Automated Churchhill Program Sequences Entire Human Genome In 90 Minutes

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Peter White, Ph.D. Principal Investigator, Center for Microbial Pathogenesis Director, Biomedical Genomics Core Director of Molecular Bioinformatics, The Research Institute at Nationwide Children's Hospital Assistant Professor of Pediatrics, The Ohio State UniversityMedicalResearch.com Interview with:
Peter White, Ph.D.
Principal Investigator, Center for Microbial Pathogenesis
Director, Biomedical Genomics Core
Director of Molecular Bioinformatics, The Research Institute at Nationwide Children’s Hospital
Assistant Professor of Pediatrics, The Ohio State University

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

Dr. White: Next generation sequencing has revolutionized genomics research and has opened the door to a new era of genomic medicine. It’s now possible to sequence a patients entire genome in about two days, but the output from the sequencer must go through multiple computationally challenging steps before it can be processed for clinically relevant information. The challenge we found is that this data analysis process was requiring days to perform, by highly qualified bioinformaticians and required enormous computational resources.

To overcome the challenges of analyzing that large amount of genomic sequence data, we developed a computational pipeline called “Churchill”, which we published in the latest issue of Genome Biology (http://genomebiology.com/2015/16/1/6/abstract). Churchill fully automates the analytical process required to take raw sequence data through a series of complex and computationally intensive processes, ultimately producing a list of genetic variants ready for clinical interpretation and tertiary analysis. The major impact of our work was the development of a novel balanced parallelization strategy that allows efficient analysis of a whole genome sequencing sample in as little as 90 minutes.

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Integrated Health Care Reduced Racial Disparities in Colon Cancer Treatment

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Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305MedicalResearch.com Interview with:
Kim F. Rhoads, MD, MS, MPH, FACS
Assistant Professor of Surgery
Director, Community Partnership Program
Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305

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

Dr. Rhoads: Colon cancer is the 3rd most common cancer in US men and women and is the 2nd most common cause of cancer death. For at least 2 decades, minorities with colon cancer have suffered a 15-20% additional risk of death when compared with non-minority patients. Our study set out to understand the influence of the location where treatment was delivered and the quality of care received, on overall survival and racial disparities.

We examined more than 30,000 patients who were diagnosed and treated for colon cancer in California from 2001 through 2006.  Using cancer registry data linked to state level inpatient data and hospital information, we compared the rates of National Comprehensive Cancer Network (NCCN) guideline adherence and mortality by location of care and by race. We found that patients treated within an integrated health system (IHS) received NCCN guideline based care at higher rates than those treated outside the system—about 3% higher rates of surgery; and more than 20% higher rates of stage appropriate chemotherapy. The rates of guideline based care were nearly equal between the racial groups treated inside the IHS.  Propensity score matched comparisons revealed a lower risk of death for all patients and no racial disparities associated with treatment within the Integrated system.  For patients treated outside IHS, the disparity in mortality was explained by accounting for differences in receipt of evidence based care by race.

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Performance Improvement CME Improved Psoriasis Care By Dermatologists

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Robert S. Kirsner, MD, PhD, FAAD Interim Chairman and Harvey Blank Professor in Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine Director, University of Miami Hospital Wound Center Chief of Dermatology, University of Miami HospitalMedicalResearch.com Interview with:
Robert S. Kirsner, MD, PhD, FAAD

Interim Chairman and Harvey Blank Professor in Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine
Director, University of Miami Hospital Wound Center
Chief of Dermatology, University of Miami Hospital

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

Dr. Kirsner: Psoriasis is common, affecting 7.5 million Americans. The major indication of psoriasis is chronic inflammation of the skin. It is characterized by disfiguring, scaling and erythematous plaques that may be painful or pruritic and may cause significant quality of life issues. Psoriasis may also cause joint pain and more recently has been associated with metabolic syndrome, diabetes, cardiovascular disease, dyslipidemia, hypertension and nonalcoholic fatty liver disease. Thus, patients may be physically and emotionally impacted by psoriasis.

