Ovarian Cancer

Dr. Anil Sood MD Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer CenterMedicalResearch.com Interview with:
Dr. Anil Sood MD

Professor of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Sood: What is the background for this approach? What are the main findings? The background involves several different issues: management approaches have varied quite a bit across the US; definition of “optimal” surgery and rates of complete surgical removal of tumor (R0) have also varied. It is quite apparent that patients who benefit the most from surgery upfront are those who have R0 resection. To address these issues, we have implanted a much more personalized approach whereby patients with suspected advanced ovarian cancer undergo laparoscopic assessment using a validated scoring system (based on the pattern and extent of disease noted during laparoscopic assessment); patients with a score <8 undergo upfront debulking surgery and those with a score ≥8 receive neoadjuvant chemotherapy followed by surgery after 3-4 cycles. To date, this program has been fully implemented as part of the Moonshot Program at M.D. Anderson. This program has already resulted in several benefits – for example, prior to this algorithm being put into place among all patients with suspected advanced ovarian cancer, around 20% would have R0 resection; after the implementation of the algorithm, of those going to upfront debulking surgery (after laparoscopic assessment), almost 85% of times R0 resection can be achieved. Also, this method of treatment is allowing for new and innovative clinical trial designs. Continue reading

Cognitive Function Test Useful In Cultural and Language Diverse Populations

Dr. Raza M. Naqvi, MD, FRCPC Assistant Professor of Medicine Division of Geriatric Medicine Western University Victoria Hospital London, ONMedicalResearch.com Interview with:
Dr. Raza M. Naqvi, MD, FRCPC
Assistant Professor of Medicine
Division of Geriatric Medicine
Western University
Victoria Hospital London, ON

Medical Research: What is the background for this study? What are the main findings?

Dr. Naqvi: The rates of dementia are rising worldwide. Currently we have over 35 million individuals with dementia in the world and this number will triple to over 100 million by 2050 according to the WHO. Many of these cases are in countries where English is not the first language and thus it is important to ensure that the diagnostic and assessment tools we use are valid in the populations being assessed.

The Rowland Universal Dementia Assessment Scale (RUDAS) was developed in Australia in 2004 specifically to address the challenges of detecting cognitive impairment in culturally and linguistically diverse populations. This assessment tool is a brief questionnaire that clinicians can use as part of their initial assessment in those with memory loss or cognitive decline. It is freely available online (Search ‘RUDAS’) and takes less than 10 minutes for a clinician to complete with the individual being assessed.

Our study was a systematic review and meta-analysis of the RUDAS which aimed to clarify the diagnostic properties of the test and see how it compares to other similar tests that are available.

Through our detailed search of the literature we found 11 studies including over 1200 patients that assessed the RUDAS. The studies showed a combined sensitivity of 77.2% and specificity of 85.9%. This means that a positive test increases one’s likelihood of having dementia more than 5-fold and a negative test decreases their likelihood by 4-fold.

Across the various studies, the Rowland Universal Dementia Assessment Scale performed similarly to the Mini-Mental State Examination (MMSE), the most commonly used cognitive assessment tool worldwide. The RUDAS appeared to be less influenced by language and education than the MMSE. Continue reading

MAYO Formula May Be Better Predictor of Mortality in Kidney Disease Patients With Acute Coronary Syndrome

Alon Eisen, MD Cardiology Department Rabin Medical Center Petah Tikva Israel Research Fellow in Medicine Brigham and Women's HospitalMedicalResearch.com Interview with:
Alon Eisen, MD
Cardiology Department Rabin Medical Center
Petah Tikva Israel
Research Fellow in Medicine
Brigham and Women’s Hospital

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Elsen: It is well established that renal dysfunction is associated with worse prognosis among patients with acute coronary syndromes (ACS). Although there are several formulas to estimate glomerular filtration rate (eGFR), as a proxy of renal function, data regarding risk stratification in ACS patients using the different formulas remain incomplete. In this study, we aimed to determine the risk implications of five different eGFR formulas in a contemporary nation- wide cohort of consecutive ACS patients and to investigate which formula better predicts mortality in these patients.

Our study revealed several findings.

First, despite the significant and strong correlation between creatinine clearance or eGFR values using all five formulas, the proportion of patients categorized into the different renal function groups varied considerably, depending on the formula used. The choice of formula used influenced the stratification of patients into the different renal function categories, including the dichotomous distinction of significant versus non-significant renal dysfunction (eGFR<60 ml/min per 1.73 m²).

Second, as prior studies, we demonstrated an increased mortality among ACS patients with renal dysfunction.

Third, although the trend for increased mortality with worse renal function was demonstrated for all formulas, the absolute mortality rates varied considerably for each renal function category using the different formulas.

Last, although creatinine clearance or eGFR were found to be an independent predictor for short-term and long-term mortality using all five formulas, only the MAYO formula had better accuracy in predicting mortality relative to the MDRD, suggesting that it may be a better prognosticator among ACS patients.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Elsen: Although MDRD, CG, and CKD-EPI are most commonly used by clinicians to calculate eGFR or creatinine clearance, currently there are sparse data regarding the ability of eGFR formulas to predict clinical outcomes in patients with ACS. Our study emphasizes that although there is a variability between different eGFR formulas used in clinical practice, mortality in ACS patients increases as renal function worsens, regardless of the formula used and in all renal function categories. Furthermore, there is a substantial group of patients whose renal function is “discordant”, meaning that they have renal dysfunction according to some eGFR formulas but no renal dysfunction according to other formulas. As shown, these patients have worse outcomes, as compared to patients without renal dysfunction according to all eGFR formulas. Although it is beyond the scope of our study, we believe that these patients, as well as all other patients with renal dysfunction, should be treated by the best available guidelines recommended therapies.

Finally, we have aimed to answer the question which eGFR formula best assesses risk in ACS patients, and although we have demonstrated that only the MAYO formula had better accuracy in predicting mortality relative to the MDRD, this finding deserves further validation in future studies.

