Genetic Cause and Clinical Cure Found For Rare Skin Disorder

MedicalResearch.com Interview with:

Keith Adam Choate, MD, PhD, FAAD Associate Professor of Dermatology, of Genetics and of Pathology Director of Research, Dermatology Yale University School of Medicine New Haven, CT

Dr Choate

Keith Adam Choate, MD, PhD, FAAD
Associate Professor of Dermatology,
Genetics and Pathology
Director of Research, Dermatology
Yale University School of Medicine
New Haven, CT

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

Response:  Over the last 10 years, we have systematically been examining patients with ichthyosis to identify new genetic causes of this group of disorders.  We found that autosomal recessive mutations in KDSR cause ichthyosis and that the resulting skin disease is effectively treated with isotretinoin.

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Phase 3 Studies Demonstrate Reduce Endometriosis-Associated Pain with Elagolix

MedicalResearch.com Interview with:

Hugh S. Taylor, M.D. Anitta O’keeffe Young Professor and Chair Departemnt of Obstetrics, Gynecology and Reproductive Sciences Yale School of Medicine Chief of Obstetrics and Gynecology Yale-New Haven Hospital

Dr. Taylor

Hugh S. Taylor, M.D.
Anitta O’keeffe Young Professor and Chair
Departemnt of Obstetrics, Gynecology and Reproductive Sciences
Yale School of Medicine
Chief of Obstetrics and Gynecology
Yale-New Haven Hospital

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

Response: Elagolix is an investigational, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that blocks endogenous GnRH signaling by binding competitively to GnRH receptors. Administration results in rapid, reversible, dose-dependent inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian production of the sex hormones, estradiol and progesterone, while on therapy.

Data from two replicate Phase 3 studies evaluating the efficacy and safety of elagolix were published in the New England Journal of Medicine. Elagolix demonstrated dose-dependent superiority in reducing daily menstrual and non-menstrual pelvic pain associated with endometriosis compared to placebo. At month three and month six, patients treated with elagolix reported statistically significant reductions in scores for menstrual pain (dysmenorrhea, DYS) and non-menstrual pelvic pain (NMPP) associated with endometriosis as measured by the Daily Assessment of Endometriosis Pain scale. The safety profile of elagolix was consistent across both Phase 3 trials and also consistent with prior elagolix studies.

Ultimately, the studies showed that both elagolix doses (150 mg QD and 200 mg BID) were effective in improving dysmenorrhea, non-menstrual pelvic pain and quality of life over 6 months in women with endometriosis-associated pain. The elagolix safety/tolerability profile was consistent with the mechanism of action.

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Fewer Heart Attacks and Strokes After Trans-Fat Restriction Laws in New York

MedicalResearch.com Interview with:

Eric J. Brandt, MD Yale University Cardiovascular Disease Fellow

Dr. Eric Brandt

Eric J. Brandt, MD
Yale University
Cardiovascular Disease Fellow

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

Response: From previous studies we know that industrial trans fatty acid (trans fat) consumption is linked to elevated risk for cardiovascular disease. Even small amounts of consumption can be deleterious to cardiovascular health. In New York state, there were 11 counties that restricted the use of trans fatty acids in eateries. We compared hospitalization for heart attacks and stroke from 2002 through 2013 in counties that did and did not have restrictions.

Our study found that when comparing populations within New York state that restricted the use of trans fat, compared to those that did not, there was an associated additional decline beyond temporal trends for heart attacks and stroke events combined by 6.2%.

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End-of-Life Care Transition Patterns of Medicare Beneficiaries

MedicalResearch.com Interview with:
Shi-Yi Wang MD, PhD.

Department of Chronic Disease Epidemiology
Yale School of Public Health
New Haven, CT

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

Response: Care at the end of life is often fragmented and poorly coordinated across different health providers. Multiple transitions in care settings can be burdensome to patients and their families as well as costly to society. Despite these concerns about care transitions in the end of life, we lack contemporary data on the number, timing, and overall pattern of healthcare transitions in the last 6 months of life.

This study adds to the extant literature by understanding transition trajectories, national variation of the transitions, and factors associated with transitions. We found that more than 80% of Medicare fee-for-service decedents had at least one health care transition and approximately one-third had ≥ 4 transitions in the last 6 months of life. We produced Sankey diagrams to visualize the sequences of healthcare transitions. The most frequent transition pattern involving at least four transitions: home-hospital-home (or skilled nursing facility)-hospital-healthcare setting other than hospital. There was substantial geographic variation in healthcare transitions in the United States. We found that several factors were associated with a significantly increased risk of having multiple transitions, including female gender, blacks, residence in lower income areas, presence of heart disease or kidney disease.

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Gene Expression-based Breast Cancer Index Can Improve Decision Making For ER+ Patients

MedicalResearch.com Interview with:

Tara Sanft, MD Assistant Professor of Medicine (Medical Oncology) Medical Director of Adult Survivorship Yale Cancer Center Survivorship Clinic

Dr. Tara Sanft

Tara Sanft, MD
Assistant Professor of Medicine (Medical Oncology)
Medical Director of Adult Survivorship
Yale Cancer Center Survivorship Clinic 

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

Response: Previous studies have demonstrated the benefit of extended endocrine therapy (EET) for hormone receptor-positive (HR+) breast cancer in preventing late relapse, however that benefit is limited to 3-5% of women where late recurrence was prevented or staved off. However, EET has become common practice and as a result we are exposing many patients to risks of side effects and toxicities associated with anti-estrogen therapies when they may not be benefitting, and, conversely may not be treating the patients that might actually benefit. There is a real need to better identify the patients who are both at most risk of late distant recurrence, and most likely to benefit from EET.

This prospective study included 141 patients with a mean age of 62. In the study, 83% of patients were postmenopausal, 73% were stage I.

Breast Cancer Index (BCI) is a gene expression-based test and is the only currently available validated biomarker that is both prognostic for late distant recurrence and predictive for likelihood of benefit from EET. The purpose of this prospective study was to assess the impact of BCI on: physician EET recommendations; physician confidence; patient satisfaction, anxiety, and decision-conflict; and the cost impact of BCI.

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Racial Disparities in Genetic Testing of Women With Breast Cancer

MedicalResearch.com Interview with:

Cary P. Gross, MD Section of General Internal Medicine Yale University School of Medicine New Haven, CT

Dr. Cary Gross

Cary P. Gross, MD
Section of General Internal Medicine
Yale University School of Medicine
New Haven, CT

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

Response: Prior work has demonstrated racial and socioeconomic disparities in breast cancer diagnosis, treatment, and outcomes.  As the oncology field has progressed over the past decade, the use of genetic testing to guide treatment decisions is one of the most exciting new developments.

Our team was concerned that these new gene tests, which can offer important benefits, may have the potential to exacerbate disparities further.  That is, if there is unequal access to gene testing among patients for whom it is recommended, then our progress against cancer will not be equitably shared among people of all races and ethnicities.

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Membership In Medical Schools’ Honor Society Skews Toward White Students

MedicalResearch.com Interview with:

Dowin Boatright, MD, MBA</strong> Department of Emergency Medicine Yale School of Medicine New Haven, Connecticut Fellow, Robert Wood Johnson Clinical Scholars Program Veterans Affairs Scholar

Dr. Dowin Boatright

Dowin Boatright, MD, MBA
Department of Emergency Medicine
Yale School of Medicine
New Haven, Connecticut
Fellow, Robert Wood Johnson Clinical Scholars Program
Veterans Affairs Scholar

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

Response: Studies have demonstrated racial and ethnic inequities in medicine, including disparities in the receipt of awards, research funding, and promotions. Yet few studies have examined the link between race and ethnicity and opportunities for medical school students.

Our results show that black and Asian medical school students are less likely to be selected for membership in a prestigious medical honor society, Alpha Omega Alpha (AΩA), than white medical school students.

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Antidepressants Have Variable Effects On Symptom Clusters

MedicalResearch.com Interview with:

Adam Chekroud PhD Candidate Human Neuroscience Lab

Adam Chekroud

Adam Chekroud
PhD Candidate
Human Neuroscience Lab
Department of Psychology
Yale University

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

Response: We know that depression includes a wide range of symptoms, from low mood and feeling worthless, to problems sleeping, slowed thinking, and suicidal ideation.

