MedicalResearch.com Interview with:
Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAAD
Director, Medical Affairs
Galderma Laboratories, L.P.
Fort Worth TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Winkelman: Rosacea is a common dermatologic facial disorder estimated to affect 16 million Americans. Rosacea is a chronic condition of the central face, including the nose, chin, cheeks and forehead, and is often characterized by flare-ups and remissions. While the cause of rosacea is unknown and there is no cure, its signs and symptoms can become markedly worse in the absence of treatment. Rosacea can be managed with topical and oral medications, and physicians often resort to using these medications in combination for more severe or resistant cases. Doxycycline 40 mg modified release (MR) and metronidazole 1% gel are FDA-approved oral and topical therapies, respectively, indicated to treat the papules and pustules of rosacea. We conducted a phase 2 study to assess the relapse rate, efficacy, and safety of doxycycline 40 mg MR compared to placebo after an initial 12-week once-daily combination regimen of doxycycline 40 mg MR and metronidazole 1% gel in subjects with moderate to severe disease.
Of the 235 subjects enrolled in the study, 71% were women, 94% were white, and 75% had Fitzpatrick skin type I, II or III. The mean age was 47.4 years. The percentage of subjects who achieved a success score of 0 (clear) or 1 (near clear) improved from 0% at baseline to 51% at week 12. Clinician’s erythema assessment scores, inflammatory lesion counts, and quality of life scores also improved. Most subjects reported no or mild scaling, stinging/burning, and dryness. Five adverse events were reported that were considered probably or definitely related to treatment: fungal infection, vulvovaginal mycotic infection, pain in extremity, erythema, and skin exfoliation.
MedicalResearch.com Interview with:
Dr Nita Forouhi, MRCP, PhD, FFPHM
MRC Programme Leader and Consultant Public Health Physician
MRC Epidemiology Unit
University of Cambridge School of Clinical Medicine
Cambridge Biomedical Campus
Cambridge UK
Medical Research: What is the background for this study? What are the main findings?
Dr. Forouhi: Consumption of soft drinks is known to cause obesity and may contribute to the development of type 2 diabetes. We had previously published findings from the EPIC-InterAct study in 8 European countries that habitual consumption of sugar sweetened beverages increases the risk of developing type 2 diabetes, and we now wanted to probe deeper to understand more about this relationship between sweet beverages and diabetes.
We conducted research in the large EPIC-Norfolk study which included more than 25,000 men and women aged 40–79 years living in Norfolk, UK. Study participants recorded everything that they ate and drank for 7 consecutive days covering weekdays and weekend days, with particular attention to type, amount and frequency of consumption, and whether sugar was added by the participants. During approximately 11 years of follow-up, 847 study participants were diagnosed with new-onset type 2 diabetes.
By using this detailed information on diet, we were able to study several different types of sugary beverages, including sugar-sweetened soft drinks, sweetened tea or coffee and sweetened milk drinks as well as artificially sweetened beverages (ASB) - such as diet soft drinks - and fruit juice, and to examine what would happen if plain water, unsweetened tea or coffee or artificially sweetened beverages were substituted for sugary drinks.
Our study provided three main findings:
First, there was an approximately 22% increased relative risk of developing type 2 diabetes per extra serving per day habitually of each of soft drinks, sweetened milk beverages and ASB consumed, even after accounting for a range of important factors including other lifestyle and social factors and for total energy intake. However, after further accounting for body mass index and waist girth as markers of obesity, there remained a higher risk of diabetes associated with consumption of both soft drinks and sweetened milk drinks, but the link with ASB consumption no longer remained, possibly because artificially sweetened beverages was likely to be consumed by those who were already overweight or obese.
Second, when we estimated the likely effects of replacing a habitual serving of soft drinks with a serving of water or unsweetened tea or coffee, we found that the risk of diabetes could have been cut by 14%; and by replacing a habitual serving of sweetened milk beverage with water or unsweetened tea or coffee, that reduction could have been 20%–25%. However, consuming ASB instead of any sugar-sweetened drink was not likely to reduce the risk of diabetes, when accounting for baseline obesity and total energy intake.
Third, we found that each 5% of higher intake of energy (as a proportion of total daily energy intake) from total sweet beverages (soft drinks, sweetened tea or coffee, sweetened milk beverages, fruit juice) was associated with a 18% higher risk of diabetes. We estimated that if study participants had reduced the energy they obtained from sweet beverages to below 10%, 5% or 2% of total daily energy, 3%, 7% or 15% respectively of new-onset type 2 diabetes cases could have been potentially avoided.
