N. Saman Wijesooriya[/caption]
N. Saman Wijesooriya
Public Health Advisor/Technical Advisor
Centers for Disease Control and Prevention
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The article Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modeling study by Wijesooriya, et al published in the August 2016 issue of The Lancet Global Health (Open source - http://dx.doi.org/10.1016/S2214-109X(16)30135-8) estimates the incidence and prevalence of maternal and congenital syphilis for both time periods and identifies gaps antenatal care access and syphilis testing and treatment services to assess progress in the global elimination of congenital syphilis, or mother-to-child transmission of syphilis, as a public health problem.
Untreated maternal syphilis is understood to be transmitted from mother-to-child in utero in 50% of cases resulting in tragic adverse pregnancy outcomes, or congenital syphilis infections, including early fetal death, stillbirth, preterm birth, low birthweight, neonatal death, and congenital infections in infants. Since most maternal syphilis infections are asymptomatic, it is recommended that screening for syphilis use a combination of serological tests for pregnant women and treatment of syphilis seropositive women with at least 2.4 million units of benzathine penicillin intramuscularly early in pregnancy to prevent most congenital syphilis infections.
In 2007, the World Health Organization responded to estimates indicating 2 million maternal and 1.5 congenital syphilis infections would occur annually without treatment and launched the global initiative for the Elimination of Congenital Syphilis (ECS). The strategy includes reducing the prevalence of syphilis in pregnant women and mother-to-child transmission of syphilis. The objective is for countries to achieve high performing antenatal care systems providing access to antenatal care to more than 95% of pregnant women, syphilis testing for more than 95% of pregnant women, and treatment for more than 95% of seropositive women to attain a congenital syphilis rate of 50 or fewer cases per 100,000 live births.
Mr. Steven Brown[/caption]
Mr Steven Brown MBChB, BMedSci,
FRCS, MD
Reader in Surgery
Honorary Secretary to the ACPGBI
Consultant colorectal surgeon
University of Sheffield, UK
MedicalResearch.com: What is the background for this study?
Response: Haemorrhoids are common. One in 4 of us will at some time have symptoms that can be directly attributed to piles. Whilst most symptoms will settle spontaneously or with improvement to our lifestyle, there remains a large group of patients who require intervention to reduce symptomatology. Numerous interventions exist ranging from relatively minor office therapy to procedures that may take several weeks to recover from. Haemorrhoidal artery ligation (HAL) is one of the more recent surgical operations for haemorrhoidal therapy. It has been introduced certainly into the UK associated with a significant element of media hype purporting ‘painless surgery for piles’. Substantial subsequent medical literature has also suggested an efficacy rivaling other more invasive procedures. Too good to be true? Perhaps. Several systematic reviews have highlighted the lack of good quality data as evidence for the advantages of the technique. A well designed randomized controlled trial was required.
The existing literature on haemorrhoidal artery ligation at the time of the trial suggested the procedure was most effective for less symptomatic haemorrhoids (those that are associated with bleeding and/or minor prolapse; grade II or mild III piles). These type of haemorrhoids also tend to be the most common requiring intervention. The most frequently used alternative procedure for these grade of haemorrhoids in the UK is rubber band ligation (RBL), a simple office therapy not requiring anaesthetic. Hence participants with this grade of haemorrhoids were chosen as the participants with RBL as the comparator. Multiple outcomes were investigated but a patient reported outcome measure of recurrence was chosen as the primary outcome.
Prof. David Richards[/caption]
MedicalResearch.com Interview with:
Professor David A. Richards, PhD
Professor of Mental Health Services Research and NIHR Senior Investigator
University of Exeter Medical School
University of Exeter
St Luke's Campus
Exeter United Kingdom
MedicalResearch.com: What is the background for this study?
Response: Depression is a common mental health disorder affecting around 350 million people worldwide. Untreated depression is expected to cost the global economy US$5.36 trillion between 2011 and 2030.
Many patients request psychological therapy, but the best-evidenced therapy—cognitive behavioural therapy (CBT)—is complex and costly. A simpler therapy—behavioural activation (BA)—might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression.