The American Academy of Dermatology (Academy) developed a Performance Improvement (PI) CME activity to enhance dermatologists’ care of psoriasis patients by allowing them to evaluate their practice using patient charts, utilize evidence-based strategies to overcome self-identified gaps, and then re-measure their performance using charts for patients seen after practice changes were implemented.

It was found that the PI CME activity significantly improved dermatologists’ overall documentation of patient history, patient counseling for lifestyle behaviors and shared decision-making ability. For example, dermatologists who participated in and completed this PI CME activity improved practice performance by either inquiring about or documenting to a greater extent comorbidities (particularly cardiovascular disease), drug costs and interactions, patient preference, other medical problems, and severity of disease, resulting in an overall improvement in documented clinical behaviors.

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Childhood Obesity Levels Stabilizing But Remain High

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Dr Cornelia HM van Jaarsveld and Prof Martin C Gulliford, Department of Primary Care and Public Health Sciences King’s College London, London, UKMedicalResearch.com Interview with:
Dr Cornelia HM van Jaarsveld and Prof Martin C Gulliford

Department of Primary Care and Public Health Sciences
King’s College London, London, UK

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

Response: Overweight and obesity in children have increased dramatically since the 1960s with important clinical and economic impacts, especially among those who become obese adults. Consequently, understanding trends in obesity is of increasing importance for monitoring population health and informing policy initiatives. Current trends suggest that a majority of the world’s population will be either overweight or obese by 2030. However, recent reports suggest that the increasing trend in overweight and obesity in children may have leveled off since 2000. But, in many countries data are based on a limited number of time points and relatively small surveys, limiting definitive conclusions and not allowing examining trends in subgroups by sex and age. Moreover, only a few countries have data on younger children (aged under 6 years).

Our study aimed to use primary care electronic health records to examine prevalence of overweight and obesity in 2 to 15 year old children in England and to compare trends over two decades, from 1994 to 2003 and from 2004 to 2013.

Medical Research: What are the main findings?

Response: We found that currently about a third of children in the UK are overweight or obese. We also found that overweight and obesity prevalence increased during decade 1 (1994-2003) but stabilized in decade 2 (2004-2013). This was observed in both sexes and the in younger age groups (2-5 year and 6-10 year). However, rates continued to increase in older children (11-15 year), albeit at a slower speed than in decade 1 (1994-2003).

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Some Prescription Formularies Discourage HIV Patient Enrollment

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Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public HealthMedicalResearch.com Interview with:
Douglas B. Jacobs B.S., MD/MPH Candidate

Harvard T.H. Chan School of Public Health

Medical Research: What is the background for this study?

Response: In May 2014, a formal complaint submitted to the Department of Health and Human Services contended that four Florida insurers were structuring their formularies in a way that discouraged enrollment from HIV positive beneficiaries. These insurers placed all HIV drugs, including generics, on the highest cost-sharing tiers.

This formal complaint served as the impetus for this research. We wanted to discover if this was a phenomenon that was isolated to Florida, or if it was national in scope, and what the implications would be for HIV positive beneficiaries. As such, we analyzed what we called “adverse tiering”—in which all drugs for certain conditions are placed in the highest cost sharing tiers—in 12 states in the federal marketplace. We compared cost-sharing for a commonly prescribed class of HIV medication, called Nucleoside Reverse Transcriptase Inhibitors, or NRTIs.

