Author Interviews, Breast Cancer, Endocrinology, Lancet, Menopause / 08.07.2015

MedicalResearch.com Interview with: Dr. Jürg Bernhard Ph.D. International Breast Cancer Study Group Coordinating Center and Bern University Hospital, Inselspital, Bern, Switzerland Medical Research: What is the background for this study? What are the main findings? Response: In the combined analysis of the SOFT and TEXT trials, the aromatase inhibitor exemestane was more effective than tamoxifen in preventing breast cancer recurrence in young women (premenopausal) who also receive ovarian function suppression (OFS) as adjuvant (post-surgery) treatment for hormone-sensitive early breast cancer, providing a new treatment option for these women. These trials were conducted by the International Breast Cancer Study Group (IBCSG) and involved more than 4700 patients of over 500 centers in 27 countries. Now we present patient-reported quality of life outcomes from these trials. In the TEXT and SOFT trials, patients assigned exemestane+OFS reported more detrimental effects of bone or joint pain, vaginal dryness, greater loss of sexual interest and difficulties becoming aroused, while patients assigned tamoxifen+OFS were more affected by hot flushes and sweats. Global quality of life domains (mood, ability to cope and physical well-being) were similar between the randomized treatment groups. (more…)
Author Interviews, Ebola, Lancet / 02.07.2015

MedicalResearch.com Interview with: Jana Broadhurst, MD, PhD Stanford University Nira R Pollock MD PhD Boston Children's Hospital, Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: At present, diagnosis of Ebola virus disease (EVD) in west Africa requires transport of venipuncture blood to field laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test (RDT) for this disease. In this study, we performed a field validation of the Corgenix ReEBOV Antigen Rapid Test kit, the only Ebola RDT authorized for emergency use by the WHO and FDA. This test is a dipstick lateral flow immunoassay designed to detect the Ebola virus VP40 protein in whole blood (collected by either fingerstick or whole blood) or plasma. We performed the rapid diagnostic test at the point-of-care on fingerstick blood samples from 106 individuals with suspected EVD presenting at two Ebola clinical centers in Sierra Leone. Separately, we performed the RDT on 284 venous whole blood samples submitted to the Public Health England field reference laboratory for clinical testing. Two readers independently scored each RDT as positive, negative, or invalid, with any disagreements resolved by a third. RDT results were compared with clinical real-time RT-PCR results obtained with the RealStar Filovirus RT-PCR kit 1.0 (altona Diagnostics GmBH). In point-of-care testing of fingerstick blood, the RDT had 100% sensitivity (95% CI 87.7-100) and 92% specificity (95% CI 83.8-97.1). Similarly, in venipuncture blood tested in the reference laboratory the rapid diagnostic test had 100% sensitivity (95% CI 92.1-100) and 92% specificity (95% CI 88.0-95.3). The two independent readers agreed for 95.2% of point-of-care and 98.6% of reference laboratory RDT results. The maximum cycle threshold (Ct) value was 26.3 in PCR-positive samples tested from both point-of-care (mean Ct 22.6) and reference laboratory (mean Ct 21.5) cohorts. Six of 16 banked plasma samples from RDT-positive and altona-negative patients were positive by an alternative real-time RT-PCR assay (the Trombley assay); 3 of 18 samples from individuals who were negative by both the RDT and altona test were also positive by Trombley. (more…)
Author Interviews, Lancet, Leukemia, Lymphoma, Occupational Health / 01.07.2015

MedicalResearch.com Interview with: Dr Klervi Leuraud, Epidemiologist Institute for Radiological Protection and Nuclear Safety Cedex, France MedicalResearch: What is the background for this study? What are the main findings? Dr. Leuraud: INWORKS was performed to quantify the risk of cancer mortality associated to protracted low doses of ionizing radiation typical of occupational or environmental exposures, as well as of diagnostic medical exposures. While such risks are well known for acute exposures as those experienced by the Japanese survivors of the A-bombs, there is still a lack of information for exposures experienced by the workers and the public. Our study confirms the existence of an association between leukemia mortality and chronic exposure to low doses received by nuclear workers. (more…)
Author Interviews, Lancet / 19.06.2015

MedicalResearch.com Interview with: Dr. Stephan Glund Ph.D. Boehringer Ingelheim Pharma GmbH & Co. KG Transl. Medicine & Clin. Pharmacology Medical Research: What is the background for this study? What are the main findings? Dr. Glund: There are currently no specific reversal agents available for any of the non-Vitamin K antagonist oral anticoagulants (NOACs). We are working on the development of idarucizumab, a specific reversal agent to dabigatran, the first approved NOAC. The study now published in The Lancet investigated, for the first time in healthy volunteers, the reversal of the anticoagulant effect of dabigatran by idarucizumab. Our study in healthy male volunteers showed that idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of dabigatran. Participants first received dabigatran and then idarucizumab. The specific reversal agent was given two hours after the last dose of dabigatran, when dabigatran concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above. Idarucizumab was well tolerated by the study participants. In addition, our study also showed that administration of idarucizumab reversed dabigatran-induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting mechanism. This suggests that idarucizumab might also reverse impaired haemostasis due to dabigatran anticoagulation at a wound site. (more…)
Author Interviews, Cannabis, Columbia, Lancet / 18.06.2015

Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032MedicalResearch.com Interview with: Deborah S. Hasin, Ph.D. Professor of Epidemiology Columbia University New York, New York 10032 MedicalResearch: What is the background for this study? What are the main findings? Dr. Hasin: The background for the study was the need to identify the causes of the marked increase in marijuana use among U.S. adolescents over the last several years, given that early adolescent marijuana use leads to a number of adverse health and psychosocial consequences, including cognitive decline, into adulthood. We had two main findings from the study:
  1. A comparison of the rates of adolescent marijuana use between states that ever passed a medical marijuana law and those that did not revealed that states with such laws had higher rates of teen marijuana use, regardless of when they passed the law; and
  2. When we compared the rates of teen marijuana use in these states before and after passage of the laws, we did not find a post-passage increase in the rates of teen marijuana use. This suggests that some common factor may be causing both the laws to be passed and the teens to be more likely to smoke marijuana in the states that passed these laws.
(more…)
Author Interviews, Diabetes, Lancet, McGill / 13.06.2015

MedicalResearch.com Interview with: Dr Ahmad Haidar Ph.D. Division of Experimental Medicine Department of Medicine, McGill University Montreal, QC, CanadaDr. Ahmad Haidar Ph.D Division of Experimental Medicine, Department of Medicine McGill University, Montreal, QC, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Haidar: This is the first head-to-head-to-head comparison in outpatient setting of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional pump therapy in children and adolescents with type 1 diabetes. The main finding is that the dual-hormone artificial pancreas seems to outperform the other two systems in reducing nocturnal hypoglycemia in camp settings when the patients are very physically active during the day. Medical Research: What should clinicians and patients take away from your report? Dr. Haidar: Glucagon has the potential to reduce nocturnal hypoglycemia if added to the artificial pancreas. However, this needs to be confirmed in larger and longer studies as the single-hormone artificial pancreas might be sufficient in home settings (this study was conducted at a camp, which is an environment different that home). (more…)
Author Interviews, Lancet, Ovarian Cancer, Surgical Research / 22.05.2015

MedicalResearch.com Interview with: Mr Matthew Nankivell MRC Clinical Trials Unit at University College London Institute of Clinical Trials and Methodology Aviation House, London UK Medical Research: What is the background for this study? What are the main findings? Response: Ovarian cancer is diagnosed in over 7000 women each year in the UK. Over 75% of these already have advanced disease, for which the standard treatment is surgery followed by platinum based chemotherapy. The prognosis for these patients remains poor however, with less than 25% surviving for 5 years. There is consistent evidence that achieving optimal debulking (meaning less than 1cm of residual tumour after surgery) is key to increasing survival. The theory tested in Chorus is that giving the chemotherapy before surgery (neo-adjuvantly) would be as least as effective as giving it post-operatively, and may in fact increase the chance of achieving optimal debulking, and subsequently living for longer. In Chorus we randomised 552 women to receiving either the current standard of immediate surgery followed by chemotherapy, or chemotherapy followed by surgery. The trial met its primary aim of showing that neo-adjuvant chemotherapy was no worse than post-operative chemotherapy, with median survival times of 24.1 and 22.6 months respectively. The proportion of women achieving optimal debulking increased from 41% in the post-operative chemotherapy group to 73% in the neo-adjuvant chemotherapy group. Additionally we saw that fewer women experienced serious post-operative complications having had neo-adjuvant chemotherapy (14% vs 24%), and fewer women died within 28 days of surgery (<1% vs 6%). There is a planned meta-analysis, to combine the data from Chorus with those from a similar European trial, which will allow further investigations to take place, and may allow the identification of groups of women who are more likely to benefit from one or other of the approaches. (more…)
Author Interviews, Genetic Research, Lancet, Pediatrics / 29.04.2015

MedicalResearch.com Interview with: Stephen F. Kingsmore MB ChB BAO DSc FRCPath Dee Lyons/Missouri Endowed Chair in Genomic Medicine, Children’s Mercy - Kansas CityMedicalResearch.com Interview with: Stephen F. Kingsmore MB ChB BAO DSc FRCPath Dee Lyons/Missouri Endowed Chair in Genomic Medicine, Children’s Mercy - Kansas City Medical Research: What is the background for this study? Response: The background to this study is that genetic diseases are the leading cause of death in infants and, especially, in infants in neonatal intensive care units. Making a molecular (etiologic) diagnosis of the specific genetic disease is critical for optimal care and decision making for acutely ill infants who are likely to have such diseases. However there are over 5000 known genetic diseases and their presentations overlap considerably in infants. Until now it has not been possible to make timely diagnoses in these infants. Medical Research: What are the main findings? Response: Rapid whole genome sequencing is a new way of making a genetic disease diagnosis in acutely ill newborns in neonatal intensive care units. It appears to be effective for diagnosis. (more…)
Author Interviews, CDC, Infections, Lancet, Vaccine Studies / 25.04.2015

