MedicalResearch.com Interview with: Kristina H. Lewis, MD, MPH, SM Kaiser Permanente Georgia, Center for Clinical and Outcomes Research, Atlanta Department of Population Medicine Harvard Medical School/Harvard...
MedicalResearch.com Interview with:
Louise Sun, MD SM FRCPC
Assistant Professor Department of Anesthesiology,
University of Ottawa Staff | Division of Cardiac Anesthesiology
University of Ottawa Heart Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Sun: Preoperative testing provides important information for perioperative
planning and decision-making. However, given the rapid increase in health
care costs, there has been growing emphasis on the more rational use of
resources and thus the need to better understand the utilization patterns
of specific tests. Preoperative pulmonary function tests (PFTs) are
important in helping perioperative physicians identify patients at risk
for postoperative pulmonary complications, but few appropriate use
guidelines exist for this test. We conducted a population-based study
using linked administrative databases in Ontario, Canada to describe
temporal trends in preoperative pulmonary function tests
and assess whether the recent 2006 American College of Physicians (ACP) guidelines on risk assessment and prevention of postoperative pulmonary complications for non-cardiothoracic surgery influenced these trends.
We examined 511,625 individuals undergoing non-cardiothoracic surgery, amongst whom
3.6% underwent preoperative pulmonary function tests while 3.3% had non-operative PFTs.
Preoperative pulmonary function tests rates decreased over the study period and following the 2006 ACP guidelines while non-operative rates remained stable. By 2013,
preoperative pulmonary function tests were performed in fewer than 8% of Ontario patients with risk factors for pulmonary complications, while preoperative testing
rates among individuals without known respiratory disease had approached
rates seen in the non-operative setting. The decreasing preoperative pulmonary function tests rates contrast starkly against concurrent increases in rates of other
perioperative interventions such as preoperative anesthesia consultations
and stress testing.
MedicalResearch.com Interview with:
Jordan M. Cloyd, MD
Department of Surgery
Stanford University
Stanford, California
Medical Research: What is the background for this study? What are the main findings?
Dr. Cloyd: The motivation for the study was that, anecdotally, we had noticed that several of our patients who had been discharged on a weekend required readmission for potentially preventable reasons. We wanted to investigate whether the data supported the idea that weekend discharge was associated with a higher risk of hospital readmission.
MedicalResearch.com Interview with:
Anne Winther Msc
Department of Health and Care Sciences, UiT The Arctic University of Norway
Division of Rehabilitation Services, University Hospital of North Norway, Tromsø, Norway
Medical Research: What is the background for this study? What are the main findings?
Response: Norway has one of the highest reported incidences of osteoporotic fractures in the world. Research on fracture risk has primarily focused on bone mass in the elderly. However, there is a growing awareness of the importance of bone mass during growth as a compensation for the inevitable bone loss and prevention of fractures in the elderly . A recent study on Norwegian adolescents´ lifestyle and bone health concluded that peak bone mass seem to be modifiable by lifestyle factors as higher physical activity levels were strongly associated with bone mass. The other way around; low levels of physical activity may have considerable negative effects on bone health, and increasing sedentary behavior in place of sports and play during growth is worrying. In this study we explored the associations between self-reported hours spent in front of television/computers during weekends along with self reported hours spent on leisure time physical activities and bone mass density (BMD) levels at the hip. This population based study, Fit Futures 1 consisting of 388 girls and 359 boys 15-17 years old was conducted in 2010/2011, and repeated two years later including 66% of the original cohort (Fit Futures 2; 312 girls and 231 boys).
Boys spent more time in front of computers and television than girls; approximately 5 and 4 hours, compared with 4 and 3 hours daily in weekends and weekdays, respectively.
Physical activity levels were adversely related to leisure time computer use at weekends. However, 20 % of the girls and 25 % of the boys balanced 2-4 hours in front of the screen daily with more than 4 hours of sports and hard training per week.
Screen time at weekends was negatively associated with bone mass density levels in boys and positively in girls, after adjustments of several confounders known to affect bone, including age, puberty, physical activity levels and weekday screen time.
Moreover; these contrasting patterns persisted two years later.
MedicalResearch.com Interview with:
Dr. rer. nat. Kristin Prehn, Dipl.-Psych.
