Author Interviews, Cancer Research, Global Health, Lancet, Weight Research / 04.02.2019 Interview with: Hyuna Sung, PHD Principal Scientist, Surveillance Research American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 What is the background for this study? Response: This project was motivated by our previous finding on the rise of colorectal cancer among young adults before age 55. Changes in cancer trends among young age group have significant implications because the newly introduced carcinogenic agents are likely to affect trends among young people before they affect those among older people. Owing to this relationship, cancer trends among young people can be often considered as a bellwether for future disease burden. Given the dramatic increase of the obesity prevalence during 3-4 decades in the US, we wanted to expand the colorectal cancer finding to the more comprehensive list of cancers and explain them in the context of obesity epidemic. (more…)
Author Interviews, Global Health, Health Care Systems, Lancet, Pediatrics / 29.01.2019 Interview with: "By @plumavioleta "Atardecer en #caracas... #avebolivar # ccs #venezuela." via @PhotoRepost_app" by Pedro Fanega is licensed under CC BY 2.0. To view a copy of this license, visit: Jenny García, PhD candidate Institut National d’Études Démographiques INED Institut de Démographie de l'université Paris 1 Panthéon Sorbonne IDUP Paris, France Prof Gerardo Correa, MSc Instituto de Investigaciones Económicas y Sociales IIES Universidad Católica Andrés Bello UCAB Caracas, Venezuela Prof Brenda Rousset, PhD Departamento de Estadística, Escuela de Sociología (FaCES) Universidad Central de Venezuela UCV Caracas, Venezuela What is the background for this study? What are the main findings?  Response: Venezuela, as many countries in Latin America, showed substantial improvements in infant mortality rates during the last 60 years. However, the decreasing pattern might be reversing. Recent socioeconomic and political events have led to a collapse in living standards, along with a breakdown of the health system. At the same time, a strict secrecy policy has ruled public institutions, and since 2013 the Venezuelan government stopped publishing mortality statistics. This study attempts to fill this gap and estimate infant mortality using hospital and census data after 2013. The main finding is that infant mortality rates in Venezuela may have stopped decreasing and started increasing in 2009 – around the time funding for the Venezuelan health system started to be substantially reduced. By 2016, the infant mortality rate was 21.1 deaths per 1000 live births, which is 1.4 times the rate in 2008 (15.0 deaths per 1000 live births), and equivalent to the rate recorded in the late 1990s, meaning 18 years of progress may have been lost.  (more…)
Aging, Author Interviews, Geriatrics, Lancet, Nutrition, UC Davis, Weight Research / 15.01.2019 Interview with: Valter Longo, PhD Edna M. Jones Professor of Gerontology Professor of Biological Sciences Leonard Davis School of Gerontology Director of the USC Longevity Institute USC What is the background for this study? What are the main findings? Response: The use of a low calorie diet that mimics fasting for 4 days twice a month starting at middle age can extend lifespan and rejuvenate mice. In humans a similar diet once a month causes improvements in cholesterol, blood pressure , inflammation, fasting glucose etc consistent with rejuvenation (more…)
Author Interviews, Depression, Hip Fractures, Lancet / 06.12.2018 Interview with: Prof. Gillian Mead Chair of Stroke and Elderly Care Medicine Prof. Martin Dennis Chair of Stroke Medicine Centre for Clinical Brain Sciences The University of Edinburgh What is the background for this study? Response: We are both practicing stroke physicians as well as clinical trialists. Therefore our interest in this area was triggered by the exciting results of the FLAME trial in 2011. This appeared to indicate that fluoxetine might boost the recovery of stroke patients. Potentially this was very important given the increasing numbers of people having disability due to stroke, and the fact that fluoxetine is inexpensive and could be introduced very easily into clinical practice. We were further encouraged by the large numbers of small RCTs we identified when we carried out a Cochrane systematic review on the topic. These trials provided more evidence of potential benefit but there was evidence that trials of greater quality showed less benefit, and benefits were greater in patients who were depressed. We felt there was a need for more evidence derived from much larger numbers of patients. (more…)