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Electronic Reminder Improved Asthma Medication Adherence

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MedicalResearch.com Interview with:
Amy Chan  
BPharm(Hons) RegPharmNZ  MPS  ANZCP
Pharmacist / PhD candidate
Department of Paediatrics Auckland Hospital
Faculty of Medical & Health Sciences
University of Auckland  Auckland, New Zealand

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

Response: Asthma is one of the most common childhood conditions, affecting 1 in 4 children in New Zealand.  Although there are many effective medications available for asthma, of which the most important are inhaled corticosteroids, asthma control remains suboptimal due to poor adherence.  In children, adherence to regular preventive asthma therapy is about 50%, and can be as low as 30%.  Our randomised controlled trial looked at use of an electronic monitoring device with an in-built audiovisual reminder to see if it improved adherence and asthma control.  We recruited 220 children aged between 6-15yrs, who presented to the emergency department with asthma and randomised them to receive the device either with the audiovisual function enabled or disabled.  It found that those who received the audiovisual reminder (the intervention arm) took a median of 84% of their inhaled corticosteroids compared to just 30% in those who did not receive the reminder (control arm).  This equates to a 180% improvement in adherence.  We found significant improvements also in asthma control (including reduced asthma symptoms and increased participation in daily activities) and a reduction in reliever use from 17.4% to 9.5% in those who received the reminder. Continue reading

Added Sugar More Harmful Than Other Carbohydrates For Promoting Diabetes

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MedicalResearch.com Interview with:
James J. DiNicolantonio, PharmD Associate Editor BMJ Open Heart Cardiovascular Research Scientist Saint Luke's Mid America Heart InstituteJames J. DiNicolantonio, PharmD
Associate Editor BMJ Open Heart
Cardiovascular Research Scientist
Saint Luke’s Mid America Heart Institute

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

Dr. DiNicolantonio: We performed a comprehensive literature review comparing the isocaloric exchange of added sugars (sucrose, also known as table sugar, or high fructose corn syrup) versus other types of carbohydrates (such as lactose found in milk, glucose, starch, or dextrose).  Our main findings were that “a calorie isn’t a calorie,” i.e., that added sugars are more harmful than other carbohydrates even when matched for calories for promoting pre-diabetes and diabetes and the related morbidity and mortality associated with these diseases

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New Mayo Model Better Predicts Breast Cancer Risk After Benign Biopsy

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MedicalResearch.com Interview with:
Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD
Professor of Surgery
Mayo Clinic, Rochester.

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

Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT).

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Study Addresses Strategies US Adults Use to Save On Prescription Drug Costs

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MedicalResearch.com Interview with:
Robin A. Cohen, Ph.D

Medical Research: What is the background for this study?

Dr. Cohen: Estimates are based on data collected from the 2013 National Health Interview Survey (NHIS). The NHIS is a survey conducted by the Centers for Disease Control and Prevention’s (CDC) National Center for Health Statistics. NHIS collects information about health and health care of the civilian noninstitutionalized population of the United States. In 2013, questions about strategies used to reduce prescription drug cost were asked of more than 34,000 adults aged 18 and over.

Medical Research: What are the main findings?

Dr. Cohen: To save money, almost 8% of U.S. adults (7.8%) did not take their medication as prescribed, 15.1% asked a doctor for a lower-cost medication, 1.6% bought prescription drugs from another country, and 4.2% used alternative therapies.

Adults aged 18–64 (8.5%) were nearly twice as likely as adults aged 65 and over (4.4%) to have not taken their medication as prescribed to save money.

Among adults aged 18–64, uninsured adults (14.0%) were more likely than those with Medicaid (10.4%) or private coverage (6.1%) to have not taken their medication as prescribed to save money.

The poorest adults—those with incomes below 139% of the federal poverty level—were the most likely to not take medication as prescribed to save money.

Among adults aged 65 and over, those living with incomes in the 139-400% FPL range were more likely than adults living in lower or higher income thresholds to have asked their provider for a lower cost prescription to save money.