We wanted to know whether antidepressants work well in treating all of these symptoms, or whether they are primarily effective on certain kinds of symptoms.

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Hospital Readmissions Fell After Penalties Instituted But Then Plateaued

MedicalResearch.com Interview with:
Nihar R. Desai, MD, MPH

Assistant Professor of Medicine
Section of Cardiovascular Medicine, Yale School of Medicine
Center for Outcomes Research and Evaluation
Yale New Haven Health System

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

Response: Reducing rates of readmissions after hospitalization has been a major focus for patients, providers, payers, and policymakers because they reflect, at least partially, the quality of care and care transitions, and account for substantial costs. The Hospital Readmission Reduction Program (HRRP) was enacted under Section 3025 of the Patient Protection and Affordable Care Act (ACA) in March 2010 and imposed financial penalties beginning in October 2012 for hospitals with higher than expected readmissions for acute myocardial infarction (AMI), congestive heart failure (HF), and pneumonia among their fee-for-service Medicare beneficiaries. In recent years, readmission rates have fallen nationally, and for both target (AMI, HF, pneumonia) and non-target conditions.

We were interested in determining whether the Hospital Readmission Reduction Program (HRRP) associated with different changes in readmission rates for targeted and non-targeted conditions for penalized vs non-penalized hospitals?

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Neuroanatomy Accounts for Age-Related Changes in Risk Preferences.

MedicalResearch.com Interview with:
Ifat Levy, PhD

Associate Professor
Comparative Med and Neuroscience
Yale School of Medicine

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

Response: The proportion of older adults in the population is rapidly rising. These older adults need to make many important decisions, including medical and financial ones, and therefore understanding age-related changes in decision making is of high importance. Prior research has shown that older adults tend to be more risk averse than their younger counterparts when making choices between sure gains and lotteries. For example, asked to choose between receiving $5 for sure and playing a lottery with 50% of gaining $12 (but also 50% of gaining nothing), older adults are more likely than young adults to prefer the safe $5. We were interested in understanding the neurobiological mechanisms that are involved in these age-related shifts in preferences.

An earlier study that we have conducted in young adults provided a clue. In that study, we measured the risk preference of each participant (based on a series of choices they made between safe and risky options), and also used MRI to obtain a 3D image of their brain. Comparing the behavioral and anatomical measures, we found an association between individual risk preferences and the gray-matter volume of a particular brain area, known as “right posterior parietal cortex” (rPPC), which is located at the back of the right side of the brain. Participants with more gray matter in that brain area were, on average, more tolerant of risk (or less risk averse).

This suggested a very interesting possibility – that perhaps the increase in risk aversion observed in older adults is linked to the thinning of gray matter which is also observed in elders. In the current study we set out to test this hypothesis, by measuring risk preference and gray matter density in a group of 52 participants between the ages of 18 and 88. We found that, as expected, older participants were more risk averse than younger ones, and also had less gray matter in their rPPC. We also replicated our previous finding – that less gray matter was associated with higher risk aversion. The critical finding, however, was that the gray matter volume was a better predictor of increased risk aversion than age itself.  Essentially, if both age and the gray matter volume of rPPC were used in the same statistical model, rPPC volume predicted risk preferences, while age did not. Moreover, the predictive power was specific to the rPPC – when we added the total gray matter volume to the model, it did not show such predictive power.

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Predictors of Chemosensitivity in Triple Negative Breast Cancer

MedicalResearch.com Interview with:

Christos Hatzis, PhD Assistant Professor of Medicine Director of Bioinformatics, Breast Medical Oncology Yale Comprehensive Cancer Center Yale School of Medicine New Haven, CT

Dr. Christos Hatzis,

Christos Hatzis, PhD
Assistant Professor of Medicine
Director of Bioinformatics, Breast Medical Oncology
Yale Comprehensive Cancer Center
Yale School of Medicine
New Haven, CT

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

Response: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients.

Identifying chemosensitive triple negative breast cancers could significantly impact
the survival of patients with these difficult to treat cancers until novel targeted
therapies become available. We hypothesized that genomic somatic aberrations may
provide important molecular clues about chemosensitivity in TNBC. Our study used
a carefully selected cohort of 29 uniformly treated TNBC patients who either achieved
pathologic complete response (pCR) or had extensive residual disease after neoadjuvant
anthracycline/taxane chemotherapy.

MedicalResearch.com: What are the main findings?

Response: We sequenced the coding genomic DNA of TNBC tumors and compared the somatic mutations found in the two groups at the two extremes of the chemosensitivity spectrum.

Our analysis revealed that, although mutations in single genes were not individually predictive, TNBC tumors bearing mutations in genes involved in the androgen receptor
(AR) and FOXA1 pathways were much more sensitive to chemotherapy.
We also found that mutations that lowered the levels of functional BRCA1 or BRCA2 RNA
were associated with significantly better survival outcomes; we derived a BRCA
deficiency signature to define this new, highly chemosensitive subtype of TNBC.
BRCA-deficient TNBC tumors have a higher rate of clonal mutation burden, defined as
more clonal tumors with a higher number of mutations per clone, and are also associated
with a higher level of immune activation, which may explain their greater chemosensitivity.

MedicalResearch.com: What should readers take away from your report?

Response: Mutations in the AR/FOXA1 pathway provide a novel marker for identifying chemosensitive TNBC patients who may benefit from current standard-of-care chemotherapy regimens.

The newly defined RNA-based BRCA-deficient subtype includes up to 50% of the
Triple negative breast cancer tumors that appear to be immune primed, and it would be of interest to investigate combinations of chemotherapy with immunotherapies, which could provide clinical benefit for these patients. Although our study showed concordant results in three different datasets, our key findings need to be further validated in a larger, prospectively designed study with archival samples.

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

Response: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in Triple negative breast cancer and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. Our results suggest that the combination of immunotherapies with ACT chemotherapy or PARP inhibitors might be an effective strategy for treating BRCA-D tumors.

The strong connection of ACT chemosensitivity and immune activity with a new transcriptionally defined BRCA-D phenotype could help inform future therapeutic strategies for TNBC patients.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic AnalysisTingting Jiang,Weiwei Shi,Vikram B. Wali,Lőrinc S. Pongor,Charles Li,Rosanna Lau,Balázs Győrffy,Richard P. Lifton,William F. Symmans,Lajos Pusztai,Christos Hatzis

PLOS Medicine Published: December 13, 2016http://dx.doi.org/10.1371/journal.pmed.1002193

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Cranberry Juice Capsules Ineffective in Reducing UTIs in Older Women

MedicalResearch.com Interview with:

Manisha Juthani-Mehta, MD, FACP, FIDSA, FSHE</strong>A Associate Professor, Section of Infectious Diseases Infectious Diseases Fellowship Program Director Yale University School of Medicine

Dr. Manisha Juthani-Mehta

Manisha Juthani-Mehta, MD, FACP, FIDSA, FSHEA
Associate Professor, Section of Infectious Diseases
Infectious Diseases Fellowship Program Director
Yale University School of Medicine

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

Response: One of the first studies that showed that cranberry juice was effective in older women living in nursing homes and assisted living facilities was published in 1994. Since that time, there have been multiple conflicting studies as to the effect of cranberry juice or capsules. We started our study in 2012. Shortly thereafter, a Cochrane review suggested that the vast body of evidence did not suggest that cranberry products work for UTI prevention, but questions still existed as to whether the appropriate dose of cranberry was being tested. Since cranberry juice is hard for older women to drink (taste, sugar load, volume), capsules at a high dose of the active ingredient (72mg type A proanthocyanidin [PAC}) was worthwhile to test.

This study was a clinical trial of two cranberry capsules with a total of 72mg of proanthocyanidin (pac) vs two placebo capsules to prevent bacteria in the urine of older women who live in nursing homes.

Unfortunately, it didn’t work. It also didn’t reduce the number of hospitalizations, deaths, antibiotics used, or antibiotic resistant bugs in the urine.