Charité Universitätsmedizin Berlin
Department of Neurology & NeuroCure Clinical Research Cente
Berlin Germany
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Prehn: The study is based on the theory by renowned American psychologist Lawrence Kohlberg stating that people progress through different levels of moral reasoning. At lower levels, individuals judge moral issues based on self-interest or laws and rules. Individuals at the post-conventional level also take into account deeper principles and shared ideals. The Kohlbergian theory influenced moral psychology and education for decades. No study to date, however, had investigated in which way moral development is reflected in human brain structure and function.
In our study, we compared gray matter brain volume in healthy young subjects who either reached the post-conventional level or did not reach that level so far. We found that subjects at the post-conventional level showed larger volume in a specific brain region of the prefrontal cortex which is essential for moral reasoning as well as the integration of emotion and cognition during human behavior.
MedicalResearch.com Interview with:
Michaela Dinan, Ph.D.
Duke Clinical Research Institute and Duke Cancer Institute
Department of Medicine
Duke University School of Medicine
Durham, North Carolina
Medical Research: What is the background for this study? What are the main findings?
Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer. The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients.
MedicalResearch.com Interview with:
Jacob Hollenberg M.D., Ph.D.
Assistant Professor, Cardiologist
Head of Research, Centre for Resuscitation Science
Karolinska Institutet, Stockholm, Sweden
Editor’s note: Dr. Hollenberg and colleagues published two articles in the NEJM this week discussing CPR performed by bystanders in out-of-hospital cardiac arrests.
MedicalResearch: What is the background for the first study?
Dr. Hollenberg: There are 10,000 cases of cardiac arrest annually in Sweden. Cardiopulmonary Resuscitation (CPR) has been taught to almost a third of Sweden’s population of 9.7 million. In recent years the value of bystander CPR has been debated, largely due to a lack of a randomized trial demonstrating that bystander CPR is lifesaving.
In this study, which included all cases of emergency medical services (EMS) treated and bystander-witnessed out-of-hospital cardiac arrests recorded in the Swedish Cardiac Arrest Registry from January 1, 1990, through December 31, 2011, our primary aim was to assess whether CPR initiated before the arrival of EMS was associated with an increase in the 30-day survival rate.
MedicalResearch: What were the main findings?
Dr. Hollenberg: Early CPR prior to arrival of an ambulance more than doubled the chance of survival. (30-day survival rate was 10.5% among patients who underwent CPR before EMS arrival, as compared with 4.0% among those who did not (P<0.001).)
This association held up in all subgroups regardless of sex, age, cause of cardiac arrest, place of arrest, EKG findings or time period (year analyzed).
MedicalResearch: How did the patients who survived cardiac arrest do from a disability standpoint?
Dr. Hollenberg: We had cerebral performance scores from 474 patients who survived for 30 days after cardiac arrest. (higher scores indicate greater disability).
At the time of discharge from the hospital, 81% of these patients had a score of category of 1. Less than 2% had category scores of 4 or 5.
MedicalResearch: What should patients and providers take away from this report?
Dr. Hollenberg:
MedicalResearch.com Interview with:
James V. Freeman MD, MPH, MS
Yale University School of Medicine
New Haven, CT
Medical Research: What is the background for this study? What are the main findings?
Dr. Freeman: Atrial fibrillation (AF) substantially increases the risk of major adverse clinical outcomes such as stroke and death, but it can also cause frequent symptoms, affect patient’s functional status, and impair their quality of life. While prior studies have reported the range of AF-related symptoms in patient populations, these studies were generally from highly selected patients and referral based practices, and may not reflect results in community practice or results with contemporary AF management. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a large, contemporary, prospective, community-based outpatient cohort, we evaluated the type and frequency of symptoms in patients with Atrial fibrillation. In addition, we measured the degree to which physician assessed symptom severity (using the European Heart Rhythm Association [EHRA] classification system) was correlated with patient reported quality of life (assessed by the Atrial Fibrillation Effect on QualiTy-of-life [AFEQT] questionnaire). Finally, we association between symptoms or quality of life with clinical outcomes, including death, hospitalization, stroke and major bleeding.
In our community-based study, the majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3-4). EHRA symptom class was well correlated with the AFEQT quality of life score (Spearman correlation coefficient -0.39). Over 1.8 years of follow-up, Atrial fibrillation symptoms were associated with a higher risk of hospitalization (adjusted HR for EHRA ≥2 vs EHRA 1 1.23, 95% CI 1.15-1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted HR for lowest quartile of AFEQT vs highest 1.49, 95% CI 1.2-1.84), but not other major adverse events including death. 
