MedicalResearch.com Interview with: Scott A. Gruber, M.D., Ph.D., MBA, FACS, FCP, FACHE, CPE
Chief of Staff, John D. Dingell VA Medical Center
Associate Dean for Veterans Affairs & Professor of Surgery
Wayne State University School of Medicine
John D. Dingell VA Medical Center Chief of Staff
Detroit, MI 48201
MedicalResearch: What are the main findings of the study?Dr. Gruber: We successfully addressed the problem of inadequate intracellular delivery of tumor- specific antigens (TSAs) to dendritic cells (DCs) by using synthetic cell-penetrating domains or peptides (CPPs) to create fusion tumor antigens (Ags) that readily penetrate through the plasma membrane. We demonstrated cloning and purification of the TSA melanoma-associated antigen 3 (MAGE-A3) in frame with CPP, producing enhanced cytosolic bioavailability in dendritic cells without altering cell functionality. Further, we showed that recombinant bacterial proteins can be easily engineered to purify large amounts of CPP-MAGE-A3. Use of full-length proteins circumvents the need to define HLA class I allele binding before vaccination and increases the number of epitopes recognized by CD8+ cytotoxic T lymphocytes (CTLs) when compared with peptide-pulsed dendritic cells. Finally, the use of proteins rather than plasmids or viral vectors for in vitro dendritic cell vaccine preparation avoids the practical and theoretical safety concerns regarding genomic modification.
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MedicalResearch.com Interview with:Dr. Sarah Hawley PhD MPH
Associate Professor in the Division of General Medicine
University of Michigan
Research Investigator, Ann Arbor VA Center of Excellence in Health Services Research & Development
MedicalResearch: What are the main findings of the study?Dr. Hawley: There are a couple of main findings.
First, we found that nearly 20% of women in our population based sample of breast cancer patients reported strongly considering having contralateral prophylactic mastectomy (CPM, which means they had their unaffected breast removed at the same time as the breast with cancer), and about 8% received it. Of those who did receive contralateral prophylactic mastectomy, most (about 70%) did not have a clinical indication for it, which included a positive genetic mutation of BRCA1 or BRCA2 or a strong family history of breast or ovarian cancer.
However, most women (90%) who received it reported having a strong amount of worry about the cancer coming back (also called worry about recurrence).
We also found that when women had an MRI as part of their diagnostic work-up for breast cancer, they more often received contralateral prophylactic mastectomy than when they did not have an MRI.
MedicalResearch.com Interview with:Neel M. Butala, AB
Medical student at Yale School of Medicine
New Haven, Connecticut
MedicalResearch.com: What are the main findings of the study?
Answer: We found that patients with diabetes had a disproportionate reduction in in-hospital mortality relative to patients without diabetes over the decade from 2000 to 2010.
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MedicalResearch.com Interview with:Scott Stroup, MD, MPH
Professor of Psychiatry
Director, Program for Intervention Effectiveness Research,
Associate Director for Adult Services, Division of Mental Health Services and Policy Research, New York State Psychiatric InstituteDepartment of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York
MedicalResearch: What are the main findings of the study?Dr. Stroup:We conducted a study sponsored by the National Institute of Mental Health that compared long-acting injectable antipsychotics for people with schizophrenia. Long-acting injectable antipsychotics, also known as depot antipsychotics, are used to promote treatment adherence. We compared a newer injectable antipsychotic, paliperidone palmitate, to an older one, haloperidol decanoate. We did not find an advantage for the newer drug in overall effectiveness. The drugs performed very similarly, and were tolerated about the same.
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MedicalResearch.com Interview with:Wei Bao MD, PhD
Postdoc fellow, Epidemiology Branch
Division of Intramural Population Health Research
NICHD/National Institutes of Health
Rockville, MD 20852
MedicalResearch: What are the main findings of the study?Dr. Wei Bao: This study, to our knowledge, is the first attempt to examine the associations of physical activity and sedentary behaviors with risk of type 2 diabetes mellitus (T2DM) among women with a history of gestational diabetes mellitus (GDM), which is a high-risk population of T2DM. The main findings are:
(1) Physical activity is inversely associated with risk of progression from GDM to T2DM. Each 5-metabolic equivalent hours per week increment of total physical activity, which is equivalent to 100 minutes per week of moderate-intensity physical activity or 50 minutes per week of vigorous physical activity, was related to a 9% lower risk of T2DM; this inverse association remained significant after additional adjustment for body mass index (BMI).
(2) An increase in physical activity is associated with a lower risk of progression from gestational diabetes mellitus to T2DM. Compared with women who maintained their total physical activity levels, women who increased their total physical activity levels by 7.5 MET-h/wk or more (equivalent to 150 minutes per week of moderate-intensity physical activityor 75 minutes per week of vigorous physical activity) had a 47% lower risk of T2DM; the association remained significant after additional adjustment for BMI.
(3) Prolonged time spent watching TV, as a common sedentary behavior, is associated with an increased risk of progression from gestational diabetes mellitus to T2DM. Compared with women who watched TV 0 to 5 hours per week, those watched TV 6 to 10, 11 to 20, and 20 or more hours per week had 28%, 41%, and 77%, respectively, higher risk of T2DM. The association was no longer significant after additional adjustment for BMI.
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MedicalResearch.com Interview with:James Chamberlain, MD
Division Chief, Emergency Medicine
Children’s National Health System
Washington, DC
MedicalResearch: What are the main findings of the study?Dr. Chamberlain: Contrary to our hypothesis, lorazepam was not superior to diazepam for treating pediatric seizures. Both medications had similar effectiveness (72-73%) and safety (15-16% incidence of assisted ventilation). Lorazepam caused a longer period of sedation prior to waking up. The difference was approximately 15 minutes.
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MedicalResearch.com Interview Professor Kim Bennell
ARC Future Fellow
Department of Physiotherapy
University of Melbourne
Parkville, Vic 3010 Australia
MedicalResearch: What are the main findings of the study?Professor Bennell: In 102 people with painful hip osteoarthritis, we compared a 'real' physical therapy program involving exercise, manual therapy techniques,education and provision of a cane if appropriate to a sham physical therapy treatment that was made to look as though it was real but instead involved turned off ultrasound and gentle application of a hand crème to the hip region. Participants in both groups went to see a physical therapist on 10 occasions over 12 weeks and performed home exercises if in the 'real' physical therapy group or lightly applied the cream at home if in the sham group. Participants were followed for 9 months in total. We found that while both groups showed improvements in pain and physical function, the improvements were similar between the two groups. That is, the real physical therapy program did not show greater benefits over a sham treatment. (more…)
MedicalResearch Interview with: Charles D. Scales, Jr MD MSHS
Assistant Professor of Surgery
Division of Urologic Surgery
Duke University Medical Center
MedicalResearch: What are the main findings of the study?Dr. Scales:When it comes to treating kidney stones, less invasive is not always better.
We used the best method short of a randomized trial to balance out patients in terms of factors that might influence the success of treatment. In other words, we achieved a “statistical toss-up” for factors that could influence the outcome of the procedure.
When we balanced out all of the factors that might influence the chance of a repeat procedure, we found that about 11% of patients treated with non-invasive SWL had a repeat procedure, as compared to <1% with minimally invasive URS.
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MedicalResearch.com Interview with:Flor M. Munoz, MDDepartment of Pediatrics
Department of Molecular Virology and Microbiology
Baylor College of Medicine, Houston, Texas
MedicalResearch.com: What are the main findings of the study?Dr. Munoz:
1. Tdap vaccine was safe and well tolerated during pregnancy
2. Women who are pregnant have adequate responses to the Tdap vaccine, similar to those of women who are not pregnant.
3. Antibodies to pertussis are efficiently transferred to the fetus through the placenta so that babies of mothers who were vaccinated during pregnancy had significantly higher concentrations of antibody at birth and up to 2 months of age, when compared to infants of mothers who were vaccinated post-partum.
4. Higher antibody concentrations in the first two months of life are likely to provide protection against pertussis during this period of high vulnerability
5. Infants of mothers who were vaccinated during pregnancy had adequate responses to their routine pertussis vaccines at 2, 4, and 6 months of age, and had expected and adequate responses to their 4th dose of vaccine at 1 year of age. The absolute concentration of antibodies to some of the pertussis antigens might be modestly lower after the primary series of vaccines in some infants of mothers who were vaccinated during pregnancy, but this difference does not persist after the 4th dose.