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US Task Force Recommends Primary Care Interventions to Support Breastfeeding

MedicalResearch.com Interview with:

Ann Kurth, Ph.D., C.N.M., R.N. USPSTF Task Force member Dean of the Yale School of Nursing

Dr. Ann Kurth

Ann Kurth, Ph.D., C.N.M., R.N.
USPSTF Task Force member
Dean of the Yale School of Nursing

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

Response: Breastfeeding is beneficial for both mothers and their babies, with the evidence showing that babies who are breastfed are less likely to get infections such as ear infections, or to develop chronic conditions such as asthma, obesity, and diabetes. For mothers, breastfeeding is associated with a lower risk for breast and ovarian cancer and type 2 diabetes. While breastfeeding rates have been rising in recent decades—with 80 percent of women starting to breastfeed and just over half still doing so at six months—they are still lower than the Healthy People 2020 targets and the Task Force wanted to review the latest evidence around how clinicians can best support breastfeeding.”

After balancing the potential benefits and harms, the Task Force found sufficient evidence to continue to recommend interventions during pregnancy and after birth to support breastfeeding. This recommendation includes the same types of interventions the Task Force recommended in 2008, such as education about the benefits of breastfeeding, guidance and encouragement, and practical help for how to breastfeed.

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Mibefradil Dihydrochoride with Hypofractionated Radiation for Recurrent Glioblastoma

MedicalResearch.com Interview with:

Nataniel Lester-Coll, MD Chief Resident in Radiation Oncology at Yale New Haven, Connecticut

Dr. Nataniel Lester-Coll

Nataniel Lester-Coll, MD
Chief Resident in Radiation Oncology at Yale
New Haven, Connecticut 

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

Response: Recurrent Glioblastoma Multiforme (GBM) has limited treatment options and the prognosis is poor. Mibefradil diydrochloride was identified using a high-throughput compound screen for DNA double stranded break repair inhibitors. Mibefradil was found to radiosensitize GBM tumor cells in vitro and in vivo. Based on these findings, we sought to determine the maximum tolerated dose of mibefradil and radiation therapy in a Phase I recurrent GBM study. Eligible patients with recurrent  Glioblastoma Multiforme received Mibefradil over a 17 day period, with hypofractionated radiation (600 cGy x 5 fractions). There are 18 patients currently enrolled who have completed treatment. Thus far, there is no clear evidence of radionecrosis. A final dose level of 200 mg/day was reached as the maximum tolerated dose. The drug was very well tolerated at this dose. We saw intriguing evidence of enhanced local control in selected cases. Patients enrolled in a translational substudy who received Mibefradil prior to surgery were found to have adequate levels of Mibefradil in resected brain tumor tissue.

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Intestinal Microbiome Linked to Obesity and Fat Storage in Children

MedicalResearch.com Interview with:

Nicola Santoro, MD, PhD Associate Research Scientist in Pediatrics (Endocrinology) Yale University

Dr. Nicola Santoro

Nicola Santoro, MD, PhD
Associate Research Scientist in Pediatrics (Endocrinology)
Yale University

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

Response: The study start from previous observations showing an association between the gut microbiota and obesity.

Similarly to what previously described in adults and in children, we found an association between the gut microbiota and obesity. We took a step further and also observed that the gut flora is associated to body fat partitioning (amount of fat in the abdomen). Moreover, we observed that the effect of microbiota could be mediated by the short chain fatty acids a product of gut flora.

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Declining Admission Rates and 30-Day Readmissions Linked

MedicalResearch.com Interview with:

Kumar Dharmarajan, MD, MBA Assistant Professor of Medicine (Cardiology) Cardiovascular Medicine: Center for Outcomes Research & Evaluation (CORE) Yale School of Medicine

Dr. Kumar Dharmarajan

Kumar Dharmarajan, MD, MBA
Assistant Professor of Medicine (Cardiology)
Cardiovascular Medicine: Center for Outcomes Research & Evaluation (CORE)
Yale School of Medicine

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

Response: Programs from the Centers for Medicare and Medicaid Services simultaneously promote strategies to lower hospital admissions and readmissions. However, there is concern that hospitals in communities that successfully reduce admissions may be penalized, as patients that are ultimately hospitalized may be sicker and at higher risk of readmission. We therefore examined the relationship between changes from 2010 to 2013 in admission rates and thirty-day readmission rates for elderly Medicare beneficiaries.

We found that communities with the greatest decline in admission rates also had the greatest decline in thirty-day readmission rates, even though hospitalized patients did grow sicker as admission rates declined. The relationship between changing admission and readmission rates persisted in models that measured observed readmission rates, risk-standardized readmission rates, and the combined rate of readmission and death.

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WATCHMAN Device to Control Atrial Fibrillation May Be More Cost Effective than Anticoagulation

MedicalResearch.com Interview with:

Dr. James V. Freeman MD Assistant professor of cardiology and Assistant Clinical Professor of Nursing Internal Medicine Yale School of Medicine

Dr. James Freeman

Dr. James V. Freeman MD
Assistant professor of cardiology and
Assistant Clinical Professor of Nursing
Internal Medicine
Yale School of Medicine

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

Dr. Freeman: Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost-effectiveness compared to anticoagulation has not been evaluated using all available contemporary trial data.

We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost-effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of PROTECT AF and PREVAIL randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios (ICER) compared to warfarin and dabigatran were $20,486 and $23,422 per quality adjusted life year (QALY), respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 QALYs, respectively) and more costly.

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Newly Discovered Phages Can Target Antibiotic Resistance

MedicalResearch.com Interview with:

Paul E. Turner Chair of Ecology and Evolutionary Biology, Yale University Microbiology Faculty, Yale School of Medicine New Haven, CT 06520

Dr. Paul Turner

Paul E. Turner Ph.D
Chair of Ecology and Evolutionary Biology,
Yale University
Microbiology Faculty,
Yale School of Medicine
New Haven, CT 06520

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

Dr. Turner:  Our study concerned the problem of multi-drug resistance in the opportunistic pathogen Pseudomonas aeruginosa, especially the search for promising bacteriophage candidates with biological properties to effectively target these bacteria. We tested whether the binding of phage to outer membrane proteins of multidrug efflux pumps would exert selection for bacteria to avoid virus attack by compromising pump performance – thus suffering increased sensitivity to traditional antibiotics. We discovered a naturally occurring phage that forced the desired evolutionary trade-off; we showed that clinical isolates of P. aeruginosa gained phage resistance, while simultaneously becoming susceptible to several antibiotics that are ordinarily useless in controlling these MDR pathogens.

MedicalResearch.com: What should readers take away from your report?

Dr. Turner: Newly discovered phages can be highly effective at targeting antibiotic resistance mechanisms in MDR bacteria, causing these pathogens to become antibiotic sensitive. Medical use of such resistance targeting phages could greatly improve clinical outcomes by reversing antibiotic resistance in MDR bacterial pathogens.

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

Dr. Turner: We recommend utilizing a ‘rational drug design’ approach to combating antibiotic resistance, especially use of phages to target efflux pump systems in MDR bacteria. This approach could greatly reduce the burden to rely on drugs of last resort and would extend the lifetime of our current antibiotic library.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Benjamin K. Chan, Mark Sistrom, John E. Wertz, Kaitlyn E. Kortright, Deepak Narayan, Paul E. Turner. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Scientific Reports, 2016; 6: 26717 DOI:10.1038/srep26717

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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IVC Filters Widely Used in Attempt To Prevent Pulmonary Embolism

MedicalResearch.com Interview with:

Behnood Bikdeli MD Department of Internal Medicine and Center for Outcomes Research and Evaluation (CORE) Yale University School of Medicine New Haven, CT 06510

Dr. Behnood Bikdeli

Behnood Bikdeli MD
Department of Internal Medicine and Center for Outcomes Research and Evaluation (CORE)
Yale University School of Medicine
New Haven, CT 06510 

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

Response: The idea of closing the path of inferior vena cava (IVC) to prevent blood clots migrating to the pulmonary circulation and causing a pulmonary embolism (PE) has been around for over 150 years. We were aware than many practitioners might think of IVC filters for that reason, and specifically with the introduction of retrievable filters in recent years; that have made it more palatable for referring physicians.