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New Hypertension Guidelines Found To Be Cost-Effective

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Andrew Moran, MD, MPH Herbert Irving Assistant Professor of Medicine Columbia University Division of General Medicine Presbyterian Hospital 9th floor East room 105 New York, NY 10032MedicalResearch.com Interview with:
Andrew Moran, MD, MPH
Herbert Irving Assistant Professor of Medicine
Columbia University Division of General Medicine
Presbyterian Hospital  New York, NY 10032

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

Response: In 2014, a panel appointed by the Eighth Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure (JNC 8) recommended new guidelines for high blood pressure (hypertension ) treatment in U.S. adults.  The guidelines made sweeping changes to the prior guidelines and stirred up controversy among hypertension and public health experts.  Essentially, the panel recommended more conservative treatment targets that narrowed the population eligible for treatment with blood pressure-lowering medications.  Nonetheless, about 28 million U.S. adults have uncontrolled hypertension even under the new more conservative guidelines.  We asked the question:  are the new guidelines cost-effective? That is, does treating this common condition with the available medicines add more health and reduce medical costs?  It is surprising that this question has rarely been answered before.

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Traumatic Brain Injury: Platelets Plus DDAVP Found Not To Improve Outcomes

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Dennis Kim, MD Los Angeles Biomedical Research Institute (LA BioMed) Researcher    MedicalResearch.com Interview with:
Dennis Kim, MD
Los Angeles Biomedical Research Institute                                                                                                                

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

Dr. Kim: More than 1.7 million people in the U.S. alone suffer a traumatic brain injury (TBI) every year, often resulting in permanent disabilities or death. Up to half of these patients will experience progression of bleeding inside or around the brain, the occurrence of which is associated with an increased risk of death.

A common treatment to prevent progression of “traumatic intracranial hemorrhage” is the transfusion of platelets, which are irregular shaped cells that cause blood to clot, and the administration of desmopressin (DDAVP), a naturally occurring hormone used to treat bleeding and a number of other medical conditions. Researchers at LA BioMed conducted a three-year retrospective study of the records of patients admitted to a Level 1 trauma center with traumatic brain injury between Jan. 1, 2010 and Dec. 31, 2012. Of the 408 patients who fit the criteria, 126 received platelet transfusions and DDAVP and 282 did not.

Overall, 37% of the patients demonstrated progression of traumatic intracranial hemorrhage within four hours of admission. We compared outcomes for patients who received platelet transfusions and DDAVP and patients who did not receive this therapy. Our comparison found no significant differences in mortality or hemorrhage progression between the two groups. We reported our findings in a study that was recently published online ahead of print in the Journal of Neurotrauma.

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Two Gene Mutations Linked To Deadly Ovarian Cancer

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Dr. Terry Magnuson PhD Vice Dean for Research Department of Genetics, School of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599MedicalResearch.com Interview with:
Dr. Terry Magnuson PhD
Vice Dean for Research
Department of Genetics, School of Medicine
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599

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

Response: Ovarian clear-cell carcinoma is a lethal form of ovarian cancer with limited therapeutic options. Recent patient-derived tumor sequencing studies support a strong genetic basis for the disease, but the roles of gene mutations in cancer causation are still unclear. We observed rapid induction of ovarian clear-cell carcinoma in mice that were genetically engineered to carry mutations in ARID1A and PIK3CA−the two most frequently mutated genes. Comparisons between human and mouse tumors uncovered a downstream role for the Interleukin-6 (IL-6) cytokine-signaling pathway in tumor progression. Thus, ARID1A and PIK3CA mutations cause ovarian clear-cell carcinoma and promote tumor cell growth by acting upon the IL-6 signaling pathway.

