Cellular Protein Nrf1 Protects Against Fatty Liver

MedicalResearch.com Interview with:

Gokhan S. Hotamisligil MD PhD

Dr. Hotamisligil

Gokhan S. Hotamisligil MD PhD
J.S. Simmons Professor of Genetics and Metabolism
Chair, Department of Genetics and Complex Diseases
Department of Genetics and Complex Diseases
Department of Nutrition
Harvard Stem Cell Institute

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

Response: Cholesterol is often considered a ‘bad’ nutrient, as it has been strongly linked to a cluster of metabolic diseases. In reality however, cholesterol is absolutely vital for the health of all animal cells, serves as an essential building block for all membranes and precursor for essential molecules.  It usually only becomes toxic when cells are exposed to high levels or free forms of cholesterol or when it is stored in excess.

The reasons why cholesterol over-accumulates or causes excessive damage in cells of some people is not entirely clear, as cells are normally should be able to remove such excesses, and there remains key mechanistic gaps in our understanding of how cells control the molecular process of sensing excess cholesterol, engage ways of removal and launch countermeasures to defend their integrity. Filling this gap may reveal a new path toward alleviating the burden of cholesterol-related diseases.

To this end, we identified a new signal pathway mediated by a protein called Nrf1, which enables cells to know when to remove cholesterol, thereby preventing excess cholesterol storage. We show that Nrf1 directly senses cholesterol in a strategic subcellular compartment called the endoplasmic reticulum and coordinates an adaptive and defensive responses that protects the cells and promotes the removal of cellular cholesterol. Continue reading

Current Statin Guidelines May Miss Young Adults At Risk of Heart Attack

MedicalResearch.com Interview with:

Avinainder Singh, M.B.B.S. Research Fellow Cardiovascular Medicine Brigham & Women's Hospital Harvard Medical School Boston, MA

Dr. Singh

Avinainder Singh, M.B.B.S.
Research Fellow
Cardiovascular Medicine
Brigham & Women’s Hospital
Harvard Medical School
Boston, MA 

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

Response: Overall, the incidence of myocardial infarction (MI) in the US has declined. However, it has remained stable in adults <50 years of age.

We evaluated the statin eligibility of a cohort of adults who had an MI at a young age using current guidelines – the 2013 ACC/AHA guidelines for cholesterol treatment and the 2016 USPSTF guidelines on use of statins for primary prevention.

In, our study we found that only 49% of these young adults would have been eligible for statin therapy prior to their MI according the 2013 ACC/AHA guidelines, and only 29% would have been eligible according to the USPSTF guidelines, despite a high prevalence of cardiovascular risk factors. These numbers were even more striking for women where only 18% were eligible for statin therapy according to the USPSTF guidelines.

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Going the Wrong Way: ACA’s Readmission Reduction Program Linked To Increased Heart Failure Deaths

MedicalResearch.com Interview with:

Ankur Gupta, MD, PhD Division of Cardiovascular Medicine Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts

Dr. Ankur Gupta

Ankur Gupta, MD, PhD
Division of Cardiovascular Medicine
Brigham and Women’s Hospital Heart & Vascular Center and
Harvard Medical School,
Boston, Massachusetts 

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

Response: The Hospital Readmissions Reduction Program (HRRP), established under the Affordable Care Act, aimed to reduce readmissions from various medical conditions including heart failure – the leading cause of readmissions among Medicare beneficiaries. The program financially penalizes hospitals with high readmission rates. However, there have been concerns of unintended consequences especially on mortality due to this program.

Using American Heart Association’s Get With The Guidelines-Heart Failure (GWTG-HF) data linked to Medicare data, we found that the policy of reducing readmissions after heart failure hospitalizations was associated with reduction in 30-day and 1-year readmissions yet an increase in 30-day and 1-year mortality.

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DASH Diet and Sodium Reduction Can Have Big Impact in Improving Blood Pressure

MedicalResearch.com Interview with:

Stephen P. Juraschek, MD, PhD Instructor of Medicine Beth Israel Deaconess Medical Center/Harvard Medical School

Dr. Juraschek

Stephen P. Juraschek, MD, PhD
Instructor of Medicine
Beth Israel Deaconess Medical Center/Harvard Medical School 

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

Response: The DASH-Sodium trial demonstrated that both the DASH diet and sodium restriction, individually and combined, lowered blood pressure in adults with pre-hypertension or stage 1 hypertension. Whether these effects varied by level of blood pressure prior to starting these interventions was unknown. In a secondary analysis of the original DASH diet it had been observed that the effects from DASH were greater among adults with higher blood pressure (systolic greater than or equal to 140 mm Hg) at baseline with the appearance of even greater effects among people with baseline systolic blood pressures above 150 mm Hg. However, this has never been shown. Furthermore, it was unknown whether sodium reduction followed a similar linear trend of greater effects among adults with more severely uncontrolled systolic blood pressure.

In our study, we found that effects were indeed greater in adults with a baseline systolic blood pressure of 150 mm Hg or greater. Furthermore, the combined systolic blood pressure-lowering effect from both interventions was as high was 20 mm Hg. This is a magnitude comparable if not greater than medications for lowering blood pressure.

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Wearable Device Study Confirms Moderate-to-Vigorous Physical Activity Linked To Decreased Mortality

MedicalResearch.com Interview with:

I-Min Lee, MD, ScD Professor of Medicine, Harvard Medical School Professor of Epidemiology, Harvard T.H. Chan School of Public Health Brigham and Women's Hospital Boston, MA 02215

Dr. Lee

I-Min Lee, MD, ScD
Professor of Medicine, Harvard Medical School
Professor of Epidemiology, Harvard T.H. Chan School of Public Health
Brigham and Women’s Hospital
Boston, MA 02215

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

Response: The fact that physical activity lowers the risk of premature mortality is not a new fact – we have many studies showing this.  However, previous studies have primarily relied on self-reported physical activity, and self-reports tend to be imprecise.  Based on these self-report studies, we know that physical activity is associated with a 20-30% reduction in mortality rates.  And, these self-report studies also have focused on moderate-to-vigorous intensity physical activity, since they are more reliably reported than lighter intensity activity.  We have little information on whether light-intensity activities (e.g., light household chores, very slow walking such as when strolling and window shopping) are associated with lower mortality rates.

We now have “wearables” – devices that can more precisely measure physical activity at low (as well as higher) intensities, and sedentary behavior.  The present study, conducted between 2011 and 2015, investigated a large cohort of older women (n=16,741; mean age, 72 years)  who were asked to wear these devices for a week – thus, providing detailed physical activity and sedentary behavior measures.  During an average follow-up of about two-and-a-half years, 207 women died.  The study confirmed that physical activity is related to lower mortality rates.