However, there is a paucity of high-quality data to suggest the efficacy of IVC filters. The two existing large trials did not show a mortality benefit from use of filters, and the guidelines have very narrow indications for use of IVC filters in patients who have already had a pulmonary embolism.

Having said that, we wondered whether despite the absence of high-quality comparative effectiveness data, filters might be commonly used in patients with PE, particularly among older adults who are a vulnerable population (at higher risk of PE, at higher risk of PE complications; but also less likely to receive other advanced therapies for PE).

Our study common use of IVC filters among older adults in the US; with over 75% relative increase in use of IVC filters from 1999 to 2010 (from ~5000 patients with PE in 1999 to ~9000 patients with PE in 2010). We also noted wide regional variations in the use of IVC filters (e.g. highest in the South Atlantic and lowest in the Mountain region). Such differences fundamentally persisted over time. In addition, we noted declining short-term and 1-year mortality rates in patients with pulmonary embolism over time, irrespective of whether or not they received an IVC filter.

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Brain Neurons That Detect Blood Glucose Identified

MedicalResearch.com Interview with:

Sabrina Diano, Ph.D. Professor Depts. Ob/Gyn, Neuroscience and Comparative Medicine Associate Chair for Faculty Development Dept Ob/Gyn and Reproductive Sciences Program in Cell Signaling and Neurobiology of Metabolism Yale University School of Medicine and Graduate School

Dr. Sabrina Diano

Sabrina Diano, Ph.D.
Professor, Depts. Ob/Gyn, Neuroscience and Comparative Medicine
Associate Chair for Faculty Development
Dept Ob/Gyn and Reproductive Sciences
Program in Cell Signaling and Neurobiology of Metabolism
Yale University School of Medicine and Graduate School 

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

Dr. Diano: We have been studying the intracellular mechanisms that regulate glucose sensing by the brain. We found that in a specific area of the brain (called ventromedial nucleus of the hypothalamus) a small group of neurons (the brain cells) are able to sense increased glucose levels in the blood via their mitochondria, the energy powerhouse of the cells. This mitochondrial change enables these neurons to get activated, which in turn, results in a reduction of  glucose levels in the blood due to an increased muscles glucose utilization.

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States That Spend More On Social Services Have Lower AIDS Deaths

MedicalResearch.com Interview with:

Kristina Marie Talbert-Slagle, PhD Lecturer in Epidemiology (Microbial Diseases) and in Public Health (Health Policy); Senior Scientific Officer, Yale Global Health Leadership Institute Yale School of Public Health

Dr. Talbert-Slagle

Kristina Marie Talbert-Slagle, PhD
Lecturer in Epidemiology (Microbial Diseases) and in Public Health (Health Policy); Senior Scientific Officer, Yale Global Health Leadership Institute
Yale School of Public Health

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

Dr. Talbert-Slagle: The interest for this study originally came as a result of work done by Elizabeth Bradley, PhD, co-author of The American Health Care Paradox.  In the book, Dr. Bradley compared spending rates of social services to health care services between the U.S. and other countries and found that while the U.S. invested more money in health care services than any other country we had worse health outcomes.  By contrast, countries that spent more on social services per dollar spent on health care had better outcomes.

We applied that same idea to AIDS.  There are still more than 50,000 cases of HIV/AIDS diagnosed in the U.S. each year.  Although many medical advances have been made in treatment and prevention of this infection, we were curious as to why rates of HIV/AIDS have remained stagnate.  We wanted to explore how spending relates to differences in case rates among the states and found a significant difference among states regarding social service and public health spending related to HIV/AIDS.  We looked at all 50 states’ spending habits over the past 10 years and discovered that states that invested more money in social services such as education, housing, and nutrition per person in poverty had significantly lower rates of HIV/AIDS deaths.

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Shave Margins During Breast Cancer Surgery Reduces Overall Costs

Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACSAssociate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT 06510

Dr.  Chagpar

MedicalResearch.com Interview with:
Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS

Associate Professor, Department of Surgery
Director, The Breast Center
Smilow Cancer Hospital at Yale-New Haven
Assistant Director — Global Oncology
Yale Comprehensive Cancer Center
Yale University School of Medicine

Medical Research: What is the background for this study?

Dr. Chagpar: Up to 40% of women undergoing breast conserving surgery for breast cancer will have to return to the operating room due to positive margins (or cancer cells being found at the edge of what was removed at the initial surgery).  We recently reported the results of a randomized controlled trial, published in the New England Journal of Medicine, in which we found that taking a little more tissue circumferentially around the cavity (called shave margins) at the time of the initial surgery could cut the need for re-excisions (or return trips to the operating room) in half.  In this analysis, we evaluate the implications of this technique on costs.

Medical Research: What are the main findings?

Dr. Chagpar: We found that taking additional tissue added 10 minutes to the initial operative time.  While taking cavity shave margins resulted in higher costs associated with the initial surgery due to increased OR time and additional tissue requiring pathologic evaluation, this is offset by the significant reduction in the need for re-excisions.  From a payer perspective, costs including facility and provider fees for the index surgery as well as any breast surgery care in the ensuing 90 days was roughly $750 less for patients who had shave margins taken than for those who did not, although this did not reach statistical significance.

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MRI May Detect More Early Contralateral Breast Cancer But Not Prevent Advanced Disease

Shiyi Wang, MD, PhD Assistant Professor of Epidemiology (Chronic Diseases) Yale School of Public Health

Dr. Wang

MedicalResearch.com Interview with:
Shiyi Wang, MD, PhD

Assistant Professor of Epidemiology (Chronic Diseases)
Yale School of Public Health

Medical Research: What is the background for this study?

Dr. Wang: As magnetic resonance imaging (MRI) of the breast has become part of medical care, there is increasing concern that this highly sensitive test might identify health problems that otherwise would not have had an impact on the patient – so called “overdiagnosis”. However, even if MRI use leads to overdiagnosis, the main “theoretical” benefit of early detection by MRI is to prevent future advanced diseases, the prognosis of which is deleterious. A systematic literature review found that, compared to mammography and/or ultrasound, MRI had a 4.1% incremental contralateral breast cancer (breast cancer in the opposite breast) detection rate. At this point, the impact of MRI on long-term contralateral breast cancer outcomes remains unclear. 

Medical Research: What are the main findings?

Dr. Wang: Analyzing the Surveillance, Epidemiology, and End Results-Medicare dataset, we compared two groups of women who had breast cancer (one group receiving an MRI, and the other not) in terms of stage-specific contralateral breast cancer occurrences. We found that after five years, the MRI group had a higher detection rate of cancer in the opposite breast than the non-MRI group (7.2 % vs. 4.0%). Specifically, MRI use approximately doubles the detection rate of early stage contralateral breast cancer, but does not decrease the incidence of advanced stage contralateral breast cancer occurrences after a 5-year follow-up. Our results indicate that nearly half of additional breast cancers detected by the preoperative MRI were overdiagnosed, which means that many of these occult cancers not detected by MRI would not have become clinically evident over the subsequent 5 years. There was no evidence that MRI use was benefiting women because the rate of advanced cancer was similar in the MRI and the non-MRI groups.

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Walnuts Improve Diet, Cardiometabolic Health in Patients At Risk of Diabetes

David L. Katz, MD, MPH, FACPM, FACP, FACLM Director, Yale University Prevention Research Center Griffin Hospital President, American College of Lifestyle Medicine Founder, True Health Initiative

Dr. David Katz

MedicalResearch.com Interview with:
David L. Katz, MD, MPH, FACPM, FACP, FACLM

Director, Yale University Prevention Research Center
Griffin Hospital
President, American College of Lifestyle Medicine
Founder, True Health Initiative

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

Dr. Katz: the evidence that nuts in general, and walnuts in particular, have health promoting properties is vast and conclusive.  In our own prior research, we have shown that daily ingestion of walnuts ameliorates overall cardiac risk in type 2 diabetics (http://www.ncbi.nlm.nih.gov/pubmed/19880586) and that the same intervention improves cardiac risk and body composition in adults at risk for diabetes (http://www.ncbi.nlm.nih.gov/pubmed/23756586).  Our prior studies, and work by others, suggest that despite their energy density, walnuts may exert a favorable influence on calorie intake and weight, because of their very high satiety factor.  We also know that walnuts are highly nutritious overall, and suspect that those who add walnuts to their diets are apt to ‘bump’ something less nutritious out, thereby improving the overall quality of their diets as measured objectively.