Dr. Shilpa Bhupathiraju[/caption]
Dr. Shilpa Bhupathiraju, PhD
Harvard T.H. Chan
School of Public Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We wanted to investigate the association between body mass index (BMI) and mortality across major global regions. In doing so, we wanted to take into account important methodological limitations which plagued prior reports of BMI and mortality. One such limitation is reverse causality where a low body weight is the result of an underlying illness rather than the cause. Another major problem is confounding due to smoking where smokers have lower body weights than non-smokers but have much higher mortality rates.
Therefore, to obtain an unbiased association between BMI and mortality, our primary pre-specified analysis was restricted to never smokers and those who had no existing chronic diseases at the start of the study.
In this group, we found that those with a BMI of 22.5-<25 kg/m2 (considered a healthy weight range) had the lowest mortality risk during the time they were followed. The risk of mortality increased significantly with excess body weight. A BMI of 25-<27.5 kg/m2 (in the overweight range) was associated with a 7% higher risk of premature death; BMI of 27.5-<30 kg/m2 (also in the overweight range) was associated with a 20% higher risk; a BMI of 30.0-<35.0 kg/m2 was associated with a 45% higher risk; a BMI of 35.0-<40.0 kg/m2 was associated with a 94% higher risk; and a BMI of 40.0-<60.0 kg/m2 was associated with a nearly 3-fold risk. In general, we found that the association of excess body weight with mortality was greater in younger than older people and in men than women. Most importantly, the associations were broadly consistent in the major global regions we examined, including Europe, North America, Australia and New Zealand, East Asia, and South Asia.
Dr. Andrea Cipriani[/caption]
Andrea Cipriani, MD PhD
Associate Professor
Department of Psychiatry
University of Oxford
Warneford Hospital
Oxford UK
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cipriani: Major depressive disorder is common in young people, with a prevalence of about 3% in school-age children (aged 6–12 years) and 6% in adolescents (aged 13–18 years). Compared with adults, children and adolescents with major depressive disorder are still underdiagnosed and undertreated, possibly because they tend to present with rather undifferentiated depressive symptoms—eg, irritability, aggressive behaviours, and school refusal. Consequences of depressive episodes in these patients include serious impairments in social functioning, and suicidal ideation and attempts. Our analysis represents the most comprehensive synthesis of data for currently available pharmacological treatments for children and adolescents with acute major depressive disorder (5620 participants, recruited in 34 trials).
Among all antidepressants, we found that only fluoxetine was significantly better than placebo. According to our results, fluoxetine should be considered the best evidence-based option among antidepressants when a pharmacological treatment is indicated for children and adolescents with moderate to severe depression. Other antidepressants do not seem to be suitable as routine treatment options.
Dr. Ramon Estruch[/caption]
Dr Ramon Estruch, MD PhD
Senior Consultant in the Internal Medicine Department of the Hospital Clinic
Barcelona
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Estruch: Although weight stability requires a balance between calories consumed and calories expended, it seems that calories from vegetable fats have different effects that calories from animals on adiposity. Thus, an increase of dietary fat intake (mainly extra virgin olive oil or nuts) achieved naturally in the setting of Mediterranean diet does not promote weight gain or increase in adiposity parameters such as waist circumference.
Dr. Alan Brown[/caption]
Alan S. Brown, M.D., M.P.H.
Professor of Psychiatry and Epidemiology
Columbia University Medical Center
Director, Program in Birth Cohort Studies, Division of Epidemiology
New York State Psychiatric Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Brown: Smoking during pregnancy is a risk factor for several pregnancy-related outcomes including low birthweight and preterm birth. Evidence for a link with schizophrenia is scant. We analyzed a maternal biomarker of smoking called cotinine, a nicotine metabolite, in mothers of nearly 1,000 schizophrenia cases and 1,000 controls in a national birth cohort in Finland. We found that heavy smoking in pregnancy was related to a 38% increase in schizophrenia risk in offspring and that as cotinine levels increased even in the more moderate smokers risk of schizophrenia also increased.
MedicalResearch.com Interview with:
Prof Andrew Mente PhD
Clinical Epidemiology and Biostatistics, McMaster University
Hamilton, Canada
MedicalResearch.com Editor's Note: Dr. Mente discusses his Lancet publication regarding salt intake below. Dr. Mente's findings are disputed by the American Heart Association (AHA). A statement from the AHA follows Dr. Mente's comments.