Mary J Hamel, M.D. Chief, Strategic and Applied Sciences Unit, And Deputy Branch Chief for Science, CDC Malaria Branch US Centers for Disease Control and Prevention 1600 Clifton Rd, NE, MS A06 Atlanta GA 30333MedicalResearch.com Interview with: Mary J Hamel, M.D. Chief, Strategic and Applied Sciences Unit, And Deputy Branch Chief for Science, CDC Malaria Branch US Centers for Disease Control and Prevention 1600 Clifton Rd, NE, MS A06 Atlanta GA 30333 Dr. Hamel was principal investigator at the Siaya site in western Kenya. Medical Research: What is the background for this study? What are the main findings? Dr. Hamel: Major progress has been made in malaria control during the past decade with the scale up of proven interventions including insecticide treated nets (ITNs), indoor residual spraying, effective diagnosis and treatment for malaria, and intermittent preventive treatment of malaria in pregnancy. Nonetheless, malaria remains a major cause of morbidity and mortality, and a leading cause of pediatric death worldwide. An estimated 198 million cases of malaria and 580,000 deaths occurred in 2013 – most of these in African children. Now we face additional challenges in malaria control – the emergence of insecticide and drug resistance threatens some of our most effective interventions. New tools are needed to reach the goal of malaria elimination and eventual eradication. Vaccines are some of our most cost-effective interventions, and an effective malaria vaccine would be an important addition to our current malaria control tools. This week, the RTS,S Clinical Trials Partnership published the final vaccine efficacy and safety results from the RTS,S/AS01 malaria vaccine phase 3 trial in the Lancet (Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial, http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60721-8/abstract). This large randomized controlled double-blind phase 3 clinical trial was conducted in 11 sites in 7 African countries across a range of malaria transmission levels. In all, 15,460 children and young infants were enrolled in two age-categories, those first vaccinated at 5-17 months of age (referred to as children), and those first vaccinated at 6-12 weeks of age (referred to as young infants) who received the RTS,S/AS01 vaccine along with their routine childhood immunizations. Participants were randomized into 3 groups – the first group received three doses of the RTS,S/AS01 vaccine followed 18 months later by a booster dose; the second group received three doses of the RTS,S/AS01 vaccine without a booster; and the third group received a comparator vaccine. All participants received an ITN. Children were followed for an average of 48 months and infants for an average of 38 months. We found that vaccine efficacy was modest. Vaccine efficacy against clinical malaria in children was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was 32% with a booster and non-significant without.   Efficacy results in young infants were lower than those in children– vaccine efficacy against clinical malaria was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was non-significant. However, impact, defined as the number of cases averted per 1000 participants vaccinated, was substantial in both age-categories, and highest where malaria burden was greatest. In children who received the booster, during 4 years follow-up, 1700 cases of clinical malaria were averted per 1000 children vaccinated. In young infants, during 3 years follow-up, nearly 1000 cases were averted per 1000 young infants vaccinated. The safety findings were comparable overall in the different study arms, but two safety findings are notable. Meningitis occurred more frequently among children (but not young infants) who received RTS,S/AS01 than among those who received the comparator vaccines. There was no relationship between when the vaccine was administered and when meningitis occurred, most cases occurred in only two study sites, and the finding may be due to chance. If RTS,S/AS01 is licensed, post-licensing studies will be done to establish the significance of this finding. Both children and young infants experienced more episodes of fever and associated febrile convulsions during the 7 days following vaccination; convulsions occurred in 2.2 - 2.5/1000 vaccine doses. (more…)
Author Interviews, Biomarkers, Lancet, Lymphoma, NIH / 06.04.2015

MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans. (more…)
Author Interviews, FDA, Flu - Influenza, Geriatrics, Lancet, Vaccine Studies / 03.04.2015

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD MedicalResearch.com Interview with: Dr Richard Forshee PhD Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD On behalf of the study authors Medical Research: What is the background for this study? What are the main findings? Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken.  The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group.  The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients. In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness.  This pathway reduces the time it takes for needed medical products to become available to the public.  Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease. As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease. A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older.  The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose. Additional background about this study: “Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis” is available at: http://dx.doi.org/10.1016/S1473-3099(14)71087-4 A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at: http://dx.doi.org/10.1016/S1473-3099(15)70020-4 (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 31.03.2015

Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, ChinaMedicalResearch.com Interview with: Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, China MedicalResearch: What is the background for this study? What are the main findings? Prof. Hu: Triple-negative breast cancer (TNBC) is associated with higher rates of recurrence, shorter disease free survival, and poorer overall survival. Molecular targeting agents tried against Triple-negative breast cancer have nearly all failed. TNBC, concordant with BRCA-associated and basal-like breast cancer, has abnormal DNA repair and genome-wide instability, supporting the use of DNA-damaging agents such as platinum. However, platinum monotherapy is not very potent, combination with other agents, such as gemcitabine has a synergistic effect. The GP regimen could be an alternative or even preferential first-line doublet chemotherapy strategy for patients with mTNBC. (more…)
Infections, Lancet, Pediatrics / 30.03.2015

MedicalResearch.com Interview with: Dr Anne K Detjen, MD Child Lung Health Consultant International Union Against Tuberculosis and Lung Disease Medical Research: What is the background for this study? What are the main findings? Dr. Detjen: The bacteriological diagnosis of tuberculosis (TB) in children is challenging due to the difficulty in obtaining specimens such as sputum and the lack of an accurate and accessible diagnostic test. In most cases, diagnosis is made on clinical grounds based on a contact history and a combination of signs and symptoms. We included 15 studies in a systematic review and meta-analysis of Xpert for the diagnosis of pulmonary TB in children. The accuracy of Xpert for diagnosing TB in children is suboptimal, and the majority of children will still have to be diagnosed clinically. However, in settings where it replaces smear microscopy Xpert will increase the likelihood of bacteriological confirmation of TB as well as MDR TB among children. Xpert does not increase the number of confirmed TB cases among culture-negative children. We also found that smear status highly impacted Xpert results, i.e. a higher yield among smear positive compared to smear negative children. Smear positivity increases with bacillary load and might be a proxy for disease severity. Unfortunately, we were not able to assess the performance among children with different stages of disease severity since this was not classified in any of the studies included. (more…)
Author Interviews, Kidney Disease, Lancet / 20.03.2015

Prof Vlado Perkovic MBBS PhD FASN FRACP George Institute for Global Health University of Sydney Sydney AustraliaMedicalResearch.com Interview with: Prof Vlado Perkovic MBBS PhD FASN FRACP George Institute for Global Health University of Sydney Sydney Australia   Medical Research: What is the background for this study? What are the main findings? Prof. Perkovic: There has been much discussion about the large number of people with kidney disease around the world- more than 10% of the population in most countries- but the current number of people with kidney failure had not been clearly defined. We therefore systematically collected information on the number of people with kidney failure around the world and found that 2.6 million people were receiving treatment for kidney failure in 2010, almost 80% of whom were undergoing dialysis while the others had received a kidney transplant. We then noticed very large differences in the number of people receiving treatment in different regions and countries, so used mathematical modeling to calculate the number of people who should be receiving treatment for kidney failure. The results of this analysis suggested there should be between 5 and 10 million people receiving treatment for kidney failure, suggesting that between half and three-quarters of people with kidney failure around the world died without access to dialysis, as a result of the high cost of dialysis treatment that is not affordable for many people around the world. These people are doomed to die of kidney failure, a condition for which we have had an effective treatment for over 50 years. (more…)
Author Interviews, Lancet, Mental Health Research / 19.03.2015

Dr. Angela WoodsMedicalResearch.com Interview with: Dr Angela Woods Associate Editor, BMJ Medical Humanities Journal Senior Lecturer in Medical Humanities Deputy Director, Centre for Medical Humanities Durham University   Medical Research: What is the background for this study? What are the main findings? Dr. Woods: We’ve known for a long time that hearing voices, or auditory hallucinations, is reported by people with a wide range of psychiatric diagnoses as well as by those who have no diagnosis. 5–15 per cent of adults will hear voices at some point during their lives – in circumstances that may be related to spiritual experiences, bereavement, trauma, sensory deprivation or impairment, as well as mental and emotional distress. However, what we know about voices clinically and empirically comes from a small handful of studies, typically conducted in mental health settings with patients with a diagnosis of schizophrenia using quantitative scales and measures. Our study asked people to describe, in their own words, what it is like to hear voices. We designed an open-ended online questionnaire which was completed by 153 people with a range of diagnoses, including 26 who had never had a psychiatric diagnosis. Our study found that a large majority of participants described hearing multiple voices (81%) with characterful qualities (70%). While fear, anxiety, depression and stress were often associated with voices, 31% of participants reported positive and 32% neutral emotions. To our surprise less than half the participants reported hearing literally auditory voices; 45% reported either thought-like or mixed experiences. Perhaps the most startling finding concerned the physicality of voices. Bodily sensations while hearing voices were reported by 66% of participants – these included feelings of tingling, numbness, burning, pressure, and a sense of being distanced or disconnected from the body. (more…)
Author Interviews, Cleveland Clinic, Heart Disease, Lancet, Surgical Research / 15.03.2015