MedicalResearch.com Interview with:
Shannon M. Dunlay, M.D. M.S.
Advanced Heart Failure and Cardiac Transplantation
Assistant Professor of Medicine and Health Care Policy and Research
Mayo Clinic Rochester
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Dunlay: Left ventricular assist devices (LVAD) are increasingly utilized as destination therapy (DT) in patients that are not candidates for heart transplantation. Optimal patient selection is essential in improving outcomes, but many of the factors associated with favorable outcomes remain poorly understood. It is important for us to better understand the role that psychosocial factors may play in outcomes after DT LVAD. Unlike transplant, where the limited organ supply requires choosing candidates with optimal psychosocial characteristics, DT LVAD therapy is more readily available as it does not rely on organ donors. There are no clear guidelines on what constitutes an acceptable psychosocial risk prior to DT LVAD. As a result, many programs will offer DT LVAD to candidates despite psychosocial concerns if it is felt they will otherwise benefit. Data are needed to inform programs about whether such candidates are truly at elevated risk of adverse outcomes.
In our single-center study including 131 patients, we found that several psychosocial characteristics are predictive of readmission after DT LVAD. A history of illegal drug use and depression are associated with a higher risk of readmission, while tobacco use is associated with lower readmission risk. Psychosocial characteristics were not significant predictors of death after DT LVAD.
MedicalResearch.com Interview with:
Yunhwan Lee, MD, DrPH
Director, Institute on Aging
Professor of Preventive Medicine & Public Health
Ajou University School of Medicine
Suwon, South Korea
Dr. Lee wishes to acknowledge Jinhee Kim, PhD, the lead author of the study.
Medical Research: What is the background for this study?
Dr. Lee: We have known for some time that there is a progressive loss of muscle mass with aging, where older people lose on average about 1% of their skeletal muscle mass per year. A decline in muscle mass is serious in that it increases the person’s risk of falls, frailty, disability, and death.
Because there is currently no “cure” for muscle mass loss, prevention is the best strategy. Over the years, researchers have studied various lifestyle factors to identify potentially modifiable behaviors that may prevent or slow the loss of muscle mass. The majority of prior research so far have found that diet, in the form of protein supplementation, and exercise, especially resistance exercise, may confer some benefits.
More recently, the scientific community have begun to pay attention to the positive role of vegetables and fruits intake on the muscle. The role of aerobic exercise on muscle mass is, however, less clear. Also, because people tend to adopt various lifestyles, we were interested in finding out whether those engaging in healthier patterns of diet and exercise retained higher muscle mass. This is why bodybuilders pay such close attention to their diet and make sure their muscle mass is at it's peak. They can also take supplements like SARMs (see SARMS.io for more information about that) to improve muscle mass but their diet has a massive effect on it too. This is where some of the inspiration for this research came from as we knew what an effect food had on bodybuilders so we wondered how it could effect the elderly.
Using data from a nationally representative sample of older adults, we investigated whether those who had healthier diet and participated in regular exercise, individually and in combination, maintained higher muscle mass. We looked at five healthy lifestyle factors that included dietary intake of three food groups (meat, fish, eggs, legumes; vegetables; and fruits) and participation in two types of exercise (aerobic and resistance).
MedicalResearch.com Interview with:
Jaime L. Tartar PhD
Behavioral Neuroscience Major Chair
Division of Social and Behavioral Sciences
Nova Southeastern University
Fort Lauderdale, Florida
Medical Research: What is the background for this study? What are the main findings?