Citation:
The Proxy of Renal Function that Most Accurately Predicts Short- and Long-Term Outcome Following Acute Coronary Syndrome

 Katia Orvin, Alon Eisen, Ilan Goldenberg, Ateret Farkash, Nir Shlomo, Natalie Gevrielov-Yusim, Zaza Iakobishvili, David Hasdai
American Heart Journal February 23 2015
http://dx.doi.org/10.1016/j.ahj.2015.01.012

 

MedicalResearch.com Interview with: Alon Eisen, MD, Cardiology Department Rabin Medical Cente  Petah Tikva Israel (2015). MAYO Formula May Be Better Predictor of Mortality in Kidney Disease Patients With Acute Coronary Syndrome 

Study Weighs Risks/Benefits of Oral Anticoagulation for Atrial Fibrillation in Hemodialysis Patients

Dr. Simonetta Genovesi MD Department of Health Science University of Milano-Bicocca, Monza Italy Nephrology Unit San Gerardo Hospital, Monza, ItalyMedicalResearch.com Interview with: Dr. Simonetta Genovesi MD
Department of Health Science
University of Milano-Bicocca, Monza
Italy Nephrology Unit
San Gerardo Hospital, Monza, Italy

MedicalResearch: What is the background for this study?  

Dr. Genovesi: The prevalence of atrial fibrillation (AF) in patients
with end-stage renal disease (ESRD) on hemodialysis (HD)
is high. The presence of atrial fibrillation increases the risk of
thrombo-embolic stroke in the general population. The
treatment of choice for reducing thrombo-embolic risk in
AF patients is oral anticoagulant therapy (OAT) with
warfarin. However, the use of warfarin in HD patients is
controversial because of the high risk of bleeding and the
fact that it is not demonstrated a clear protection
against the risk of stroke in this population. The purpose
of the study was to prospectively evaluate the effect of
OAT on the risk of mortality, stroke and bleeding in HD
population.

MedicalResearch: What are the main findings?  

Dr. Genovesi: In our hemodialysis population oral anticoagulant therapy does not increase the risk of total mortality, while antiplatelet agents are associated
with an increased risk of death of about 70%. The
continuous use of warfarin tends to be associated with
improved survival as compared with individuals who
discontinued the medication during the follow-up, but the
incidence of thrombo-embolic events is not different in
OAT subjects as compared with those who do not take it.
Moreover, bleeding events are more frequent in patients
taking warfarin, although the maintenance over time of an
INR in the therapeutic range wards against the risk of
bleeding.
Continue reading

Many Patients With Heart Failure Report Impairment of Daily Activities

dr-shannon-dunlayMedicalResearch.com Interview with:
Shannon M. Dunlay, M.D. M.S.
Advanced Heart Failure and Cardiac Transplantation
Assistant Professor of Medicine and Health Care Policy and Research
Mayo Clinic Rochester
MedicalResearch: What is the background for this study?

Dr. Dunlay: Loss of mobility and independence can complicate the care of patients with chronic conditions such as heart failure, and can degrade their quality of life.  However, we have a very poor understanding of the burden of disability in patients with heart failure and how it impacts outcomes.  What are the main findings?  In this study, patients with heart failure were asked whether they had difficulty performing activities of daily living (ADLs)—these include normal activities that most people do in daily life such as eating, bathing, dressing, and walking.  Most patients with heart failure reported having difficulty with at least one ADL at the beginning of the study, and over 1/3 had moderate or severe difficulty with activities of daily living.  Patients who were older, female and had other chronic conditions such as diabetes, dementia and obesity had more difficulty with activities of daily living.  Patients that reported more difficulty with ADLs (worse mobility) were more likely to die and be hospitalized over time.  Some patients had a decline in function over time, and this was also predictive of worse outcomes.

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Cellular Energy Sensor Links Calorie Restriction With Healthy Aging

William Mair, Ph.D Assistant Professor Department of Genetics and Complex Diseases Harvard T. H Chan School of Public Health Boston, MA 02115MedicalResearch.com Interview with:
William Mair, Ph.D
Assistant Professor
Department of Genetics and Complex Diseases
Harvard T. H Chan School of Public Health
Boston, MA 02115

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Mair: Dietary restriction, the reduction of food intake without malnutrition has been known for 80 years to prolong lifespan in organisms ranging from single celled yeast to non human primates, and early signs suggest improvement of metabolic parameters in patients undergoing clinical trials. However, negative side effects associated with low calorie intake remain, and compliance and lifestyle factors make it an unappealing therapeutic. Since calorie restriction (CR) can have remarkable protective effects against multiple age onset diseases in mouse models – ranging from cancer to neurodegeneration to metabolic disease – finding molecular mechanisms though which calorie restriction functions might provide novel therapeutic targets that promote healthy aging. Using a model system, the nematode worm C. elegans, we show that perception of energy intake in the nervous system may be as critical for the effects of low energy on aging as actual calorie intake itself. Animals expressing an active form of a protein called AMPK, which is a cellular energy sensor, were long lived despite eating normally but this longevity could be turned off or on by changes to a neurotransmitter in just a few neurons. This suggests that therapeutic targets that modulate the perception of energy status in the nervous system might provide novel ways to gain the benefit of calorie restriction and promote healthy aging.