MedicalResearch.com Interview with:
Eyal Leshem, MD
Division of Viral Diseases,
US Centers for Disease Control and Prevention,
Atlanta, Georgia
Medical Research: What is the background for this study? What are the main findings?
Response: Routine vaccination of US children to protect against rotavirus began in 2006. The purpose of this study was to examine the effect of implementation of rotavirus vaccine on gastroenteritis and rotavirus hospitalizations of children younger than 5 years old.
The main finding from this study is that hospitalizations for diarrhea in U.S. children younger than 5 years old decreased dramatically during 2008 to 2012 following implementation of routine rotavirus vaccination in 2006. Additionally, seasonal peaks of hospitalizations for rotavirus illness were considerably reduced after the vaccine was implemented compared to years prior to rotavirus vaccination.
By 2012, rates of rotavirus hospitalization declined by approximately 90% across all settings and age groups. Factors such as increasing vaccine coverage as well as herd immunity resulting in less transmission of rotavirus may be responsible for this large decrease.
MedicalResearch.com Interview with: Kelvin TSOI BSc, PhD Research Associate Professor, Stanley Ho Big Data Decision Analytics Research Centre Associate Professor (by Courtesy), School...
MedicalResearch.com Interview with:
Emmanuel S. Antonarakis, M.B.B.CH
Department of Urology and Oncology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Medical Research: What is the background for this study? What are the main findings?
Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies.
MedicalResearch.com Interview with:
Marie Marklund, DDS senior lecturer
Department of Odontology, Faculty of Medicine
Umeå University
Sweden
MedicalResearch: What is the background for this study? What are the main findings?
Response: Snoring and obstructive sleep apnea are common in the population and these disorders continuously increase because of the ongoing obesity epidemic in many countries. Today, 34% of men and 17% of women in the US suffer from obstructive sleep apnea of all severities. Symptoms include daytime sleepiness, poor sleep quality, headache, insomnia and restless legs. In the longer term, a more severe sleep apnea is associated with serious consequences, such as hypertension, stroke, cancer, traffic accidents and early death.
Continuous positive airway pressure is a highly effective treatment for sleep apnea patients. Adherence problems, for instance from nasal stuffiness and claustrophobia reduces its effectiveness. An oral appliance holds the lower jaw forwards during sleep in order to reduce snoring and sleep apneas. This therapy has primarily been suggested for snorers and patients with mild and moderate sleep apnea. No previous placebo-controlled study has, however, evaluated this specific group of patients. Results from more severe sleep apnea patients have shown a good effect on sleep apneas. The effect of oral appliances on daytime symptoms is unclear. Symptomatic improvement is an important outcome for milder sleep apnea patients.
The primary aims of the present study were to study the effects on daytime sleepiness and quality of life of a custom-made, adjustable oral appliance in patients with daytime sleepiness and snoring or mild to moderate sleep apnea, i.e. the primary target group for this type of therapy. Secondary aims included the effects on sleep apnea, snoring and various other symptoms of sleep disordered breathing such as headaches and restless legs. We found that oral appliance therapy was effective in reducing sleep apneas, snoring and symptoms of restless legs. The apnea-hypopnea index was normal (<5) in 49% of patients using the active appliance and in 11% using placebo, with a numbers needed to treat of three. Daytime sleepiness and quality of life did not differ during active treatment and the placebo intervention. The patients experienced reduced headaches with active treatment, but the results did not differ from placebo. It was concluded, that a custom-made, adjustable oral appliance reduces obstructive sleep apneas, snoring and possibly restless legs. The efficacy on daytime sleepiness and quality of life was weak and did not differ from placebo in this group of patients. 
MedicalResearch.com Interview with:
Julia E. Richards, Ph.D.
Harold F. Falls Professor of Ophthalmology and Visual Sciences
Professor of Epidemiology
Director, Glaucoma Research Center
The University of Michigan
Medical Research: What is the background for this study?
Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes.
Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma.
Medical Research: What are the main findings?
Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes.
In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases. 
MedicalResearch.com Interview with:
Robin Mathews, MD
Duke Clinical Research Institute
Duke University Medical Center
Durham, NC
Medical Research: What is the background for this study? What are the main findings?