What is new and important is how strong this association is when we have more precise measures of physical activity – the most active women had a 60-70% reduction in mortality rates, compared with the least active, during the study.  For context, non-smokers have about a 50% risk reduction, compared to smokers, which is why patients (and doctors) should pay attention to being physically active.

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Medical Tetrahydrocannabinol May Be Beneficial For Seizures and Chemotherapy Side Effects

MedicalResearch.com Interview with:

Dr. Wong

Dr. Wong

Shane Shucheng Wong, MD
Massachusetts General Hospital
Boston, Massachusetts 

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

Response: Medical cannabis is now legal in 29 states and the District of Columbia, and in those areas with active programs, children and adolescents can legally access medical cannabis with certification from their doctor and consent from a parent. This means that doctors and families need to understand what we know and what we don’t yet know about medical cannabis in order to make the best decision for the health of the individual child. Two synthetic cannabinoids – compounds that act on specific receptors in the brain – have been approved for medical use in the U.S., both of which mimic a form of THC (tetrahydrocannabinol), the compound responsible for the “high” of recreational cannabis use. Dronabinol (Marinol) is approved to treat chemotherapy-induced nausea and vomiting in both children and adults, while the pediatric use of nabilone (Cesamet) carries a caution. A third cannabinoid, cannabidiol, is currently in phase 3 trials for treatment of seizures.

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Chocolate Milk May Promote Weight Gain in Children and Adolescents

MedicalResearch.com Interview with:

Jorge E. Chavarro, M.D., Sc.D. Assistant Professor of Nutrition and Epidemiology Harvard T.H. Chan School of Public Health Assistant Professor of Medicine Harvard Medical School Boston, MA 02113

Dr. Chavarro

Jorge E. Chavarro, MD, ScD
Associate Professor
Departments of Nutrition and Epidemiology
Harvard T.H. Chan School of Public Health
Channing Division of Network Medicine
Department of Medicine
Brigham and Women’s Hospital and Harvard Medical School
Boston, MA 02115

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

Response: It is well known that sugared sweetened beverages (SSBs) promote excessive weight gain and obesity in children. The excess sugars in chocolate milk and other flavored milks puts them in a category that may be closer to sugared sweetened beverages than to plain milk. However, data on whether flavored milks promote weight gain is scarce.

We followed a cohort of 5,321 children and adolescents over a four year period to evaluate whether intake of chocolate milks was related to weight gain. We found that children who increased their intake of flavored milk gained more weight than children whose intake of flavored milk remained stable over this period. Moreover, among those children who did not drink any chocolate milk at baseline, those who started drinking chocolate milk over the course of the study gained substantially more weight than children who remained non-consumers of chocolate milk.

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Pesticide Residues On Fruits & Vegetables Associated With Increased Risk of Pregnancy Loss

MedicalResearch.com Interview with:

“Pesticide spraying” by jetsandzeppelins is licensed under CC BY 2.0

“Pesticide spraying” by jetsandzeppelins

Yu-Han Chiu, M.D., M.P.H., Sc.D
Department of Nutrition
Harvard T.H. Chan School of Public Health

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

Response:  Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born pups. However, it is unclear whether intake of pesticide residues has any adverse effects in humans, especially for susceptible populations such as pregnant women and their fetuses. Therefore, in this study we examined the association of preconception intake of pesticide residues in fruits and vegetables with pregnancy outcomes among 325 women undergoing assisted reproduction.

We found that intake of high pesticide residue fruits and vegetables were associated with higher risks of pregnancy loss, while low pesticide residue fruit and vegetable intake was associated with lower risks of early pregnancy loss. These data suggest dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences

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Machine Learning Applied To Predicting High-Risk Breast Lesions May Reduce Unnecessary Surgeries

MedicalResearch.com Interview with:

Manisha Bahl, MD, MPH Director, Breast Imaging Fellowship Program, Massachusetts General Hospital Assistant Professor of Radiology, Harvard Medical School

Dr. Bahl

Manisha Bahl, MD, MPH
Director, Breast Imaging Fellowship Program,
Massachusetts General Hospital
Assistant Professor of Radiology,
Harvard Medical School

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

Response: Image-guided biopsies that we perform based on suspicious findings on mammography can yield one of three pathology results: cancer, high-risk, or benign. Most high-risk breast lesions are noncancerous, but surgical excision is typically recommended because some high-risk lesions can be upgraded to cancer at surgery. Currently, there are no imaging or other features that reliably allow us to distinguish between high-risk lesions that warrant surgery from those that can be safely followed, which has led to unnecessary surgery of high-risk lesions that are not associated with cancer.

We decided to apply machine learning algorithms to help us with this challenging clinical scenario: to distinguish between high-risk lesions that warrant surgery from those that can be safely followed. Machine learning allows us to incorporate the full spectrum of diverse and complex data that we have available, such as patient risk factors and imaging features, in order to predict which high-risk lesions are likely to be upgraded to cancer and, ultimately, to help our patients make more informed decisions about surgery versus surveillance.

We developed the machine learning model with almost 700 high-risk lesions, then tested it with more than 300 high-risk lesions. Instead of surgical excision of all high-risk lesions, if those categorized with the model to be at low risk for upgrade were surveilled and the remainder were excised, then 97.4% malignancies would have been diagnosed at surgery, and 30.6% of surgeries of benign lesions could have been avoided.

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Does Brand Name 17P Work Better Than Generic In Reducing Preterm Births?

MedicalResearch.com Interview with:

Andrew L. Beam, PhD Instructor in Biomedical Informatics Department of Biomedical Informatics Harvard Medical School

Dr. Beam

Andrew L. Beam, PhD
Instructor in Biomedical Informatics
Department of Biomedical Informatics
Harvard Medical School

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

Response: This study is one piece of a larger story regarding the use of 17-alpha-hydroxyprogesterone caproate (17P) to treat recurrent preterm birth. This drug was originally only available in a compounded form, but since receiving an orphan drug designation in 2011, a branded and manufactured form was marketed under the name “Makena”. This branded form was then sold for a much higher price than the compounded version, but a study that provided concrete data on pricing and outcomes had not been done.
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Participation in SNAP Food Assistance Linked To Lower Health Care Costs

MedicalResearch.com Interview with:

Seth A. Berkowitz, MD, MPH Division of General Internal Medicine Diabetes Population Health Unit Harvard Medical School Massachusetts General Hospital, Boston

Dr. Berkowitz

Seth A. Berkowitz, MD, MPH
Division of General Internal Medicine
Diabetes Population Health Unit
Harvard Medical School
Massachusetts General Hospital, Boston

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

Response: There is ever growing pressure to contain healthcare costs in the US. Increasingly, attention is turning to programs that address social determinants of health–that is, those factors which affect health but lie outside the realm of clinical medicine.

Prior research has highlighted food insecurity as having a clear association with poor health and higher healthcare costs. SNAP is the nation’s largest program to combat food insecurity. However, we did not know whether SNAP participation would be associated with any difference in healthcare costs, compared with eligible non-participants.