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Mente: Several prospective cohort studies have recently reported that both too little and too much sodium intake is associated with cardiovascular disease or mortality. Whether these associations vary between those individuals with and without high blood pressure (hypertension) is unknown.
We found that low sodium intake (below 3 g/day), compared to average intake (3 to 6 g/day), is associated with more cardiovascular events and mortality, both in those with high blood pressure and in those without high blood pressure. So following the guidelines would put you at increased risk, compared to consuming an sodium at the population average level, regardless of whether you have high blood pressure or normal blood pressure.
High sodium intake (above 6 g/day) compared to average intake, was associated with harm, but only in people with high blood pressure (no association in people without high blood pressure).
Dr. Riyaz Bashir[/caption]
Riyaz Bashir MD, FACC, RVT
Professor of Medicine
Director, Vascular and Endovascular Medicine
Department of Medicine
Division of Cardiovascular Diseases
Temple University Hospital
Philadelphia, PA 19140
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Bashir: The use of compression stockings in the prevention of post thrombotic syndrome following an episode of deep vein thrombosis is common in clinical practice. However, the evidence to suggest its efficacy has been put into question by the recent publication of the SOX trial. Since this was the largest randomized controlled trial to date addressing this issue, it has led to clinicians questioning whether compression stockings should be used at all in these patients.
The main finding of this meta-analysis was that in patients with deep venous thrombosis, use of elastic compression stockings does not significantly reduce the development of post thrombotic syndrome. However the current body of evidence is limited and we believe at present it is too early to give up on the use of this therapy, which may benefit many subgroups of patients.
Dr. Saira Saeed Mirza[/caption]
Saira Saeed Mirza, MD, PhD
Department of Epidemiology
Erasmus MC, Rotterdam
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mirza: Depressive symptoms appearing in late-life have been extensively studied for their relationship with dementia. They not only very frequently occur in demented patients, but also predict dementia. In this context, depressive symptoms have largely been assessed at a single time point only. However, depression is a disorder which remits and relapses, and symptoms do not remain same over the years. Given this pattern of disease progression, it is more important to study the course of depression over time in relation to long-term health outcomes such as dementia, rather than assessing it at a single time-point, which will neglect the course of depression. This is important as people follow different courses of depression, and different courses of depression might carry different risks of dementia.
When we studied the course of depressive symptoms over 11 years in community dwelling older adults in Rotterdam, and the subsequent risks of dementia, we observed that only those who had increasing or worsening depressive symptoms were at a higher risk of dementia. In this group of people, about one in five persons developed dementia. Interestingly, people suffering from high depressive symptoms at a single time point were not at a higher dementia risk than those without depressive symptoms.
Dr. Danny MvBryan[/caption]
Danny McBryan, MD
Vice president, Clinical Development & Medical Affairs, Respiratory
Boehringer Ingelheim Pharmaceuticals, Inc.
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. MvBryan: The new post-hoc analysis from the WISDOM study shows a routine blood test could help identify the small minority of patients with severe or very severe COPD who may benefit from the addition of inhaled corticosteroids (ICS). This post-hoc analysis was recently published online in The Lancet Respiratory Medicine.
For 80 percent of patients in the WISDOM study, the use of ICS on top of SPIRIVA HANDIHALER (a long-acting muscarinic antagonist – LAMA) and salmeterol (a long-acting beta-agonist – LABA) had no additional benefit in reducing the risk of exacerbations, compared to SPIRIVA HANDIHALER and the LABA without ICS.
The post-hoc analysis shows that these patients can be easily identified by measuring the level of white blood cells, called eosinophils. Patients with levels lower than 4 percent (300 cells/µL) were associated with a lack of response to ICS.
The WISDOM study evaluated stepwise withdrawal of inhaled corticosteroids (ICS) in severe to very severe COPD patients with a history of exacerbation. WISDOM was a 12-month, double-blind, parallel-group, active-controlled study in which all patients received triple therapy (tiotropium 18 μg once daily, salmeterol 50 μg twice daily and fluticasone 500 μg twice daily) for a six-week run-in period. Patients were randomized 1:1 to continue triple therapy or stepwise withdrawal of ICS over 12 weeks (dose reduction every six weeks).
The WISDOM data show that in patients with severe to very severe COPD, the risk of moderate/severe exacerbations during one year of follow-up was non-inferior between those patients who continued on inhaled corticosteroids and those where ICS therapy was withdrawn in a stepwise manner.