Prof Samir R Kapadia MD Director, Sones Cardiac Catheterization Laboratories Cleveland Clinic Cleveland, OH For patients with severe symptomatic aortic stenosis (AS) who are not candidates for surgical valve replacement, transcatheter aortic valve replacement (TAVR) offers superior benefit to standard therapy, as measured by all-cause mortality, cardiovascular mortality, repeat hospital admission and functional status. PARTNER 1B 5 year data were published simultaneously with PARTNER 1A 5 year data in 2 separate manuscripts in the Lancet (March 15 2105). In this landmark trial, TAVR produced a 22 percent survival benefit and a 28 percent reduced risk of cardiovascular mortality, compared with standard treatment. According to Cleveland Clinic interventional cardiologist Samir Kapadia, MD, lead author of PARTNER 1B, these findings have changed the treatment paradigm for severe Aortic Stenosis patients who can’t undergo surgical Aortic Valve Replacement. “This trial is the first—and will probably be the only—randomized AS trial that includes a standard treatment group, since these results will make it unethical to treat severe AS patients with medical therapy alone without aortic valve replacement. ” he says. Superior survival benefit with TAVR PARTNER 1B is the only rigorous randomized trial of extreme-risk aortic stenosis patients that has prospectively reported the outcomes of TAVR versus standard treatment in patients for whom the estimated probability of death or serious irreversible morbidity after surgical aortic valve replacement was 50 percent or greater. The trial enrolled 358 patients between May 11, 2007 and March 16, 2009; 179 patients were assigned to TAVR with the first-generation Sapien valve and 179 to standard therapy which includes medical therapy and balloon aortic valvuloplasty. TAVR was performed under general anesthesia with common femoral artery access. Guidance was provided by transesophagel echocardiography and fluoroscopy. The mean age of participants was 83. The primary endpoint was all-cause survival. Secondary endpoints included cardiovascular mortality, stroke, vascular complications, major bleeding and functional status. (more…)
Alzheimer's - Dementia, Author Interviews, Karolinski Institute, Lancet / 13.03.2015

MedicalResearch.com Interview with: Miia Kivipelto MD, PhD, Professor Deputy Head, Senior Geriatrician Aging Research Center and Alzheimer Disease Research Center Karolinska Institutet Clinical Trials Unit, Memory Clinic Karolinska University Hospital Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Kivipelto: Epidemiological studies have linked several modifiable risk factors to cognitive impairment and dementia but evidence from randomized controlled trials (RCT) has been lacking showing the efficacy of the interventions. Because cognitive impairment, dementia and Alzheimer’s disease are complex, multi-factorial disorders, multidomain interventions targeting several risk factors and disease mechanisms simultaneously could be needed for optimum preventive effect. The FINGER study is the first large, long-term RCT indicating that multi-domain intervention can improve and maintain cognitive functioning in at risk elderly people from the general population. We observed a significant intervention effects on the primary outcome (overall cognition), main secondary outcomes (executive functioning and processing speed) as well as on complex memory tasks and risk of cognitive decline. The multidomain lifestyle intervention was feasible and safe. (more…)
Author Interviews, HPV, Lancet, Vaccine Studies / 05.03.2015

MedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université LavalMedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université Laval Medical Research: What is the background for this study? What are the main findings? Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions.  Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs. In countries with high female vaccination coverage (<50%), our main findings indicate:
  • sharp declines in HPV-related outcomes among females targeted for vaccination (e.g., HPV-16/18 infection and anogenital warts declined by more than 60% in females younger than 20 years), and
  • evidence of cross-protection with significant reductions in HPV-31/33/45 infection among females younger than 20 years
  • evidence of herd effects (indirect benefit of vaccination among unvaccinated individuals) with significant reductions in anogenital warts among males and older females.
In countries with low coverage (<50%), we report:
  • significant reductions in HPV-16/18 infection and anogenital warts among young females, with no indication of herd effects or cross-protection. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2015

MedicalResearch.com Interview with: Dr. Lucia Del Mastro MD Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genova, Italy Medical Research: What is the background for this study? What are the main findings? Response: Adjuvant chemotherapy regimens with anthracyclines and taxanes improve the outcome of patients with early breast cancer. Among the most widely used anthracycline-based chemotherapy in sequential combinations with the taxane paclitaxel (P) there are epirubicin and cyclophosphamide (EC) and fluorouracil, epirubicin, and cyclophosphamide (FEC). The contribution of fluorouracil to the anthracycline-cyclophosphamide regimen (EC) was unclear until now. Various randomized trials attempted to assess the role of a more intense schedule of chemotherapy (i.e. dose-dense chemotherapy with cycles administered every 2 weeks instead of every 3 weeks) in patients with early breast cancer. However, most of these trials compared dose-dense chemotherapy with regimens that use standard intervals but with different drugs or dose in the treatment groups, thus making difficult to extrapolate the true role of the dose-dense strategy. The results of GIM2 study show that the addition of fluorouracil to  a sequential regimen with epirubicin, cyclophosphamide and paclitaxel increases the toxicity, in terms of neutropenia, fever, nausea, and vomiting, and is not associated with an improved outcome compared with the same treatment without fluorouracil. (more…)
Author Interviews, Infections, Lancet / 27.02.2015