Author Interviews, Lancet, Mental Health Research, PTSD / 16.11.2018 Interview with: Sanford Nidich, Ed.D. Director, Center for Social-Emotional Health Maharishi University of Management Research Institute Fairfield, Iowa What is the background for this study? What are the main findings? Response: Posttraumatic stress disorder (PTSD) is a complex and difficult-to-treat disorder, affecting 10-20% of veterans across eras. Previous research raised the question of whether a non-trauma focused treatment can be as effective as trauma exposure therapy in reducing PTSD symptoms. The overall objective of the study was to compare Transcendental Meditation (TM), a non-trauma focused practice, to prolonged exposure (PE) in a non-inferiority clinical trial, and to compare both to a PTSD health education control group. Transcendental Meditation was found to be as effective as PE in reducing PTSD symptoms severity from baseline to three-month posttest. In standard superiority comparisons, significant reductions in PTSD symptoms were found for TM vs. HE, and PE vs. HE. Percentages of participants with clinically significant improvement, as measured by the Clinician-Administered PTSD Scale (CAPS) interview (≥10 point reduction), were TM=61%, PE=42%, and HE=32%  (more…)
Author Interviews, Global Health, Hospital Acquired, Infections, Lancet / 07.11.2018 Interview with: "Antibiotics" by Michael Mortensen is licensed under CC BY-SA 2.0Dr Alessandro Cassini MD Epidemiologist, European Centre for Disease Prevention and Control Solna, Sweden What is the background for this study? Response: We published an ECDC study estimating attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the European Union and the European Economic Area (EU/EEA). This study is based on 2015 data from the European Antimicrobial Resistance Surveillance Network (EARS-Net). The study was developed by experts at ECDC and the Burden of AMR Collaborative Group, and published in The Lancet Infectious Diseases. (more…)
Author Interviews, Infections, Lancet, Urinary Tract Infections / 27.10.2018 Interview with: Portsmouth, MD Senior Medical Director Shionogi Inc. What is the background for this study? What are the main findings? Response: Antibiotics for multidrug resistant  Gram-negative infections are desperately needed. Cefiderocol is the first siderophore antibiotic to reach patients. Siderophore antibiotics bind to free iron and use the bacterial active iron transport channels to cross the outer membrane of Gram-negative bacteria. Laboratory studies have shown that cefiderocol is active against multi-drug resistant Gram-negative bacteria, often where no other antibiotics are active. It is able to overcome most types of antibiotic resistance due to its active transport into cells and stability against all carbapenemases. The need for antibiotics for carbapenem resistant Gram-negative infections is described as a critical need by the WHO. This trial was the first in humans with serious infections and demonstrated excellent efficacy in a complicated patient population where almost ¼ were over 75 years of age. Additionally cefiderocol did not appear to have any safety problems, and was well tolerated. (more…)
Author Interviews, Brain Injury, CT Scanning, Emergency Care, Lancet, Technology / 16.10.2018 Interview with: Qure-ai.jpgSasank Chilamkurthy AI Scientist, What is the background for this study? Response: Head CT scan is one of the most commonly used imaging protocols besides chest x-ray. They are used for patients with symptoms suggesting stroke, rise in intracranial pressure or head trauma. These manifest in findings like intracranial haemorrhage, midline shift or fracture. Scans with these critical findings need to be read immediately. But radiologists evaluate the scans on first-come-first-serve basis or based on stat/routine markers set by clinicians. If the scans with critical findings are somehow pushed to the top of radiologists’ work list, it could substantially decrease time to diagnosis and therefore decrease mortality and morbidity associated with stroke/head trauma. (more…)
Author Interviews, Diabetes, Gluten, Lancet, OBGYNE, Pediatrics / 21.09.2018 Interview with: Knud Josefsen, senior researcher Bartholin Institute, Rigshospitalet, Copenhagen K, Denmark What is the background for this study? What are the main findings? Response: In a large population of pregnant women, we found that the risk of the offspring being diagnosed with type 1 diabetes before the age of 15.6 years (the follow up period) was doubled in the group of women ingesting the highest amounts of gluten (20-66 g/day) versus the group of women ingesting the lowest amounts of gluten (0-7 g/day). For every additional 10 grams of gluten ingested, the risk for type 1 diabetes in the child increased by a factor of 1.31. It the sense that it was a hypothesis that we specifically tested, we were not surprised. We had seen in animal experiments that a gluten-free diet during pregnancy protected the offspring from diabetes, and we wanted to see if we could prove the same pattern in humans. There could be many reasons why we would not be able to show the association, even if it was there (sample size, low quality data, covariates we could not correct for and so on), but we were off course pleasantly surprised that we found the association that we were looking for, in particular because it is quite robust (more…)