Accordingly, we designed the new study to look at the effects of daily walnut ingestion on diet quality, weight, and cardiac risk measures in a larger cohort of adults at risk for type 2 diabetes (ie, central obesity, indications of insulin resistance) over a longer period of time.  We also wondered whether the addition of some 350 daily calories from walnuts would result in the displacement of a comparable number of calories from other sources, so we compared the effects of the intervention with, and without, counseling to help people ‘make room’ for the walnut calories.

We found again that walnuts improved overall cardiac risk status, as measured by endothelial function- essentially, a direct measure of blood vessel health and blood flow.  We also found that adding walnuts to the diet significantly improved overall diet quality, and did not lead to weight gain.  Walnuts also improved the lipid profile.  When walnut intake was combined with counseling for overall calorie intake, there was a significant decline in waist circumference.

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Less Than 50% of Type 1 Diabetic Youth Receive Insulin Pump Therapy

MedicalResearch.com Interview with:
Jennifer Lynn Sherr, MD, PhD
Assistant Professor of Pediatrics (Endocrinology)
Yale School of Medicine

Medical Research: What is the background for this study?

Dr. Sherr: A joint consensus statement released in 2007 by leading pediatric diabetologists recommended pump therapy be considered in children and adolescents with suboptimal diabetes control, wide fluctuations in blood glucose levels regardless of HbA1c, and when insulin regimen compromises lifestyle, indications which would encompass the vast majority of youth living with type 1 diabetes. Yet, variations in the support for and use of pump technology has been reported even in developed Western countries. Therefore, the present study was undertaken to assess the frequency of pump use across three large registries of pediatric type 1 diabetes patients: the German/Austrian Prospective Diabetes Follow-up Registry (DPV), the US T1D Exchange (T1DX), and the English/Welsh National Paediatric Diabetes Audit (NPDA).

Medical Research: What are the main findings?

Dr. Sherr: Our data demonstrate that fewer than 50% of youth in these five countries are using pump therapy. Those on pump therapy had mean lower HbA1c levels as compared to those on injection therapy. Notably, a three-fold greater use of insulin pumps was noted in thetype 1 diabetes and DPV as compared to the NPDA, which may be due to the National Institute for Health Care Excellence (NICE) guidelines limiting pump use in these countries.
Pump use amongst the registries varied widely by age. Additionally, the data demonstrate lower pump use in both ethnic minorities and males.

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

Dr. Sherr: As data from three trans-Atlantic registries have identified the beneficial glycemic effect of insulin pump use with mean A1c being 0.5% lower than what is achieved by those on injection therapy, application of this technology for all youth with type 1 diabetes should be a focus of care. Clinicians should investigate their prescribing patterns and be aware that pump use can be applied regardless of patient age, gender, or ethnic background. Patients should advocate for themselves in order assure they are being considered for this treatment modality.

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

Dr. Sherr: Assessment of factors related to determining who is eligible for pump therapy and how we can assure equal access regardless of age, ethnic status or gender will be important. Additionally, exploration of health policy allowing for coverage of such medical devices is warranted to assure our youth are afforded the best care possible. This will become critically important, as the next revolution of diabetes care is a mechanical solution, specifically the artificial pancreas, which relies on insulin pump use for system performance.

Citation:

Diabetologia. 2015 Nov 7. [Epub ahead of print]

Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries.

Sherr JL1, Hermann JM2, Campbell F3, Foster NC4, Hofer SE5, Allgrove J6, Maahs DM7, Kapellen TM8, Holman N9, Tamborlane WV1, Holl RW2, Beck RW10,Warner JT11; T1D Exchange Clinic Network, the DPV Initiative, and the National Paediatric Diabetes Audit and the Royal College of Paediatrics and Child Health registries.

 

Jennifer Lynn Sherr, MD, PhD (2015). Less Than 50% of Type 1 Diabetic Youth Receive Insulin Pump Therapy 

Genetic Testing Can Detect, Protect Patients Prone To Thoracic Aortic Aneurysm

John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of MedicineMedicalResearch.com Interview with:
John A. Elefteriades, MD
William W.L. Glenn Professor of Surgery
Chief of Cardiothoracic Surgery
Director, Aortic Institute at Yale-New Haven
Yale University School of Medicine

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

Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems.

In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm.

In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm–all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent.  Continue reading

Hospital Costs For Maternity Care Vary Widely

Xiao Xu, Ph.D. Assistant Professor Department of Obstetrics, Gynecology & Reproductive Sciences Yale School of MedicineMedicalResearch.com Interview with:
Xiao Xu, Ph.D. Assistant Professor

Department of Obstetrics, Gynecology & Reproductive Sciences
Yale School of Medicine

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

Dr. Xiao Xu: While research has shown hospital variation in costs of care for other conditions, we know little about whether and how hospitals differ in costs of childbirth related care. With nearly 4 million births each year, childbirth is the most common reason for hospital admission in the U.S. Understanding the pattern and causes of variation in resource utilization during childbirth among hospitals can help inform strategies to reduce costs. Our study used data from 463 hospitals across the country and analyzed hospital costs of maternity care for low-risk births. We found that hospital varied widely in average facility costs per maternity stay. Continue reading

Health Care Organizations Require Different Tactics To Implement Change

MedicaIngrid Nembhard, PhD, MS Associate Professor, Yale School of Public Health & Yale School of Management Associate Director, Health Care Management Program YalelResearch.com Interview with:
Ingrid M. Nembhard PhD MS
Yale University
New Haven, CT

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

Dr. Nembhard: Many health care organizations (hospital, medical groups,  etc.) have sought to address well-documented quality problems by implementing evidence-based innovations, that is, practices, policies, or technologies that have been proven to work in other organizations. The benefits of these innovations are often not realized because adopting organizations experience implementation failure—lack of skillful and consistent use of innovations by intended users (e.g., clinicians). Past research estimates that implementation failure occurs at rates greater than 50% in health care. The past work also shows organizational factors expected to be facilitators of implementation are not always helpful.

In this work, we examined a possible explanation for the mixed results: different innovation types have distinct enabling factors. Based on observation and statistical analyses, we differentiated role-changing innovations, altering what workers do, from time-changing innovations, altering when tasks are performed or for how long. We then examined our hypothesis that the degree to which access to groups that can alter organizational learning—staff, management, and external network— facilitates implementation depends on innovation type. Our longitudinal study of 517 hospitals’ implementation of evidence-based practices for treating heart attack confirmed our thesis for factors granting access to each group: improvement team’s representativeness (of affected staff), senior management engagement, and network membership. Although team representativeness and network membership were positively associated with implementing role-changing practices, senior management engagement was not. In contrast, senior management engagement was positively associated with implementing time-changing practices, whereas team representativeness was not, and network membership was not unless there was limited management engagement.

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JAK Inhibitors Offer Hope For Vitiligo

Brett King, M.D., Ph.D. Assistant Professor of Dermatology Yale University School of Medicine MedicalResearch.com Interview with:
Brett King, M.D., Ph.D.
Assistant Professor of Dermatology
Yale University School of Medicine

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

Dr. King: Treatment options for vitiligo are limited and often ineffective. This report highlights the possibility of targeted therapy of vitiligo using a relatively new class of medicines called Janus kinase (JAK) inhibitors. Based upon our understanding of vitiligo, JAK inhibition interrupts interferon gamma signaling, which perpetuates depigmentation.

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

Dr. King: There is hope that effective treatments will soon be available for vitiligo.

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

Dr. King: Clinical trials using different JAK inhibitors, both topically and orally, are needed. Also, we need to better understand how important JAK 1/2 vs JAK 1/3 inhibition is to repigmentation.

Citation:

Craiglow BG, King BA. Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy. JAMA Dermatol. Published online June 24, 2015. doi:10.1001/jamadermatol.2015.1520.