This study found that participating in SNAP was associated with approximately $1400 lower healthcare expenditures per year in low-income adults.

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Ruptured Biceps Tendon and Wild-type Transthyretin Amyloidosis

MedicalResearch.com Interview with:

Avinainder Singh, M.B.B.S. Research Fellow Cardiovascular Medicine Brigham & Women's Hospital Harvard Medical School Boston, MA

Dr. Singh

Avinainder Singh, M.B.B.S.
Research Fellow
Cardiovascular Medicine
Brigham & Women’s Hospital
Harvard Medical School
Boston, MA

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

Response: Amyloidosis due to aberrant folding of proteins. These misfolded proteins can deposit in various parts of the body and lead to organ dysfunction. The two most common types of amyloidosis affecting the heart include transthyretin and light chain amyloidosis. Transthyretin is a protein produced by the liver which supports the transport of thyroxine and retinol.

Wild-type transthyretin amyloidosis (ATTRwt, previously known as senile amyloidosis) occurs due to deposition of misfolded fibrils derived from transthyretin and primarily affects elderly men. Once considered a rare disease, it is now reported to be responsible for nearly 13% of heart failure with preserved ejected fraction and increased wall thickness.

Rupture of the biceps tendon is a rare occurrence in the general population (<1 per 1000). We noticed a ruptured biceps tendon in several patients with wild-type transthyretin amyloidosis and performed this study to further evaluate this finding in a group of patients with wild-type transthyretin amyloidosis and in a control group of age-matched patients with non-amyloid heart failure.

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Low Adverse Event Rates Related to the CardioMEMS Heart Failure System

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: Muthiah Vaduganathan, MD, MPH Brigham and Women’s Hospital Heart &  Vascular Center and Harvard Medical School Boston, Massachusetts

Dr. Vaduganathan

Muthiah Vaduganathan, MD, MPH
Brigham and Women’s Hospital Heart &
Vascular Center and Harvard Medical School
Boston, Massachusetts

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

Response: The CardioMEMS™ HF System (Abbott, Sylmar, CA) is a commercially-available, wireless hemodynamic monitor that can be permanently implanted in the pulmonary artery (PA) to permit real-time, remote monitoring of PA pressures to enhance clinical decision-making in patients with heart failure (HF). Based on a favorable safety profile and the results of the CHAMPION trial, the US Food and Drug Administration (FDA) approved the device in May 2014. Since FDA approval, the device is being implanted in older patients with greater comorbidities compared with those enrolled in CHAMPION. Limited safety data are available after market introduction in this higher-risk pool.

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Study Finds 5-7 Years Post-Menopausal Hormone Therapy Not Associated with Increased Risk of Mortality

MedicalResearch.com Interview with:

JoAnn E. Manson, MD, DrPH Chief, Division of Preventive Medicine Brigham and Women's Hospital Professor of Medicine and the Michael and Lee Bell Professor of Women's Health Harvard Medical School Boston, Massachusetts  02215

Dr. Manson

JoAnn E. Manson, MD, DrPH
Chief, Division of Preventive Medicine
Brigham and Women’s Hospital
Professor of Medicine and the
Michael and Lee Bell Professor of Women’s Health
Harvard Medical School
Boston, Massachusetts  02215 

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

Response: The current report provides new information on total mortality and the rates of death from specific causes (cardiovascular disease, cancer, other major illnesses) over 18 years of follow-up in the Women’s Health Initiative (WHI) randomized trials of hormone therapy (estrogen + progestin and estrogen alone). This is the first WHI report to focus on all-cause and cause-specific mortality. It includes all of the 27,347 women in the 2 hormone therapy trials with >98% follow-up over 18 years, during which time 7,489 deaths occurred. This is more than twice as many deaths as were included in earlier reports. The report also provides detailed information on differences in results by age group (ages 50-59, 60-69, 70-79) at time of study enrollment.

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Longer Breastfeeding Linked To Lower Risk of Endometriosis

MedicalResearch.com Interview with:

Leslie V. Farland, ScD Assistant Director of Epidemiologic Research Center for Infertility and Reproductive Surgery Brigham and Women's Hospital | Harvard Medical School  Instructor | Harvard T.H. Chan School of Public Health

Dr. Farland

Leslie V. Farland, ScD
Assistant Director of Epidemiologic Research
Center for Infertility and Reproductive Surgery
Brigham and Women’s Hospital | Harvard Medical School
Instructor | Harvard T.H. Chan School of Public Health

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

Response: Endometriosis is chronic gynecologic condition that affects approximately ten percent of women. Women with endometriosis can experience painful menstrual periods, general chronic pelvic pain, and pain associated with intercourse. Currently we know very few modifiable risk factors for endometriosis.

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Small Kit Can Easily Detect Food Allergens On-Site

MedicalResearch.com Interview with:

Lee, Hakho, PhD Department of Systems Biology Harvard Medical School Boston, Massachusetts

Dr. Lee

Lee, Hakho, PhD
Department of Systems Biology
Harvard Medical School
Boston, Massachusetts

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

Response: The incidence of food allergy is increasing worldwide, particularly among children, and yet no handy test is available for general public. We wanted to solve this issue. Our pilot test showed wide variation in allergen contents in packaged food products and restaurant meals. Hidden allergens (like gluten in salad dressing, likely from additives) were also found.

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More Babies Experiencing Neonatal Drug Withdrawal After Exposure To Opioids and Psychotropic Meds

MedicalResearch.com Interview with:

Krista F. Huybrechts, M.S., Ph.D. Assistant Professor of Medicine at Harvard Medical School Epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital. Boston, MA 02120

Dr. Krista Huybrechts

Krista F. Huybrechts, MS PhD
Assistant Professor of Medicine
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA 02120

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

Response: Neonatal drug withdrawal is common; in the U.S. about 1 infant is born every 25 minutes with signs of drug withdrawal. Neonatal drug withdrawal is a well-recognized complication of intrauterine exposure to illicit or prescription opioids, but other psychotropic medications can also cause signs of withdrawal. Psychotropic medications are frequently co-prescribed with opioids in pregnancy, and the use of both has increased significantly, raising concerns about an increase in the incidence and severity of neonatal drug withdrawal due to potential drug-drug interactions, but these risks are not well understood.

In this study, we found a 30-60% increase in the risk of neonatal drug withdrawal associated with co-exposure to antidepressants, benzodiazepines and gabapentin, compared to opioids alone; no significant increase in risk was observed for atypical antipsychotics and Z-drugs. Exposure to psychotropic polypharmacy along with opioids was associated with a two-fold increased risk of withdrawal.