Dr. Mathews: Though treatment for patients with an acute myocardial infarction with evidence based therapies has increased significantly over the years, adherence to these therapies after discharge remain sub optimal. We used a validated instrument, the Morisky scale, to assess patient medication adherence. We found that in a contemporary population of 7,425 patients across 216 hospitals, about 30% of patients were not adherent to prescribed cardiovascular medications as early as 6 weeks after discharge. Patients with low adherence were more likely to report financial hardship as well as have signs of depression. In addition, we found that patients who had follow up arranged prior to discharge and those that received explanations from the provider on the specific medications, were more often adherent to therapies. There was a non significant increase in risk of death or readmission at 2 months (HR [95% CI]: 1.35 [0.98-1.87]) among low adherence patients.
MedicalResearch.com Interview with:
Timothy Michael Pawlik, M.D., M.P.H., Ph.D.
Chief, Division of Surgical Oncology
Professor of Surgery
John Hopkins
Medical Research: What is the background for this study?
Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies.
We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies.
Medical Research: What are the main findings?
Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort. MedicalResearch.com Interview with: Elliot B Tapper, M.D. Clinical Fellow in Medicine (EXT) Beth Israel Deaconess Medical Center Boston MA 02215 Medical Research: What is...
MedicalResearch.com Interview with:
Alexander N Yatsenko, MD, PhD
Assistant Professor,
Department of OBGYN and Reproductive Science,
Magee-Womens Research Institute,
University of Pittsburgh, PA
Pittsburgh, PA 15213
Medical Research: What is the background for this study? What are the main findings?
Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem.
We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies.
MedicalResearch.com Interview with:
Patrick M. Schlievert Ph.D
Professor and Chair
Department of Microbiology
Carver College of Medicine
Iowa City Iowa 52242
Medical Research: What is the background for this study? Dr. Schlievert:
MedicalResearch.com Interview with:
Dr. Lucy Bowes Ph.D
Leverhulme Early Career Research Fellow
Fellow of Magdalen College
Department of Experimental Psychology
University of Oxford Oxford
Medical Research: What is the background for this study? What are the main findings?
Response: Major depression is a severe mental illness, and a leading contributor to the global burden of disease. Rates of depression begin to rise in the teenage years, though the reasons for this remain unclear. Peers become particularly important during this time, and victimisation by peers or “bullying” has been proposed as one potentially modifiable risk factor for depression. There are robust findings that peer victimisation in childhood is associated with short-term internalizing symptoms, however it remains unclear whether victimization in the teenage years is associated with major depression. Only a relatively small number of longitudinal studies have prospectively investigated victimisation in relation to depression meeting diagnostic criteria in late adolescence or adulthood. Limitations of these studies include poor measures of bullying, lack of adjustment for key confounders such as baseline emotional and behavioral difficulties and child maltreatment.
Our prospective cohort observational study, published in The BMJ, used detailed self-report data on peer victimisation at 13 years from 6,719 participants of the ALSPAC or ‘Children of the 90s’ study. The outcome was depression at 18 years, measured using a self-administered computerised version of the Clinical Interview Schedule Revised, CIS-R (data available for 3,898 participants). We adjusted for a range of confounders including baseline emotional and behavioral problems, family background and other risk factors. Of the 683 children who reported frequent victimisation at 13 years, 101 (14.8%) were depressed at 18 years. Of the 1,446 children reporting some victimisation, 103 (7.1%) were depressed, and of the 1,769 children reporting no victimisation at 13 years, 98 (5.5%) were depressed. Children who were frequently victimized had over a two-fold increase in odds of depression compared with children who were not victimized by peers. This association was slightly reduced when adjusting for key confounders. The population attributable fraction suggested that 29% of depression at 18 could be explained by peer victimisation if this were a causal relationship.
MedicalResearch.com Interview with:
Wiliam C. Huang, MD FACS
Associate Professor of Urology
Division of Urologic Oncology
NYU Langone Medical Center/Perlmutter Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved. Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option.
We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium. We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians.
MedicalResearch.com Interview with:
Harley Goldberg, DO
Physical Medicine and Rehabilitation
Kaiser Permanente
Medical Research: What is the background for this study? What are the main findings?
Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with a herniated lumbar disk.
Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common source of pain and disability for many adults. It is thought that inflammation from a disk herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory, such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has shown that lumbar diskectomy does not affect the one year outcome for most patients, and epidural steroid injections do not have strong support by clinical trials. If the use of epidural steroids injections is based on application of steroid anti-inflammatory to the affected nerve root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many physicians and have been included in some clinical guidelines, no large-scale clinical trials of oral steroids for sciatica have been conducted before.
Our study found that among patients with acute radiculopathy associated with a herniated lumbar disk, a short course of oral steroids resulted in only modest improvement in function and no significant improvement in pain.