Brett King, M.D., Ph.D., Assistant Professor of Dermatology, & Yale University School of Medicine (2015). JAK Inhibitors Offer Hope For Vitiligo 

Immediate Postpartum Contraception Implant Is Cost Effective, But Most Insurance Plans Don’t Cover It

Aileen Gariepy, MD, MPH Assistant Professor Section of Family Planning Department of Obstetrics, Gynecology, and Reproductive Sciences Yale School of Medicine New Haven, CT 06510MedicalResearch.com Interview with:
Aileen Gariepy, MD, MPH

Assistant Professor Section of Family Planning
Department of Obstetrics, Gynecology, and Reproductive Sciences
Yale School of Medicine
New Haven, CT

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

Dr. Gariepy: Women who have just given birth are often highly motivated to prevent a rapid, repeat pregnancy.  For women who desire the contraceptive implant, a highly effective reversible form of contraception that is placed in the arm and can last for 3 years, new research shows that it is more cost-effective to place the implant while women are still in the hospital after giving birth, compared to delaying insertion to the postpartum visit 6-8 weeks later which is currently the most common practice.

When the costs associated with the implant insertion and the costs of unintended pregnancy are compared in women who receive immediate contraceptive implant insertion (while still in the hospital after giving birth) to women who are asked to come back in 6-8 weeks for the implant insertion (delayed insertion), immediate insertion is expected to save $1,263 per patient.  Based on these estimates, for every 1,000 women using postpartum implant, immediate placement is expected to avert 191 unintended pregnancies and save $1,263,000 compared with delayed insertion in the first year. Cost savings would continue to increase for the second and third year after insertion.

In fact, over half of U.S. pregnancies are unintended.  Maternal and infant care costs for unintended pregnancies amount to $11.1 billion annually for public insurance programs alone. The immediate postpartum period (after delivery but before discharge home) provides an ideal opportunity for initiating contraceptives as patients are motivated and timing is convenient.

However, the majority of insurance company policies do not provide coverage for insertion of the contraceptive implant when the new mother is still in the hospital.  This lack of reimbursement is the most significant barrier to providing this highly effective contraceptive method for women who have just delivered a baby.  Surprisingly, the reason most insurance companies do not offer reimbursement for immediate insertion is due to an outdated insurance protocol, “the global obstetric fee” which precludes separate reimbursement of individual procedures (like inserting the implant).

The main reason that immediate insertion results in cost savings is because more women will get the implant compared to a strategy of delayed insertion.  Women can get pregnant again within 4 weeks of delivering a baby.  Starting contraception as soon as possible after giving birth is important because most women will resume sexual activity before their postpartum office visit and therefore will be at risk of pregnancy. And approximately 35% of women do not return for a postpartum visit.

Even for women who want another pregnancy soon, the implant has benefits.  When women conceive and deliver a baby within 2 years of last giving birth, there is a significantly higher risk of poor maternal and neonatal outcomes, including preterm birth, low birth weight, and even early neonatal and maternal death.  Birth spacing is better for moms and babies.
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Most Patients With Atrial Fibrillation Are Symptomatic and Have Impaired Quality of Life

James V. Freeman MD, MPH, MS Yale University School of Medicine New Haven, CTMedicalResearch.com Interview with:
James V. Freeman MD, MPH, MS
Yale University School of Medicine
New Haven, CT

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

Dr. Freeman: Atrial fibrillation (AF) substantially increases the risk of major adverse clinical outcomes such as stroke and death, but it can also cause frequent symptoms, affect patient’s functional status, and impair their quality of life. While prior studies have reported the range of AF-related symptoms in patient populations, these studies were generally from highly selected patients and referral based practices, and may not reflect results in community practice or results with contemporary AF management. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a large, contemporary, prospective, community-based outpatient cohort, we evaluated the type and frequency of symptoms in patients with Atrial fibrillation. In addition, we measured the degree to which physician assessed symptom severity (using the European Heart Rhythm Association [EHRA] classification system) was correlated with patient reported quality of life (assessed by the Atrial Fibrillation Effect on QualiTy-of-life [AFEQT] questionnaire). Finally, we association between symptoms or quality of life with clinical outcomes, including death, hospitalization, stroke and major bleeding.

In our community-based study, the majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3-4). EHRA symptom class was well correlated with the AFEQT quality of life score (Spearman correlation coefficient -0.39). Over 1.8 years of follow-up, Atrial fibrillation symptoms were associated with a higher risk of hospitalization (adjusted HR for EHRA ≥2 vs EHRA 1 1.23, 95% CI 1.15-1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted HR for lowest quartile of AFEQT vs highest 1.49, 95% CI 1.2-1.84), but not other major adverse events including death. Continue reading

Taking A Little More Tissue After Breast Cancer Removal May Save Reduce Need For Further Surgery

Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACSAssociate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT 06510MedicalResearch.com Interview with:
Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery
Director, The Breast Center — Smilow Cancer Hospital at Yale-New Haven, Assistant Director — Global Oncology, Yale Comprehensive Cancer Center
Program Director, Yale Interdisciplinary Breast Fellowship
Yale University School of Medicine Breast Centerm
New Haven, CT,

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

Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer — the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease.  The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind.  No one likes to go back to the operating room — so we asked the question, “How can we do better?”.  Surgeons have debated various means of obtaining clear margins.  Some have advocated taking routine cavity shave margins — a little bit more tissue all the way around the cavity after the tumor is removed at the first operation.  Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) — i.e., selective margins.  We conducted a randomized controlled trial to answer this question.  We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit.  After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would (“NO SHAVE”), or take a bit more tissue all the way around the cavity (“SHAVE”).

Patients in both groups were evenly matched in terms of baseline characteristics.  The key finding was that patients who were randomized to the “SHAVE” group half as likely to have positive final margins and require a re-operation than patients in the “NO SHAVE” group.  On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results.  While the volume of tissue excised in the “SHAVE” group was higher than in the “NO SHAVE” group, the distribution of patient-perceived cosmetic outcomes were identical in both groups.  Complication rate was also no different between the two groups.  We will be following patients for five years for long-term cosmetic and recurrence outcomes. Continue reading

Disability At End Of Life Linked To Number Of Acute Hospitalizations

Thomas M. Gill, M.D Humana Foundation Professor of Medicine (Geriatrics) Professor of Epidemiology (Chronic Diseases) and of Investigative Medicine Director Yale Program on Aging and Yale Center for Disability and Disabling Disorders Director, Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related ResearchMedicalResearch.com Interview with:
Thomas M. Gill, M.D
Humana Foundation Professor of Medicine (Geriatrics)
Professor of Epidemiology  and of Investigative Medicine
Director Yale Program on Aging and Yale Center for Disability and Disabling Disorders
Director, Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related Research

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

Response: Understanding the disabling process at the end of life is essential for informed decision-making among older persons, their families, and their physicians.

We know from prior research that the course of disability at the end of life does not follow a predictable pattern for most older persons.  This raises the question about what is driving the development and progression of disability at the end of life.

We identified six distinct trajectories of disability in the last year of life, ranging from the least disabled to most disabled.  We found that the course of disability in the last year of life closely tracked the monthly prevalence of hospitalization for each of the six trajectories.

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Breast Cancer Costs Rise But So Has Survival

Cary P. Gross MD Professor of General Medicine, of Epidemiology (Chronic Diseases) and of Faculty of Arts and Sciences Yale University School of MedicinMedicalResearch.com Interview with:
Cary P. Gross MD
Professor of General Medicine, of Epidemiology (Chronic Diseases) and of Faculty of Arts and Sciences
Yale University School of Medicine

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

Dr. Gross: There has been increasing concern about the rising cost of healthcare overall and in the medicare program in particular.  Yet little is known about how key aspects of value – costs and outcomes – have changed for breast cancer care over time.  We showing that there was a substantial increase in the cost of Breast cancer care between. 1990s and 2000s but also an improvement in survival.