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Best To Measure Orthostatic Hypotension Within A Minute of Standing

MedicalResearch.com Interview with:

Stephen P. Juraschek, MD, PhD Instructor of Medicine Beth Israel Deaconess Medical Center Harvard Medical School

Dr. Juraschek

Stephen P. Juraschek, MD, PhD
Instructor of Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School

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

Response: Many adults experience dizziness and light-headedness when they stand up. This is more common in older adults and is related to risk of falling, fractures, fainting, car crashes, and early death. These symptoms are thought to be caused by a drop in blood pressure after standing also called orthostatic hypotension. However, if measured at the wrong time it is possible to miss this important clinical sign.

For over 2 decades (since 1996), it has been recommended that orthostatic hypotension be identified by measuring blood pressure within 3 minutes of standing. Furthermore, it was also thought that measurements immediately after standing be avoided because they might be inaccurate (based on fluctuation in blood pressure immediately after standing). As a result, a lot of clinical protocols instructing healthcare staff on measuring orthostatic blood pressure encourage measurement at 3 minutes, but this has not been scientifically evaluated.

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Cross-Sex Hormone Therapy Associated With Medical Risks and Psychosocial Benefits in Transgender Patients

MedicalResearch.com Interview with:

Carl G Streed Jr. M.D. Pronouns: he, him, his, himself Fellow, Division General Internal Medicine & Primary Care Brigham & Women’s Hospital

Dr. Streed

Carl G Streed Jr. M.D.
Pronouns: he, him, his, himself
Fellow, Division General Internal Medicine & Primary Care
Brigham & Women’s Hospital 

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

Response: Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT.

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Trying Statins Again After Adverse Effect Linked To Lower Risk of Heart Attack

MedicalResearch.com Interview with:

Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA

Dr. Turchin

Alexander TurchinMD,MS
Director of Quality in Diabetes
Associate Professor, Harvard Medical School
Brigham and Women’s Hospital
Boston, MA

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

Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events.

However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction.

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Higher Cost Sharing For Mental Health Services Could Increase Downstream Costs

MedicalResearch.com Interview with:

Bastian Ravesteijn PhD Department of Health Care Policy Harvard Medical School

Dr. Ravesteijn

Bastian Ravesteijn PhD
Department of Health Care Policy
Harvard Medical School 

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

Response: We find that higher out-of-pocket costs for mental health care could have the unintended consequence of increasing the use of acute and involuntary mental health care among those suffering from the most debilitating disorders. Continue reading

Lifestyle-Based Tool Estimates Premature Cardiovascular Events in Young Adults

MedicalResearch.com Interview with:

Holly Gooding, MD, MSc Assistant Professor of Medicine and Pediatrics, Harvard Medical School Division of Adolescent/Young Adult Medicine, Boston Children's Hospital Division of General Internal Medicine, Brigham and Women's Hospital Boston, MA

Dr. Gooding

Holly Gooding, MD, MSc
Assistant Professor of Medicine and Pediatrics
Harvard Medical School
Division of Adolescent/Young Adult Medicine
Boston Children’s Hospital
Division of General Internal Medicine
Brigham and Women’s Hospital
Boston, MA

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

Response: Dr Stephanie Chiuve and colleagues at the Harvard TH Chan School of Public Health developed the Healthy Heart Score to predict the risk of heart disease in older adults based on lifestyle factors measured in middle age. We have known for some time that the precursor to heart disease – known as atherosclerosis – actually starts in childhood and adolescence. We calculated the Healthy Heart Score for young adults ages 18-30 years old and found it works in this age group as well.

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Midlife Weight Gain Raises Risks of Chronic Disease and Premature Death

MedicalResearch.com Interview with:
Yan Zheng Research Fellow, Department of Nutrition Harvard T.H. Chan School of Public HealthYan Zheng
Research Fellow, Department of Nutrition
Harvard T.H. Chan School of Public Health

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

Response: Most people gain weight cumulatively during young and middle adulthood. Because the amount of weight gain per year may be relatively small, it may go unnoticed by individuals and their doctors—but the cumulative weight gain during adulthood may eventually lead to obesity over time. Compared to studies of attained body weight or BMI, the investigation of weight change may better capture the effect of excess body fat because it factors in individual differences in frame size and lean mass.

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Higher HIV Viral Loads Linked to Increased Squamous Cell Cancers of Skin

MedicalResearch.com Interview with:

Maryam M. Asgari, MD, MPH Department of Dermatology, Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland

Dr. Asgari

Maryam M. Asgari, MD, MPH
Department of Dermatology
Massachusetts General Hospital,
Department of Population Medicine
Harvard Medical School, Boston, Massachusetts
Division of Research, Kaiser Permanente
Northern California, Oakland

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

Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised.

We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan.

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Healthy Diet Translates Into Longer Life

MedicalResearch.com Interview with:

Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health 

Dr. Sotos-Prieto

Mercedes Sotos Prieto PhD
Research Fellow
Department of Nutrition
Harvard T. H. Chan School of Public Health

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

Response: Previous research have found that adherence to the 2010 Alternate Heathy Eating Index, the Mediterranean Diet pattern, and DASH pattern is associated with health benefits, but none of those studies have examined dynamic changes in diet quality over time and subsequent risk of mortality.

This is the first study to demonstrate that improvement in these three diet scores over time is associated with reduced risk of total and cardiovascular mortality. In contrast, worsening diet quality over 12-years was associated with 6%-12% increased mortality.

In addition, not only improvement in diet quality but maintaining a high adherence to any of the three dietary patterns over 12 years was significantly associated with 9%-14% lower total mortality.
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Clinical Perineural Invasion of Cutaneous SCC May Warrant Adjuvant Treatment

MedicalResearch.com Interview with:
Dr. Chrysalyne D. Schmults, MD, MSCE
Associate Professor of Dermatology, Harvard Medical School
Director, Mohs and Dermatologic Surgery Center and
Mr. Pritesh S. Karia, MPH
Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Department of Dermatology
Brigham and Women’s Faulkner Hospital
Harvard Medical School, Boston, Massachusetts
Jamaica Plain, MA 02130-3446 

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

Response: Perineural nerve invasion (PNI) is a well-recognized risk factor for poor prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Most cases of CSCC with PNI are identified on histologic examination at the time of surgery and the patient has no clinical symptoms or radiologic evidence of PNI. These cases are classified as incidental PNI (IPNI). However, some patients with PNI present with clinical symptoms and/or radiologic evidence of PNI. These cases are classified as clinical PNI (CPNI). A few studies have shown differences in disease-related outcomes between CSCC patients with IPNI and CPNI but consensus regarding adjuvant treatment and detailed guidelines on follow-up schedules have not yet materialized.