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Lab Turns Stem Cells Into Hair Bulbs That Grow Hair

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Alexey Terskikh, Ph.D. Associate Professor Department of Developmental and Stem Cell Biology Sanford-Burnham Medical Research Institute La Jolla, CAMedicalResearch.com Interview with:
Alexey Terskikh, Ph.D. Associate Professor
Department of Developmental and Stem Cell Biology
Sanford-Burnham Medical Research Institute
La Jolla, CA

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

Dr. Terskikh: Hair loss is a wide spread human condition with an unmet need for hair replacement. In the United States alone, over 40 million men and 21 million women are affected by hair loss. I have been interested in the differentiation of human pluripotent stem cells into various cell including neural crest cells. In-vivo neural crest cells give rise to a multitude of cell types, including dermal papilla cells, which populate the bulb of hair follicles and regulate hair growth. We have established new method to differentiate human pluripotent stem cells into dermal papilla-like (DP-like) cells, with a goal of inducing hair growth. To find out whether DP-like cells induce hair growth we transplanted these cells under the skin of mice (which have a small amounts of white hair) along with the skin cells from dark-haired mice. We observed the growth of new black hairs suggesting the induction of hair growth by transplanted human DP-like cells.

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Study Attacks Breast Cancer Metastases With Seizure Medication

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William J. Brackenbury, Ph.D. MRC Fellow Department of Biology University of York, Heslington, York UKMedicalResearch.com Interview with:
William J. Brackenbury, Ph.D
.
MRC Fellow Department of Biology
University of York, Heslington, York UK

Medical Research: What is the background for this study?

Dr. Brackenbury: Metastasis, the spread of cancer cells from the primary tumour to secondary sites, e.g. the lungs or bones, is the main cause of deaths from cancer. However, there are no effective treatments available to slow or stop this devastating aspect of the disease. We and others have found that sodium channels, normally present in neurons and muscle cells, are up-regulated in metastatic breast cancer cells. Sodium channels appear to regulate the behaviour of these cancer cells, helping them to move and squeeze their way out of the primary tumour as they invade and metastasise on their way to distant sites. This suggests that sodium channels might be useful new therapeutic targets for drugs that could slow metastasis.

Medical Research: What are the main findings?

Dr. Brackenbury: Sodium channels are important drug targets for treating epilepsy. We have found that the antiepileptic drug phenytoin, which is a sodium channel blocker, reduces tumour growth and metastasis in a preclinical model of breast cancer. We found that phenytoin reduces proliferation of cancer cells within the primary tumour. It also reduces local invasion of cancer cells into the surrounding fat and muscle, and reduces the number of cells metastasising to distant sites in the liver, lungs and spleen. Continue reading

Genetic Basis For Acute Lymphoblastic Leukemia Drug Toxicity Identified

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MedicalResearch.com Interview with:
Jun J. Yang  Ph.D.

Assistant Member Dept. of Pharm. Sci.
St. Jude Children’s Research Hospital
Memphis, TN 38105

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

Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine).

In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics.

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Targeted MR/Ultrasound Biopsy May Improve Prostate Cancer Diagnosis

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MedicalResearch.com Interview with:
Mohummad Minhaj Siddiqui, MD
AssiMohummad Minhaj Siddiqui, MD Assistant Professor of Surgery - Urology Director of Urologic Robotic Surgery University of Maryland School of Medicine andstant Professor of Surgery – Urology
Director of Urologic Robotic Surgery
University of Maryland School of Medicine and

Peter A. Pinto, M.D Head, Prostate Cancer Section  Director, Fellowship Program  Urologic Oncology Branch National Cancer Institute  National Institutes of Health  Bethesda, Maryland 20892-1210 Peter A. Pinto, M.D
Head, Prostate Cancer Section  Director, Fellowship Program
Urologic Oncology Branch National Cancer Institute  National Institutes of Health  Bethesda, Maryland

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

Response: For men suspected of having prostate cancer due to an elevated PSA or abnormal digital rectal exam, the next step in their diagnostic workup has traditionally been a standard 12-core biopsy to evenly sample the entire gland.  Unlike most other cancers, prostate cancer is one of the few solid tumors left which is diagnosed by randomly sampling the gland with the hope of biopsying the tumor, if it is present.  This paradigm has been largely due to the fact that imaging to date has been limited in its ability to identify prostate cancer.  Recent advancements in multiparametric MRI of the prostate however has significantly improved clinician’s ability to identify regions in the prostate suspicious for cancer.  This has led to the emergence of MR/Ultrasound fusion technology which allows for targeted biopsy of the prostate into regions suspicious for cancer.