Prof. Jean Pierre Allain[/caption]
Prof Jean-Pierre Allain
Principal Investigator, Department of Haematology
University of Cambridge, Cambridge Blood Centre
Cambridge UK
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Allain: In sub-Saharan Africa (SSA), 70% of the transfusions are in the form of whole blood units (generally 1 or 2). Lack of resources limit the safety
measures to donor questionnaire, viral/bacterial testing (HIV, HCV, HBV
and Syphilis). Other measures used in rich countries i.e. nucleic acid
testing, filtration, bacterial culture etc. are not done because of cost.
Pathogen reduction would be an effective way to overcome these issues as
it is able to inactivate viruses, bacteria, parasites and nucleated
cells in one go, provided it is applied to whole blood and affordable.
The study consisted in assessing the efficacy of such a method (Mirasol
using riboflavin and UV illumination) taking inactivation of plasmodium
as major endpoint of a randomised controlled clinical trial called AIMS
(African Investigation of Mirasol System).
MedicalResearch.com Interview with: Silvia Marsoni, M.D. Director Clinical Research Office FPO - Istituto di Candiolo IRCCS Institute for Cancer Research @ Candiolo 10060 Candiolo (TO) - Italy MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Marsoni: In the Lancet Oncology of April 20 2016, clinical investigators of 4 major Italian academic...
Prof. Jeffrey Lipton[/caption]
Prof Jeffrey H Lipton, PhD, MD, FRCPC
Princess Margaret Cancer Centre
Toronto, ON Canada
MedicalResearch.com: What is the background and purpose for this study?
Dr. Lipton: Ponatinib is a third generation tyrosine kinase inhibitor that has been shown to be extremely effective in treating patients with chronic myeloid leukemia resistant to other drugs. Because of this, it was decided to look at it in newly diagnosed patients in a randomized study against imatinib. The study was terminated prematurely because of evidence of vascular toxicity that became evident in the phase 1 and 2 studies of ponatinib in previously treated patients with resistant disease.
Dr. Henning Kelbæk[/caption]
Dr Henning Kelbæk MD
Department of Cardiology
Roskilde Hospital,Denmark
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kelbæk : In some patients with large acute myocardial infarcts, stent implantation has been connected with an increased risk of downstream embolization of thrombus material and disturbances in flow impairing the prognosis of the patients. In accordance, previous smaller studies have shown a benefit in angiographic and other parameters in patients having their stent implanted several hours after the artery was opened, allowing the infarct-related lesion to ’cool down’ and residual thrombus to dissolve under antithrombotic treatment, whereas larger randomised trials focusing on clinical data have been missing.
Our trial demonstrates, a bit surprisingly, that delaying or deferring stent implantation does not improve the clinical outcome of these patients.
Mascha Nuijten[/caption]
Mascha Nuijten MSc
Researcher/ PhD candidate
Brijder Research (PARC)
The Hague
The Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Crack-cocaine dependence is a complex disorder, for which no proven effective pharmacotherapy is yet available. Prior to our study, sustained-release dexamfetamine was found to be a promising treatment for cocaine dependence in several studies, but no studies so far had shown a convincing benefit in terms of substantial cocaine use reductions. Therefore, we investigated the efficacy of sustained-release (SR) dexamphetamine in a robust dose of 60 mg/day in chronic crack-cocaine dependent patients.
We found that the number of days of cocaine use decreased with almost 40% in the dexamfetamine group, compared with 9% in the matched placebo group. In addition, the number of cocaine self-administrations on days that patients used crack-cocaine decreased with 43% in the dexamfetamine group and with 7% in the placebo group. Thus, SR dexamfetamine both contributed to cocaine abstinence and to cocaine use reductions.
MedicalResearch.com Interview with: [caption id="attachment_22896" align="alignleft" width="175"] Dr. Eric Chow[/caption] Eric J. Chow, MD, MPH Hematology-Oncology Attending physician, Seattle Childrens Hospital Assistant professor of Pediatrics, University of Washington School of Medicine Member of the Clinical Research and Public Health Sciences Divisions Fred Hutchinson Cancer Research Center MedicalResearch.com: What is the background for this study? Dr. Chow: Adverse effects on...