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Ozone Air Pollution Linked To US Deaths, Even At Levels Below Current Safety Standards

MedicalResearch.com Interview with:
Qian Di, M.S, Doctoral Student
Department of Environmental Health and
Francesca Dominici, Ph.D.
Principal Investigator of this study
Professor of Biostatistics
co-Director of the Harvard Data Science Initiative
Harvard T.H. Chan School of Public Health
Boston, MA

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

Response: The Clean Air Act requires Environmental Protection Agency to set National Ambient Air Quality Standard (NAAQS). Currently the annual NAAQS for PM2.5 is 12 microgram per cubic meter; and there is no annual or seasonal ozone standard. However, is current air quality standard stringent enough to protect human health? This is our main motivation.

We conducted the largest attainable cohort study, including over 60 million Medicare participants, to investigate the association between long-term exposure to ozone/PM2.5 and all-cause mortality.

We found significant harmful effect of PM2.5 even below current NAAQS. Each 10 microgram per cubic meter increase in PM2.5 is associated with 13.6% (95% CI: 13.1%~14.1%) increase in all-cause mortality. For ozone, 10 ppb increase in ozone exposure is associated with 1.1% (95% CI: 1.0%~1.2%) increase in mortality. Also, there is no appreciable level below which mortality risk tapered off. In other words, there is no “safe” level for PM2.5 and ozone.

In other words, if we would reduce the annual average of PM2.5 by just 1 microgram per cubic meter nationwide, we should save 12,000 lives among elder Americans every year; 5 microgram — 63,817 lives every year. Similarly, if we would reduce the annual summer average of ozone by just 1 ppb nationwide, we would save 1,900 lives every year; 5 ppb — 9537 lives.

Besides, we found black people, males and people of low SES are more vulnerable to air pollution.

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New Cream May Lead To Non Sun-Induced Tanning

MedicalResearch.com Interview with:

David E. Fisher MD, PhD</strong> Edward Wigglesworth Professor & Chairman Dept of Dermatology Director, Melanoma Program MGH Cancer Center Director, Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Boston, MA 02114

Dr. Fisher

David E. Fisher MD, PhD
Edward Wigglesworth Professor & Chairman
Dept of Dermatology
Director, Melanoma Program MGH Cancer Center
Director, Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Boston, MA 02114

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

Response: This study grew from an interest to mimic the dark pigmentation patterns in human skin which are known from epidemiology to be associated with low skin cancer risk. In the current work, a molecular inhibitor of the SIK enzyme was used to block the inhibitory action of SIK relative to melanin synthesis. The result was stimulation of dark pigmentation within human skin.

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Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage

MedicalResearch.com Interview with:
Andrea Morotti, M.D.
Research Fellow in Neurology
Massachusetts General Hospital
Harvard Medical School

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

Response: The CT angiography (CTA) spot sign is a validated marker of Intracerebral Hemorrhage (ICH) expansion and may identify those subjects more likely to benefit from intensive blood pressure reduction.

We observed that less than 20% of ICH patients received a CTA as part of their diagnostic workup in a large, international randomized clinical trial. The performance of the spot sign in predicting ICH growth was suboptimal compared with what was reported in previous studies. Intensive blood pressure reduction did not improve functional outcome in spot sign positive patients.

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If High School Students Are Naturally Owls, Shouldn’t School Start Later?

MedicalResearch.com Interview with:
Dr. Dorothee Fischer
Department of Environmental Health
Harvard T.H. Chan School of Public Health, Boston, Massachusetts
Center for Injury Epidemiology, Liberty Mutual Research Institute for Safety
Hopkinton, Massachusetts,

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

Response: Chronotypes are a result of how the circadian clock embeds itself into the 24h light-dark cycle, producing earlier and later individuals (“larks and owls”) with regards to rhythms in physiology, cognition and behavior, including sleep.

It can be beneficial for health and safety to sync forced wake times (work, school) with individual chronotypes, thereby reducing the misalignment between sleep, circadian rhythms and external demands.

To better inform potential interventions such as tailored work schedules, more information is needed about the prevalence of different chronotypes and how chronotype differs by age and sex.

To the best of our knowledge, this is the first large-scale and nationally representative study of chronotypes in the US.
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Lithium Use in Pregnancy and Risk of Fetal Cardiac Malformations

MedicalResearch.com Interview with:

Elisabetta Patorno, MD, DrPH Assistant Professor of Medicine, Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital

Dr. Patorno

Elisabetta Patorno, MD, DrPH
Assistant Professor of Medicine, Harvard Medical School
Division of Pharmacoepidemiology and Pharmacoeconomics,
Department of Medicine, Brigham and Women’s Hospital

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

Response: Lithium, a widely used medicine to treat bipolar disorder, has been associated with a 400 fold increased risk of Ebstein’s anomaly, a congenital malformation of the heart, and a 5 fold increased risk of cardiac defects overall in infants when taken early in pregnancy, based on the results from the International Register of Lithium Babies in the 1970’s. Beyond this data, most of the information on the safety of lithium during pregnancy accumulated in the last 40 years is based on case reports and small studies with conflicting results. Despite these concerns and the limited information, lithium remains a first-line treatment for the 1% of women of reproductive age with bipolar disorder in the U.S. population, due to its recognized efficacy during pregnancy and the postpartum period, and due to the presence of a larger body of evidence showing increased risk of congenital malformations for other mood stabilizers, such as valproate.

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Gender Minorities More Likely To Report Physical and Mental Health Challenges

MedicalResearch.com Interview with:

Carl G Streed Jr. M.D. Pronouns: he, him, his, himself Fellow, Division General Internal Medicine & Primary Care Brigham & Women’s Hospital

Dr. Streed

Carl G Streed Jr. M.D.
Pronouns: he, him, his, himself
Fellow, Division General Internal Medicine & Primary Care 
Brigham & Women’s Hospital

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

Response: The National Institutes of Health (NIH) has underscored the need to better understand the health of gender minorities, including transgender and gender non-conforming individuals. Prior investigations of gender minorities are limited by the lack of national gender identity data. In 2013, the Centers for Disease Control and Prevention (CDC) developed a gender identity question for the Behavioral Risk Factors Surveillance System (BRFSS); states had the option to administer this module beginning 2014. Our study aims to examine the health status of gender minorities in the US compared to cisgender peers.

Compared to cisgender adults, gender minority adults are younger, less likely to be non-Hispanic white, married or living with a partner, have a minor child in the household, or be English speaking; but are more likely to have lower income, be unemployed, be uninsured, have unmet medical care due to cost, be overweight, and report depression.

Gender minority adults, compared to cisgender adults, are more likely to report: poor or fair health; difficulty concentrating, remembering, or making decisions; and being limited in any way. These outcomes remained significant after adjustment.

