Author Interviews, NEJM, Rheumatology / 02.06.2016
Chewing Gum Test Unmasks Jaw Claudication of Giant Cell Arteritis
MedicalResearch.com Interview with:
Chih-Hung Kuo, M.B., B.S.
Peter McCluskey, M.D.
Clare L. Fraser, M.B., B.S.
University of Sydney
Sydney, NSW, Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Giant cell arteritis is a life and sight threatening systemic inflammatory condition, which remains difficult to diagnose. Jaw claudication (cramping of muscle from ischemia) is a highly specific symptom with significant diagnostic and prognostic (risk of permanent blindness) values. The reporting of jaw symptoms may be affected by many factors, such as diet. There remains no standardized clinical test available for clinicians. We study the use of chewing gum as a standardized test (like a stress test for angina pain) to better characterize this critical symptom.
The pilot study of two cases with abnormal results were published in the New England Journal of Medicine. Chewing gum at a rate of 1 chew/second can reproduce the jaw claudication symptom around 2-3 minutes. In one case, the jaw claudication was unmasked by the test with a subsequent positive biopsy result. The test result became negative after corticosteroid treatment.
Dr. Sanjay Saint[/caption]
MedicalResearch.com Interview with:
Sanjay Saint, MD, MPH
Chief of Medicine
VA Ann Arbor Healthcare System
George Dock Professor of Internal Medicine & Senior Associate Chair -
Department of Internal Medicine
University of Michigan Medical School
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Saint: Catheter-associated urinary tract infection (CAUTI) is a common, costly, and morbid complication of hospitalization. Urinary tract infection (UTI) is one of the most common device-related infections in the United States. CAUTI rates rose nationally between 2009 and 2013.
We put in place a national program to reduce CAUTI. Specifically, we enrolled 926 intensive care unit (ICU) and non-ICU hospital units in 603 hospitals spread over 32 states, the District of Columbia and Puerto Rico between March 2011 and November 2013.
By the end of the 18-month program, UTI rates among hospital patients in general wards had dropped by a third. Specifically:
• The rate of CAUTIs dropped from 2.40 per 1000 days of catheter use to 2.05 (a ~14 percent overall drop).
• Nearly all of the decrease in CAUTI rates was due to changes in infection rates in non-ICUs, which went from 2.28 to 1.54 infections per 1,000 catheter-days – a drop of 32 percent. In non-ICUs, the overall use of catheters decreased by 7%.
• ICUs didn’t see a substantial change in either CAUTI or catheter use, likely because the nature of patients treated in ICUs means more frequent urine output monitoring and culturing of urine, so UTIs are more likely to be spotted.
Mark de Jong, MD, Psychiatrist
Yulius Academy, Yulius Mental Health
Barendrecht, the Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Compulsory psychiatric admission, defined as admission against the will of the patient, has a strong effect on psychiatric patients and their relatives, and can be traumatic. Compulsory admission also conflicts with human rights, principles of autonomy, shared decision making, and recovery focused care. We also see, that rates of compulsory admissions in several European countries are tending to rise. So, interventions that prevent patients from being compulsory admitted are urgently needed.
We reviewed and meta-analyzed all currently available RCTs, that were designed to reduce compulsory admission rates in adult psychiatric patients with severe mental illnesses in outpatients settings. We found, that advance statements, like crisis plans, showed a significant 23% risk reduction in compulsory admissions. In contrast, community treatment orders and interventions for compliance enhancement showed no significant risk reduction in compulsory admissions. Although RCTs on integrated treatment showed no statistically significant risk reduction, we found a potentially clinically relevant risk reduction of 29%.
Dr. Daniel Murphy[/caption]
Daniel R. Murphy, M.D., M.B.A.
Assistant Professor - Interim Director of GIM at Baylor Clinic
Department of Medicine
Health Svc Research & General Internal Medicine
Baylor College of Medicine
Houston, TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Murphy: Electronic health records (EHRs) have improved communication in health care, but they have not eliminated the problem of patients failing to receive appropriate and timely follow up after abnormal test results. For example, after a chest x-ray result where a radiologist identifies a potentially cancerous mass and suggests additional evaluation, about 8% of patients do not receive follow-up imaging or have a visit with an appropriate specialist within 30 days. Identifying patients experiencing a delay with traditional methods, like randomly reviewing charts, is not practical. Fortunately, EHRs collect large amounts of data each day that can be useful in automating the process of identifying such patients.
