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:
Dr. Li-Huei Tsai Ph.D.
Professor and Director - Picower Institute
For Learning and Memory
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Medical Research: What is the background for this study? What are the main findings?
Dr. Tsai: For a while now, we have been interested in observations made by many labs, including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders. However, the precise contribution of unrepaired DNA lesions to the development of neurological disorders remains poorly understood. A major confounding factor is that the sources that generate DNA lesions in the brain are not well characterized, and it is not known whether damage accumulates non-specifically throughout the genome, or whether there are certain regions that are more prone to accumulate DNA damage.
In this regard, our study reports three major findings:
(1) Physiological neuronal activity itself results in the formation of DNA breaks;
(2) Neuronal activity-induced DNA breaks form at highly specific locations, including within the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in experience-driven changes to synapses, and learning and memory;
(3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes following neuronal stimulation. (more…)
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.
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MedicalResearch.com Interview with:
Nicholas Tatonetti, PhD
Department of Biomedical Informatics
Department of Systems Biology, Department of Medicine
Columbia University
New York, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Tatonetti: For decades, researchers have studied the link between disease incidence and the seasons. We’ve known, for example, that those born when the dust mite population is highest (summer) will have an increased chance of developing asthma. Traditionally, diseases have been studied one at a time to identify these seasonal trends. Because of the rapid adoption of electronic health records, it is now possible to study thousands of diseases, simultaneously. That is what we did in this study. We evaluated over 1,600 diseases and discovered 55 that showed this seasonal trend. Many of these had been studied previously, but several are new discoveries — most prominently, we found that the lifetime risk of developing cardiovascular disease is highest for those born in the spring.
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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.
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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.
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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.
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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.
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MedicalResearch.com Interview with:
Jeffrey C. Schneider, M.D.
Medical Director, Trauma, Burn & Orthopedic Program
Assistant Professor, Dept. of Physical Medicine and Rehabilitation
Harvard Medical School
Spaulding Rehabilitation Hospital
Boston, MA 02129
Medical Research: What is the background for this study? What are the main findings?
Response: Hospitalizations account for the largest share of healthcare costs in the U.S., comprising nearly one-third of all healthcare expenditures. In 2011, readmissions within 30 days of hospital discharge represented more than $41 billion in hospital costs. Financial penalties for excess 30-day hospital readmissions were instituted by the Centers for Medicare and Medicaid Services in 20124; more than 2,200 hospitals were fined a total of $280 million in reduced Medicare payments in fiscal year 2013.
Most readmission risk prediction models have targeted specific medical diagnoses and have utilized comorbidities and demographic data as the central risk factors for hospital readmission. Yet, large U.S. administrative datasets have demonstrated poor discriminative ability (c-statistics: 0.55-0.65) in predicting readmissions. However, few studies have considered functional status as potential readmission risk factors.
There is increasing evidence that functional status is a good predictor of other health outcomes. To date, acute care hospital administrative databases do not routinely include functional status measures. Therefore, inpatient rehabilitation setting is an ideal population in which to examine the impact of functional status on readmission risk, because:
(1) inpatient rehabilitation patients often have complex care transitions after acute care discharge, and represent a significant proportion of total readmissions;
2) inpatient rehabilitation facilities routinely document functional status using a valid instrument—the FIM®; and
(3) a majority of U.S. IRFs participate in one of the only national datasets that contain standardized functional data—the Uniform Data System for Medical Rehabilitation.
Limitations of prior work include small and single-center study designs, narrowly defined patient populations, and defining readmissions beyond the 30-day period. Overall, there is a lack of literature on the utility of function as a readmission predictor in a large population of medical patients. Moreover, function is a modifiable risk factor with potential to impact readmission outcomes if function-based interventions are instituted early. Therefore, the objective of this study was to compare functional status with medical comorbidities as predictors of acute care readmissions in the medically complex rehabilitation population. We hypothesized that acute care readmission prediction models based on functional status would outperform models based on comorbidities,and that the addition of comorbidity variables to function-based models would not significantly enhance predictive performance.
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MedicalResearch.com Interview with:
Yan S. Kim, MD PhD
Delivery Science Fellow Division of Research
Kaiser Permanente Northern California
Oakland, CA 94612
Medical Research: What is the background for this study? What are the main findings?
Dr. Kim: Long-term care hospitals first emerged in the 1980s as an alternative to lengthy acute-care hospital stays for patients with complex medical problems who need prolonged hospital-level care. In 2002, Medicare changed its payment method for these facilities from cost-based to a lump sum per admission based on the diagnosis. Under this system, which is still in place, Medicare pays these hospitals a higher rate for patients who stay a minimum number of days based on the patient's condition. Shorter stays are paid much less and longer stays do not necessary generate higher reimbursements.