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Asthma Outcomes Worse in Low Income Groups

MedicalResearch.com Interview with:

Wanda Phipatanakul, MD, MS Associate Professor of Pediatrics Harvard Medical School Director, Asthma Clinical Research Center Boston Children's Hospital Asthma, Allergy and Immunology Boston, MA 02115

Dr. Phipatanakul

Wanda Phipatanakul, MD, MS
Associate Professor of Pediatrics
Harvard Medical School
Director, Asthma Clinical Research Center
Boston Children’s Hospital
Asthma, Allergy and Immunology
Boston, MA 02115

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

Response: Observational studies have limitations in their ability to examine disparities in asthma, as these studies have relied on self-reported measures of medication use, asthma diagnosis, severity, outcomes, and access to care.

Using data collected from a randomized controlled trial, we found that subjects with lower income had a significantly higher number of asthma treatment failures and asthma exacerbations, independent of race, BMI, education, perceived stress, baseline lung function, hospitalizations, inhaled corticosteroid adherence, inhaled corticosteroid dose, environmental allergen sensitization, and second-hand smoke exposure.

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Whose Patients Have Lower 30-Day Mortality? Younger or Older Doctors?

MedicalResearch.com Interview with:

Yusuke Tsugawa, MD, MPH, PhD</strong> Harvard T. H. Chan School of Public Health Department of Health Policy and Management Cambridge, MA 02138

Dr. Tsugawa

Yusuke Tsugawa, MD, MPH, PhD
Harvard T. H. Chan School of Public Health
Department of Health Policy and Management
Cambridge, MA 02138

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

Response: Although evidence has suggested that older physicians may experience a
decline in medical knowledge and are less likely to adhere to standard care, patients in general had a perception that older doctors are more
experienced and therefore provide superior care.

Using a nationally representative sample of Medicare beneficiaries who were hospitalized
for medical conditions in 2011-2014, we found that patients treated by
younger doctors have lower 30-day mortality compared to those cared
for by older doctors, after adjusting for patient, physician, and
hospital characteristics.

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Study Finds Disconnect Between Price and Quality in Health Care

MedicalResearch.com Interview with:
Eric Roberts, PhD

Post-doctoral fellow
Department of Health Care Policy
Harvard Medical School

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

Response: Increasing consolidation of health care providers has raised regulatory concerns that less competition will lead to higher health care prices and possibly lower quality care for patients. On the other hand, some industry observers have contended that larger and higher-priced practices are better able invest in systems to support care management, and ultimately, better patient care. In this study, we examined whether larger and higher-priced physician practices provided better and more efficient care to their patients.

Higher-priced physician groups were paid an average of 36% more by commercial insurers, and were substantially larger than lower-priced practices located within the same geographic areas. Despite large differences in practices’ prices and size, we found few differences in their patients’ quality and efficiency of care. For example, when we compared patients who received care in high-priced versus low-priced practices, we found no differences in patients’ overall care ratings, physician ratings, access to care, physician communication, and use of preventive services. We also found no differences in patients’ hospital admissions or total spending, suggesting that higher-priced practices were not managing their patients’ care more efficiently than their lower-priced counterparts.

We did find that patients in higher-priced practices were more likely to receive recommended vaccinations, review of their medications, and results of medical tests, and that they spent less time in the waiting room for a scheduled doctor’s appointment. However, once practice prices exceeded the average for their geographic area, we observed no further gains in quality on most of these measures.

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Late Menopause and Oral Hormone Therapy Linked To High Risk of Hearing Loss

MedicalResearch.com Interview with:

Sharon G. Curhan, MD, ScM Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA 02115

Dr. Curhan

Sharon G. Curhan, MD, ScM
Channing Division of Network Medicine
Department of Medicine
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA 02115

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

Response: Hearing loss affects approximately 48 million Americans and the number is expected to increase as the population ages. Some previous studies suggested that menopause may increase the risk for hearing loss, presumably due to the reduction in circulating estrogen levels, and that postmenopausal hormone therapy might slow hearing decline by “replacing” estrogen. To evaluate the role of menopause and postmenopausal hormone therapy as risk factors for hearing loss, we examined the independent associations between menopausal status, oral hormone therapy, and risk of self-reported hearing loss in 80,972 women who are participants in the Nurses’ Health Study II, aged 27-44 years at baseline, and were followed from 1991 to 2013.

After more than 1.4 million person-years of follow-up, 18,558 cases of hearing loss were reported (~23% of the women developed hearing loss). We did not observe an overall independent association between menopausal status and risk of hearing loss.

However, the risk among women who underwent natural menopause at an older age was higher. Specifically, the risk among women who underwent natural menopause at age 50 or older was 10% higher than among those who underwent natural menopause before age 50 [multivariable-adjusted relative risk (MVRR): 1.10, 95% CI 1.03, 1.17]. When we conducted an analysis restricted to women who underwent natural menopause and did not use hormone therapy (HT), the multivariable-adjusted relative risk among women who underwent natural menopause at age 50-54 years was 21% higher (MVRR: 1.12, 95% CI: 1.10, 1.34), and among women who underwent natural menopause at age 55+ years was 29% higher (MVRR: 1.29, 95% CI: 1.11, 1.50), compared with women who underwent natural menopause before age 50.

Among postmenopausal women, we also found that use of oral HT was associated with higher risk of hearing loss, and the magnitude of the risk tended to increase with longer duration of use (p-trend < 0.001). Compared with women who never used any type of HT, the MVRR of hearing loss among women who used oral HT for 5-9.9 years was 15% higher (MVRR: 1.15, 95% CI: 1.06, 1.24), and for 10+ years was 21% higher (MVRR: 1.21, 95% CI: 1.07, 1.37). When specific types of oral HT were examined, longer duration of use of either oral estrogen-only or of combined estrogen plus progestogen HT were each associated with higher risk. Fewer women reported use of progestogen-only oral HT, yet among these women a higher risk was suggested, but not significant (MVRR: 1.15, 95% CI: 0.98, 1.35). Transdermal HT use was less common, but the associations observed were similar to those with oral hormone therapy. When examined separately by type of menopause, the results for HT use were similar.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

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

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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Adolescents Perinatally Infected with HIV Are At Increased Risk of Serious Physical and Mental Health Problems

MedicalResearch.com Interview with:

Anne M Neilan, MD,MPH Assistant In Medicine, Massachusetts General Hospital Research Fellow, Harvard Medical School Department: Medicine Service Division: Infectious Disease Department: Pediatric Service Massachusetts General Hospital Boston, MA 02114

Dr. Neilan

Anne M Neilan, MD,MPH
Assistant in Medicine and Pediatrics
Massachusetts General Hospital
Instructor at Harvard Medical School
Department: Medicine Service
Division: Infectious Disease
Department: Pediatric Service
Massachusetts General Hospital
Boston, MA 02114

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

Response: Adolescents infected with HIV – either at birth or later in life – experience poorer health outcomes compared to adults with HIV in nearly every respect. This study found that U.S. youth infected with HIV around the time of their birth are at higher risk throughout their adolescence and young adulthood for experiencing serious health problems, poor control of the HIV virus (having high levels of HIV virus in their bodies and fewer CD4 immune cells which protect the body from infection), or death. The study also found that among those with good HIV control, serious health problems are rare.