Citation:

Older Women With Localized Breast Cancer: Costs And Survival Rates Increased Across Two Time Periods Aaron J. Feinstein,

Jessica Long, Pamela R. Soulos, Xiaomei Ma, Jeph Herrin, Kevin D. Frick, Anees B. Chagpar, Harlan M. Krumholz, James B. Yu, Joseph S. Ross, and Cary P. Gross

Health Aff April 2015 34:4592-600; doi:10.1377/hlthaff.2014.1119

 
MedicalResearch.com Interview with: Cary P. Gross MD (2015). Breast Cancer Costs Rise But So Has Survival 

Law Brings More Student Athletes To ER For Sports-Related Concussions

Dr. Pina Violano, RN, PhD Trauma Department, Yale-New Haven Hospital, Injury Free Coalition for Kids of New Haven Yale-New Haven Children’s Hospital New Haven 06510, CTMedicalResearch.com Interview with:
Dr. Pina Violano, RN, PhD

Trauma Department, Yale-New Haven Hospital,
Injury Free Coalition for Kids of New Haven
Yale-New Haven Children’s Hospital
New Haven 06510, CT

MedicalResearch: What is the background for this study?

Dr. Violano: In July of 2012, Connecticut became one of the first states to enact legislation to ensure the safety and appropriate evaluation and management of sports-related concussions (SRC) among High School students. SRCs are a common occurrence in high school sports with their diagnosis increasing over the last decade. While the exact reasons are not known, public health campaign efforts and education may have facilitated improvement in the evaluation and detection of sports-related concussions and may have contributed to increase awareness and treatment.

MedicalResearch: What are the main findings?

Dr. Violano: Evaluation of two emergency department records revealed a marked increase in the frequency of high school student athletes being treated for sports-related concussions after the implementation of Connecticut’s SRC law. This suggests that Connecticut’s legislation is effective in improving the evaluation and detection of sports-related concussions in high school students.

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Skin Damaged by Sunlight Even When Out of the Sun

Douglas E. Brash, PhD Professor of Therapeutic Radiology and Dermatology Yale School of Medicine New Haven, CTMedicalResearch.com Interview with:
Douglas E. Brash, PhD

Professor of Therapeutic Radiology and Dermatology
Yale School of Medicine New Haven, CT

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

Dr. Brash: We wanted to know whether the origin of melanoma differed from other cancers because of the melanin. It has long been known that blondes and redheads are sensitive to sunlight, but the prevailing view was that this was because their skin is light. But there are light-skinned, dark-haired people in countries near the equator and they don’t have the high skin cancer incidence seen in Australia. Several labs, including ours, had irradiated cells or mice with UV and found more cell death in cells containing melanin than cells lacking melanin. In the last couple of years, two papers have focused attention on the issue; one study found that irradiating mice with UVA only gave melanomas if the skin contained melanin and the other study found that mice genetically predisposed to UV-induced melanoma developed melanomas even without UV if they also had red melanin.

The most important findings are:

First, our skin continues to be damaged by sunlight even when we’re out of the sun.

Second, the melanin pigment in your skin is bad for you as well as good: it may be carcinogenic as well as protective.

Third, the chemistry underlying these events, chemical excitation of electrons, has not been seen in mammals before. Continue reading

Risk of Rehospitalization After Cardiac Admission Remain Elevated For Protracted Period

MedicalResearch.com Interview with:
Kumar Dharmarajan MD MBA
Section of Cardiovascular Medicine
Yale University School of Medicine, New Haven, CT 06510

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

Dr. Dharmarajan: We know that patients are at high risk for rehospitalization and death in the month after hospital discharge. Yet little is known about how these risks dynamically change over time for the full year after hospitalization. This information is needed for patients and hospitals to set realistic goals and plan for appropriate care.

We found that the risk of rehospitalization and death decline slowly following hospitalization and remain elevated for many months. We also found that specific risk trajectories vary by discharge diagnosis and outcome. For example, risk remains elevated for a longer period of time following hospitalization for heart failure compared with hospitalization for acute myocardial infarction. For all 3 conditions we studied (heart failure, heart attacks, and pneumonia), risk of rehospitalization remained elevated for a longer period of time than the risk of death.

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Coffee May Lower Melanoma Risk

MedicalResearch.com Interview with:
Erikka Loftfield
Doctoral student at the Yale School of Public Health
Fellow at the National Cancer Institute

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

Response: Previous studies have reported conflicting results on the association between coffee drinking and melanoma. We sought to clarify this relationship using data from the large NIH-AARP Diet and Health Study. We followed over 400,000 retirees aged 50 to 71 years at study entry for an average of 10 years. Participants were asked to report typical coffee intake. During the course of follow-up nearly 3,000 cases of malignant melanoma occurred. In our study, we observed that individuals who reported the highest total coffee intake (4 cups/day) had about 20% lower risk of malignant melanoma compared with those who did not consume coffee.

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Banishing Eggs From Diet May Lead To Worse Food Choices

David L. Katz, MD MPH FACPM FACP President of the American College of Lifestyle Medicine Yale University Prevention Research Center Derby, CT; Griffin Hospital, Derby, CTMedicalResearch.com Interview with:
David L. Katz, MD MPH FACPM FACP
President of the American College of Lifestyle Medicine
Yale University Prevention Research Center
Derby, CT; Griffin Hospital, Derby, CT

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

Dr. Katz: We have long advised patients at risk for heart disease to avoid eggs- but have thought relatively little about what they might wind up eating instead.  While coronary care units banish eggs, they routinely serve white bread, bagels, pancakes, etc.  In general, the exclusion of eggs from the diet may result in more sugary, starchy foods- and if so, might do net harm.  We have previously studied egg intake in healthy and dyslipidemic adults, and seen no adverse effects on blood flow or biomarkers in the short term (6 wks).  This study examined this issue in adults with coronary artery disease- and again, no adverse effects were seen.

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Elders Requiring Fewer Hospital Days After Aortic Valve Surgery

Karthik Murugiah MBBS Fellow in Cardiovascular Medicine Yale School of Medicine Center for Outcomes Research and Evaluation (CORE) New Haven, CT 06510MedicalResearch.com Interview with:
Karthik Murugiah MBBS

Fellow in Cardiovascular Medicine
Yale School of Medicine
Center for Outcomes Research and Evaluation (CORE)
New Haven, CT 06510

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

Response: Aortic valve disease is common among older people and frequently requires valve replacement. 1-year survival after open surgical aortic valve replacement is high (9 in 10 survive the year after surgery). Our study focuses on the experience of these survivors in terms of the need for hospitalization during the year after surgery.

Among patients >65 years of age enrolled in Medicare who underwent surgical replacement of their aortic valve and survived at least one year, 3 in 5 were free from hospitalization during that year. Both, the rates of hospitalization and the average total number of days spent in the hospital in the year following surgery have been decreasing all through the last decade (1999 to 2010).

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Hypofractionated Whole-Breast Irradiation for Early-Stage Breast Cancer

Dr. James Yu Yale School of Medicine Cancer Outcomes, Public Policy, and Effectiveness Research Center Yale School of Medicine Department of Therapeutic Radiology New Haven, Connecticut MedicalResearch.com Interview with:
Dr. James Yu
Yale School of Medicine
Cancer Outcomes, Public Policy, and Effectiveness Research Center
Yale School of Medicine
Department of Therapeutic Radiology
New Haven, Connecticut

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

Response: Hypo fractionated radiation has been shown to be safe and effective, and more convenient for women with early stage breast cancer after lumpectomy.  It also has been identified by ASTRO as a practice that physicians can adopt to reduce healthcare expenses for patients and for society.  We looked at the National Cancer Database, a database created by the American College of Surgeons for trends in the use of hypo fractionated radiation for breast cancer through 2011.  We found that the use of hypofractionated radiation had increased to 22.8% in 2011.  I found this remarkable as it predated the ASTRO choosing widely guidelines, and indicated to me that physicians were already thinking of ways of making treatment more convenient and affordable for patients and insurers.
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Lifestyle Modifications Decrease Coronary and Carotid Atherosclerosis

MedicalResearch.com Interview with
Dr. Sunny Jhamnani MD
Clinical Fellow in Cardiology at Yale School of Medicine

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

Dr. Jhamnani:  Lifestyle modifications are the crux of atherosclerotic disease management. However adherence to them is not adequate. Additionally, randomized controlled trials (RCTs) looking effects of diet and exercise on atherosclerotic disease progression have not been convincing.