Dr. Tartar: We set out to understand how poor sleep quality can influence emotion processing. Our rationale for this study was that although sleep perturbations are known to impair cognitive performance, it is not currently clear how poor sleep alters emotion processes. However, given that poor sleep quality is closely associated with the development of mood disorders, it is important to understand how sleep quality affects emotional functioning. We specifically examined the possibility that poor sleep quality creates a cognitive bias in memory and interpretation for emotionally negative stimuli. This would result in maladaptive emotional experiences- for example, through enhanced memory for emotionally negative events (which is also a common characteristic of depression). The idea that negative cognitive bias occurs with poor sleep quality is also consistent with the finding that sleep loss increases sensitivity to emotional stimuli as well as increases undesirable mood states like irritability, anger, and hostility. It is particularly noteworthy that sleep perturbations result in increased emotionality since sleep perturbations are shown to result in a decrease in non-emotional cognitive processes (attention and memory). In order to clarify the role of sleep quality on emotion processing, we tested the relationship between sleep quality and a negative cognitive bias through the use of an emotional memory task. We also aimed to contrast these findings with performance on a non-emotional attention task since sleep impairments have previously been shown to cause impairments in (non-emotional) sustained attention. An interesting feature of the study was that we also accounted for potential confounding effects of stress sensitivity and chronotype (ones preferred time of day) since these are both factors known to be related to sleep quality. We found that, compared to those who reported good subjective sleep quality, participants who reported poor subjective sleep quality showed a negative cognitive bias towards emotionally negative stimuli. Also in agreement with previous work, we show that poor sleep quality has a negative effect on affective symptom measures- poor sleep quality relates to increased depressive symptoms, greater state and trait anxiety, and higher total mood disturbance (increased tension, fatigue, confusion and less vigor). Consistent with previous findings, we also found that subjective sleep quality was related to a decrease in performance on a sustained attention task. Although previous research suggests that stress sensitivity and chronotype would be important variables to consider in the impact of sleep perturbations on emotion processing, we did not find any stress, chronotype, or time of testing effects on these measures.
MedicalResearch.com Interview with:
Dr. Stephen Wank MD
Digestive Diseases Branch, NIDDK
National Institutes of Health, Bethesda, Maryland
MedicalResearch: What is the background for this study?
Dr. Wank: Small intestinal carcinoids are rare and difficult to diagnose because symptoms may be absent or mistaken for more common diseases. Because carcinoids usually grow slowly over several years before spreading or causing symptoms, patients often seek medical attention late with advanced, incurable disease. However, when diagnosed at an early stage, carcinoid can be surgically cured. Presently, there are no long-term effective therapies for surgically non-resectable disease. Although carcinoids occur sporadically, there have been reports of family clusters (more than one blood relative with carcinoid). Hereditary small intestinal carcinoid has not been recognized as a disease and causative genetic factors have not been identified in either sporadic cases or families with multiple affected members.
If small intestinal carcinoid occurs in families on a hereditary basis, we hypothesized that asymptomatic relatives in families with carcinoid are at a high risk of harboring an undiscovered tumor. To test this, we established a clinical research protocol at the National Institutes of Health in Bethesda, Maryland to screen asymptomatic relatives in families with at least two cases of small intestinal carcinoid in the hope of detecting their tumors at an early surgically curable stage. If successful in our endeavor, we would improve the outcome of the disease in these asymptomatic relatives and position ourselves to discover the genetic basis for their disease. Understanding the gene mutations causing small intestinal carcinoid would allow us to screen for the disease with a blood test, help us understand what causes the disease, and treat the disease with specific targeted therapies.
MedicalResearch.com Interview with
Silvia S. Martins, MD, PHD
Associate Professor of Epidemiology
Department of Epidemiology
Mailman School Of Public Health
Columbia University New York, NY 10032
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Martins: The background for this study is former studies showing links between nonmedical use of prescription opioids and transition to heroin and other illegal substances, prescription opioid-related and heroin-related fatal overdoses . In addition, a particular public health concern is that the transition to heroin and further injecting heroin may increase the risk of bloodborne infections.
We used data from the National Survey on Drug Use and Health, a large nationally representative household sample of 67,500 people, and self-reported heroin use within the last 12 months, the researchers examined the change in patterns of past-year non-prescription drug and heroin use between 2002-2005 and 2008-2011 across racial and ethnic groups. The most significant rise in heroin use was among Hispanics and non-Hispanic whites, where the rate of heroin use for the latter group increased by 75 percent in 2008-2011 compared to earlier years. Regarding frequency of use, for Hispanics, increases were significant only among those using opioids about 1-29 days in the past year. Among blacks and whites, significant increases in the rate of heroin use were observed among those using prescription opioids more frequently (100-365 days) in the past year.
MedicalResearch.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.
MedicalResearch.com Interview with:
Maria Pagano, PhD
Case Western Reserve University School of Medicine
Department of Psychiatry, Division of Child Psychiatry
Cleveland, OH
MedicalResearch: What is the background for this study?