We evaluated whether an electronic “trigger” algorithm designed to detect delays in follow up of abnormal lung imaging tests could help medical facilities identify patients likely to have experienced a delay. Of 40,218 imaging tests performed, the trigger found 655 with a possible delay. Reviewing a subset of these records showed that 61% were truly delays in care that required action. We also found that the trigger had a sensitivity of 99%, indicating that it missed very few actual delays.
Dr. Johannes Neumann[/caption]
Dr. med. Johannes Neumann
Resident physician
University Heart Center Hamburg
Department of General and Interventional Cardiology
Universitätsklinikum Hamburg-Eppendorf
Hamburg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The early decision making in patients with suspected acute myocardial infarction is important. Current guidelines recommend measurement of cardiac troponin at admission and after 3 hours. In our study we evaluated the performance of a high-sensitivity troponin I assay with a rapid measurement after only 1 hour. We included 1040 patients with new onset chest pain and could show, that a low cutoff concentration of 6 ng/L after 1 hour allows safe rule-out of acute myocardial infarction. The results were comparable to the recommended 3-hour approach and were validated in 2 external cohorts. When using the 99th percentile to rule-out myocardial infarction, as recommended by current guidelines, the negative predictive value was much lower. Furthermore, a troponin I concentration above 6 ng/L in combination with an absolute change of 12 ng/L after 1 hour showed a high positive predictive value for the final diagnosis of myocardial infarction. This allows early decision making after only 1 hour.
Dr. Nicole Pratt[/caption]
Nicole Pratt PhD
Senior Research Fellow
Quality Use of Medicines and Pharmacy Research Centre
Sansom Institute, School of Pharmacy and Medical Sciences
University of South Australia
Adelaide South Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pratt: The cardiac safety of methylphenidate has been debated. This study aimed to measure the risk of cardiac events in a large population of children treated with these medicines. We found that there was a significantly raised risk of arrhythmia in time periods when children were treated with methylphenidate compared to time periods when they were not. While the relative risk of cardiac events was significant the absolute risk is likely to be low as cardiac events are rare in children.
Dr. Nina Berentzen[/caption]
Dr. Nina Berentzen PhD
National Institute for Public Health and the Environment
Bilthoven, the Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Berentzen: Cardiovascular disease and type 2 diabetes often occur together and share risk factors including an unhealthy diet, a lack of physical activity, and being overweight or obese. This study is the first to investigate the occurrence of both diabetes and CVD across two generations of parents and grandparents, and relate it to measurable risk factors in children. We found that one third of the 12-year-olds studied had a strong family history of one or both of cardiovascular disease (myocardial infarction and stroke) and type 2 diabetes. Children had a ‘strong family history’ if they had one affected parent, or at least one grandparent with early disease onset, or 3–4 grandparents with late disease onset. These children had higher levels of total cholesterol, and a higher ratio of total/HDL cholesterol than children with no family history of disease.
Dr. Markus Juonala[/caption]
Markus Juonala, MD, PhD
Murdoch Childrens Research Institute, Parkville
Victoria, Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Juonala: This is an epidemiological follow-up study investigating whether childhood infections and socieconomic status are associated with cardiovasular risk factor and early chances in vasculature.
The main finding was that childhood infections were associated with obesity and impaired vascular function in adulthood among those individuals with low socioeconomic status.
Dr. Steven Kyle Grinspoon[/caption]
Steven Grinspoon, MD
Professor of Medicine, Harvard Medical School
MGH Endowed Chair in Neuroendocrinology and Metabolism
Director, MGH Program in Nutritional Metabolism
and Nutrition Obesity Research Center at Harvard
MGH
Boston, MA 02114
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Grinspoon: Numerous epidemiologic studies have shown that people living with HIV face a 1.5 to 2-fold increased risk of heart attack, or myocardial infarction, as compared to individuals without the virus. Mechanisms underlying the increased risk of myocardial infarction in HIV are incompletely understood. It is possible that among people living with HIV, increased systemic immune activation fuels arterial inflammation. Arterial inflammation may, in turn, promote the development of high-risk morphology coronary atherosclerotic plaque, which is liable to rupture and result in myocardial infarction.
For people diagnosed with HIV, the overall health benefits of immediate antiretroviral therapy (ART) are clear. However, the effects of newly-initiated antiretroviral therapy on arterial inflammation have not previously been studied. In this study, we set out to assess among a cohort of treatment-naive HIV-infected subjects, the effects of newly-initiated ART with a contemporary regimen on both immune function and arterial inflammation. We found that among treatment-naive HIV-infected individuals without clinical cardiovascular disease, newly initiated combined antiretroviral therapy has discordant effects to restore immune function without reducing the degree of arterial inflammation.