Author Interviews, Diabetes, Heart Disease, Lancet / 12.08.2018 Interview with: Dr Araz Rawshani, PhD Department of Molecular and Clinical Medicine Institute of Medicine University of Gothenburg Gothenburg, Sweden What is the background for this study?  Response: Patients with type 2 diabetes have 2 to 4 times greater risk for death and cardiovascular events compared to the general population. There are several randomized trails that encourage a range of interventions that target traditional and modifiable risk factors, such as elevated levels for glycated hemoglobin, blood pressure and low-density lipoprotein cholesterol to reduce the risk for complications of type 2 diabetes. However, there are few randomized trails that have investigated the effects of multifactorial risk factor intervention in reducing the risk for death and cardiovascular events, as compared to patients that are treated with usual care. We set out to investigate the extent to which the excess risk associated with type 2 diabetes may be mitigated or potentially eliminated by means of evidence-based treatment and multifactorial risk factor modification. In addition, we estimated the relative importance between various risk factors and the incremental risk of death and cardiovascular events associated with diabetes. Furthermore, we investigated the association between glycated hemoglobin, systolic blood pressure and low-density lipoprotein cholesterol (LDL-C) within evidence based target ranges and the abovementioned outcomes. (more…)
Author Interviews, Eli Lilly, Lancet, Pharmacology, Rheumatology, UCLA / 26.07.2018 Interview with: Daniel J. Wallace M.D., FACP, MACR Associate Director, Rheumatology Fellowship Program Board of Governors, Cedars-Sinai Medical Center Professor of Medicine, Cedars-Sinai Medical Center David Geffen School of Medicine Center at UCLA In affiliation with Attune Health Beverly Hills, Ca 90211 What is the background for this study? What are the main findings?   Response: This is the first positive study of systemic lupus erythematosus (SLE) using baricitinib,  a small oral molecule that blocks the JAK system. The human kinome consists of 500 genes and helps regulate cell surface receptor interaction. While agents that inhibit certain pathways are approved for rheumatoid arthritis and certain malignancies, this is the first study of its kind in SLE. (more…)
Author Interviews, Cancer Research, Lancet / 10.07.2018 Interview with: Paul Lyon DPhil, MRCS Academic Clinical Fellow in Radiology Oxford University Hospitals NHS Foundation Trust Oxford, UK What is the background for this study? What are the main findings? Response: Delivering therapeutic doses of systemic chemotherapy to solid tumours, whilst ensuring side effects remain tolerable, has a presented a long-standing and unsolved challenge in oncology. With the advent of smart nanomedicines for clinical use, such as Lyso-Thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox®, Celsion, USA), which has been formulated to release its doxorubicin content at 2.5°C above body temperature, there is now opportunity for targeted tumour therapy in combination with therapeutic devices. Much like a magnifying glass can focus energy from the sun to burn a hole in paper, ultrasound can be focused deep within the body to induce therapeutic effects in tumours, including ablation, hyperthermia and other bioeffects. Since its inception in the 1940s, focused (or therapeutic) ultrasound has evolved and is now FDA-approved for a variety of indications including ablation of several tumour types, virtue of being safe, non-invasive and non-ionising. Building on decades of preclinical research efforts worldwide, the TARDOX study is the first clinical trial to attempt triggered drug delivery to a target tumour non-invasively using an external focused ultrasound device. This phase 1 study which ran between March 2015-March 2017 in Oxford, UK, treated 10 patients with inoperable primary or secondary liver tumours which were either stable or refractory to previous chemotherapies. In each patient, a single intervention under general anaesthetic was performed during which a selected liver tumour was targeted and gently heated with focused ultrasound following an intravenous infusion of LTLD. Biopsies were used to determine the quantity of intratumoral doxorubicin before and after the ultrasound exposure.  (more…)
Author Interviews, Beth Israel Deaconess, HIV, Lancet, Vaccine Studies / 08.07.2018 Interview with: Dan Barouch, M.D., Ph.D. Professor of Medicine Harvard Medical School Ragon Institute of MGH, MIT, and Harvard Director, Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Boston, MA 02215 What is the background for this study? What are the main findings? Response: This study demonstrates that the mosaic Ad26/Env HIV vaccine candidate induced robust and comparable immune responses in humans and monkeys. Moreover, the vaccine provided 67% protection against viral challenge in monkeys.    (more…)