Although conceptually, it makes sense that a targeted biopsy has the potential to perform better than the standard random sampling of the prostate in the diagnosis of prostate cancer, studies were needed to understand if this is true, and if so, if the improvement was substantial enough to justify the extra expense and effort needed to obtain a MRI guided biopsy.  This study performed at the National Cancer Institute’s Clinical Center sought to address this clinical question of interest.  From 2007-2014, a total of 1003 men suspected to have prostate cancer underwent an MRI of the prostate.  If an area of suspicion was seen in the prostate, these men underwent both the targeted biopsy of the suspicious region in the prostate as well as the standard 12-core needle biopsy during the same session.  The results from the targeted biopsy were compared to the results of the standard biopsy.

The key findings in this study was that targeted biopsy improved the rate at which high-risk clinically significant cancer was diagnosed by 30%.  Of interest, the study also found that low-risk, clinically insignificant disease (the type of prostate cancer that is unlikely to cause any harm to the patient over the course of his natural life) was decreased in diagnosis by 17%.  Decrease of diagnosis of such disease has the potential benefit that it could lead to less over-treatment of cancer that never needed to be treated.  In a subset of 170 men that ultimately underwent surgery to remove the prostate to treat their cancer, we were further able to examine how well the prostate biopsy reflected the actual cancer burden in the whole gland.   It is well known that standard biopsy can actually underestimate the total cancer grade in the whole prostate in upwards of 30-40% of cases.  We found that the targeted biopsy was significantly better at predicting whether the patient had intermediate to high-risk cancer compared to standard biopsy.  Through further analysis using a statistical method called decision curve analysis, we further found that for men who wish to undergo surgery for intermediate to high-risk cancer, but wish to go on active surveillance for low-risk cancer, targeted biopsy led to better decision making compared to standard biopsy, or even the two techniques combined.

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Negative Patient-Doctor Communication More Powerful Than Positive Interaction

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Dr Maddy Greville-Harris Research Fellow University of SouthamptoMedicalResearch.com Interview with:
Dr Maddy Greville-Harris
Research Fellow
University of Southampton

 

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

Dr. Greville-Harris: Our research looks at the effects of non-understanding feedback (‘invalidation’) and discusses its implications in the medical consultation in eliciting the nocebo response. We carried out interviews with five patients and four healthcare providers to explore their experiences of receiving non-understanding feedback during their chronic pain consultations. Patients reported feeling dismissed and disbelieved by healthcare providers. As a result of these encounters, patients reported feeling angry or hopeless after invalidating consultations, describing an increased need to justify their condition or to avoid treatment altogether.

Our earlier work too, suggests that receiving non-understanding feedback can have very powerful effects. Participants who received such feedback were more physiologically aroused, reported more negative mood and were less willing to participate in the research again. These effects were much more powerful than the positive effects of receiving understanding feedback. Our research suggests that the power of negative communication is stronger than that of positive communication, and that invalidating feedback may be a nocebo effect that has largely been overlooked.

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US Opioid Death Rate Flattens, Heroin Deaths Increase

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Richard C. Dart, M.D., Ph.D Denver Health & Hospital Authority Professor, University of Colorado School of MedicineMedicalResearch.com Interview with:
Richard C. Dart, M.D., Ph.D

Denver Health & Hospital Authority
Professor, University of Colorado School of Medicine

 

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

Dr. Dart: For the past two decades, prescription opioid medication abuse has increased significantly in the US. An estimated 25 million people initiated nonmedical use of pain relievers between 2002 and 2011.  In 2010 the number of death attributed to prescription opioid medications reached 16,651. The  RADARS® System (Researched Abuse, Diversion and Addiction Related Surveillance) has been monitoring prescription drug abuse and diversion for over 13 years. We use a “mosaic” approach, measuring abuse and diversion from multiple perspectives, to describe this hidden phenomenon as comprehensively as possible.