Dr. Pagano: Socially anxious adolescents quickly figure out that alcohol and drugs can provide ease and comfort in social situations that are anxiety provoking. Reaching for a substance to change how you feel can quickly become a knee-jerk reaction, can develop into an addiction, and robs youths of learning how to tolerate interpersonal differences and uncomfortable feelings, developing emotional maturity, and cultivating self acceptance.
Adolescents who fear being criticized by their peers are likely to not speak up in group therapies during treatment, which can limit their benefit from treatment. There is a lot of healing that comes sharing your insides with others. Socially anxious patients may not get this healing nor let others really get to know who they are and give input to their lives
Higher peer helping in AA during treatment means getting active in low intensity tasks like putting away chairs, or making coffee at a 12-step meeting. It is less about needing peer assistance or expecting praise or recognition from giving service. It is more about adopting the attitude of "how can I be helpful?"
MedicalResearch.com Interview with:
Lynn L. Moore, DSc, MPH
Department of Medicine
Boston University School of Medicine
Boston, Massachusetts
Medical Research: What is the background for this study?
Dr. Moore: The USDA’s current Dietary Guidelines for sodium intake have become increasingly controversial. Current recommendations include restricting sodium intake after the age of 2 years to no more than 2300 mg per day. For African-American adults and children, intakes should be restricted to no more than 1500 mg per day. Actual intake levels are much higher, with most Americans consuming about 3500 mg per day. Our goal was to estimate the effects of dietary sodium and potassium intakes on the change in blood pressure throughout adolescence.
We used data from the National Growth and Health Study, a prospective study of more than 2000 girls who were 9-10 years of age at the time of enrollment. Lifestyle factors were assessed repeatedly throughout the study, and blood pressure was measured annually. Dietary sodium and potassium were assessed using multiple sets of three-day diet records. We used longitudinal modeling to estimate the effects of dietary sodium and potassium on blood pressure change over 10 years.
Medical Research: What are the main findings?
Dr. Moore: In this study, there was no evidence for a beneficial effect of reduced sodium intake on blood pressure change during adolescence. By 19-20 years of age, girls who consumed more than 4000 mg of sodium per day had systolic and diastolic blood pressure levels that were similar to those seen among girls with lower levels of sodium intake. Specifically, there was no beneficial effect on blood pressure associated with sodium intakes of less than 2500 mg per day. These results were similar for blacks and whites. In contrast, the repeated measures analyses showed that girls who consumed more than 2400 mg of potassium per day had lower blood pressures throughout adolescence compared with girls consuming less than 1800 mg per day of potassium.
MedicalResearch.com Interview with:
Matthias Eikermann, MD, PhD
Associate Professor of Anaesthesia, Harvard Medical School
Director of Research, Critical Care Division
Massachusetts General Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Eikermann: Obstructive sleep apnea occurs in about 5% of pregnant women, worsens as pregnancy progresses and is likely to persist into the early postpartum period. A main cause of anesthesia-related maternal death is postpartum airway obstruction. We observed among early postpartum women, that 45° upper body elevation increased upper airway diameter and mitigated sleep apnea, without adverse effects on quality of sleep after delivery.
MedicalResearch.com Interview with:
George S. Stergiou, MD, FRCP
Professor of Medicine & Hypertension
Hypertension Center STRIDE-7
Third University Department of Medicine
Sotiria Hospital Athens, Greece
Medical Research: What is the background for this study? What are the main findings?
Dr. Stergiou: This study explored the relationship among blood pressure measurements taken in the office, at home and with daytime ambulatory monitoring in 642 untreated subjects aged from 5 to 78 years referred to a university hospital hypertension clinic.
The main finding is that the relationship between office and out-of-office blood pressure (home and ambulatory) differs across different age groups. More specifically, in children daytime ambulatory blood pressure is higher than both office and home blood pressure. The differences are progressively eliminated with increasing age and after the age of 30 years daytime ambulatory blood pressure is similar to home blood pressure and both are lower than office blood pressure. In individuals aged 60 years and older daytime ambulatory blood pressure may be lower than home blood pressure. Age, gender and hypertension status are the main predictors of the differences among blood pressure values obtained by different methods.
MedicalResearch.com Interview with:
Mark D. DeBoer, MD, MSc, MCR
Associate Professor of Pediatrics
Division of Pediatric Endocrinology, University of Virginia
Medical Research: What is the background for this study? What are the main findings?