Asthma, AstraZeneca, Author Interviews, Immunotherapy, Lancet, Pulmonary Disease / 27.06.2018 Interview with: Reynold A. Panettieri, Jr., M.D. Professor of Medicine, Robert Wood Johnson Medical School Vice Chancellor, Clinical & Translational Science Director, Rutgers Institute for Translational Medicine & Science Emeritus Professor of Medicine, University of Pennsylvania Child Health Institute of New Jersey Rutgers, The State University of New Jersey New Brunswick, NJ  08901 What is the background for this study? Response: Severe asthma is characterized by Type 2 inflammation manifested by increases in IL-13, IL-4 and Il-5 levels in the airways that promotes airway hyperresponsiveness and in part irreversible airway obstruction.  These clinical manifestations profoundly increase asthma morbidity and mortality. To address an unmet therapeutic need, Tralokinumab was developed as a monoclonal antibody targeting soluble IL-13 with the goal of improving lung function and patient reported outcomes while decreasing annual exacerbation rates.  Stratus 1 and 2 represent two identical randomized, double-blind, placebo-controlled, phase 3 clinical trials in severe asthma.  These international trials enrolled approximately 2000 subjects with severe asthma and examined whether Tralokinumab decreased annualized exacerbation rates (AER) as compared with placebo (primary outcome). (more…)
Author Interviews, Diabetes, Heart Disease, Lancet, Metabolic Syndrome, Weight Research / 01.06.2018 Interview with: Nathalie Eckel, MSc German Diabetes Center Düsseldorf, Germany What is the background for this study?  Response: Obesity is associated with metabolic disorders such as diabetes, high blood pressure and hypercholesterolemia, and with a higher risk of cardiovacular disease compared to normal weight. However, there is also the phenomenon of the so-called "metabolically healthy obesity" and "metabolically unhealthy normal-weight". So far it has been unclear how metabolic risk factors change over time in metabolically healthy people depending on body weight and what cardiovascular disease risk results from this. (more…)
Author Interviews, Circadian Rhythm, Lancet, Mental Health Research / 16.05.2018 Interview with: Laura Lyall MA; MSc; PhD Research Associate Institute of Health and Wellbeing University of Glasgow What is the background for this study? Response: Previous studies have suggested a link between disturbed circadian rhythms and depression and bipolar disorder. These studies have however usually used small samples, subjective measures of circadian disruption, or have not accounted for potential confounding factors like sociodemographic and lifestyle characteristics. The UK Biobank cohort has accelerometry (activity monitor) data as well as mental health, lifestyle, BMI and sociodemographic data for over 91,000 individuals, and means we can address this question using objective measures of circadian rhythmicity on a large scale. We derived a measure of relative amplitude from the UK Biobank’s accelerometry data, which was recorded for 7 days between 2013-2014 from around 100,000 participants. Relative amplitude reflects the distinction, in terms of activity levels, between an individual’s most active 10 hours and least active 5 hours, in an average day. If an individual is inactive during the day, or has disturbed sleep at night, the will show low relative amplitude, consistent with disturbed circadian rest-activity patterns. (more…)
Author Interviews, Lancet, Neurological Disorders, Neurology / 23.03.2018 Interview with: David Birnkrant, MD Professor of Pediatrics, Case Western Reserve University School of Medicine Director of Pediatric Pulmonology & Student Education, MetroHealth Medical Center What is the background for this study? What are the main findings? Response: This study updates guidance on all aspects of the multi-disciplinary care of patients with Duchenne muscular dystrophy (DMD). The project was funded by the CDC’s National Center on Birth Defects and Developmental Disabilities and the results were recently published as three articles in The Lancet Neurology. The project was guided by a 25-member steering committee. Eleven expert committees worked over a period of three years to develop guidelines based on the RAND/UCLA appropriateness method, in which assessments and interventions were evaluated for appropriateness and necessity. The recommendations update those originally published in 2010. Duchenne muscular dystrophy is transmitted by X-linked recessive inheritance and thus affects primarily boys and men. Patients affected by DMD do not produce functional dystrophin protein, resulting in progressive weakness of skeletal, respiratory, and heart muscles, causing a shortened life span. Teens and young men may require surgery for curvature of the spine, a ventilator device to assist breathing, and a feeding tube to help ensure adequate nutrition. The approach of the various subspecialties involved in DMD management has evolved, with more anticipatory assessment and therapy, identifying and addressing predictable medical