Dr. Masae Kawamura MD Director and TB Controller City and County of San Francisco Department of Health Principal investigator for the Regional TB Training and Medical Consultation CenterMedicalResearch.com Interview with: Dr. Masae Kawamura MD Senior Director, QuantiFERON Medical and Scientific Affairs QIAGEN MedicalResearch: What is the background for this study? What are the main findings? Dr. Kawamura:  The report in The Lancet presents the baseline phase of China’s first large-scale, multi-center prospective study of the epidemiology of latent tuberculosis infection. The comparison study of more than 21,000 patients allowed detailed analysis of demographics and risk factors, along with robust comparisons within subgroups. The study’s follow-up phase is now underway, and patients with Latent Tuberculosis Infection (LTBI) will be evaluated for rates of disease and associated risks. Generally, up to 10% of people with Latent Tuberculosis Infection will develop active, contagious Tuberculosis (TB) disease at some point. The overall TB infection rate was 18.8% measured by QuantiFERON-TB Gold compared to 28% by the traditional tuberculin skin test (TST), a difference of over 125 million people (based on 2014 population estimates from China). Unlike the tuberculin skin test, positive rates of QuantiFERON-TB Gold were not related to prior Bacille Calmette-Guérin (BCG) vaccination, but correlated with background active TB and suspect rates, as well as known risks for TB. BCG vaccination is recommended to newborns by the World Health Organization (WHO) as a matter of TB control policy in many countries, including China.         (more…)
Author Interviews, Lancet, Surgical Research, Technology / 26.02.2015

MedicalResearch.com Interview with: Aidan Roche MBBS, PhD, BEng and Prof Oskar C Aszmann MD Director of the Christian Doppler Laboratory for Restoration of Extremity Function Division of Plastic and Reconstructive Surgery Department of Surgery Medical University of Vienna, Vienna, Austria Medical Research: What is the background for this study? What are the main findings? Response: The study was prompted by lack of techniques to restore hand function in patients with global plexopathies with avulsion of the lower roots. In simple terms, this is a tearing injury to parts of the brachial plexus. The brachial plexus is a complex junction of nerves that leaves the spinal cord and supplies the arm. If this junction of nerves is severely damaged, information cannot reach the hand to control it or to receive sensation from it.  In some of these cases, traditional reconstructive surgical techniques are only able to restore shoulder and elbow function, not the hand itself. In severe cases, this might leave the patient with a useless hand.  In previous clinical studies with existing amputees, advancing research has shown that good prosthetic control can be achieved by selectively transferring nerves. However, our study differs as our patients had intact, but functionless hands. The innovation here was to selectively transfer nerves and muscles to create useable signals for prosthetic control. Together with a comprehensive rehabilitation regime, followed by elective amputation, this formed the bionic reconstruction process. The main finding is that all three patients had excellent hand function restored through bionic reconstruction (as measured by the uniform improvement in all patients in the clinical outcome scores of the Action Research Arm Test, the Disability of Arm, Shoulder and Hand Questionairre, and the Southampton Hand Assessment Procedure and reported in detail in The Lancet). (more…)
Author Interviews, Hormone Therapy, Lancet, Prostate Cancer, Radiation Therapy / 22.02.2015

Almudena Zapatero MD PhD Senior Consultant Dpt Radiation Oncology Instituto Investigación Sanitaria IIS-IP Hospital Universitario de la Princesa MadridMedicalResearch.com Interview with: Almudena Zapatero MD PhD Senior Consultant Dpt Radiation Oncology Instituto Investigación Sanitaria IIS-IP Hospital Universitario de la Princesa Madrid Medical Research: What is the background for this study? What are the main findings? Dr. Zapatero: There is a significant body of evidence from randomized trials showing a significant improvement in clinical outcome with the combination of androgen deprivation and conventional-dose radiotherapy (≤70 Gy) in patients with high-risk and intermediate-risk prostate cancer. However, the optimal duration the optimum duration of androgen deprivation in the setting of high-dose radiotherapy remained to be determined. The results of our trial (DART01/05) show that 2 years of adjuvant androgen deprivation is superior to 4 months androgen deprivation when combined with plus high-dose radiotherapy  in terms of biochemical control, freedom from metastasis and overall survival, particularly in patients with high-risk prostate cancer. (more…)
Author Interviews, Lancet, Lifestyle & Health / 07.02.2015