Amanda Sierra, PhD
Research Professor and Group Leader
Ramón y Cajal Fellow
Achucarro Basque Center for Neuroscience
Laida Bidea
Bizkaia Science and Technology Park
Zamudio, Bizkaia, Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sierra: Microglia phagocytosis of apoptotic cells is at the core of the brain regenerative response to recover the homeostasis of the brain parenchyma after damage because it prevents the spillover of toxic intracellular contents and is actively anti-inflammatory. However, while neuronal death is widespread in neurodegenerative diseases (Alzheimer´s, Parkinson´s, multiple sclerosis) and well as in ischemic and traumatic brain injuries, we have a complete lack of knowledge of the efficiency of microglial phagocytosis in the diseased brain.
In this paper we have discovered that microglia have a generalized response to apoptotic challenges: when confronted to a rise in the number of newborn cells, microglia display a combination of different strategies to boost their phagocytic output: increase the phagocytic capacity of each cell, recruit more cells to become phagocytic, or increase the total number of microglia (Abiega et al., PLoS Biol 2015). Thus, microglia have a very large potential for phagocytosis that could be summoned when needed.
To our surprise, however, in pathological conditions such as epilepsy (mouse and human), microglial phagocytosis was blocked. We have made use of the adult neurogenic cascade, where newborn cells undergo apoptosis naturally and are engulfed by “unchallenged microglia” (Sierra et al. Cell Stem Cell 2010), to establish the baseline of microglial phagocytosis efficiency. Whereas in physiological conditions microglia phagocytose over 90% of the apoptotic cells and remove them in under 1.5h, soon after the seizures it only engulfed 10% of the apoptotic cells and took up to 6h to digest them. This is the first quantification of microglial phagocytosis efficiency in the diseased mouse and human brain..
The block in phagocytosis was a rather complex phenomenon related to an impaired recognition (reduction of phagocytosis receptors) as well as impaired motility and targeting (reduced basal motility). We have also shown that the impairment is mediated at least partially by altered ATP microgradients: ATP is not only a neuro- and gliotransmitter widely released during seizures but is also a well-known “find-me” signal released by apoptotic cells. Thus, during seizures microglia became “blinded” by the neuronal hyperactivity and could not find the apoptotic cells.
In addition, we have shown that impairing phagocytosis releases the break on the inflammatory response. In fact, the impaired microglia were in a pro-inflammatory state and produced more cytokines such as tumor necrosis factor alfa (TNFa) or interleukin-1beta (IL-1b), which are well known neurotoxic and epileptogenic factors.
Dr. Clara van Karnebeek[/caption]
Dr. Clara van Karnebeek PhD
Certified Pediatrician and Biochemical Geneticist at the BC Children’s Hospital
Principal Investigator, University of British Columbia
MedicalResearch.com: What is the background for this study?
Dr. van Karnebeek: The goal of the study was to diagnose patients with genetic conditions and discover and describe new diseases with potential for treatment. The study included patients with neurodevelopmental conditions that doctors suspected were genetic or metabolic in origin but had not been diagnosed using conventional methods. Our team tested the children and their parents using a combination of metabolomic (large scale chemical) analysis and a type of genomic sequencing called whole exome sequencing. With this state-of-the-art technique, experts analyze and interpret the portion of DNA called genes that hold the codes for proteins.
Some people’s intellectual disability is due to rare genetic conditions that interfere with the processes the body uses to break down food. Because of these metabolic dysfunctions, there is an energy deficit and build-up of toxic substances in the brain and body leading to symptoms such as developmental and cognitive delays, epilepsy, and organ dysfunction. Some of these rare diseases respond to treatments targeting the metabolic dysfunction at the cellular level and range from simple interventions like dietary modifications, vitamin supplements and medications to more invasive procedures like bone marrow transplants. Because the right treatment can improve cognitive functioning or slow or stop irreversible brain damage, early intervention can improve lifelong outcomes for affected children and their families.
Dr. Robert Ursano[/caption]
Robert J. Ursano, M.D.
Professor and Chair
Department of Psychiatry/ Director
Center for the Study of Traumatic Stress
Uniformed Services University of the Health Sciences
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ursano: This study is part of STARRS-LS (Study to address risk and resilience in service members-longitudinal study). STARRS is a group of studies that address suicide risk in the US Army. Suicidal behavior includes suicide ideation, plans, attempts and completions. Understanding the transitions between these is an important goal.