complications as early as possible for optimal patient outcomes. With this kind of multi-disciplinary care, people with DMD now live into their 30s and beyond. Along with the emergence of new genetic and molecular therapies, the recognition that people with DMD are living longer was one of the main motivations behind the need for these updated care considerations. Patients with DMD, their families and their advocacy organizations are driving a new emphasis on optimizing quality of life, not just prolongation of survival. Thus, there was a need to address issues related to transitions of care from childhood to adulthood, coordination of care across subspecialties, and other topics related to education, vocation, independence, personal relationships, emotional health, and intimacy. The updated care considerations thus include eleven topic areas, eight of which were part of the 2010 guidelines. These are: (1) diagnosis, (2) neuromuscular management, (3) rehabilitation management, (4) gastrointestinal and nutritional management, (5) respiratory management, (6) cardiac management, (7) orthopedic and surgical management, and (8) psychosocial management. Three topics are new: (9) primary care and emergency management, (10) endocrine management (including growth, puberty, adrenal insufficiency, and bone health), and (11) transitions of care across the lifespan. (more…)
Author Interviews, Heart Disease, Lancet, Menopause, Women's Heart Health / 10.03.2018 Interview with: Mihir Sanghvi Academic Junior Doctor Barts Health NHS Trust What is the background for this study? What are the main findings? Response: The effect of menopausal hormone therapy (MHT), previously known as hormone replacement therapy, on cardiovascular health in post-menopausal women remains controversial and unclear. Extensive observational data had suggested MHT to be cardioprotective, leading to MHT being routinely prescribed for both primary and secondary prevention of coronary heart disease (CHD). However, subsequent data from the Women’s Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS) studies cast doubt on the beneficial cardiovascular effects of MHT; this was reflected in learned societies’ clinical guidance concerning MHT’s role in CHD prevention. The most recent randomised trial data on the subject arose from the Danish Osteoporosis Prevention Study, which indicated that women taking menopausal hormone therapy had a reduced risk of the composite endpoint of mortality, heart failure and myocardial infarction but the study has been subject to criticism [10]. In more recent work, again from the WHI, there was no difference in cardiovascular mortality in MHT users compared to placebo, although the authors themselves state that cause-specific mortality data should be interpreted “cautiously”. The UK Biobank is an ongoing, large-scale, population-based study designed to examine determinants of health in middle and old age. Besides extensive collection of health questionnaire data, biological samples and physical measurements, it has incorporated cardiovascular magnetic resonance (CMR) imaging – the gold standard for analysis of cardiac structure and function – to provide detailed imaging phenotypes. At present, there is a paucity of data on the effects of  menopausal hormone therapy on left ventricular (LV) and left atrial (LA) volumes and function, alterations in which are markers of subclinical cardiovascular disease and have prognostic implications. We found that in a large, population-based cohort of post-menopausal women free of cardiovascular disease, use of menopausal hormone therapy is not associated with adverse, subclinical changes in cardiac structure and function. Indeed, we demonstrate significantly smaller LV and LA chamber volumes which have been linked to favorable cardiovascular outcomes in other settings. (more…)
Abuse and Neglect, Hematology, Lancet, Medical Imaging, Transplantation / 07.03.2018 Interview with: Kirsten Williams, M.D. Blood and marrow transplant specialist Children’s National Health System What is the background for this study? What are the main findings?  Response: This study addressed a life-threatening complication of bone marrow transplantation called bone marrow failure. Bone marrow transplantation has provided a cure for patients with aggressive leukemias or acquired or genetic marrow dysfunction. The process of bone marrow transplantation involves giving chemotherapy and/or radiation, which removes the diseased blood cells from the bone marrow. After this, new bone marrow stem cells are infused from a healthy individual. They travel to the bone marrow and start the slow process of remaking the blood system. Because these new cells start from infancy, it takes upwards of four to five weeks for new mature healthy cells to emerge into the blood, where they can be identified. Historically, there has been no timely way to determine if the new cells have successfully repopulated unless they can be seen in the blood compartment. This condition of bone marrow failure is