Prof. Jack Cuzick[/caption]
Professor Jack Cuzick, PhD, FMedSci, FRCP(hon)
Director, Wolfson Institute of Preventive Medicine and
Head, Centre for Cancer Prevention
Queen Mary University of London.
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cuzick: Ductal carcinoma in situ (DCIS) is a very early form of breast cancer, where cancer cells are present in milk ducts, but have not spread to the surrounding breast tissue. It is estimated that approximately a fifth of all screen-detected breast cancers are DCIS, with around 4,800 people diagnosed with DCIS in the UK each year.
Our IBIS-II DCIS trial looked at 2,980 postmenopausal women with DCIS in 14 countries, who were either given anastrozole or tamoxifen for five years after surgery.
The two groups had a similar number of cases of the disease recurring, whether they took tamoxifen or anastrozole. Those who took anastrozole had an 11 per cent lower rate of recurrence of DCIS or invasive cancer than those who took tamoxifen, but this difference was not significant. The similar NSABP B-35 trial found a 29% reduction with anastrozole and the combined analysis of the two trials indicated a significant 21% reduction.
The key difference between the two groups were in the side effects of the medication. Women who took anastrozole experienced fewer womb and ovarian cancers and non melanoma skin cancers, and fewer deep vein thromboses and gynecological issues, compared with those who took tamoxifen. However more fractures and musculoskeletal side effects were seen among those receiving anastrozole.
Dr. Charles Lockwood[/caption]
Charles J. Lockwood, MD
Member of of the March of Dimes Board of Trustees
Dean at Morsani College of Medicine
Senior Vice President, USF Health and Professor of Obstetrics & Gynecology, and Public Health The University of South Florida
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Lockwood: There remain questions about the utility of vaginal progesterone therapy in asymptomatic women with singleton gestations at risk for preterm birth. The OPPTIMUM study investigators conducted a double-blind, randomized, placebo-controlled trial of vaginal progesterone delivered via a pessary releasing 200 mg per day (n=618) vs. placebo (n=610) from around 22 to 34 weeks gestation among women at high risk for prematurity on the basis of a characteristic history and/or the presence of cervicovaginal fetal fibronectin or a cervical length less than 25 mm in length on transvaginal ultrasound. The primary endpoints were fetal death or preterm birth before 34 weeks (obstetrical outcome), or a composite of neonatal mortality or morbidities (neonatal outcome). The authors found that progesterone had no significant impact on either primary endpoint, with an adjusted OR of 0·86, 95% CI: 0·61-1·22 for obstetrical outcomes and an OR of 0·62, 95% CI:0·38-1·03 for neonatal outcomes.
Dr. Erin Marcotte[/caption]
Erin Marcotte, Ph.D.
Assistant Professor
Division of Epidemiology and Clinical Research
Department of Pediatrics
University of Minnesota
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Marcotte: Recently there have been several studies that indicate a higher risk of immune-related disorders, such as type-I diabetes, asthma, and allergies, among children born by cesarean delivery. Our analysis used pooled data from 13 independent studies of childhood leukemia that were conducted in 9 different countries. We used data on over 33,000 children to investigate the relationship between birth by cesarean delivery and risk of childhood leukemia. We did not find an association between cesarean delivery overall and childhood leukemia. However, when we looked at emergency cesarean deliveries and pre-labor (planned) cesarean deliveries separately, we found a 23% increase in risk of acute lymphoblastic leukemia among children born by pre-labor cesarean delivery.
Dr. Massimo Cristofanilli[/caption]
Massimo Cristofanilli, MD, FACP
Professor of Medicine
Associate Director of Translational Research and Precision Medicine
Department of Medicine-Hematology and Oncology
Robert H Lurie Comprehensive Cancer Center
Feinberg School of Medicine
Chicago, IL 60611
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.
Theresa Wimberley[/caption]
MedicalResearch.com Interview with:
Theresa Wimberley
PhD student
National Centre for Register-based Research
School of Business and Social Sciences
Aarhus University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Approximately 30% of patients with schizophrenia suffer from treatment-resistant schizophrenia, i.e. they do not respond to first-line antipsychotic treatment. Identification of high-risk patients as early as possible is crucial in order to optimize treatment and improve prognosis. In a large population-based cohort of patients diagnosed with schizophrenia we found the following candidate predictors of treatment resistance: