MedicalResearch.com: Interview with Sirimon Reutrakul MD
Section of Endocrinology Department of Medicine
Rush University Medical Center
Chicago, Illinois 60612
MedicalResearch.com: What are the main findings of the study?Answer: We found a strong association between obstructive sleep apnea and gestational diabetes mellitus. In pregnant women diagnosed with gestational diabetes, the risk of obstructive sleep apnea is increased nearly 7-fold compared to those without gestational diabetes. In addition, we found that in non-diabetic women, pregnancy is associated with more disrupted sleep.
MedicalResearch.com Interview with Dr. Anthony Bavry, MD MPH
Assistant Professor of Medicine
University of Florida
1600 SW Archer Road
Gainesville, FL 32610
MedicalResearch.com: What are the main findings of the study?Dr. Bavry: Among individuals with chronic stable coronary artery disease, it is possible to define a group who are at relatively low risk for adverse cardiovascular events.
MedicalResearch.com:Were any of the findings unexpected?(more…)
Medical Research.com Interview with:
Katrin Streckfuss-Boemeke, PhD
Department of Cardiology and Pneumology
Heart Research Center Göttingen (HRCG)
University Medical Center Göttingen
37075 Göttingen Germany
Medical ResearcH.com: What are the main findings of the study?Answer: The main finding is that human induced pluripotent stem cells (hiPSCs) can be generated from different somatic cell sources including bone marrow mesenchymal stem cells (MSCs), hair keratinocytes, and skin fibroblasts, but MSCs and fibroblasts are more easily reprogrammed than keratinocytes.
All generated hiPSCs can differentiate into cardiomyocytes with an efficiency ranging from 3 to 42%. However, the highest cardiac differentiation efficiency was achieved from MSC-derived hiPSCs.
Although the cardiac differentiation efficiency varied among different cell lines, there is no significant difference in the functionalities of cardiomyocytes derived from different hiPSC lines.
MedicalResearch.com: Interview withLeonardo Trasande, MD, MPP
Departments of Pediatrics, Environmental Medicine, Population Health, and Medicine, School of Medicine, and Wagner School of Public Service, and Steinhardt School of Culture, Education, and Human Development, Department of Nutrition
MedicalResearch.com: What are the main findings of the study?Answer: We detect associations of urinary phthalate metabolites in a cross-sectional study of US adolescents. The association is highly robust to multiple sensitivity analyses, and specific to phthalates commonly found in food. Further, longitudinal study of dietary phthalate exposures is needed.
MedicalResearch.com: Interview with: Therese Koops Grønborg PhD student/ph.d.-studerende, MSc
Section of Biostatistics/Sektion for Biostatistisk
Department of Public Health/Institut for Folkesundhed
Bartholins Allé 2, DK-8000 Aarhus C, Denmark
MedicalResearch.com: What are the main findings of the study?Answer: There are three important findings in our study.
We estimated a population-based Autism Spectrum Disorder (ASD) sibling recurrence risk relative to the background population and found an almost seven-fold increase. While this indeed is an increased risk, it is also lower than what other recent studies have suggested.
We also compared the relative recurrence risk for full and maternal/paternal half siblings and found a lower relative recurrence risk in half siblings than in full siblings, which supports the genetic pathway to ASD. The recurrence risk for maternal half siblings is still higher than for the background population suggesting that factors unique to the mother, such as the intrauterine environment and perinatal history, may contribute to ASD.
Last, but not least, we estimated the time trends in the relative recurrence risk. While the ASD prevalence has been increasing for several years, we found no time trends in the relative recurrence risk, suggesting that the factors contributing to the risk for ASDs recurrence in siblings (perhaps a combination of genes and environment) have not changed over time.
MedicalResearch.com Interview with:
Dr.Csaba P. Kovesdy MD FASN.
The Fred Hatch Professor of Medicine
Director, Clinical Outcomes and Clinical Trials Program in Nephrology
University of Tennessee Health Science Center
Chief of Nephrology
Division of Nephrology, Memphis VA Medical Center
MedicalResearch.com: What are the main findings of the study?Dr. Kovesdy: In this study of >650,000 US veterans with CKD we found that categories of lower SBP/DBP combinations are associated with lower mortality only as long as the DBP component remains above a threshold of approximately 70 mmHg, and that patients with BP values in the range of 130-159/70-89 mmHg had the lowest mortality. Patients who might be considered to have “ideal” blood pressure (<130/80) actually had increased mortality due to the inclusion of individuals with low systolic and diastolic blood pressures.
MedicalResearch.com Interview with:Leora I. Horwitz, MD, MHSSection of General Internal Medicine, Department of Medicine,
Yale School of Medicine,
Center for Outcomes Research and Evaluation,
Yale–New Haven Hospital, New Haven, Connecticut
MedicalResearch.com: What are the main findings of the study?Answer: We interviewed nearly 400 older patients who had been admitted with heart failure, pneumonia or heart attack within one week of going home from the hospital. We also reviewed the medical records of 377 of the patients. We found, for example, that:
40% of patients could not understand or explain the reason they were in the hospital in the first place;
A fourth of discharge instructions were written in medical jargon that a patient was not likely to understand;
Only a third of patients were discharged with scheduled follow-up with a primary care physician or cardiology specialist;
Only 44% accurately recalled details of their appointments.
In other words, we didn't do a very good job of preparing patients for discharge, and perhaps as a result, patients were pretty confused about important things they needed to know after they were home.
We just published a companion paper in the Journal of Hospital Medicine last week in which we looked at the discharge summaries for the same patients - that is, the summary of the hospitalization that is meant to help the outpatient doctor understand what happened in the hospital. Turns out we were just as bad at communicating with doctors as with patients - we focused on details of the hospitalization rather than what needed to happen next or what needed to be followed up, and in a third of cases, we didn't even send the summary to the outpatient doctor. In fact out of 377 discharge summaries, we didn't find a single one that was done on the day of discharge, sent to the outpatient doctor, and included all key content recommended by major specialty societies.
MedicalResearch.com Interview with:
Sandra Ryeom, PhD,
Assistant professor of Cancer Biology,
Perelman School of Medicine, University of Pennsylvania
MedicalResearch.com: What are the main findings of the study?Answer: We identified an important pathway (calcineurin-NFAT-Angiopoeitin2) in the vasculature of early metastatic lung lesions that is critical for promoting lung metastases.
MedicalResearch.com: Were any of the findings unexpected?Answer: Since there is limited understanding of regulation of tumor angiogenesis at metastatic sites, identification of the calcineurin pathway and a newly identified target of calcineurin-NFAT signaling was all unexpected.
MedicalResearch.com Interview with: Dr. Finlay McAlister
Division of General Internal Medicine
Patient Health Outcomes Research and Clinical Effectiveness Unit
University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ont.
MedicalResearch.com: What are the main findings of the study?Answer: Heart Failure carries a high risk of readmission/death in the first 30 days after hospital discharge (approximately 20%) - even in this cohort of patients with first time diagnosis of heart failure who were discharged home to the community. Patients who do not have an outpatient physician follow-up visit in the first 30 days after discharge have poorer outcomes at 30 days, 3 months, 6 months, and 12 months. Although outcomes are similar for patients who see an unfamiliar or a familiar physician in that first 30 days, over the longer term follow-up with a familiar physician is associated with better outcomes than follow-up with unfamiliar physician(s).
MedicalResearch.com Interview with:John P. Cooke MD PhD
Chair, Department of Cardiovascular Sciences
Director, Center for Cardiovascular Regeneration
Houston Methodist Research Institute
6670 Bertner St MS: R6-414, Houston, TX 77030
MedicalResearch.com: What are the main findings of the study?Answer: We discovered that the proton pump inhibitors PPIs), as a class, impair vascular relaxation. The PPIs have this effect by suppressing the activity of a key enzyme required for cardiovascular health. The enzyme is known as DDAH (for dimethylarginine dimethylaminohydrolase). This enzyme is critical in clearing ADMA (asymmetric dimethylarginine) from tissues and the circulation. Because ADMA is an endogenous inhibitor of nitric oxide synthase, accumulation of ADMA impairs vascular relaxation and vascular homeostasis. Previously, we and others have found that, by inhibiting endothelium-derived nitric oxide, ADMA accelerates vascular disease in preclinical models. In humans, ADMA is linked to the severity of vascular disease, and is an independent risk factor for major adverse cardiovascular events (MACE). Thus, the effect of PPIs to inhibit DDAH would be anticipated to impair cardiovascular health, and to increase the risk of MACE.
MedicalResearch.com Author Interview:
Steven A. Narod, MD Women’s College Research Institute
790 Bay St, 7th Floor
Toronto, ON, M5G 1N8 Canada
MedicalResearch.com: What are the main findings of the study?Answer:We found that the survival of women with breast cancer and a brca1 mutation was similar to that of women with breast cancer and no mutation.
MedicalResearch.com: Orly Vardeny, PharmD, MS
Associate Professor of Pharmacy and Medicine
University of Wisconsin-Madison
MedicalResearch.com What are the main findings of the study?Answer: We performed a post-hoc analysis of the RALES study to assess rates of hyperkalemia and hypokalemia among African American (AA) and non-AA study participants, and examined clinical outcomes by race. We found that AA had less overall increases in potassium compared to non-AA, and exhibited less hyperkalemia with spironolactone. AA subjects were also found to have higher rates of hypokalemia, even among those randomized to spironolactone. Moreover, AA participants appeared to derive less clinical benefit from spironolactone. While non-AA demonstrated reduced risk for death and the combined endpoint of death or heart failure hospitalizations when randomized to spironolactone, African Americans did not derive benefit, and the risk of these outcomes were not different between spironolactone and placebo among AA.
MedicalResearch.com Interview with: Michiyo Yamakawa MHSc
Department of Epidemiology
Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences,
MedicalResearch.com: What are the main findings of the study?Answer: We found that breastfeeding was associated with decreased risk of overweight and obesity at the age of 7 and 8 years compared with formula feeding. Moreover, the protective associations for obesity were greater than those for overweight.
MedicalResearch.com Interview with: Dr. Ramon Trullas
CSIC Institute of Biomedical Research of Barcelona
MedicalResearch.com: What are the main findings of the study?Answer: The findings reported in this manuscript that we consider can be underscored are:
1) Asymptomatic subjects at risk of developing sporadic Alzheimer’s disease (AD), as well as symptomatic patients diagnosed with probable sporadic AD show a low concentration of circulating cell free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF).
2) Pre-symptomatic subjects carrying pathogenic PSEN1 gene mutations which cause early onset familial AD, also exhibit low mtDNA content in CSF.
3) Reduced mtDNA content in CSF occurs in preclinical PSEN1 mutation carriers at least one decade before patients are expected to manifest clinical signs of dementia and well before any alteration in currently known AD biomarkers.
4) Low mtDNA content in CSF distinguishes patients diagnosed with AD from either controls or patients with fronto-temporal lobar degeneration.
These findings indicate that the amount of circulating cell-free mtDNA content in CSF may be a novel biomarker for the early detection of AD in the preclinical stage of AD. Moreover, the observation that low mtDNA content in the CSF is associated with both sporadic and familial forms of AD suggests that, independently of the etiology, regulation of mtDNA content is a converging factor in the pathophysiology of AD.
MedicalResearch.com Interview with: Steve Estus PhD
Dept. of Physiology University of Kentucky
Office: Room 332 Sanders-Brown Building
800 S. Limestone Street
Lexington, KY 40536-0230
MedicalResearch.com: What are the main findings of the study?Answer: We report evidence for the function of a Alzheimer's genetic risk factor. This protective allele of the polymorphism decreases the splicing efficiency of exon 2 in CD33, a receptor protein that regulates microglial activation. Loss of exon 2 appears to produce a dormant CD33 protein, resulting in increased microglial phagocytosis activity. Overall, these findings confirm and extend recent papers in Neuron and Nature Neuroscience (discussed further in our report) that described decreased CD33 activity with the protective SNP allele.
MedicalResearch.com Interview with: Rakesh M. Suri MD, D.Phil.
Mayo Clinic College of Medicine, Rochester, Minnesota
MedicalResearch.com: What might clinicians “take home” from this study?
a. The contemporary outcomes of surgical correction of mitral regurgitation are excellent based upon results observed in this large multinational, multi-institutional study, Mitral valve surgery now has a low peri-operative risk of death or complications, and a very high likelihood of saving a patient’s own heart valve (>90% - repair); thereby avoiding the need for replacement with an artificial valve substitute.
b. All patients with severe degenerative mitral regurgitation are at risk for heart failure and/or death when surgical correction is delayed. A safe period of “watchful waiting” in those with severe mitral regurgitation due to flail leaflets, even in the absence of traditional Class I triggers for surgery (symptoms or left ventricular dilation/dysfunction) does not exist.
c. Prompt mitral valve surgery within months following the diagnosis of severe degenerative mitral regurgitation, even in those without symptoms, is associated with important and sustained long term benefits including a 40% decrease in death and 60% less heart failure risk, sustained many years following surgical intervention
MedicalResearch.com Interview with:Dr. Takahisa Fujikawa, MD, PhD, FACS.
Director, Dept of Surgery, Kokura Memorial Hospital,
3-2-1 Asano, Kokurakita-ku, Kitakyushu, Fukuoka 802-8555, JAPAN.
MedicalResearch.com: What are the main findings of the study?Answer:
A total of consecutive 1,075 patients undergoing abdominal laparoscopic surgery between 2005 and 2011, including 715 basic and 360 advanced laparoscopic surgeries, were reviewed. The perioperative management protocol consists of interruption of antiplatelet therapy (APT) one week before surgery and early postoperative re-institution in low thromboembolic risk patients (n=160, iAPT group), whereas preoperative APT was maintained in patients with high thromboembolic risk or emergent situation (n=52, cAPT group). Perioperative and outcome variables of cAPT and iAPT groups, including bleeding and thromboembolic complications, were compared to those of patients without APT (non-APT group, n=863).
No case suffering excessive intraoperative bleeding due to continuation of APT was observed. There were 10 postoperative bleeding complications (0.9%) and 3 thromboembolic events (0.3%), but surgery was free of both complications in cAPT group. No significant differences were found between the groups in operative blood loss, blood transfusion rate, and the occurrence of bleeding and thromboembolic complications.
Multivariable analyses showed that multiple antiplatelet agents (p=0.015) and intraoperative blood transfusion (p=0.046) were significant prognostic factors for postoperative bleeding complications. Increased thromboembolic complications were independently associated with high New York Heart Association class (p=0.019) and history of cerebral infarction (p=0.048), but not associated with APT use. (more…)
MedicalResearch.com Interview with: Daniela Di Giuseppe
Division of Nutritional Epidemiology
Institute of Environmental Medicine
Stockholm 171 77, Sweden
MedicalResearch.com: What are the main findings of the study?Answer: Women whose long-term intake of omega 3 PUFAs exceeded 0.21 g a day, equivalent to at least one serving of fatty fish or four servings of lean fish a week, had half the risk (52% lower) of rheumatoid arthritis of women who consumed less.
MedicalResearch.com Interview with: Martin Köbel M.D.
Assistant Professor, Pathology and Lab Medicine
Calgary Laboratory Services
9 3535 Research Road Nw
Calgary, Alberta T2L 2K8 Canada
MedicalResearch.com: What are the main findings of the study?Answer: Ovarian carcinomas are now divided into five histological types, which differ with respect to biology and clinical behaviour. However, the histological type assessment varies from center to center. Our study emphasizes the need for a standardized method to identify them. Until such consistent approach is established, histological types from various centers may not comprise the same entities and studies will give inconsistent results.
MedicalResearch.com Interview with:Marina Klein, MD, MSc, FRCP(C)
Associate Professor of Medicine
McGill University Health Centre
Division of Infectious Diseases and Chronic Viral Illness Service
3650 Saint Urbain
Montreal, Quebec H2X 2P4
Disease in HIV–Hepatitis C Coinfection: A Longitudinal Cohort Analysis MedicalResearch.com: What are the main findings of the study?Dr. Klein: We showed that people with HIV and hepatitis C infection who smoked marijuana did not tend to progress more rapidly to liver fibrosis, liver cirrhosis or end-stage liver disease, even with increasing numbers of joints smoked per week. Previous studies that reported that marijuana was harmful to the liver were likely biased because they did not ensure that marijuana smoking occurred before the development of liver problems.
Prof. Steve Allen
Professor of Paediatrics and International Health; RCPCH International Officer and David Baum Fellow
Room 314, The College of Medicine, Swansea University,
Swansea, SA2 8PP, UK.
MedicalResearch.com: What are the main findings of the study?Answer: Overall, diarrhoea occurred in just over 10% participants and diarrhoea caused by C. difficile in about 1%. These outcomes were equally common in those taking the microbial preparation and those taking placebo.
Other outcomes (e.g. common GI symptoms, length of hospital stay, quality of life) were also much the same in the two groups. So, there was no evidence that the microbial preparation had prevented diarrhoea or had led to any other health benefit.
In agreement with previous research, serious adverse events were also similar in the two groups – so we found no evidence that the microbial preparation caused any harm.
MedicalResearch.com Interview with: Rebecca M Reynolds, Professor of Metabolic Medicine
Endocrinology Unit, BHF/University Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH14 6TJ, UK
MedicalResearch.com: What are the main findings of the study?Answer: We found that the adult offspring of women who were obese at the start
of pregnancy were 35% more likely to die prematurely than offspring of
normal-weight women. We also found that children born to mothers who
were overweight when they became pregnant had an 11% increased risk of
premature death. Adult offspring of mothers who were obese were also
at increase risk of hospital admissions for cardiovascular events.
MedicalResearch.com Interview with: Dr. Richard Adair
Medicine Clinic, 2800 Chicago Avenue South, #250, Minneapolis, MN 55407
MedicalResearch.com: What are the main findings of the study?Answer: Layperson "care guides" working in primary care offices can help chronic disease patients reach recommended care goals at a reasonable cost.
MedicalResearch.com Interview with: Miles D. Witham, PhD
Aging and Health, University of Dundee, Dundee, United Kingdom
MedicalResearch.com: What are the main findings of the study?Answer: We gave high dose vitamin D3 (100,000 units) or placebo every 3 months to people aged 70 or over, who all had isolated systolic hypertension (ISH). The main focus of the trial was to test whether vitamin D supplementation could reduce blood pressure in this group of patients – this pattern of blood pressure, whether the systolic (top number) is high, and the diastolic (bottom number) is normal, is very common in older people. Previous studies have suggested a link between low vitamin D levels and higher blood pressure, but no trial has yet tested this idea in older patients with ISH.
Despite the treatment causing a significant increase in circulating vitamin D levels, we saw no significant reduction in blood pressure with vitamin D supplementation, despite the trial running for a year. We tested whether certain groups might still benefit – e.g. those with very high blood pressure or very low vitamin D levels, but even these groups did not show a reduction in blood pressure.
We also tested whether vitamin D supplementation reduced the health and stiffness of arteries – both important predictors of future heart attack or stroke. Unfortunately, vitamin D did not affect these measures either, and didn’t reduce cholesterol or glucose levels.
On the more positive side, vitamin D supplements did appear safe, and the number of falls in the vitamin D group was slightly lower than in those people who received placebo. This is reassuring, as an earlier study (Sanders et al) had suggested that very high doses of vitamin D might make falls more likely, in contrast to previous low dose studies that show a protective effect of vitamin D against falls.
MedicalResearch.com: Interview with Peter Nordström Ph.D
Umeå University in Sweden
MedicalResearch.com: What are the main findings of the study?Answer: I would say that the main finding of our study is the nine independent risk factors identified for Young-Onset Dementia.
MedicalResearch.com: Interview with Alice Chen-Plotkin, MD
Department of Neurology
University of Pennsylvania School of Medicine
MedicalResearch.com: What are the main findings of the study?Answer: Parkinson's disease (PD) is an incurable neurodegenerative disease. Many neurons die, but the neurons that make dopamine (dopaminergic neurons) are particularly vulnerable. We think that the disease actually starts well before the time when people show clinical symptoms. We were therefore interested in finding proteins from the blood that correlated with better or worse dopaminergic neuron integrity. Since it's hard to access the dopaminergic neurons directly, we looked at a tracer that labels the ends of the dopaminergic neurons in people who do not have Parkinson's disease but are at high risk for developing it, and we also looked at the age at onset of PD in people who are already symptomatic. Screening just under 100 different proteins from the blood, we found that higher plasma levels of apolipoprotein A1 (ApoA1) were correlated with better tracer uptake in the people who did not yet have PD, and with older ages at onset in the people who already had PD. These data suggest that plasma ApoA1 may be a marker for PD risk, with higher levels being relatively protective.
MedicalResearch.com Interview with: Tina Costacou, Ph.D.
Assistant Professor of Epidemiology
University of Pittsburgh
MedicalResearch.com: What are the main findings of the study?Answer: The generation of reactive oxygen species is a natural and essential feature of human physiology, although excess production of free radicals has been related to the development and progression of diabetes complications. Simply put, a “balance” is required between the pro- and the anti-oxidant forces to maintain good health. Our aim in this study of people with type 1 diabetes was to evaluate whether an individual’s antioxidant vitamin levels in blood can modify the heart disease risk conferred by increased oxidative stress.
Indeed, we observed that higher concentrations of α-tocopherol (a form of vitamin E) in blood overtime were related to lower risk of developing coronary heart disease, whereas greater oxidative stress (as measured by urinary 15-isoprostane F2t) was related to greater risk of disease. Interestingly, the ratio of α-tocopherol to urinary 15-isoprostane F2t, which we used as a measure of an individual’s ability to respond to / counteract oxidative stress, also was a strong predictor of subsequent coronary heart disease development.
Our findings thus point to a different way of assessing a person’s risk for developing disease. Currently in clinical practice, physicians assess an individual’s risk factors (e.g. oxidative stress) for a pathologic condition (e.g. heart disease) to make inferences about the person’s risk to develop this condition and take preventive measures if needed (e.g. assign a treatment regimen). Our findings, however, suggest that an individual’s risk for disease may be better evaluated by simultaneously assessing factors representing the risk and those representing protection from or resistance to the risk. Thus, though two individuals may have similarly high levels of oxidative stress, there may be differences in the concentration of antioxidant vitamins between the two (and vice versa), which may put them at different risk categories, with one person potentially requiring vitamin supplementation while the second not needing to use supplements.
MedicalResearch.com Interview with: Kornelia Polyak, MD, PhD
Professor of Medicine
Dana-Farber Cancer Institute
Harvard Medical School
Boston, MA 02215
MedicalResearch.com: What are the main findings of the study?Dr. Polyak: We found that when comparing normal breast tissue of women who have not had children (nulliparous) and those who had children in their early 20s, the largest changes are in breast epithelial progenitors. The frequency of these cells is lower in parous women (women who had children) and the properties are also altered in a way that they are less likely to proliferate. Women with high risk of breast cancer, such as BRCA1 and BRCA2 mutation carriers, have very high frequency of these cells, and also parous women who did get cancer have more than those who did not. These results indicate that the frequency of these cells may predict breast cancer risk.
MedicalResearch.com Interview with: Dr. Orit Twito
Department of Endocrinology, Hillel Yaffe Medical Center, Hadera, Israel
MedicalResearch.com: What are the main findings of the study?Answer: An HbA1c level above 7.5% (58mmol/mol) is associated with increased risk for all-cause mortality and with a lower revascularization rate in elderly patient with new onset diabetes mellitus. HbA1c above 8.5 %( 69nmol/mol) was associated with even higher mortality rate, although this difference did not reach statistical significance. (more…)
MedicalResearch.com Interview with: Gerdien Dalmeijer
Postdoc | Julius Centrum | Universitair Medisch Centrum Utrecht
Kamernummer STR. 6.119 | Huispostnummer STR. 6.131 |
Postbus 85500| 3508GA UTRECHT
MedicalResearch.com: What are the main findings of the study?Answer: The main findings of our prospective study among type 2 diabetes patients show that high circulating desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) concentrations, reflecting a poor vitamin K status, are associated with increased cardiovascular disease risk, especially with peripheral arterial disease and heart failure. These results suggest that a poor vitamin K status is associated with increased cardiovascular disease risk.
MedicalResearch.com: Were any of the findings unexpected?
Answer: To our knowledge, this is the first study investigating the association of circulating MGP species with the risk of cardiovascular events; thus far only the association between dp-ucMGP and calcification has been investigated. Several studies but not all have shown that high dp-ucMGP concentrations are associated with increased calcification. We now extend these findings by showing the high circulating dp-ucMGP concentration is also associated with increased CVD risk, especially with peripheral arterial disease and heart failure.
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