Dr Sandra L Jackson PhD Atlanta VA Medical Center, Decatur, GA, Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences Emory University, Atlanta, GA, USAMedicalResearch.com Interview with: Dr Sandra L Jackson PhD  Atlanta VA Medical Center, Decatur, GA, Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences Emory University, Atlanta, GA, USA Medical Research: What is the background for this study? What are the main findings? Dr. Jackson: Lifestyle change programs are aimed to improve health, yet little is known about their impact once translated into clinical settings. The Veterans Health Administration (VA) MOVE! program is the largest lifestyle change program in the U.S. Participation is a key challenge of the program, as only 13% of the eligible population participated. However, among patients who did not have diabetes at baseline, we found that MOVE! participation was associated with lower diabetes incidence. (more…)
Author Interviews, Geriatrics, Hip Fractures, Lancet / 06.02.2015

Ingvild Saltvedt PhD Department of Neuroscience, Norwegian University of Science and Technology, Medical Faculty Trondheim, Norway MedicalResearch.com Interview with: Ingvild Saltvedt PhD Department of Neuroscience, Norwegian University of Science and Technology, Medical Faculty Trondheim, Norway Medical Research: What is the background for this study? What are the main findings? Dr. Saltvedt: Hip fracture patients are often old, frail and have many comorbidities. When treated with a traditional orthopaedic approach the outcomes are often poor, and many patients get functionally impaired with reduced ability to walk independently and impairment in daily life activities and with high costs for the society.  In many ways these patients are geriatric patients with hip-fractures. It has previously been shown that acutely sick geriatric patients benefit from treatment in geriatric wards and different kind of  orthogeriatric treatment models where orthopaedic surgeons and geriatricians collaborate have been studied and have shown beneficial results on short term outcomes. In the present study patients home-dwelling hip-fracture patients were randomised to orthogeriatric treatment or traditional orthopaedic treatment from admission to the hospital and during the entire stay except for the surgery that was performed similar in both groups. The study focused on long-term outcomes and also on use of health care services and cost-effectiveness.  Patients in the orthogeriatric group got comprehensive geriatric assessment and treatment performed by an interdisciplinary team that emphasised early mobilisation and rehabilitation and started discharge planning early. In the orthopaedic group traditional treatment according to national and international guidelines was offered. The primary endpoint was mobility at four months, that was better in the orthogeriatric group than in the orthopaedic group, the same difference was also shown at 12 months. In addition there were differences in instrumental activities of daily living and personal activities of daily living, quality of life and fear of falling, all differences were statistically and clinically significant and in favour of the orthoegeriatric group. The length of hospital stay was 1,7 days longer in the geriatric group, while there was no differences in days spent in hospital during one year of follow-up. One of four orthogeriatric patients were discharged directly home as compared to one of ten in the orthopaedic group. The orthopaedic group spent more days in nursing homes and rehabilitation institutions during one year of follow-up. The treatment was cost-effective in favour of the orthogeriatric group. (more…)
Author Interviews, Hepatitis - Liver Disease, HIV, Lancet / 05.02.2015

MedicalResearch.com Interview with: Prof Jean-Michel Molina Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris France MedicalResearch.com Interview with: Prof Jean-Michel Molina Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris France Medical Research: What is the background for this study? What are the main findings? Prof. Molina: Treatment of co-infected patients is complicated by drug drug interactions with HIV drugs, and the news DAAs are not very potent on HCV G2 and 3 infections. (more…)
Author Interviews, Depression, Lancet, Multiple Sclerosis / 04.02.2015

Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, GermanyMedicalResearch.com Interview with: Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Gold: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (brain and the spinal cord). In addition to motor symptoms such as walking impairment, patients with Multiple sclerosis frequently suffer from psychological problems including difficulties with learning and memory as well as depressed mood. Depression is particularly common in this patient group with a 3-4 fold elevated risk for developing major depressive disorder compared to the general population. Depression in Multiple sclerosis is associated with decreased quality of life, absence from work, and numerous other psychosocial problems. Despite this major impact on patients’ lives, depression in Multiple sclerosis is often not adequately diagnosed and treated: Antidepressant medication in this patient group often has side effects and the neurological problems associated with MS such as difficulties with concentration and fatigue make it particularly difficult for MS patients to complete “classical” depression treatments such as psychotherapy. The goal of our study was to make psychological treatments available for the many patients with Multiple sclerosis suffering from depression, who often have difficulties to find adequate treatment. For this study, published in The Lancet Psychiatry, we conducted a randomized controlled trial of a fully-automated, computer-based program that can be accessed directly from patients’ homes over the internet. The program called “deprexis” was developed by the Hamburg-based company GAIA and uses methods of “cognitive behavioral therapy” or “CBT”. Ninety Multiple sclerosis patients were enrolled in the trial and randomly assigned to a 3 months therapy using the deprexis program or a waitlist control group. At the end of the intervention, depression had significantly decreased in the treatment group but remained unchanged in patients who did not have access to the program. In addition, patients using the computer program also reported reduced fatigue and improved quality of life. (more…)
Author Interviews, CDC, Infections, Lancet, Vaccine Studies / 04.02.2015