Dr. DeBoer: The American Academy of Pediatrics recommends that children watch no more than 2 hours of TV daily. We wanted to see if children watching shorter amounts of TV were more likely to have higher weight status. We found that children in kindergarten who watched 1-2 hours a day were more than 40% more likely to be overweight and obese and gained more unhealthy weight over the next year.
MedicalResearch.com Interview with: Dennis Tsilimingras, M.D., M.P.H. Assistant Professor, Co-Director of Michigan AHEC (Area Health Education Center), Director of Patient Safety, Department of Family Medicine and Public Health Sciences Wayne State University School of Medicine Detroit, Michigan Medical Research: What is the background for this study? Dr. Tsilimingras: There has been little research to examine post-discharge adverse events (AEs)...
MedicalResearch.com Interview with:
Jacqueline Hirth, PhD, MPH
Assistant Professor and
Dr. Abbey B. Berenson MD, MMS, PhD
Center for Interdisciplinary Research in Women's Health
Obstetrics and Gynecology
The University of Texas Medical Branch at Galveston Texas
MedicalResearch.com Interview with:
Lisa M. Nyberg, MD, MPH
Transplant Hepatologist
Director, Hepatology Research
Kaiser Permanente, Garfield Specialty Center
San Diego, CA 92111
Medical Research: What is the background for this study? What are the main findings?
Dr. Nyberg: The overall cancer rates were higher in patients with Hepatitis C (HCV) vs those without HCV. Of note, though, the HCV cohort had higher rates of alcohol abuse, tobacco use, cirrhosis and diabetes mellitus (DM). However, even after stratification for the variables alcohol abuse, tobacco use, body mass index (BMI) and DM; the increased cancer rates remained significant for total cancer sites, liver cancer and NHL.
Note that this study does not establish a cause and effect relationship between Hepatitis C and cancer. A strength of this study is that it is an evaluation of a large patient population (n=35,712 with HCV and 5,297,191 without HCV). Limitations of the study are those inherent in epidemiological studies using large databases. For example, confounders may not be accurately recorded in automated databases (smoking and alcohol abuse may be under-recorded).
MedicalResearch.com Interview with:
Esther Lopez-Garcia, PhD
Dept. Preventive Medicine and Public Health
School of Medicine
Universidad Autónoma de Madrid
Madrid,Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Lopez-Garcia: Health-related quality of life (HRQL) is a global indicator of perceived health status, which includes physical and mental domains. Assessing the association between individual foods and HRQL is important because both the food industry and the population as a whole are interested in knowing whether general well-being could be improved by consuming specific foods. Several biological mechanisms might support an association between consumption of yogurt and better Health-related quality of life. However, to our knowledge, the effect of yogurt on HRQL has not yet been studied in epidemiological investigations in the general population. Thus, the objective of this article was to examine the prospective association between habitual yogurt consumption and the physical and mental components of HRQL among the general adult population.
In this study, we found no association between yogurt consumption and the physical and mental components of HRQL after 3.5 years of follow-up of a population-based cohort. The results also held for whole-milk and reduced-fat yogurt.
MedicalResearch.com Interview with:
Nasim Mavaddat M.B.B.S. MPhil PhD PhD
Centre for Cancer Genetic Epidemiology
Department of Public Health and Primary Care
University of Cambridge, Cambridge, UK
MedicalResearch: What is the background for this study?
What are the main findings?
Dr. Mavaddat: Recent large-scale genome wide association analyses have led to the discovery of genetic variation- called single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Individually these variants confer risks that are too small to be useful for risk prediction. But when combined as a single score, called a polygenic risk score (PRS), this score may be used to stratify women according to their risk of developing breast cancer. This stratification could guide strategies for screening and prevention.
Our study was a large international collaboration involving 41 research groups from many different countries and included 33,673 breast cancer patients and 33,381 controls. We found that the genetic variants act more or less independently, and that the more risk variants a woman has the higher her risk of breast cancer. When women were ranked according to their PRS, women with scores in the top 1% had a threefold increased risk of breast cancer. This translates into an absolute risk of breast cancer of 29% by age 80. By contrast, women with the lowest 1% scores had a risk of 3.5%.