Using Medicare data, we analyzed a national sample of patients who required prolonged mechanical ventilation – the most common, and among the most costly, conditions for patients in long-term care hospitals – to examine whether this payment policy has created incentives to base discharge decisions on payments. We found that in the years after the policy’s implementation there was a substantial spike in the percentage of discharges on and immediately after the minimum-stay threshold was met, while very few patients were discharged before the threshold. By contrast, prior to 2002, discharges were evenly distributed around the day that later became the short-stay threshold. These findings confirm that the current payment policy has created unintended incentives for long-term care hospitals to base the timing of patient discharges on payments and highlight how responsive these hospitals are to payment incentives.
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Qihong Huang, M.D., Ph.D.
Associate professor in the Tumor Microenvironment and Metastasis Program
The Wistar Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Huang: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and results in more deaths globally than breast, prostate and colon cancers combined. While the five year survival rate for early stage non-small cell lung cancer (NSCLC) is above 50%, it is less than 5% in patients with metastatic disease. Clearly, early detection can save lives, but accurate screening tests for high-risk individuals are still lacking. Although low dose computed tomography (LDCT) has been successfully used for screening in high-risk populations, multiple negative factors are associated with recurrent LDCT screening, including false-positives and false-negatives, unnecessary invasive procedures, radiation exposure, global availability of the technology and cost. Although several non-invasive tests for lung cancer using body fluids such as blood, urine or sputum are under investigation, none are currently available.
When low dose computed tomography is used for screening, patients who are 50 years old or older are frequently diagnosed with pulmonary nodules. However, only a small fraction of the nodules detected are subsequently diagnosed as lung cancer. In cases where it is difficult to differentiate malignant from benign nodules, it is recommended that patients with these indeterminate nodules be followed with serial LDCT, which increases radiation exposure and financial cost. A simple, inexpensive blood test that differentiates malignant from benign nodules would fill an important clinical need.
In this study, we validated AKAP4 as a highly accurate biomarker in a cohort of 264 blood samples from patients with known non-small cell lung cance and 135 controls samples from two different sites including a subset of controls with high risk lung nodules. When all 264 lung cancers were compared with all 135 controls, the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC is 0.9795, and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules – a comparison of significant clinical importance – the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage but independently of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer, lung cancer recurrence, and distinguishing malignant from benign lung nodules. (more…)
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. (more…)
MedicalResearch.com Interview with:
Annette Estes, Ph.D.
Research Associate Professor of Speech and Hearing Sciences
Adjunct Research Associate Professor of Psychology
Director, University of Washington Autism Center
Susan & Richard Fade Endowed Chair
Center on Human Development and Disability
University of Washington
Medical Research: What is the background for this study? What are the main findings?
Dr. Estes: Although a number of studies have shown the positive effects of early intervention on children’s abilities during the preschool period, there have been few studies to date that have followed children longitudinally to find out if these gains are sustained. We found that two years after completing the intervention, children maintained their gains in cognitive and adaptive behavior skills and also showed a reduction in autism symptoms. The results suggest that early intervention results in long term benefits for children across a wide range of skills. Children who received the ESDM intervention as toddlers later showed fewer autism symptoms at school age.
Medical Research: What should clinicians and patients take away from your report?
Dr. Estes: Early intensive behavioral intervention has been found to be efficacious in improving developmental outcomes for young children with autism spectrum disorder. Children were able to maintain the developmental gains that they made in early, intensive, in-home intervention over a 2-year follow-up period. These children did not exhibit developmental regression or lose skills, even after substantial reductions in services. Intellectual, language, and adaptive functioning gains made as a result of early intervention may generalize to new domains of functioning, such as reduced Autism Spectrum Disorder symptom severity, 2 years later.
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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.
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MedicalResearch.com Interview with:
Stephanie Bonne, MD, FACS
Assistant Professor
Trauma, Acute, and Critical Care Surgery
Washington University in St. Louis
Medical Research: What is the background for this study? What are the main findings?
Response: We had previously implemented education programs in our ICU in an attempt to decrease our Central Line-Associated Bloodstream Infection (CLABSI) rate. We were, however, unable to come to zero. We were looking for innovative ways to lower our CLABSI rate, and the use of Clorhexidine/Silver Sulfadiazine catheters was unable to move our CLABSI rate. We decided to try Minocycline/Rifampin catheters, and monitor our Central Line-Associated Bloodstream Infection rate.
Medical Research: What should clinicians and patients take away from your report?
Response: The use of Minocycline/Rifampin impregnated catheters can lower Central Line-Associated Bloodstream Infection rate, particularly in ICUs who have been unable to reach a Central Line-Associated Bloodstream Infection rate of zero with other measures.
(more…)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
Dr. Karin Rådholm MD Ph.D. student
Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University
Department of Local Care West, County Council of Östergötland,
Linköping, Sweden
MedicalResearch: What is the background for this study?
Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease.
Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study.
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