We did a systematic review and a meta-analysis of all RCTs looking at the effects of diet and exercise on coronary and carotid atherosclerotic disease progression. We found that , lifestyle modifications were associated with a decrease in coronary atherosclerotic burden in percent stenosis by -0.34 (95% CI: -0.48 to -0.21) standardized mean difference (SMD), with no significant publication bias and heterogeneity (p:0.21, I2:28.25). Similarly, in the carotids, there was a decrease in the carotid intimal medial thickness in mm by -0.21 (95% CI: -0.36 to -0.05) SMD and by -0.13 (95% CI: -0.25 to -0.02) SMD, before and after accounting for publication bias and heterogeneity (p:0.13, I2:39.91 and p:0.54, I2:0), respectively.
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Ebola: Infectiousness Greatly Increases With Disease Progression

Dr. Dan YasminMedicalResearch.com Interview with:
Dan Yamin PhD
Postdoctoral Associate
Yale School of Public Health
New Haven, CT 06520

 

Medical Research: What is the background for this study?

Dr. Yamin: With limited resources, West Africa is currently overwhelmed by the most devastating Ebola epidemic known to date. In our research, we seek to address two questions:

  • 1) who is mostly responsible for transmission? and
    2) what intervention programs should be applied to contain the current Ebola outbreak?

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Opioid Dependence: Buprenorphine Maintenance May Be Better Than Taper for Treatment Retention

David A. Fiellin, M.D. Professor of Medicine, Investigative Medicine and Public Health Yale University School of MedicineMedicalResearch.com Interview with
David A. Fiellin, M.D.
Professor of Medicine, Investigative Medicine and Public Health
Yale University School of Medicine

 

Medical Research: What are the main findings of the study?

Dr. Fiellin: The main finding of our randomized clinical trial, conducted in primary care, was that among prescription opioid dependent patients, ongoing buprenorphine therapy resulted in better treatment retention and reduced illicit opioid use when compared to buprenorphine taper (detoxification).

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No Adverse Effects of Short-Term Daily Egg Ingestion in Coronary Artery Disease

David L. Katz, MD, MPH, FACPM, FACP Director, Yale University Prevention Research Center Griffin HospitalMedicalResearch.com Interview with:
David L. Katz, MD, MPH, FACPM, FACP
Director, Yale University Prevention Research Center
Griffin Hospital

 

Medical Research: What are the main findings of the study?

Dr. Katz: We did not see any adverse effects of short-term, daily egg ingestion in adults with established coronary artery disease.

Medical Research: What was most surprising about the results?

Dr. Katz: Eggs are routinely banned from ‘heart healthy diets.’  in particular eggs are always absent from cardiac care units, with egg beaters substituting.  However, these same units routinely serve products with refined starch and added sugar.  The scientific basis for excluding eggs from diets to improve cardiac health has long been suspect.  Here, we show that in the short term at least, there are no discernible harms of daily egg ingestion even in adults with heart disease.
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Can A Video Game Help Your Teenagers Understand HIV Risks?

Lynn E. Fiellin, M.D. Associate Professor of Medicine Director, play2PREVENT Lab Yale University School of Medicine New Haven, CT 06510MedicalResearch.com Interview with
Lynn E. Fiellin, M.D.
Associate Professor of Medicine
Director, play2PREVENT Lab
Yale University School of Medicine
New Haven, CT 06510

Medical Research: What are the main findings of the study?

Dr. Fiellin: The current findings are part of a larger study evaluating an interactive evidence-based video game, PlayForward: Elm City Stories, developed on the iPad and targeting risk reduction and HIV prevention in 333 young teens (ages 11-14). The larger study is examining a range of outcomes including knowledge, intentions, self-efficacy and actual behaviors and we are collecting at baseline, 6 weeks, 3, 6, 12, and 24 months. We are examining these outcomes in our experimental group compared with a control group playing a set of off-the-shelf games on the iPad. The current findings of the 196 teens who have completed the 6 weeks of gameplay and for whom we have baseline and 3 month data, reveal that, while the two groups had no differences in their baseline HIV risk knowledge, the PlayForward group had statistically significant gains in knowledge at 6 weeks (p<0.0001), sustained at 3 months (p<0.01). In addition, examining the association between exposure to the game and performance on the standardized assessments revealed that the number of game levels completed (a measure of exposure to the intervention) was positively correlated with knowledge gains measured at 3 months (r=0.42; p<0.001).

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Heart Attack: Young and Female Patients Have Worse Outcomes

Aakriti Gupta, MD, MBBS  Center for Outcomes Research and Evaluation Yale-New Haven Hospital, New Haven, ConnecticutMedicalResearch.com Interview with:
Aakriti Gupta, MD, MBBS
Center for Outcomes Research and Evaluation
Yale-New Haven Hospital,
New Haven, Connecticut

Medical Research: What were the main findings?


Dr. Gupta:
Using a national database, we found that heart attack hospitalization rates for patients under the age of 55 have not declined in the past decade while their Medicare-age counterparts have seen a 20 percent drop.

We also found that among younger patients below 55 years of age, women fare worse because they have longer hospital stays, and are more likely to die in the hospital after a heart attack. Young women were also more likely to have higher prevalence of co-existing medical conditions including diabetes, high blood pressure and higher cholesterol levels. Overall, all patient groups in the study saw increases in these conditions including diabetes and high blood pressure in the past decade.

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12 Percent of American Children Experience Maltreatment

Dr. Christopher Wildeman PhD Associate Professor of Sociology Faculty fellow at the Center for Research on Inequalities and the Life Course (CIQLE), and at the Institution for Social and Policy Studies (ISPS) at Yale University.MedicalResearch.com Interview with
Dr. Christopher Wildeman PhD
Associate Professor of Sociology
Faculty fellow at the Center for Research on Inequalities and the Life Course (CIQLE), and at the Institution for Social and Policy Studies (ISPS) at Yale University.

MedicalResearch.com: What are the main findings of the study?

Dr. Wildeman: There are four key findings in the study.

First, the cumulative risk of having a confirmed maltreatment report any time between birth and age 18 is much higher than most people would have thought. Fully 1 in 8 American children will experience this event at some point.

Second, the risk of experiencing this event is highly unequally distributed, with Black and Hispanic experiencing it much more than Hispanic, White, and (especially) Asian children. Between 1 in 4 and 1 in 5 Black children will have a confirmed maltreatment report at any time in their childhood. For Native American, the risk is about 1 in 7.

Third, the risk of maltreatment is quite similar for boys and girls.

Finally, the highest risks of child maltreatment are in the first few years of life, suggesting that interventions aiming to diminish maltreatment should focus on parents with very young children.
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Diabetes: In-Hospital Mortality Risk Has Decreased Over Time

MedicalResearch.com Interview with:
Neel M. Butala, AB
Medical student at Yale School of Medicine
New Haven, Connecticut

MedicalResearch.com: What are the main findings of the study?

Answer: We found that patients with diabetes had a disproportionate reduction in in-hospital mortality relative to patients without diabetes over the decade from 2000 to 2010.

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Mutated Gene Associated with Metabolic Syndrome

MedicalResearch Interview with:
Arya Mani, M.D. Department of Internal Medicine and Genetics Yale Cardiovascular Research Center Yale, New Haven CT Arya Mani, M.D.
Department of Internal Medicine and Genetics
Yale Cardiovascular Research Center
Yale, New Haven CT

MedicalResearch: What are the main findings of the study?

Dr. Mani: Our group has identified a gene that when mutated it causes a form of truncal (central) obesity that is associated with a cluster of coronary artery disease risk factors, including high blood pressure, insulin resistance and possibly elevated blood lipids. These associated risk factors are collectively known as the metabolic syndrome, which may lead to development of diseases such as diabetes and coronary artery disease, both of which were very prevalent in the populations we studied. All identified mutations by our group have been so far gain of function mutations, which means they increased the activity of the gene in pathways related to adipogenesis and gluconeogenesis.
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