MedicalResearch.com Interview with: Dr Matthew R Moore, MD National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USADr Matthew R Moore, MD National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA MedicalResearch: What is the background for this study? Dr. Moore: Since introduction, pneumococcal conjugate vaccines have resulted in dramatic decreases in the number of cases of invasive pneumococcal disease in both children and adults.  The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine infant immunization program in the United States in 2000. It was recommended for infants using a 4-dose schedule: 2, 4, 6, and 12 through 15 months of age. Studies showed that PCV7 was highly effective in preventing invasive pneumococcal disease. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 using the same 4-dose schedule. PCV13 is similar to PCV7, but includes protection against six additional serotypes of Streptococcus pneumoniae. There are more than 90 serotypes of pneumococcal bacteria. Streptococcus pneumoniae, or pneumococcus, is a major cause of illness and death globally. Pneumococcus can cause many types of illness that ranging from mild to life-threatening, including pneumonia, ear and sinus infections, meningitis, and bacteremia. Some of these infections are considered invasive because they invade parts of the body that are normally free from bacteria. Invasive pneumococcal disease, including meningitis and bacteremia, is often severe and can be deadly. MedicalResearch: What are the main findings? Dr. Moore: Invasive pneumococcal disease decreased substantially in the first 3 years after PCV13 was introduced into the U.S. infant immunization schedule. By June 2013, more than 30,000 cases of invasive pneumococcal disease and 3,000 deaths are estimated to have been prevented in the United States due to PCV13. Children under the age of five, which is the age group that actually received the vaccine, experienced the greatest and quickest benefit from PCV13.  For example, the overall number of cases of invasive pneumococcal disease decreased by 64% in this age group between 2010 and 2013. Significant decreases were seen as early as six months after the immunization recommendation was made. Adults, who were not targeted for vaccination, also experienced health benefits from PCV13 introduction. For example, the overall number of cases of invasive pneumococcal disease decreased by 32% for adults aged 18 to 49 years, while adults 65 and older experienced a more modest 12% decrease.  These reductions are further evidence that both PCV7 and PCV13 reduce the spread of pneumococcus, which is why vaccinating children leads to disease reductions in adults. For both children and adults, the greatest reductions were seen in the number of cases of invasive pneumococcal disease that were caused by serotypes that are covered by PCV13 but not PCV7 (serotypes 19A and 7F specifically). (more…)
Author Interviews, Lancet, Neurological Disorders, Pediatrics, Respiratory / 31.01.2015

Samuel Dominguez MD Departments of Pediatric Infectious Diseases Children's Hospital Colorado and University of Colorado School of Medicine Aurora, COMedicalResearch.com Interview with: Samuel Dominguez MD Departments of Pediatric Infectious Diseases Children's Hospital Colorado and University of Colorado School of Medicine Aurora, CO Medical Research: What is the background for this study? What are the main findings? Dr. Dominguez: Due to global poliovirus eradication efforts, clusters of acute flaccid paralysis (AFP) and/or cranial nerve dysfunction in children are rare and associated with few pathogens, primarily enteroviruses and flaviviruses.  Our study reports the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of EV-D68 respiratory illness, strengthening the potential link between EV-D68 and neurologic disease in children. (more…)
Asthma, Author Interviews, Compliance, Lancet, Technology / 30.01.2015

Amy Chan BPharm(Hons) RegPharmNZ MPS ANZCP Pharmacist / PhD candidate Department of Paediatrics Auckland Hospital Faculty of Medical & Health Sciences University of Auckland Auckland, New ZealandMedicalResearch.com Interview with: Amy Chan   BPharm(Hons) RegPharmNZ  MPS  ANZCP Pharmacist / PhD candidate Department of Paediatrics Auckland Hospital Faculty of Medical & Health Sciences University of Auckland  Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Response: Asthma is one of the most common childhood conditions, affecting 1 in 4 children in New Zealand.  Although there are many effective medications available for asthma, of which the most important are inhaled corticosteroids, asthma control remains suboptimal due to poor adherence.  In children, adherence to regular preventive asthma therapy is about 50%, and can be as low as 30%.  Our randomised controlled trial looked at use of an electronic monitoring device with an in-built audiovisual reminder to see if it improved adherence and asthma control.  We recruited 220 children aged between 6-15yrs, who presented to the emergency department with asthma and randomised them to receive the device either with the audiovisual function enabled or disabled.  It found that those who received the audiovisual reminder (the intervention arm) took a median of 84% of their inhaled corticosteroids compared to just 30% in those who did not receive the reminder (control arm).  This equates to a 180% improvement in adherence.  We found significant improvements also in asthma control (including reduced asthma symptoms and increased participation in daily activities) and a reduction in reliever use from 17.4% to 9.5% in those who received the reminder. (more…)