One component of STARRS is the examination of data available on all soldiers who were in the Army 2004-2009. This study examines suicide attempts in soldiers serving 2004-2009 in order to understand the association with deployment and the timing of suicide attempts as well as their association with mental health problems. STARRS is directed to identifying the who, when and where of service member risk. Then interventions can better be developed for these soldiers.
Nana Keum[/caption]
NaNa Keum, ScD|
Harvard T. H. Chan
School of Public Health Department of Nutrition
Departments of Nutrition and Epidemiology,
Harvard T.H. Chan School of Public Health
Boston, MA 02115
MedicalResearch.com: What is the background for this study?
Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity.
MedicalResearch.com: What are the main findings?
Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity.
Dr. Bo Qin[/caption]
Bo (Bonnie) Qin, Ph.D.
Postdoctoral Scholar
Rutgers Cancer Institute of New Jersey
New Brunswick, NJ 08903
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Qin: Preventing or delaying the age-related cognitive decline that typically precedes the onset of dementia is particularly important considering that no effective strategies for dementia treatment have been identified. Vascular conditions such as hypertension are thought to be risk factors for cognitive decline, but important gaps in the literature on this topic remain.
Randomized clinical trials of blood pressure-lowering treatments for reducing the risk of cognitive decline or dementia have largely failed to achieve beneficial effects. However, over the past 6 years, scientific evidence has accumulated that blood pressure variability over monthly or yearly visits may lead to greater risk of stroke and small and larger vessel cerebrovascular diseases. They could lead to subsequent changes related to cognitive dysfunction among older adults. We, therefore, hypothesized that blood pressure variability between visits is associated with a faster rate of cognitive function among older adults.
Dr. Alan Brown[/caption]
Alan S. Brown, M.D., M.P.H.
Professor of Psychiatry and Epidemiology
Columbia University Medical Center
Director, Program in Birth Cohort Studies, Division of Epidemiology
New York State Psychiatric Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Brown: Smoking during pregnancy is a risk factor for several pregnancy-related outcomes including low birthweight and preterm birth. Evidence for a link with schizophrenia is scant. We analyzed a maternal biomarker of smoking called cotinine, a nicotine metabolite, in mothers of nearly 1,000 schizophrenia cases and 1,000 controls in a national birth cohort in Finland. We found that heavy smoking in pregnancy was related to a 38% increase in schizophrenia risk in offspring and that as cotinine levels increased even in the more moderate smokers risk of schizophrenia also increased.
Dr. Jiang He[/caption]
Jiang He, M.D., Ph.D.
Joseph S. Copes Chair and Professor
Department of Epidemiology
School of Public Health and Tropical Medicine
Tulane University, New Orleans
MedicalResearch: What is the background for this study?
Dr. Jiang He: Chronic kidney disease is associated with increased risk of end-stage renal disease, cardiovascular disease, and all-cause mortality. A positive association between sodium intake and blood pressure is well established in observational studies and clinical trials. However, the association between sodium intake and clinical cardiovascular disease remains less clear. Positive monotonic, J-shaped, and U-shaped associations have been reported. Methodologic limitations, including inconsistencies in dietary sodium measurement methods, could be contributing to these conflicting findings. Furthermore, no previous studies have examined the association between sodium intake and incident cardiovascular disease among patients with chronic kidney disease.
Dr. James Kirkpatrick[/caption]
James N. Kirkpatrick, MD
Director of the Echocardiography Laboratory
Division of Cardiology
Ethics Consultation Service
University of Washington, Seattle
MedicalResearch.com: What is the background for this study?
Dr. Kirkpatrick: With significant advances in technology, implanted cardiac devices like pacemakers and defibrillators, replacement heart valves, and mechanical pumps which assist or replace the pumping function of the heart have become standard therapies for patients with severe cardiac disease. Many patients who would previously have died after living with severe symptoms live longer and with improved quality of life. This is particularly true for elderly patients who receive transcatheter aortic valve replacement (TAVR—valve replacement that doesn’t require open heart surgery) and ventricular assist device (VAD—a durable mechanical heart pump) implantation.
However, like everyone, these patients will die, and some of the patients will experience device complications which will shorten their lives. Elderly patients, in particular, are at risk for device complications, high symptom burden, and loss of the ability to make healthcare decisions, due to illnesses like strokes or dementia. Symptom management and advance care planning are the hallmarks of the medical specialty of Palliative Care and are particularly important in patients with TAVR and VADs, yet patients and clinicians don’t often think of Palliative Care when considering high tech, life-prolonging therapies. The Palliative Care Working Group of the American College of Cardiology’s Geriatrics Section therefore sought to gather data on the attitudes toward Palliative Care among cardiovascular clinicians and the current state of involvement of Palliative Care in the care of patients with TAVR and VAD.
