weekly GLP-1RAs, dulaglutide 1.5mg, once weekly exenatide, and taspoglutide 20mg showed a greater reduction of HbA1c, fasting plasma glucose, and body weight. Marginal or no differences were found for blood pressure and blood lipid levels. While taspoglutide 20mg had the highest risk of nausea, the risk of hypoglycaemia among once-weekly GLP-1RAs was comparable.

[caption id="attachment_20060" align="alignleft" width="137"]Dr Franco Radaelli Division of Digestive Endoscopy and Gastroenterology Valduce Hospital Como, Italy Dr. Franco Radaelli[/caption] MedicalResearch.com Interview with: Dr Franco Radaelli Division of Digestive Endoscopy and Gastroenterology Valduce Hospital Como, Italy  Medical Research: What is the background for this study? Dr. Radaelli: Split regimens of bowel preparation are strongly recommended by European and American Guidelines as they have been associated with a higher level of colon cleansing. However, there is still uncertainty on whether the higher level of cleansing associated with a split regimen also results in a higher proportion of subjects with at least one adenoma (adenoma detection rate, ADR), that represents by far a more relevant quality indicator than the level of cleansing itself. On this background, we designed a randomized investigator-blinded controlled trial to evaluate whether a “split regimen” of low-volume 2-L PEG-ascorbate solution was superior to the traditional “full dose, the day before regimen” in terms of ADR. Differently from other studies on bowel preparation, we considered adenoma detection rate  instead of the level of colon cleansing, the primary study end-point, and we designed the sample size accordingly. A precise estimation of the sample size was facilitated by including an homogeneous population of asymptomatic subjects undergoing first colonoscopy after positive-FIT within CRC organized screening program. Besides, ADR represents a very solid end-point due to the very low inter-pathology variability in the differential diagnosis between neoplastic and non-neoplastic lesions, while the assessment of the level of cleansing is hampered by unavoidable degree of subjectivity and higher degree of inter-operator variability.