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MedicalResearch Interview with: Patrick S. F. Bellgowan, PhD
Laureate Institute for Brain Research
Faculty of Community Medicine, The University of Tulsa,
Tulsa, Oklahoma
MedicalResearch: What are the main findings of the study?Dr. Bellgowan: These results demonstrate 14% and 24% smaller hippocampal volumes in collegiate football players with and without a history of concussion relative to education-, sex- and age-matched controls participants. Further, the number of years of tackle football experience was correlated with smaller hippocampi and slower baseline reaction times. The hippocampus plays a key role in memory and emotional regulation. Volumetrics of other medial temporal lobe structures (I.e. The amygdala) did NOT show differences among groups suggesting that this effect is localized to the hippocampus.
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MedicalResearch.com Interview with:
Jennifer G. Robinson, MD, MPH
Professor ,Departments of Epidemiology & Medicine
Director, Prevention Intervention Center
Department of Epidemiology
College of Public Health
University of Iowa
Iowa City, IA 52242-2007
MedicalResearch: What are the main findings of the study?Dr. Robinson: The PCSK9 antibody, evolocumab, reduced LDL (or bad) cholesterol by about 65-70% regardless of the dose or type of statin used. This is a greater percentage reduction than ezetimibe, another drug used to lower LDL cholesterol in statin-treated patients, which lowered LDL cholesterol 15-20%. Side effects of evolocumab were similar to those for ezetimibe or placebo.
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MedicalResearch.com Interview with: Aaron L. Leppin, MD
Knowledge and Evaluation Research Unit
Mayo Clinic, Rochester, Minnesota
MedicalResearch.com: What are the main findings of the study?Dr. Leppin: We conducted a systematic review and meta-analysis of randomized trials assessing the effectiveness of hospital discharge interventions on reducing 30-day readmission rates. We identified 47 trials, 42 of which contributed to the primary meta-analysis.
Overall, the interventions that have been tested to reduce early hospital readmissions reduce them by about 20%.
The ones that are most effective, though, reduce them by almost 40% and use a consistent but complex approach. These interventions make a robust effort to fully understand the patient’s post-discharge context, often by visiting the patient’s home. They focus on identifying all the things the patient needs to do to be well—whether that’s organizing medications, getting a ride to the clinic, or paying the electric bill—and they determine whether the patient has the necessary resources and capacity to pull it all off. When limitations are found, these interventions have a strategy in place to support the patient through the post-discharge period.
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MedicalResearch Interview with: Charbel El Bcheraoui, PhD, MSc
Acting Assistant Professor, Global Health
Institute for Health Metrics and Evaluation
University of Washington
Seattle, WA 98121
MedicalResearch: What are the main findings of the study?Dr. El Bcheraoui: We found a low rate of adverse events associated with male circumcision from U.S. hospital settings, especially if the procedure is performed within the first year of life. The rate of adverse events increased about 10 - 20 times if the procedure was performed later in life.
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MedicalResearch.com Interview with:Richard D. Semba, MD MPH
W. Richard Green Professor of Ophthalmology
The Johns Hopkins University School of Medicine
Baltimore, MD 21287
MedicalResearch: What are the main findings of the study?Dr. Semba: Resveratrol levels in older adults are not related to the risk of heart disease or cancer and are not related with lifespan. These findings were made in the InCHIANTI Study, a rigorously conducted study of human aging that is sponsored by the National Institute on Aging.
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MedicalResearch.com Interview with: Dr. Carlo Riccardo Rossi, MD
Melanoma and Sarcoma Unit, Veneto Institute of Oncology
Surgery Branch, Department of Surgery
Oncology, and Gastroenterology, University of Padova,
Padova, Italy
MedicalResearch: What are the main findings of the study?
Dr. Rossi: A total of 90% patients undergone lymph node dissection for melanoma had 12, 7, 14, 6 and 13 excised lymph nodes (10th percentile of the distribution) after 3 level axillary, 3 level or less neck, 4 level or more neck, inguinal, or ilio-inguinal dissections, respectively.