life-threatening, because patients don't have white blood cells to protect them from infection. Once bone marrow failure is diagnosed, a second new set of stem cells are infused, often after more chemotherapy is given. However, for many individuals this re-transplantation is too late, because severe infections can be fatal while waiting cells to recover. We were the first group to use a new imaging test to understand how the newly infused bone marrow cells develop inside the patient. We have recently published a way to detect the new bone marrow cell growth as early as five days after the cells are given. We used an investigational nuclear medicine test to reveal this early cell growth, which could be detected weeks before the cells appear in the blood. This radiology test is safe, does not cause any problems and is not invasive. It is called FLT (18F-fluorothymidine) and the contrast is taken up by dividing hematopoietic stem cells. The patients could even see the growth of their new cells inside the bone marrow (which they very much enjoyed while waiting to see recovery of the cells in their blood). We could use the brightness of the image (called SUV) to determine approximately how many weeks remained before the cells were visible in the blood. Finally, we actually could see where the new cells went after they were infused, tracking their settling in various organs and bones. Through this, we could see that cells did not travel directly to all of the bones right away as was previously thought, but rather first went to the liver and spleen, then to the mid-spine (thorax), then to the remainder of the spine and breastplate, and finally to the arms and legs. This pattern of bone marrow development is seen in healthy developing fetuses. In this case, it occurs in a similar pattern in adults undergoing bone marrow transplant. (more…)
Alcohol, Author Interviews, Cognitive Issues, Lancet / 21.02.2018 Interview with: “undefined” by Iñaki Queralt is licensed under CC BY 2.0Michaël Schwarzinger, MD, PhD Translational Health Economics Network (THEN) Paris What is the background for this study? What are the main findings? Response: The association of heavy drinking with dementia has been known for decades. For instance, there is about no Wernicke–Korsakoff syndrome without heavy drinking and the syndrome was described in 1890. But this type of dementia is very rare. Also, heavy drinking is knowingly associated with multiple risk factors for dementia onset such as hypertension or diabetes. But heavy drinkers generally refuse to participate to cohort studies and declaration of alcohol use among participants is generally biased downward... So the study rationale is very strong, but supporting empirical evidence is quite scarce. This nationwide study included all 31+ million adults discharged from hospitals over 6 years, i.e., 50% of the French population before 65 years old and 80% above that age. Of 1.1+ million adults diagnosed with dementia, one in twenty had an early-onset (before 65 years old). Heavy drinking was recorded in most (56%) early-onset dementia cases: two-third in men; one-third in women. In addition, the association of heavy drinking with dementia goes far beyond 65 years old, both directly (>3 times higher risk for dementia onset after controlling for more than 30 known risk factors for dementia) and indirectly as heavy drinking was associated with all other independent risk factors for dementia onset. Accordingly, heavy drinking had the largest effect on dementia risk of all independent modifiable risk factors such as hypertension or diabetes. The effects were found whatever dementia case definition or population studies. (more…)
Author Interviews, Lancet, Melanoma, Weight Research / 14.02.2018 Interview with: Jennifer McQuade, M.D., lead author Melanoma Medical Oncology The University of Texas MD Anderson Cancer Center What is the background for this study? What are the main findings? Response: Melanoma is the most deadly of the common skin cancers, and for many years we lacked effective therapies for patients with disease that had spread (metastatic). Over the past 7 years, there has been FDA approval of 2 new classes of drugs that have dramatically improved the survival of patients with metastatic melanoma. Checkpoint inhibitor immunotherapies “take the brakes” off patients’ immune system to allow the immune system to eliminate the cancer. Targeted therapies turn off key molecules expressed by some tumors (BRAF mutant) that they rely on for sustained growth and division. While these types of therapies can result in dramatic long-term disease control in some patients, others may not have any shrinkage of their tumors. Some differences may lie in the tumors themselves, but there is also increasing evidence that “host” factors such as the microbiome and lifestyle choices might influence outcomes in cancer patients. Obesity has been associated with an increased risk of many cancers, and is in fact poised to overtake smoking as the leading preventable cause of cancer. One of the ways that obesity may increase tumor growth is by increasing levels of insulin and other growth factors which then activate a pathway called the PI3K pathway that leads to continued tumor growth. As that PI3K pathway has also been shown to cause resistance to targeted and immune therapies in melanoma, we hypothesized that obesity would be associated with worse outcomes in patients with metastatic melanoma treated with these therapies. (more…)