Dr. Jill Cameron[/caption]
Jill Cameron, PhD
Canadian Institutes of Health Research New Investigator
Associate Professor,
Department of Occupational Science and Occupational Therapy
Rehabilitation Sciences Institute
Faculty of Medicine,
University of Toronto
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cameron: In the world of critical illness, a lot of research has focused on helping people to survive – and now that more people are surviving, we need to ask ourselves, what does quality of life and wellbeing look like afterwards for both patients and caregivers? The aim of our research was to identify factors associated with family caregiver health and wellbeing during the first year after patients were discharged from the Intensive Care Unit. We examined factors related to the patient and their functional wellbeing, the caregiving situation including the impact it has on caregivers everyday lives, and caregiver including their sense of control over their lives and available social support. We used Pearlin’s Caregiving Stress Process model to guide this research.
From 2007-2014, caregivers of patients who received seven or more days of mechanical ventilation in an ICU across 10 Canadian university-affiliated hospitals were given self-administered questionnaires to assess caregiver and patient characteristics, caregiver depression symptoms, psychological wellbeing, and health-related quality of life. Assessments occurred seven days and three, six and 12-months after ICU discharge.
The study found that most caregivers reported high levels of depression symptoms, which commonly persisted up to one year and did not improve in some. Caregiver sense of control, impact on caregivers’ everyday lives, and social support had the largest relationships with the outcomes. Caregivers’ experienced better health outcomes when they were older, caring for a spouse, had higher income, better social support, sense of control, and caregiving had less of a negative impact on their everyday lives. No patient characteristics or indicators of illness severity were associated with caregiver outcomes.
Poor caregiver outcomes may compromise patients’ rehabilitation potential and sustainability of home care. Identifying risk factors for caregiver distress is an important first step to prevent more suffering and allow ICU survivors and caregivers to regain active and fulfilling lives.
Prof. Luis. Rohde[/caption]
Luis Augusto Rohde MD, PhD
Full Professor
Department of Psychiatry
Federal University of Rio Grande do Sul
Director
ADHD Program
Hospital de Clínicas de Porto Alegre
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The idea that Attention-deficit/Hyperactivity Disorder always begins in childhood has been held for decades even without proper testing. The main manuals of psychiatric diagnoses require age at onset in childhood as a core feature of the disorder. In a large birth cohort followed until age 18, we identified many young adults presenting with a full impairing ADHD syndrome. They had consistently worse outcomes - criminality, substance abuse, traffic accidents, among others - than their counterparts without ADHD. However, most of these young adults (84.6%) presenting with a full impairing syndrome did not have a prior diagnosis in their childhood years. This surprising observation held after many secondary analyses exploring possible biases, like comorbidities in young adulthood, subthreshold ADHD in childhood and change of information source.
Dr. Steven Moore[/caption]
Steven C. Moore PhD, MPH
Division of Cancer Epidemiology and Genetics
Rockville, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Moore: More than half of Americans fail to meet recommended levels of regular physical activity; physical inactivity has become a major public health concern.
Physical activity during leisure time is known to reduce risks of heart-disease and all-cause mortality, as well as risks of colon, breast, and endometrial cancers. However, less is known about whether physical activity reduces risk of other cancers.
Hundreds of prospective studies have examined associations between physical activity and risk of different cancers. Due to small case numbers, results have been inconclusive for most cancer types.
In this study, we examined how leisure-time physical activity relates to risk of 26 different cancer types in a pooled analysis of 12 prospective cohort studies with 1.44 million participants. Our objectives were to identify cancers associated with leisure-time physical activity, and determine whether associations varied by body size and/or smoking history.
Dr. Kazem Rahimi[/caption]
Kazem Rahimi, DM, MSc
Oxford Martin School
University of Oxford
United Kingdom
MedicalResearch.com: What is the background for this study?
Dr. Rahimi: Vascular dementia is the second most common cause of dementia and is increasing in prevalence worldwide. Vascular dementia often occurs after stroke and can cause apathy, depression, and a decline in cognitive function, and can eventually result in death. High blood pressure (BP) has been identified as a potential risk factor for the development of vascular dementia. However, previous studies, which have been small in size, have reported conflicting results on the relationship between blood pressure and vascular dementia.