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MedicalResearch.com Interview with:Kwang-il Kim, MD, PhD
Associate Professor, Department of Internal Medicine,
Seoul National University College of Medicine,
Seoul National University Bundang Hospital,
Seoul, Republic of Korea
MedicalResearch: What are the main findings of the study?Answer: There are few tools of preoperative risk stratification for the older adults. We found that not only disease itself but also frailty can lead to post-operative complication and mortality. So we made a scoring model to predict post-operative mortality and morbidity based on comprehensive geriatric assessment and it worked exactly.
MedicalResearch: Were any of the findings unexpected?Answer: Under our predictive model, there was inflection point of mortality slope at point 5. Post-operative mortality of someone who scores 4~5 is below 10%, but it of other who scores 6~7 is about 30%. It was unexpected drastic change, so we think that there is physiologic threshold point.
MedicalResearch: What should clinicians and patients take away from your report?Answer: Because the elderly are different from adults, clinicians have to focus on functional capacity, co-morbidity, and frailty for their older surgical patients. Make operative decision base on comprehensive geriatric assessment or our scoring model. If you depend on your own feeling, some older patients will suffer from post-operative complication and someone will forfeit his chance of surgery.
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MedicalResearch.com Interview with: Dana Dabelea, MD, PhD
Professor and Associate Dean, Faculty Affairs
Colorado School of Public Health
University of Colorado Denver
Aurora, CO 80045
MedicalResearch.com: What are the main findings of the study?Dr. Dabelea: We found that the proportion of US youth living with Type 1 Diabetes has increased by at least 21% over a period of only 8 years. This increase was seen in both boys and girls, most age-groups and race/ethnic groups. While we do not completely understand the reasons for this increase, since the causes of Type 1 Diabetes are still unclear, it is likely that something has changed in our environment- both in the US and elsewhere in the world- causing more youth to develop the disease, maybe at increasingly younger ages.
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MedicalResearch.com Interview with:Takehiro Sugiyama, MD, MSHS, PhD
Project Director, Diabetes Policy Planning Office
Management and Planning Bureau
Fellow, Department of Diabetes, Endocrinology and Metabolism
National Center for Global Health and Medicine
Shinjuku-ku, Tokyo Japan
MedicalResearch.com: What are the main findings of the study?Dr. Sugiyama:In the US nationally representative sample from the National Health and Nutrition Examination Survey 1999-2010, we found that statin users in 2009-2010 eat 9.6% more calories and 14.4% more fat than statin users in 1999-2000. These increases were not observed in statin non-users; the trends of caloric and fat intake were statistically different between statin users and non-users. In 1999-2000, caloric and fat intake was significantly less for statin users compared with non-users, but the difference between the groups because smaller as time went by and there was no statistical difference in 2009-2010. Body mass index increased more rapidly for statin users compared to non-users.
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MedicalResearch.com Interview with:Tara Lagu MD PhD
Assistant Professor of Medicine
Tufts University School of Medicine
MedicalResearch.com: What are the main findings of the study?Dr. Lagu:We found that use of mechanical ventilation in patients 65 and older is increasing rapidly. If current rates of increase continue, we expect that by 2020 there will be more than 600,000 hospitalizations per year that involve mechanical ventilation. This is a doubling in 20 years (2001-2020), and represents demand that could easily exceed the capacity of the US critical care system. We also found that increase in use among patients with dementia is 4 times faster than those without dementia. This is important because dementia is a terminal illness, and use of mechanical ventilation in patients with end-stage dementia is associated with poor 30-day and 1-year outcomes.
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MedicalResearch.com Interview with:Juliana C. N. Chan, MBChB MD FHKAM FRCP
Professor Juliana Chan is Professor of Medicine and Therapeutics, Director, Hong Kong Institute of Diabetes and Obesity and International Diabetes Federation Centre of Education at the Chinese University of Hong Kong, Prince of Wales Hospital and Chief Executive Officer of Asia Diabetes Foundation Hong Kong.
MedicalResearch.com: What are the main findings of the study?Dr. Chan: In this 1-year randomized study, we asked the question whether type 2 diabetic patients receiving team-based integrated care augmented by information technology would further improve in their glycemic control if given additional peer support through the telephone. All patients underwent comprehensive risk assessment guided by the web-based JADE portal which generated personalized risk report with attained treatment targets and decision support. After 1 year, all patients improved significantly in all risk factors including A1c with improved treatment adherence, self efficacy and psychological wellbeing. Although the peer support group did not further improve in A1c, short-stay hospitalization rates were substantially reduced by 50% , especially amongst those with emotional distress. These patients accounted for 20% of the intervention group, in whom peer support further reduced psychological distress and treatment non-adherence.
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MedicalResearch.com Interview Invitation Karin J. H. Verweij, PhDDepartment of Developmental Psychology and EMGO Institute for Health and Care Research, VU University
Amsterdam, the Netherlands
MedicalResearch.com: What are the main findings of the study?Dr. Verweij:We performed a twin study using over 10,000 adult Australian twins to determine the relative importance of genetic and environmental influences on individual differences in non-suicidal self-injury (NSSI) and suicidal ideation and their covariation.
We found that individuals that report self-harm are approximately eight times more likely to also report suicidal ideation. Results from the bivariate genetic model indicated that the substantial correlation between non-suicidal self-injury and suicidal ideation (r=0.49 for males and 0.61 for females) is largely explained by overlapping genetic factors: 62% and 76% for males and females, respectively. Overlapping residual influences, including nonshared environmental influences and measurement error, also explain part of the covariance between the two traits. These findings suggest that the two behaviors share similar biological underpinnings.
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MedicalResearch.com Interview with: Michael Wall, MD
Department of Neurology,
University of Iowa Hospitals and Clinics, 200 Hawkins D
Iowa City, IA 52242-1091
MedicalResearch.com: What are the main findings of the study?Dr. Wall: We studied patients with idiopathic intracranial hypertension (formerly called pseudotumor cerebri) with mild visual loss. We found that subjects taking acetazolamide, a type of diuretic, along with a low sodium weight loss program had significantly better visual outcomes than those taking placebo along with the diet.
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MedicalResearch.com Interview with:Dr. Gregg C. Fonarow MD
Director, Ahmanson-UCLA Cardiomyopathy Center
Professor, Department of Medicine
Associate Chief, Cardiology
David Geffen School of Medicine Los Angeles, CA
MedicalResearch.com: What are the main findings of the study?Dr. Fonarow: This study examined data from hospitals that have adopted the American Heart Association/ American Stroke Association’s national quality initiative, Target: Stroke, which aims to increase the number of stroke patients treated with clot-busting drugs for ischemic stroke within 60 minutes or less after hospital arrival. Initiated nationwide in 2010, Target: Stroke provided 10 key strategies as well as tools to facilitate timely tPA administration, as well as additional approaches to improve stroke care and outcome.
Data from 71,169 tPA-treated stroke patients at 1,030 hospitals participating in Target: Stroke were analyzed to compared the time to treatment and incidence of complications before implementation, from 2003 to 2009, to the post-implementation years, from 2010 to 2013.
This study found that the percentage of patients treated within the recommended timeframe increased from less than one-third before Target: Stroke to more than half afterwards. The Target: Stroke program goal of 50 percent or more of patients having door-to-needle times within 60 minutes was successfully achieved. In addition, the average time to treatment dropped by 15 minutes, from 74 to 59 minutes.
Faster treatment was associated with lower rates of complications, including death. Before Target: Stroke, 9.9% of stroke patients died in the hospital, compared to 8.3% of patients treated after the initiative started, a difference which was statistically significant. In addition, patients treated by Target: Stroke strategies were less likely to develop the complication of symptomatic intracranial hemorrhage.
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MedicalResearch.com Interview with:Li-Ching Lee, PhD, ScM
Associate Scientist,
Departments of Epidemiology and Mental Health
Johns Hopkins Bloomberg School of Public Health
Baltimore MD 21205
MedicalResearch.com: What are the main findings of the study?Dr. Li-Ching Lee: This population-based case-control study in young children provides evidence that prenatal selective serotonin reuptake inhibitor (SSRI) use may be a risk factor for autism and other developmental delays (DD). Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with autism spectrum disorder (ASD) relative to children with typical development; the strongest association occurred with first-trimester exposure. Exposure was also elevated among boys with DD and was strongest in the third trimester.
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MedicalResearch.com Interview with: Priv.-Doz. Dr. med. Dr. phil. Martin Ebinger
Oberarzt der Klinik und Hochschulambulanz
für Neurologie am Campus Charité Mitte
Center for Stroke Research Berlin (CSB)
Charité - Universitätsmedizin Berlin | CCM
Charitéplatz 1 | 10117 Berlin | Germany
MedicalResearch.com: What are the main findings of the study?Dr. Ebinger: The main findings of our study was a significant time reduction during randomized weeks with prehospital thrombolysis compared to control weeks with regular care.
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MedicalResearch.com Interview with: Rustam Al-Shahi Salman
Professor of clinical neurology and MRC senior clinical fellow
University of Edinburgh
Honorary consultant neurologist, NHS Lothian
MedicalResearch.com: What are the main findings of the study?Prof. Al-Shahi Salman: Patients with arteriovenous malformations (abnormal connection between arteries and veins) in the brain that have not ruptured had a lower risk of stroke or death for up to 12 years if they received conservative management of the condition compared to an interventional treatment.
Interventional treatment for brain arteriovenous malformations (bAVMs)
with procedures such as neurosurgical excision, endovascular
embolization, or stereotactic radiosurgery can be used alone or in
combination to attempt to obliterate bAVMs. Because interventions may
have complications and the untreated clinical course of unruptured
bAVMs can be benign, some patients choose conservative management (no
intervention). Guidelines have endorsed both intervention and
conservative management for unruptured brain arteriovenous malformations. Whether conservative management is superior to interventional treatment for unruptured
bAVMs is uncertain because of the lack of long-term experience,
according to background information in the article.
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MedicalResearch.com Interview with:John I. Nurnberger, Jr., M.D., Ph.D.
Professor of Psychiatry
Joyce and Iver Small Professor of Psychiatry
Indiana University School of Medicine
MedicalResearch.com: What are the main findings of this study?Dr. Nurnberger: The main findings of the study are the biological pathways identified to be associated with bipolar disorder, including those involved in hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicated neuronal development pathways as well.
These findings highlight the role of certain neurobiological processes that have been considered in prior hypotheses of bipolar disorder. They underline a role for calcium signaling, which has only been clearly implicated in the genetics of bipolar disorder in recent years. They also feature hormonal processes such as the hypothalamic-pituitary-adrenal axis, which has been known to be involved in stress responses, but has not been prominent in many recent theories of the pathogenesis of bipolar disorder.
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MedicalResearch.com Interview InvitationDorna Jafari, M.D. and
Michael J Stamos, MD
Professor of Surgery
John E. Connolly Chair,
Department of Surgery
University of California, Irvine
Orange, CA 92868
MedicalResearch.com: What are the main findings of the study?Answer: Surgeons are faced with an aging population and data regarding outcomes is rare given that many studies preclude the elderly from the study population. Therefore, it is difficult to accurately discuss risk of surgical resection given the lack of data. Therefore we aimed to report the national trends and outcomes of colorectal cancer treatment in the elderly population.
We demonstrated that the majority of resections are performed in patients >65yeras old. There is a trend towards a decrease in incidence of colorectal resection and a decrease in rate of mortality during 2001-2010. However, the unique physiological changes associated with aging contribute to increase morbidity and morality as demonstrated by our findings. In fact patients >85 years have a 472% increase in risk-adjusted mortality during a hospital admission compared to younger patients. However, despite the substantially higher mortality and morbidity associated with age, there has been a marked improvement in surgical outcomes in the elderly population.
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MedicalResearch.com Interview with:Renda Soylemez Wiener, MD, MPH
Assistant Professor of Medicine
The Pulmonary Center
Boston University School of Medicine
Center for Healthcare Organization & Implementation Research
Edith Nourse Rogers Memorial VA Hospital
MedicalResearch.com: What are the main findings of the study?Dr. Soylemez Wiener: The main finding is that evaluation of pulmonary nodules to determine whether or not they are cancerous is inconsistent with clinical practice guideline recommendations in almost half of cases, suggesting there is room for improvement in clinical care of these patients. Patients with pulmonary nodules are sometimes evaluated more aggressively than they should be (18%), which can cause harms to patients from unnecessary invasive tests (biopsies or surgery) or unneeded radiation exposure from imaging studies. Still more patients (27%) are followed less aggressively than they should be, which in the worst case scenario could lead to delays in the diagnosis and treatment of cancer. It is particularly important to improve care of these patients now, because new guidelines from the US Preventive Services Task Force recommend CT screening for lung cancer screening, which often finds pulmonary nodules that require evaluation. (more…)
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