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HPV-16/18 Vaccine Provides Some Cross Protection To Other Cancer-Causing Subtypes

MedicalResearch.com Interview Invitation
Frank Struyf MD PhD
Director, Lead Clinical Development HPV vaccines at GlaxoSmithKline Biologicals GlaxoSmithKline Vaccines,
Rixensart, Belgium

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Struyf: Cervical cancer is the fourth most common cancer among women, with estimates from 2012 indicating that there are 528,000 new cases and 266,000 deaths each year worldwide, the majority of cases occurring in developing countries (reference: Globocan 2012 at http://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp). Persistent infection with oncogenic human papillomavirus (HPV) is a necessary condition for the development of invasive cervical cancer. HPV type 16 (HPV-16) and HPV-18 are found in approximately 70% of cases. We conducted the Papilloma Trial Against Cancer in Young Adults (PATRICIA), a multinational clinical trial in 14 countries in Europe, the Asia-Pacific region, North America, and Latin America and enrolled over 18,000 women. The trial showed that the HPV-16/18 AS04-adjuvanted vaccine not only prevented persistent infections and high-grade cervical lesions associated with HPV types 16 and/or 18 included in the vaccine, but also protected against some common related oncogenic HPV types not included in the vaccine. However, during the analysis of this trial, we also noticed that for some rare nonvaccine oncogenic HPV types, the vaccine efficacy against infections did not seem to match the efficacy against lesions associated with the same HPV type. To investigate this, we re-analyzed the samples from the trial using a different PCR method and found that the HPV PCR methodology used per protocol may have underestimated the efficacy for non-vaccine HPV types in cases of multiple infections. While these results do not replace the results generated according to the study protocol and included in the product label, they are reassuring, as they confirm the cross-protective efficacy of the HPV-16/18 vaccine against some HPV types related to those included in the vaccine.
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Epigenetics: More Than 30 Genes Affect Allergies and Asthma

Dr. Liming Liang PhD Assistant Professor of Statistical Genetics Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts Dr. Liming Liang PhD
Assistant Professor of Statistical Genetics
Departments of Epidemiology and Biostatistics,
Harvard School of Public Health, Boston, Massachusetts

 

Allergies affect 30% of the population and 10% of children suffer from asthma. Researchers in the United Kingdom, the United States, Sweden and Canada report in Nature that they have discovered more than 30 genes that have strong effects on Immunoglobulin E (IgE), allergies and asthma. IgE is the antibody that triggers allergic responses.

Amongst the genes are promising novel drug targets for treating allergies and asthma.

The researchers also found that the genes are concentrated in eosinophils, a white cell that ignites inflammation in asthmatic airways. The genes indicate when the eosinophils are activated and primed to cause the most damage.

Therapies that neutralise eosinophils already exist, but they are very expensive and only efficacious in some asthmatics. The newly found activation signals provide a possible means of directing treatments by predicting who will respond before starting therapy.

The research team used a novel technique to discover these genes, known as an “epigenome wide association study (EWAS)”. Epigenetic changes to DNA do not alter the underling sequence of the genetic code but can still be passed on as cells divide. They program the cells to form specialised types and tissues.

Epigenetic changes are most easily detected by alterations in methyl molecules that are attached at the side of the DNA chain. The researchers therefore concentrated on 27,000 methylation hotspots known as CpG islands that are positioned near many genes. They tested whether methylation levels in these islands in white cells from UK families with asthma was correlated with the level of the IgE in the blood.

To be sure of their positive results the researchers tested whether they held true in additional volunteers with high and low levels of IgE from Wales and further asthmatic families from Québèc.

They found strong associations between IgE and CGI methylation at 36 places in 34 genes. Some of the IgE-related genes were known to be present in eosinophil cells. The researchers therefore separated eosinophils from the blood of 24 subjects and showed all 34 genes to have their strongest effects in asthmatics with high IgE levels.

The paper shows the power of epigenome wide association analyses. Previous genetic association studies for IgE levels (looking at changes in DNA sequences) had only found genes that could explain 1% of individual differences in IgE, and did not discover any novel therapeutic targets or pathways underlying IgE regulation

By contrast the epigenetic associations accounted for more than 13% of IgE variation, 10 fold higher than that derived from traditional genetics. The associations identify novel potential drug targets for allergic diseases as well as biomarkers that may determine which patients will respond to particular therapies.

The increased power from epigenetic studies comes at the cost of controlling for many factors such as ageing and gender that are not important for simple genetic studies. The authors had to use advanced statistical techniques to be sure of their results, and as well as testing their validity in multiple additional sample sets.

The Freemasons’ Grand Charity, the Wellcome Trust and grants from the Québec Government provided the principal funding for the study.

Citation:

An epigenome-wide association study of total serum immunoglobulin E concentration

Liming Liang, Saffron A. G. Willis-Owen, Catherine Laprise, Kenny C. C. Wong, Gwyneth A. Davies, Thomas J. Hudson, Aristea Binia, Julian M. Hopkin, Ivana V. Yang, Elin Grundberg, Stephan Busche, Marie Hudson, Lars Rönnblom, Tomi M. Pastinen, David A. Schwartz, G. Mark Lathrop, Miriam F. Moffatt, William O. C. M. Cookson. An epigenome-wide association study of total serum immunoglobulin E concentration. Nature, 2015; DOI: 10.1038/nature14125

 

 

Oral Medication For Hepatitis C- HIV Combined Infection

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with:
Shyamasundaran Kottilil MBBS, PhD
Division of Infectious Diseases, Institute of Human Virology, University of Maryland, Baltimore
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Medical Research: What is the background for this study? What are the main findings?

Dr. Kottilil:  Due to shared routes of transmission, almost half of all HIV-infected patients also have HCV infection. Traditionally, interferon based therapies have resulted in lower cure rates of HCV in HIV-infected subjects. Treatment for HCV is rapidly changing from an injection (interferon) based therapy to oral well tolerated pill based therapy for a shorter duration.Our intention was to test whether a treatment regimen without the use of interferon and ribavirin can be effective in HIV/HCV infected patients.

Our study demonstrated that HIV/HCV connected patients without cirrhosis can be effectively treated with ledipasvir and sofosbuvir in 12 weeks. Overall 98% of patients were cured.

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Equation Helps Predict Mortality In Elderly Patients With Chronic Kidney Disease

Nisha Bansal MD MAS Assistant Professor Associate Program Director for Research Kidney Research Institute Division of Nephrology University of WashingtonMedicalResearch.com Interview with:
Nisha Bansal MD MAS
Assistant Professor
Associate Program Director for Research
Kidney Research Institute Division of Nephrology
University of Washington

Medical Research: What is the background for this study? What are the main findings?