Author Interviews, HIV, Infections, Lancet, STD / 12.12.2017 Interview with: Professor Jean-Michel Molina MD Head of Department of Infectious Diseases, Hôpital Saint-Louis Paris France What is the background for this study? What are the main findings? Response: There is a high rate of sexually transmitted infections (STIs) among Pre-exposure prophylaxis users and we wished to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of sexually transmitted infections in this population. We have found indeed a high rate of STIs most of them (71%) being asymptomatic and warranting therefore systematic testing. Also PEP reduced the incidence of syphilis and chlamydiae infection by 70%, not for gonorrhea due to the high rate of detection in throat swabs without any impact of PEP. (more…)
Author Interviews, Dengue, Lancet, Vaccine Studies / 29.11.2017 Interview with: Vianney Tricou DPhil Takeda Vaccines Pte Ltd Singapore What is the background for this study? What are the main findings? Response: Dengue fever is a painful, debilitating mosquito-borne disease caused by any one of the four closely related dengue virus serotypes. Forty percent of the world’s population lives under the threat of dengue, with approximately 390 million infections and 20,000 deaths occurring globally each year. Dengue virus can infect people of all ages and is a leading cause of serious illness among children in some countries in Latin America and Asia. Takeda is developing a dengue vaccine candidate to safely protect children and adults living in, or traveling to, endemic areas against all four dengue virus serotypes, regardless of previous dengue virus exposure.  Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a live, attenuated dengue serotype 2 virus, which provides the genetic ‘backbone’ for all four vaccine viruses. Takeda’s ongoing Phase 2 DEN-204 study was designed to assess the safety and immunogenicity of different dose schedules of TAK-003 in approximately 1,800 healthy children and adolescents ages two through 17 years living in dengue-endemic countries in Latin America and Asia. Participants of the DEN-204 trial received either one primary dose of TAK-003, two primary doses of TAK-003 administered three months apart, one primary dose of TAK-003 followed by a booster dose one year later, or a placebo. Eighteen-month interim data showed that that TAK-003 is associated with a reduction in the incidence of dengue in the study participants. Data also showed that TAK-003 induced sustained antibody responses against all four serotypes of dengue virus, regardless of previous dengue exposure and dosing schedule. (more…)
Aging, Author Interviews, Heart Disease, Lancet, Social Issues / 26.11.2017 Interview with: Prof Kazem Rahimi FRCP The George Institute for Global Health Oxford Martin School University of Oxford, Oxford What is the background for this study? Response: We decided to investigate this topic because disease incidence data is very important for public health bodies; for example, for the allocation of healthcare resources or for the design and assessment of disease prevention measures. When we reviewed the literature, we found that estimates of heart failure incidence, temporal trends, and association by patient features were scarce. Studies often referred to restricted populations (such as relatively small cohorts that may or may not be representative of the general population), or limited data sources (for example, only including patients hospitalized for their heart failure and not considering those diagnosed by clinicians outside of hospitals). Few studies reported comparable, age-standardized rates, with the result that the rates reported varied considerably across the literature. (more…)
Author Interviews, Cost of Health Care, HIV, Lancet / 13.11.2017 Interview with: Dr Valentina Cambiano PhD Institute for Global Health University College London London UK What is the background for this study? Response: Pre-Exposure Prophylaxis (PrEP) which involves the use of drugs, which are used to treat HIV, in people without HIV to prevent them from getting is a critical new advance in HIV prevention. It has been shown to reduce the risk of HIV infection by 86% and the benefits heavily out-weigh any concerns. However, introducing this intervention has a cost. When we started working on this study the National Health Services was discussing whether to introduce PrEP and if so for which populations. Unfortunately, at the moment NHS England is not providing Pre-exposure prophylaxis. However, a large study, the PrEP impact trial, funded by the NHS, has just started and this will provide PrEP to 10,000 people. (more…)