By combining data from two large, long-term U.S. studies – the Pediatric HIV/AIDS Cohort Study (PHACS, www.phacsstudy.org) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT, www.impaactnetwork.org) Network – we were able to study the health of more than 1,400 perinatally HIV-infected children, adolescents and young adults ages 7 to 30 years between 2007 and 2015. The study found that youth ages 13 to 30 were most likely to have poor HIV control AIDS-related illnesses, and death compared to younger participants. Among 18 – 30 year-olds, the study found that poor control of the HIV virus – meaning higher levels of HIV virus and lower levels of CD4 immune cells which protect the body from infection –35 percent of the time, increasing the risk that these youth would stop responding to certain HIV medications and could transmit HIV to others. These findings are consistent with other U.S. and European reports. Despite being engaged in health care, the number of deaths among youth born with HIV in the U.S. is 6 to12 times higher than for youth without HIV of the same age, sex and race.

Along with HIV-related health problems, the most commonly reported health conditions concerned mental health and brain and nervous system development. Many women in the study also had sexually transmitted infections, which was found to be associated with lower CD4 immune cell counts. This may suggest a biological mechanism or may reflect that patients who have difficulty with their medications are also engaging in more frequent risky sexual behaviors.

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Skin Testing Plus APP May Reduce Overdiagnosis of Penicillin Allergy

MedicalResearch.com Interview with:
Kimberly Gold Blumenthal, M.D
Assistant Professor of Medicine
Massachusetts General Hospital

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

Response: Over-reported penicillin allergies negatively impact patient care, as alternative drugs that are often used can be less effective, more toxic, more broad-spectrum (killing all of the good bacteria and leaving patients increasingly vulnerable to C.diff colitis), and more expensive. Most hospitalized patients who have a recorded penicillin allergy are not actually allergic. This has drawn attention by national organizations such as the CDC, National Quality Forum, and both allergy and infectious diseases professional societies. The message is clear: Address reported penicillin allergies in some way to improve care.
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Increased Physician Spending On Hospital Care Does Not Improve Outcomes

MedicalResearch.com Interview with:
Yusuke Tsugawa, research associate

Department of Health Policy and Management
Harvard T H Chan School of Public
Division of General Internal Medicine and Primary Care
Brigham and Women’s Hospital, Boston, MA     

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

Response: It is well known that health spending varies substantially across geographical regions, and yet regions that spend more on health care dot not achieve better health outcomes. These findings has led to many to conclude that at least 20% of U.S. health care spending could be reduced without compromising quality of care. However, while physicians play a critical role in health care decision making, little is known as to how much health care spending varies between physicians, and its implications for patient outcomes.

In this study, we found that the variation in spending across physicians is slightly larger than the variation across hospitals. More importantly, higher spending by physicians did not lead to lower patient mortality or readmission rates, within the same hospital.

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Family Input Improves Hospital Safety Surveillance

MedicalResearch.com Interview with:

Alisa Khan, MD, MPH Staff Physician Instructor in Pediatrics Boston Children's Hospital

Dr. Khan

Alisa Khan, MD, MPH
Staff Physician
Instructor in Pediatrics
Boston Children’s Hospital 

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

Response: ​Medical errors are known to be a leading cause of death in the United States. However, the true rate at which errors and adverse events occur in medicine is believed to be even higher than what has been found through the most rigorous patient safety studies.

Families are typically excluded from safety surveillance efforts, both in research and operationally in hospitals. We found that including families in safety reporting at four pediatric hospitals led to significantly higher error/adverse event detection rates, compared to the safety surveillance methodology typically considered most rigorous and highest yield in safety research. In addition, families reported errors/adverse events at similar rates as providers and at several-fold higher rates than the hospital incident reports which typically form the basis of operational hospital safety surveillance.
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Stopping Warfarin in Dementia Patients with Atrial Fib Associated With Increased Risk of Stroke and Death

MedicalResearch.com Interview with:

Ariela Orkaby, MD, MPH Geriatrics & Preventive Cardiology Associate Epidemiologist Division of Aging, Brigham and Women's Hospital Instructor in Medicine, Harvard Medical School

Dr. Ariela Orkaby

Ariela Orkaby, MD, MPH
Geriatrics & Preventive Cardiology
Associate Epidemiologist
Division of Aging, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical School

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

Response: Atrial Fibrillation is a common heart rhythm that affects 1 in 25 adults over age 60 and 1 in 10 adults over age 80. The feared consequence of atrial fibrillation is stroke, leading to the prescription of blood thinning medications (anticoagulants such as warfarin) to prevent strokes. However, there is an underutilization of these life-saving medications in older adults, and particularly in those who have dementia. In part, this is due to a lack of research and inclusion of older adults with dementia in prior studies.

In this study, we used clinical Veterans Administration data, linked to Medicare, to follow 2,572 individuals over age 65 who had atrial fibrillation and until a diagnosis of dementia. The average age was 80 years, and 99% were male. We found that only 16% remained on warfarin. We used statistical methods to account for reasons why a patient would or would not be treated with warfarin and found that those who continued to take warfarin had a significantly lower risk of stroke (HR 0.74, 95% Confidence interval 0.54- 0.99, p=0.47) and death (HR 0.72, 95% CI 0.60-0.87, p<0.01) compared to those who did not continue to take warfarin, without an increased risk of bleeding.

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Diabetes Drug May Enhance Melanoma Chemotherapy

MedicalResearch.com Interview with:

Bin Zheng, PhD Assistant Professor Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Charlestown, MA 02129

Dr. Bin Zheng

Bin Zheng, PhD
Assistant Professor
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.

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Gene Therapy Restores Hearing Down To A Whisper, in Mice

MedicalResearch.com Interview with:

Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA

Dr. Gwenaelle Geleoc

Gwenaelle Geleoc, PhD
Assistant Professor
Department of Otolaryngology
F.M. Kirby Neurobiology Center
Children’s Hospital and Harvard Medical School
Boston, MA

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

Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.

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Study Validates Good Quality Care Provided By Foreign-Trained Doctors

MedicalResearch.com Interview with:

Yusuke Tsugawa, MD, MPH, PhD Research Associate at Department of Health Policy and Management Harvard T.H. Chan School of Public Health

Dr. Yusuke Tsugawa

Yusuke Tsugawa, MD, MPH, PhD
Research Associate at Department of Health Policy and Management
Harvard T.H. Chan School of Public Health  

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

Response: Prior evidence has been mixed as to whether or not patient outcomes
differ between U.S. and foreign medical graduates.

However, previous studies used small sample sizes or data from a small number of states.
Therefore, it was largely unknown how international medical graduates
perform compared with US medical graduates.

To answer this question, we analyzed a nationally representative
sample of Medicare beneficiaries admitted to hospitals with a medical
condition in 2011-2014. Our sample included approximately 1.2 million
hospitalizations treated by 40,000 physicians. After adjusting for
severity of illness of patients and hospitals (we compared physicians
within the same hospital), we found that patient treated by
international medical graduates had lower mortality than patients
cared for by US medical graduates (adjusted 30-day mortality rate
11.2% vs 11.6%, p<0.001). We observed no difference in readmissions,
whereas costs of care was slightly higher for international medical
graduates.

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Intestinal and Blood-Brain Barrier Alterations Linked to Autism Spectrum Disorders

MedicalResearch.com Interview with:

Maria Rosaria Fiorentino, PhD

Dr. Maria Rosaria Fiorentino

Maria Rosaria Fiorentino, PhD
Assistant Professor at Harvard Medical School
Molecular Biologist at Mucosal Immunology and Biology Research Center
Massachusetts General Hospital East
Charlestown, MA 02129-4404

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

Response: Autism Spectrum Disorders (ASD) refers to complex neurodevelopmental disorders arising from the interaction of genes and environmental factors. There are no defined mechanisms explaining how environmental triggers can lead to these conditions. One hypothesis based on the gut-brain axis connection suggests that inappropriate antigens trafficking through an impaired intestinal barrier, followed by passage of these antigens through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to the disease.

Many Autism Spectrum Disorders children experience co-morbid medical conditions, including gastrointestinal (GI) dysfunctions whose underlying nature is poorly understood. Several clinical observations describe increased intestinal permeability in ASD with often conflicting findings. Permeability to neuroactive food antigens derived from the partial digestion of wheat (gliadorphins) and cow’s milk (casomorphins) has been reported in ASD. However, while evidence of a permeable gut barrier in ASD is increasingly reported, no information is available concerning a similar breach for the BBB. The BBB is a critical line of defense in the Central Nervous System, limiting the access of circulating solutes, macromolecules, and cells that could negatively impact neuronal activity. Dysfunctions of the BBB have been associated with numerous inflammatory neurologic disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson’s and Alzheimer’s disease.

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Physical Activity Linked to Improved Survival from Metastatic Colon Cancer

MedicalResearch.com Interview with:

Brendan John Guercio, M.D. Clinical Fellow in Medicine (EXT) Brigham and Women's Hospital

Dr. Brendan Guercio

Brendan John Guercio, M.D.
Clinical Fellow in Medicine (EXT)
Brigham and Women’s Hospital

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

Response: Sedentary lifestyle is a known risk factor for the development of colon cancer and has been associated with increased disease recurrence and mortality in patients with early stage colorectal cancer. This is the first study to our knowledge to show an association between increased physical activity (i.e. non-sedentary lifestyle) and improved survival and progression-free survival in patients with metastatic colorectal cancer.

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Migraine Increases Risk of Perioperative Stroke and Hospital Readmission

MedicalResearch.com Interview with:

Dr. Matthias Eikermann, MD, PhD Associate Professor of Anaesthesia, Harvard Medical School Clinical Director, Critical Care Division

Dr. Matthias Eikermann

Dr. Matthias Eikermann, MD, PhD
Associate Professor of Anaesthesia
Harvard Medical School
Clinical Director, Critical Care Division 

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

Response: Up to one fifth of the general population have migraine, a primary, chronic-intermittent headache disorder affecting the neuronal and vascular systems and characterized by severe headache accompanied by nausea and/or sensory hypersensitivities such as photophobia and phonophobia. In approximately 20-30% of patients, the headache phase is preceded or accompanied by transient focal neurological disturbances presenting as visual symptoms but also sensory, aphasic, or motor symptoms known as migraine aura.

Stroke is responsible for approximately 6.2 million deaths a year and is a leading global cause of long term disability. Considering that more than 50 million patients in hospital and 53 million ambulatory patients undergo surgical procedures in the United States every year.

We found that patients with migraine, particularly migraine with aura, undergoing a surgical procedure are at increased risk of perioperative ischemic stroke and readmission to hospital within 30 days after discharge.

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PET Scanning Highlights Link Between Stress and Heart Disease

MedicalResearch.com Interview with:

Dr Ahmed Tawakol MD Massachusetts General Hospital and Harvard Medical Schoo

Dr Ahmed Tawakol

Dr Ahmed Tawakol MD
Co-Director, Cardiac MR PET CT Program
Massachusetts General Hospital and
Harvard Medical School 

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

Response: While the link between stress and heart disease has long been established, the mechanism mediating that risk hasn’t been clearly understood. Animal studies showed that stress activates bone marrow to produce white blood cells, leading to arterial inflammation.  This study suggests an analogous path exists in humans. Moreover, this study identifies, for the first time in animal models or humans, the region of the brain (the amygdala) that links stress to the risk of heart attack and stroke.

The paper reports on two complementary studies.

The first analyzed imaging and medical records data from almost 300 individuals who had PET/CT brain imaging, primarily for cancer screening, using a radiopharmaceutical called FDG that both measures the activity of areas within the brain and reflects inflammation within arteries.  All participants in that study had no active cancer or cardiovascular disease at the time of imaging and each had information in their medical records on at least three additional clinical visits after imaging.

The second study enrolled 13 individuals with a history of post-traumatic stress disorder, who were evaluated for their current levels of perceived stress and received FDG-PET scanning to measure both amygdala activity and arterial inflammation.

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Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing PCI

MedicalResearch.com Interview with:

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center Professor of Medicine, Harvard Medical School Boston, MA 02115

Dr. Deepak L. Bhatt

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC
Executive Director of Interventional Cardiovascular Programs,
Brigham and Women’s Hospital Heart & Vascular Center
Professor of Medicine, Harvard Medical School
Boston, MA 02115

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

Response: Cangrelor is a potent, fast on, fast off, intravenous ADP receptor antagonist that is now available for use during PCI. Glycoprotein IIb/IIIa inhibitors are intravenous antiplatelet agents that work by a different mechanism. Doctors have asked whether there is any advantage to combining them or whether one class is preferable to the other during PCI.

We analyzed close to 25,000 patients from the CHAMPION trials. Cangrelor’s efficacy in reducing peri-procedural ischemic complications in patients undergoing PCI was present
irrespective of glycoprotein IIb/IIIa inhibitor administration. However, glycoprotein IIb/IIIa inhibitor use resulted in substantially higher bleeding rates, regardless of whether the patient was randomized to cangrelor or to clopidogrel.

Thus, in general, cangrelor and glycoprotein IIb/IIIa inhibitors should not routinely be combined. If an operator wishes to use a potent intravenous antiplatelet during PCI, cangrelor is similarly efficacious as glycoprotein IIb/IIIa inhibitors, but with less bleeding risk.

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