Dr. Bansal: We pursued this study to develop a prediction equation for death among elderly patients with chronic kidney disease (CKD), a high-risk patient population that is often difficult to manage given competing risks of end stage renal disease (ESRD) vs. death. In this paper, we developed and validated a simple prediction equation using variables that are readily available to all clinicians.

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Bigger Breakfast, Smaller Dinner May Improve Glycemic Control

Professor Daniela Jakubowicz MD Diabetes Unit. E. Wolfson Medical Center Sackler Faculty of Medicine, Tel Aviv University and Tel Aviv Medical  Center IsraelMedicalResearch.com Interview with:
Professor Daniela Jakubowicz MD

Diabetes Unit. E. Wolfson Medical Center
Sackler Faculty of Medicine,
Tel Aviv University and Tel Aviv Medical  Center
Israel

MedicalResearch: What is the background for this study? What are the main findings?

Professor Jakubowicz: Obesity epidemic have lead to alarming rise of type 2 diabetes. It is estimated that more than 382 million worldwide have diabetes, predominately type 2 diabetes.

In these persons the cardiovascular disease is the leading complication, carrying 10 to 20-fold increase in the risk compared with persons without diabetes.

It has been shown that large glucose peaks after meals along the day, are strongly associated with increased a risk for cardiovascular complications.

Therefore the mitigation of glucose excursions after meals becomes a major target in the treatment of type 2 diabetes in order to improve glucose balance and prevent complications.

Accordingly, dietary modification focused on reduction post meal glucose peaks is needed. Even though still there is no consensus on which of the dietary strategies (i.e. low-fat diet, Mediterranean and low-carbohydrate, higher fiber, low GI glycemic index meals, etc.) is more suitable in improving post-meal glycemic responses along the day.

However in none of these interventions has been considered that modifying the meal timing pattern or daily caloric distribution, may lead to improved post-meal glycemic responses in type 2 diabetic patients.

The circadian clock genes existing in the pancreatic β-cells, gut, liver and in skeletal muscle, regulate the diurnal (circadian) oscillation of post-meal glucose responses. In fact, post-meal glycemia displays a clear diurnal variation: it is higher and more prolonged in the evening than in the morning. Meal timing schedule, on the other hand, exerts strong controlling influence on circadian clock regulation, thereby influencing the variation and degree of the post meal glycemic elevations. Indeed meal timing non-aligned with the clock gene circadian rhythms, such as breakfast skipping or high-energy intake at dinner, is associated with obesity, higher HbA1C and poor glycaemic control in type 2 diabetes.

To clarify the impact of meal timing and composition on overall post-meal glucose responses, we tested the effect of 2 isocaloric diets with different meal timing one with high energy breakfast (704 kcal), mid-sized lunch (600 kcal) and reduced dinner (200 kcal) and other with similar lunch but reduced breakfast (704 kcal) and high energy dinner(704 kcal).

The study clearly demonstrated that in type 2 diabetic patients, a diet consisting on high energy breakfast, and reduced dinner, resulted in significantly reduced glucose response after meals and lower overall plasma glucose levels along the entire day, when compared to a diet with the same caloric content but inverse distribution: breakfast (200 kcal) , lunch (600 kcal) and high energy dinner(704 kcal).

Moreover, when we compared the glucose response after high energy meal consumed at breakfast (700 kcal) versus in the dinner (700 kcal), it comes out that the glucose response was significantly higher after dinner than after breakfast. It shows that just by changing the time of the high energy meal we may achieve significant reduction in the glucose response.

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One Case Of Hepatitis C Transmitted From Shared Kidney Perfusion Machine

MedicalResearch.com Interview with:
Gwen Borlaug, CIC, MPH

Coordinator, HAI Prevention Program
Wisconsin Division of Public Health
Madison, WI 53702

MedicalResearch: What is the background for this study? What are the main findings?

Response: Healthcare-associated transmission of blood borne pathogens such as hepatitis C and B viruses is previously documented.

A single incident of HCV transmission likely occurred in an operating room where two kidneys were attached to the same perfusion machine at the same time, the two kidneys and the perfusion machine were shared between two operating rooms when patients were present in each operating room, and the two kidneys housed in the same perfusion machine were ultimately transplanted into two different recipients.

No additional healthcare-associated cases of hepatitis C virus transmission were identified among patients receiving hospital care at the same time and in the same locations as these transplant patients.

MedicalResearch: What should clinicians and patients take away from your report?

Response: Observing basic infection control practices is paramount to preventing transmission of blood borne pathogens in the healthcare setting.  Healthcare personnel should ensure strict adherence to protocols for cleaning and disinfecting used medical equipment and for safe injection practices.

 Citation:

Transmission of Hepatitis C Virus Associated with Surgical Procedures — New Jersey 2010 and Wisconsin 2011

 MMWR Weekly February 27, 2015 / 64(07);165-17

MedicalResearch.com Interview with: Gwen Borlaug, CIC, MPH (2015). One Case Of Hepatitis C Transmitted From Shared Kidney Perfusion Machine 

Melatonin Has Endocrine Risks For Children

Dave Kennaway, PhD Professor, Lloyd Cox Senior Research Fellow, Head Circadian Physiology Laboratory School of Paediatrics and Reproductive Health Robinson Research Institute, Faculty of Health Sciences, Medical School, University of Adelaide AustraliaMedicalResearch.com Interview with:
Dave Kennaway, PhD Professor

Lloyd Cox Senior Research Fellow,
Head Circadian Physiology Laboratory
School of Paediatrics and Reproductive Health
Robinson Research Institute,
Faculty of Health Sciences, Medical School,
University of Adelaide Australia

MedicalResearch: What is the background for this review? What are the main findings?