Author Interviews, Biomarkers, Brain Injury, Lancet / 09.11.2017 Interview with: Prof.dr. J van der Naalt PhD Department of Neurology University Medical Center Groningen Groningen, The Netherlands What is the background for this study? What are the main findings? Response: Mild traumatic brain injury occurs frequently and is one of the leading cause of morbidity in adults worldwide. It is a major social-economic problem with one in three patients had persistent complaints several months after injury that interfere with resumption of daily activities and work. One of the most important questions concerns the finding that some patients recover without complaints and others do not after sustaining a mild traumatic brain injury. In a follow-up study with more than 1000 participants we found that personality factors are a major factor in the recovery process. In particular coping, that is the way patients adapt to persistent complaints, is important next to emotional distress and impact of the injury. In an add-on study with fMRI we found that in the early phase after injury, the interaction between specific brain networks was temporarily changed. However, when regarding persistent posttraumatic complaints , specific personality characteristics significantly determine long term outcome. (more…)
Abuse and Neglect, Circadian Rhythm, Heart Disease, Lancet, Surgical Research / 03.11.2017 Interview with: Prof David Montaigne MD Faculté de Médecine de Lille H Warembourg Lille, France What is the background for this study? What are the main findings? Response: It is well known for many decades that cardiovascular diseases exhibit a diurnal variation with for instance higher incidence of myocardial infarction in the early morning as opposed to the evening. Although studies on circadian gene knock-out and mutant mice argue for a biorhythm in myocardial ischemia-reperfusion tolerance, whether a biorhythm in the myocardial tolerance to ischemia, exists in humans was unclear because of conflicting reports in the context of myocardial infarction. We demonstrated for the first time in humans that the myocardial tolerance to ischemia-reperfusion is different along the day, in line with rodent experiments performed in the early 2010s. We demonstrated that this biorhythm is clinically meaningful and that it can be targeted as a cardioprotective strategy. In this topic, Rever-alpha is of specific interest. It belongs at the same time to circadian genes and nuclear receptor families: being a nuclear receptor, it is a feasible pharmacological target, conversely to other circadian genes. (more…)
Author Interviews, Cancer Research, Lancet / 30.10.2017 Interview with: Dr Miranda M Fidler, PhD Section of Cancer Surveillance International Agency for Research on Cancer Lyon, France What is the background for this study? What are the main findings? Response: The burden of cancer among young adults has been rarely studied in depth. To our knowledge, we describe for the first time the scale and profile of cancer incidence and mortality worldwide among 20-39 year-olds, highlighting major patterns by age, sex, development level, and geographic region. Although cancer is less frequent than that observed at older ages, its impact remains considerable because these individuals have a large proportion of their expected lifespans remaining, contribute substantially to the economy, and play a major role in caring for their families. Worldwide, almost 1 million new cases of cancer and 400 000 cancer-related deaths occurred among young adults aged 20–39 years in 2012. Overall, the most common cancer types in terms of new cases were female breast cancer, cervical cancer, thyroid cancer, leukemia, and colorectal cancer, and the most common types of cancer-related deaths were those due to female breast cancer, liver cancer, leukemia, and cervical cancer. The burden was disproportionately greater among women, with an estimated 633 000 new cancer cases (65% of all new cancer cases in that age group) and 194 000 cancer-related deaths (54% of all cancer-related deaths in that age group) in 2012. (more…)
Author Interviews, Gastrointestinal Disease, Global Health, Lancet / 18.10.2017 Interview with: Gilaad Kaplan, MD, MPH, FRCPC Associate Professor CIHR New Investigator & AI-HS Population Health Investigator Co-Director, Environmental Health Research Group Snyder Institute for Chronic Diseases & Institute of Public Health Departments of Medicine & Community Health Sciences University of Calgary What is the background for this study? What are the main findings? Response: The aim of the study was to provide a global perspective on the epidemiology of the inflammatory bowel diseases in the 21st century. During the 20th century IBD was considered a disease of the Western world. At the turn of the 21st century, IBD has become a global disease with accelerating number of cases in the developing world as it transition towards a westernized society. (more…)