The PRS was effective in stratifying women with and without a family history of breast cancer, so that highest risk was for women with a family history and a high PRS. Finally, we showed that the PRS was better at predicting the risk of ER-positive breast cancer (potentially relevant to the application of risk stratification to chemoprevention for example, with tamoxifen, raloxifene or aromatase inhibitors).
There has been much debate as to whether genomic profiles are useful for individual risk prediction, especially in the context of the preventative strategies available at the present time. The estimates provided in this study will help inform these debates.
MedicalResearch.com Interview with:
Henry J. Michtalik MD, MPH, MHS
Department of Medicine, Johns Hopkins University
Armstrong Institute for Patient Safety and Quality
Baltimore, Maryland
Medical Research: What is the background for this study? What are the main findings?
Dr. Michtalik: Current healthcare reform emphasizes providing high-value, evidence-based care. Compliance with practice guidelines and best-practices remains a challenge in the ever-changing healthcare environment. Multiple methods are typically used to enhance compliance with these guidelines, including physician education, computerized order entry systems with clinical decision support, provider feedback, and payment incentives. These strategies are used for many conditions, including heart failure and venous thromboembolism (VTE), blood clots.
The purpose of this study was to examine the impact of an individualized physician dashboard and pay-for-performance program on improving VTE prophylaxis rates amongst hospitalists. We performed a retrospective analysis of over 3000 inpatient admissions to a hospitalist service. We examined the impact of a web-based hospitalist dashboard which provided VTE prophylaxis feedback, both alone and in combination with a pay-for performance program which provided a small financial payment for achieving compliance rates greater than 80%.
We found that compliance significantly increased from 86% during baseline to 90% during the dashboard alone phase. Addition of the pay-for-performance program further increased compliance to 94%. The fastest improvement occurred during the dashboard only phase. Annual physician payments ranged from $53 to $1244, with 17 of the 19 payments under $1000.
MedicalResearch.com Interview with:
Stefan Zeuzem, MD
Professor of Medicine
Chief Department of Medicine
Goethe University Hospital
Frankfurt
Medical Research: What is the background for this study? What are the main findings?
Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C (without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299/316 achieved SVR12 (undetectable HCV 12 weeks after treatment), including 144/157 with genotype-1a, 129/131 with genotype-1b, 18/18 with genotype-4, 8/10 with genotype-6, 68/70 with cirrhosis, and 231/246 without cirrhosis. Virologic failure occurred in 13 patients including 1 breakthrough and 12 relapses, and was associated with baseline NS5A-polymorphisms and emergent NS3- and/or NS5A-variants. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo arms, respectively; none were considered drug-related.
MedicalResearch.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.
MedicalResearch.com Interview with
Jay Giri, MD MPH
Director, Peripheral Intervention
Assistant Professor of Clinical Medicine
University of Pennsylvania
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Giri: Carotid artery stents are placed by vascular surgeons or interventional cardiologists to decrease the risk of long-term stroke in patients with severe atherosclerotic disease of the carotid artery. When these procedures are performed, there is a risk of releasing small amounts of debris into the brain’s circulation, causing a stroke around the time of the procedure (peri-procedural stroke). In order to mitigate this issue, embolic protection devices (EPD) have been developed to decrease the chances of small debris reaching the brain.
Two types of EPD exist. The first is a small filter meant to catch the debris released by placement of the carotid stent (distal filter EPD).
The second is a more complex device type that leads to transient halting of blood flow to the brain in the carotid artery being stented (proximal EPD). Debris-containing blood is removed from the body prior to allowing normal blood flow to proceed back to the brain after stent placement.
Our prior research has shown that nearly all (>95%) of domestic carotid stenting procedures are performed with utilization of one of these devices. We sought to compare important clinical outcomes of stroke and death between these 2 device types within a large national sample of patients undergoing carotid stenting.
Some small prior studies have investigated whether the total amount of debris reaching the brain is less with proximal embolic protection devices. These studies have shown mixed results. However, no prior study has investigated important clinical outcomes of stroke and death in relation to these devices.
We found that overall uptake of proximal embolic protection devices utilization in America has not been robust. Less than 7% of all domestic CAS procedures are performed with this technology. Our analysis showed that in-hospital and 30-day stroke/death rates with proximal EPD and distal filter EPD were similar (1.6% vs. 2.0%, p = 0.56 and 2.7% vs. 4.0%, p = 0.22, respectively).