Dr. Kennaway: There is evidence that melatonin is being prescribed to for sleep disorders in children and adolescents who are developing normally despite the fact that there have been no properly designed studies on the effects of prolonged administration to children. In countries where melatonin has been registered, it is for use as a monotherapy for the short term treatment of primary insomnia, characterised by poor quality of sleep in patients who are aged 55 years and over. Use in Paediatrics is always “off-label”. After more than 50 years of melatonin research in animals there is overwhelming evidence that melatonin administration affects many organ systems. These include important effects on the reproductive organs of rodents, cats, ruminants and primates and melatonin is in fact registered as a veterinary drug for this purpose. The effects of melatonin, however, go beyond the potential reproductive consequences, including effects on cardiovascular, immune and metabolic systems. It is clear that many paediatricians, practitioners and parents are unaware of this.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Kennaway: Clinicians and patients need to recognise that melatonin is a hormone and not a drug developed for a specific purpose or illness. There have been no appropriate trials in children addressing the effects of prolonged administration of melatonin in children. Given the extensive literature on the role of the hormone in normal physiology it is unlikely that such trials would ever be approved. Should endocrine or other abnormalities appear in the future in children previously treated with melatonin it will not be tenable to argue that we were surprised.

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HIV Diagnosis and Care Critical To Preventing Spread Of Virus To Others

Jacek Skarbinski, MDMedicalResearch.com Interview With
Jacek Skarbinski, MD

Medical officer
Centers for Disease Control and Prevention

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Skarbinski: Previous research has indicated that HIV diagnosis and viral suppression are important prevention tools that can help reduce continued transmission. However, this analysis is the first to estimate precisely what proportion of transmission can be attributed to individuals engaged in 5 stages of HIV care – including those who are unaware of their infection, those who are retained in care, and those who have their virus under control through treatment.

Our analysis shows that more than 90 percent of new HIV infections in the United States could be averted by diagnosing people living with HIV and ensuring they receive prompt, ongoing care and treatment. It also shows that the further people progress in HIV care, the less likely they are to transmit their virus.

More specifically, the analysis shows that 30 percent of new HIV infections were transmitted from people who did know they were infected, highlighting the importance of getting tested. People who had been diagnosed were less likely to transmit their infection, in part because people who know they have HIV are more likely to take steps to protect their partners from infection.

Finally, the model suggests that simply being in care can help people living with HIV avoid transmission of their virus. According to the model, people who were engaged in ongoing HIV care, but not prescribed antiretroviral treatment, were half as likely (51.8 percent) as those who are diagnosed but not in care to transmit their virus. Being prescribed HIV treatment further lowers the risk that a person will pass the virus to others. People who were successfully keeping the virus under control through treatment were 94 percent less likely than those who did not know they were infected to transmit their virus. But, previous national estimates have indicated that just 30 percent of people with HIV have reached this critical step in care.

In short, this analysis validates the nation’s current prevention efforts, reminding us that HIV diagnosis and care improves the lives of people living with HIV and that it is also critical for reducing the chances of transmitting the virus to others.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Skarbinski: Both patients and clinicians should know that this is the latest in a growing body of evidence that prevention of new infections depends on reaching people who are HIV-positive with testing, care and treatment.

Once people know they have HIV, they take steps to prevent transmission to their partners. In fact, our study shows a 19 percent drop in the transmission rate after diagnosis – largely because people who found out they had HIV decreased the number of times they had sex without a condom with a negative partner.

After diagnosis, simply being in care can help prevent transmission by giving people living with HIV tools and information they can use to protect themselves and their partners. In addition to treatment, HIV care should include risk reduction counseling, STI screening and treatment, treatment for mental health and substance use disorders, and other prevention services.

The ultimate goal is to provide ongoing care and treatment so all people living with HIV can achieve viral suppression. U.S. guidelines now recommend that everyone diagnosed with HIV should get treatment, regardless of their viral load count. According to our model, people who are virally suppression are 94 percent less likely to transmit their virus than people who are unaware of their infections.

Bottom line: improving the health of people living with HIV is critical for both those with HIV and for those at risk for HIV.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Skarbinski: The study published today is the just the first in a series. Our next step is to expand the current model and assess the potential impact and costs of different interventions that target different steps of the HIV care continuum. The ability to compare the impact and associated cost of combinations of interventions, such as expanded HIV testing and improved retention in care, on prevention will be critical to guiding public health programs and improve HIV prevention. Moreover, we are also expanding the model to better understand patterns of transmission among particular sub-groups, such as men who have sex with men, to help guide prevention efforts.

You may also view the brief, 60-second video the CDC has put together highlighting the key data from the manuscript and putting them into the context of the nation’s prevention efforts here:  http://www.cdc.gov/nchhstp/newsroom/2015/HIV-Testing-infographic.html?s_cid=nchhstp-hcso-nwsrm-hiv-care-004.

Jacek Skarbinski, Eli Rosenberg, Gabriela Paz-Bailey, H. Irene Hall, Charles E. Rose, Abigail H. Viall, Jennifer L. Fagan, Amy Lansky, Jonathan H. Mermin. Human Immunodeficiency Virus Transmission at Each Step of the Care Continuum in the United States. JAMA Internal Medicine, 2015; DOI: 10.1001/jamainternmed.2014.8180

 

New Ninevalent HPV Vaccine Gives Greater Protection Against Cervical Cancer and Genital Warts

Elmar A. Joura, M.D Gynecologist University of ViennaMedicalResearch.com Interview with:
Elmar A. Joura, M.D
Gynecologist
University of Vienna

MedicalResearch: What are the main findings of this study?

Dr. Joura: This study demonstrates that the new ninevalent HPV vaccine induces a good immunogenicity against HPV 6/11/16/18 and gives a 97% protection against disease caused by HPV 31/33/45/52/58. This has a potential of a 90% reduction of cervical cancer and other HPV related cancers and a similar protection against genital warts. The full benefit is seen in persons without current HPV infection, this reinforces early vaccination against HPV. The safety profile was favourable.
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QuantiFERON-TB Gold Testing For Latent TB Eliminates False Positives From BCG Vaccination

Dr. Masae Kawamura MD Director and TB Controller City and County of San Francisco Department of Health Principal investigator for the Regional TB Training and Medical Consultation CenterMedicalResearch.com Interview with:
Dr. Masae Kawamura MD
Director and TB Controller
City and County of San Francisco Department of Health
Principal investigator for the Regional TB Training and Medical Consultation Center

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Kawamura:  The report in The Lancet presents the baseline phase of China’s first large-scale, multi-center prospective study of the epidemiology of latent tuberculosis infection. The comparison study of more than 21,000 patients allowed detailed analysis of demographics and risk factors, along with robust comparisons within subgroups. The study’s follow-up phase is now underway, and patients with Latent Tuberculosis Infection (LTBI) will be evaluated for rates of disease and associated risks. Generally, up to 10% of people with Latent Tuberculosis Infection will develop active, contagious Tuberculosis (TB) disease at some point.

The overall TB infection rate was 18.8% measured by QuantiFERON-TB Gold compared to 28% by the traditional tuberculin skin test (TST), a difference of over 125 million people (based on 2014 population estimates from China). Unlike the tuberculin skin test, positive rates of QuantiFERON-TB Gold were not related to prior Bacille Calmette-Guérin (BCG) vaccination, but correlated with background active TB and suspect rates, as well as known risks for TB. BCG vaccination is recommended to newborns by the World Health Organization (WHO) as a matter of TB control policy in many countries, including China.         Continue reading

NSAIDS After Heart Attack Increase Risk of Bleeding and Further Heart Attacks

MedicalResearch.com Interview with:
Anne-Marie Schjerning Olsen, MD, PhD Department of Cardiology Gentofte Hospital, University of Copenhagen DenmarkAnne-Marie Schjerning Olsen, MD, PhD
Department of Cardiology
Gentofte Hospital, University of Copenhagen
Denmark

MedicalResearch.com: What is the background for this study?

Dr. Olsen: The question addressed in the study was: Do people who have had a myocardial infarction (heart attack) and are who taking drugs (known as antithrombotics) to reduce their risk of further heart attacks have an increased risk of serious bleeding, especially gastrointestinal bleeding, and of further heart attacks if they also take painkillers known as non-steroidal anti-inflammatory drugs (NSAIDs)?

We found that taking NSAIDs, even for periods of under one week (3-4 days for bleeding), was associated with increased risks of both bleeding and of further heart attacks.

Background: People who have suffered a heart attack are prescribed medicines afterwards to reduce their risk of another one. The medicines usually include two ’antithrombotic drugs’ which make platelets in the blood less sticky – the two most commonly used drugs are aspirin and clopidogrel. A side effect of antithrombotic treatment is that the drugs increase bleeding risk.

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation. They are very effective and are among the most widely used drugs in the world. Some NSAIDs can be bought across the counter without a prescription, for example, ibuprofen. NSAIDs have side effects too. All of them increase the risk of bleeding, especially gastro-intestinal bleeding arising from damage (ulcers) caused to the gut lining. Some NSAIDs, for example diclofenac, are also associated with a small increase in the risk of heart attack – this risk matters most for people already at risk of a heart attack. The medical advice is for these patients to avoid NSAIDs and for their doctors to avoid prescribing them if possible.

But pain is a common problem and very distressing for people – so in practice, NSAIDs are used quite often by patients who have had a heart attack. If NSAIDs are to be taken by heart attack patients, then it is important that both they and their doctors know the risks so that they can weigh up the benefits and downsides and make an informed decision.

What this study did: This was a cohort study that included everyone in Denmark aged 30 years or older who had had a first heart attack and who was taking antithrombotic medicines. Using hospital and dispensing registries, we examined patients who had suffered serious bleeding (causing admission to hospital and/or death) or who had another heart attack or cardiac event to see if they had been prescribed NSAIDs or not.

Dr. Olsen: The study findings: In this study of over 60,000 patients in Denmark taking antithrombotic medicines, one third of them had at least one prescription for NSAIDs, commonly ibuprofen or diclofenac, dispensed over a median study time of 3.5 years. In the same period, 8.5% (5,288 patients or 1 in 12 of the study group) had a gastrointestinal bleed (of whom 799 or 15% died) and 30% (18,568; 1 in 3) had a new cardiac event, mostly heart attack. While these events happened to patients who were prescribed NSAIDs and also to patients were not prescribed NSAIDs, we found that the risk of bleeding was doubled when patients were taking NSAIDs compared with not taking them. The risk occurred within 3 days of starting a NSAID. The risk of a cardiac event (mainly heart attack) was increased by 40% when taking NSAIDs compared with not taking them and also occurred within days of starting a NSAID.

In other words, the NSAIDs appeared 1) to increase the bleeding risk already existing with antithrombotics and 2) to diminish the cardiac protection that antithrombotics provided.

Limitations: This is just one study, although it is a big one. It was a ’real-life’ observational study not a randomised controlled clinical trial. More studies are needed to confirm what we have found.

MedicalResearch:  Why is this important information for patients and doctors to know?

Dr. Olsen: NSAIDs were used a lot by the patients in this study – pain is a common problem and can cause great suffering. There has been a tendency to think that short-term use of NSAIDs is safe – our study suggests this in not the case and that even a few days of use is associated with increased risks of both bleeding and cardiac events, mainly heart attacks. People may be happy to take these risks to have relief from pain but it is very important that they aware of the risks and can make an informed decision about taking NSAIDs for pain relief.

Citation:

Schjerning Olsen A, Gislason GH, McGettigan P, et al. Association of NSAID Use With Risk of Bleeding and Cardiovascular Events in Patients Receiving Antithrombotic Therapy After Myocardial Infarction. JAMA. 2015;313(8):805-814. doi:10.1001/jama.2015.0809.

Anne-Marie Schjerning Olsen, MD, PhD Department of Cardiology (2015). NSAIDS After Heart Attack Increase Risk of Bleeding and Further Heart Attacks 

History Of Bariatric Surgery Has Risks and Benefits For Pregnancy

Kari Johansson, Phd Department of Medicine Solna, Karolinska Institutet Clinical Epidemiology Karolinska University Hospital Stockholm, SwedenMedicalResearch.com Interview with:
Kari Johansson, PhD

Department of Medicine Solna, Karolinska Institutet
Clinical Epidemiology
Karolinska University Hospital
Stockholm, Sweden

 

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Johannson: The number of women who are obese in early pregnancy has increased dramatically over the last decades. Consequently, there has been a dramatic rise in the number of women becoming pregnant after bariatric surgery. In Sweden the number of births of women with a history of bariatric surgery has increased from 150 (≈0.15%) to more than 500 (0.5%) per year between 2006 and 2011. The positive effects of bariatric surgery on health outcomes, such as diabetes and cardiovascular disease, are reasonably well-studied, but less is known about the effects on pregnancy and perinatal outcomes. We therefore conducted a population-based study, using data from nationwide Swedish registers.

The main findings are that women who had a history of bariatric surgery were much less likely to develop gestational diabetes (2% compared to 7%; P<0.001) and give birth to large-for-gestational age babies (9% vs 22%; P<0.001). On the other hand, the operated women were twice as likely to give birth to babies who were small for gestational age (16% vs 8%), and have pregnancies of shorter duration (273 vs 277.5; P<0.001). 
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Respiratory Viral Infections Leading to Pediatric Pneumonia

Seema Jain, MD Medical Epidemiologist Epidemiology and Prevention Branch, Influenza Division Centers for Disease Control and Prevention Atlanta, GA 30329MedicalResearch.com Interview with:
Seema Jain, MD

Medical Epidemiologist
Epidemiology and Prevention Branch, Influenza Division
Centers for Disease Control and Prevention
Atlanta, GA 30329

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Jain: Pneumonia is the leading cause of hospitalization among children in the United States with medical costs estimated at almost $1 billion in 2009.  The Centers for Disease Control and Prevention’s Etiology of Pneumonia in the Community (EPIC) study was a multi-center, active population-based surveillance study that aimed to estimate the incidence and etiology of community-acquired pneumonia requiring hospitalization in U.S. children.  Children in the study were enrolled from January 2010 to June 2012 in three U.S. children’s hospitals in Memphis, Nashville, and Salt Lake City. Study staff tested children using a range of laboratory tests for viral and bacterial respiratory pathogen detection.

During the study period, the EPIC study team enrolled 2,638 children, of which 2,358 (89 percent) had radiographically-confirmed pneumonia. The median age of children in the study was 2 years old. Intensive care was required for 497 (21 percent) of the children, and three children died.  Among 2,222 children with radiographic pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 1802 (81%).  One or more viruses were detected in 1,472 (66%) of these children.  Bacteria were detected in 175 (8%), and bacterial and viral co-detection occurred in 155 (7%).  The study estimated that annual pneumonia incidence was 15.7/10,000 children during the study period.  The highest incidence was among children younger than 2 years old (62.2/10,000).  Respiratory syncytial virus (RSV) was the most common pathogen detected (28%), and it was associated with the highest incidence among children younger than 2 years old with pneumonia.  Human rhinovirus was detected in 22 percent of cases, but it was also identified in 17 percent of asymptomatic controls who were enrolled, by convenience sample, at the same site during the same time period; thus, making it challenging to interpret the meaning of human rhinovirus detection in children hospitalized with pneumonia.  Other detected pathogens were human metapneumovirus (13%), adenovirus (11%), Mycoplasma pneumoniae (8%), parainfluenza viruses (7%), influenza (7%), coronaviruses (5%), Streptococcus pneumoniae (4%), Staphylococcus aureus (1%), and Streptococcus pyogenes (<1%).  The low prevalence of bacterial detections likely reflects both the effectiveness of bacterial conjugate vaccines and suboptimal sensitivity of bacterial diagnostic tests. Continue reading

Primary Care Residents Ill-Equiped To Screen For Binge Alcohol

Dr. Kristy Barnes Le MD Department of Internal Medicine Wake Forest School of Medicine Winston-Salem, NCMedicalResearch.com Interview with:
Dr. Kristy Barnes Le MD
Department of Internal Medicine
Wake Forest School of Medicine
Winston-Salem, NC

Medical Research: What is the background for this study? What are the main findings?
Response: Because about 1 in 6 Americans binge drink, it is important that physicians know how to screen for at-risk drinking and be able to effectively address alcohol use with their patients.   Alcohol screening and brief intervention (SBI) has been shown to be an effective tool to detect and reduce hazardous alcohol use, but it has not yet gained wide acceptance in practice or in medical education.  We know that lack of confidence contributes to practicing physicians’ hesitancy to screen and intervene with at-risk drinkers, but this had not been studied in resident physicians.

We set out to determine how primary care resident physicians screen and intervene with their patients who drink, how they feel about discussing at-risk drinking, and what barriers they have to performing  Alcohol screening and brief intervention.

Our main findings are:

1.)  Resident physicians are using the wrong screening instruments at the wrong times, and are not adequately performing the brief intervention when they do detect hazardous drinking.

Less than 20% of residents in this study used screening instruments that are capable of detecting at-risk or binge drinking, while the remainder used instruments designed to detect alcohol use disorders.  And, only 17% screened for at-risk drinking at acute-care visits, where the consequences of binge drinking (such as injuries) are most likely to appear.  Additionally, when a brief intervention was performed, only a quarter of residents usually or always included the three recommended elements of feedback, advice, and goal-setting.

2.)  Resident physicians do not feel confident addressing at-risk drinking with their patients.

Only 21% felt they could help their patient with hazardous drinking cut down or stop using alcohol and only 17% felt they had been successful in doing so in the past.  Interestingly, U.S.-born residents and those reporting no religious affiliation were even more likely to express lack of confidence.

3.)  Lastly, residents report barriers that include lack of adequate training (53 %), the belief that talking with patients is unlikely to make a difference (44 %), and just being too busy (39%).  The hours of reported  Alcohol screening training did not vary with residency year, perhaps indicating that most of it was done prior to residency.

Clearly, the several hours they report getting (mean of 9.8 hours) is either not covering the right topics, or not teaching them in a way that leads to changes in practice. Continue reading

Majority of Asthma Patients Do Not Use Inhalers Correctly

Rana Suzette Bonds, MD The University of Texas Medical BranchMedicalResearch.com Interview with:
Rana Suzette Bonds, MD
The University of Texas Medical Branch

MedicalResearch: What is the background for this study?

Dr. Bonds: Both anaphylaxis and asthma can be life threatening disorders requiring prompt treatment. Each disorder can be successfully treated with medication which is delivered by devices designed for self-administration. Unfortunately there has been evidence in the literature that patients frequently do not use the devices appropriately. We sought to determine which factors were associated with incorrect use of metered dose inhalers and epinephrine autoinjectors, and to determine if rates of correct use have improved since earlier reports.

MedicalResearch: What are the main findings?

Dr. Bonds: Sixteen percent of patients used the epinephrine autoinjector properly and 7 percent of patients used the metered dose inhaler correctly. The most common error with the autoinjector was not holding the unit in place for at least 10 seconds after triggering. For patients using the metered dose inhaler the most commonly missed step was exhaling to functional residual capacity or residual volume prior to actuating the canister. Male sex, Caucasian race, and previous medical education correlated with correct use of epinephrine autoinjector device.

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Amblyopia Helped By Two Hours of Patching

Eric Crouch, MD, FAAO, FAAP, FACS Vice Chair, PEDIGAssociate Professor Department of Ophthalmology Eastern Virginia Medical School Assistant Professor Department of Pediatrics Eastern Virginia Medical School Chief of Ophthalmology Children's Hospital of the King's Daughters Norfolk, VirginiaMedicalResearch.com Interview with:
Eric Crouch, MD, FAAO, FAAP, FACS

Vice Chair, PEDIGAssociate Professor
Department of Ophthalmology
Eastern Virginia Medical School Assistant Professor
Department of Pediatrics Eastern Virginia Medical School
Chief of Ophthalmology, Children’s Hospital of the King’s Daughters Norfolk, Virginia

MedicalResearch: What is the background for this study? 

Dr. Crouch: In this letter PEDIG is reporting on the improvement in vision during the run-in phase of a study in children 3 years of age to less than 8 years old.  During the run-in phase, the children were followed at 6 weeks intervals and served as the baseline for entering into a randomized trial for increasing the amount of patching. The patients were randomized to either 2 hours of prescribed patching or 6 hours of prescribed patching once they completed the run-in phase.

MedicalResearch: What are the main findings?

Dr. Crouch: For amblyopic children, even those who have moderate or severe amblyopia in the 20/100 – 20/400 range, clinicians can start treatment with patching two hours a day.

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Research Aims To Understand Heart Failure In Women

Dawn Pedrotty, MD, PhD Cardiovascular Medicine Fellowship University of PennsylvaniaMedicalResearch.com Interview with:
Dawn Pedrotty, MD, PhD

Cardiovascular Medicine Fellowship
University of Pennsylvania

MedicalResearch: What is the background for this review? What are the main findings?

Dr. Pedrotty: Heart failure (HF) is the most common cause for hospitalization among patients 65 years and older, affecting approximately 6 million Americans; at 40 years of age, American males and females have a one in five lifetime risk of developing heart failure. There are two distinct heart failure phenotypes: a syndrome with normal or near-normal left ventricular ejection fraction (LVEF) referred to as HF with preserved ejection fraction (HFpEF), and the phenotype associated with poor cardiac contractility or heart failure with reduced ejection fraction (HFrEF). Risk factors associated with HFpEF include female gender, especially women with diabetes, higher body mass index, smoking, hypertension, concentric left ventricular hypertrophy (LVH), and atrial fibrillation (AF). There has been a growing interest in the development of criteria for specific subsets of HFpEF, a syndromal disease where multiple cardiac and vascular abnormalities exist. One approach is to implement phenomapping, identifying phenotypically distinct HFpEF categories and developing a classification system to group together pathophysiologically similar individuals who may respond in a more homogeneous, predictable way to intervention. Another option would be to focus on a known physiologic differences which might shed light on pathologic mechanisms e.g. gender and the influences of obesity and atrial fibrillation.
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Women With Atrial Fibrillation At Greater Risk Of Stroke Than Men

Gregory YH Lip MD, FRCP (London, Edinburgh, Glasgow), DFM, FACC, FESC Professor of Cardiovascular Medicine, University of Birmingham, UK; Adjunct Professor of Cardiovascular Sciences, Thrombosis Research Unit, Aalborg University, Denmark; Visiting Professor of Haemostasis Thrombosis & Vascular Sciences, Aston University, Birmingham, UK; Visiting Professor of Cardiology, University of Belgrade, Serbia Centre for Cardiovascular Sciences City Hospital Birmingham  England UKMedicalResearch.com Interview with:
Gregory YH Lip MD, FRCP (London, Edinburgh, Glasgow), DFM, FACC, FESC
Professor of Cardiovascular Medicine,
Adjunct Professor of Cardiovascular Sciences,
Thrombosis Research Unit, Aalborg University, Denmark;
Aston Centre for Cardiovascular Sciences City Hospital Birmingham
England UK

Medical Research: What is the background for this study? What are the main findings?

Prof. Lip: Women with atrial fibrillation are at higher risk of stroke than men with atrial fibrillation.

The reasons for this elevated risk remain unclear.

The results from our worldwide study suggest that women are treated no differently to men in terms of anticoagulant therapy for stroke prevention.

Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk.

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Children’s Diet Not Affected By Healthy Supermarket in Previous ‘Food Desert’

Brian Elbel, PhD, MPH Associate Professor, Department of Population Health; Associate Professor, Department of Medicine Population Health NYU School of MedicineMedicalResearch.com Interview with:
Brian Elbel, PhD, MPH
Associate Professor, Department of Population Health;
Associate Professor, Department of Medicine
Population Health NYU School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Elbel: This study tried to determine whether a new supermarket that received tax and zoning credits from New York City, locating in a high need area, impacted healthy eating for children.  No previous controlled study has looked at children, and supermarkets are tool being increasingly used to improve healthy eating.  We did not find, at least one year after the store opened, any appreciable change in shopping or eating.
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