For the current publication we used 5 separate RADARS® System programs to collect data and the study period was from January 2002 through December 2013. We noticed a substantial increase  of prescription drug abuse from 2002 through 2010, followed by a flattening or decrease in 2010 and, lastly, a decline in 2011 through 2013. We also noticed a similar pattern in opioid-related deaths. Nonmedical use did not change significantly among college students.

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Cochlear Implants Work Equally Well In Younger and Older Patients

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Margaret T. Dillon, AuD University of North Carolina School of MedicineMedicalResearch.com Interview with:
Margaret T. Dillon, AuD

University of North Carolina School of Medicine

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

Dr. Dillon: The goal of this study was to evaluate whether age at revision cochlear implantation influences post-revision speech perception performance. A cochlear implant is an implantable auditory prosthesis that aims to provide sound to patients with certain degrees of hearing loss, by converting and transmitting the acoustic sound into electric stimulation. Research has shown cochlear implant recipients experience improved speech perception in quiet and noise as compared to preoperative performance with conventional amplification (ie, hearing aids). There is variability in postoperative performance. Understanding the cause or causes of this variability is the primary goal of a number of research studies. One suspected indicator for this variability is advanced age at the time of surgery.

Though the incidence of revision cochlear implantation is low, it may be warranted when the internal device is no longer functional or not functioning optimally. We reviewed the pre-revision and post-revision speech perception performance of younger (< 65 years of age) and older (> 65 years of age) adult cochlear implant recipients. There was no difference between the post-revision speech perception performance between the two groups.

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Sugar-Sweetened Beverages Linked To Earlier Puberty in Girls

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Karin B. Michels, MPH, PhD, ScD Department of Epidemiology, Harvard School of Public Health Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical SchoolMedicalResearch.com Interview with:
Karin B. Michels, MPH, PhD, ScD

Department of Epidemiology, Harvard School of Public Health
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School,
Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School Boston MA

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

Response: Sugar-Sweetened Beverage consumption is associated with earlier age at menopause.

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

Response: Sugar-Sweetened Beverage consumption may explain part of why puberty is starting earlier and earlier in girls. This is another reason besides childhood obesity which also results from Sugar-Sweetened Beverage consumption to curb the consumption of Sugar-Sweetened Beverage in children.

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

Response: We would like to better understand the underlying mechanisms.

Citation:

Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls
J.L Carwile, W.C Willett, D. Spiegelman, E. Hertzmark, J. Rich-Edwards, A.L Frazier, and K.B Michels

Hum. Reprod. first published online January 27, 2015 doi:10.1093/humrep/deu349

 

MedicalResearch.com Interview with:, & Karin B. Michels, MPH, PhD, ScD (2015). Sugar-Sweetened Beverages Linked To Earlier Puberty in Girls http://MedicalResearch.com

Many Breast Cancer Patient Have Limited Understanding Of Their Own Disease

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Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, MassachusettsMedicalResearch.com Interview with:
Rachel A. Freedman MD, MPH
Assistant Professor of Medicine, Harvard Medical School
Department of Medical Oncology
Dana-Farber Cancer Institute, Boston, Massachusetts

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

Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases.
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Cancer Drug May Overcome Physiological Resistance To Tuberculosis Medications

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Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114MedicalResearch.com Interview with:
Rakesh K. Jain, Ph.D.

A.W.Cook Professor of Tumor Biology
Director, E.L. Steele Laboratory
Department of Radiation Oncology
Harvard Medical School and
Massachusetts General Hospital Boston, MA    02114

Medical Research: What are the primary findings of this study and why are they important?

Dr. Jain: Pulmonary granulomas are the hallmark of the Tuberculosis (TB) infection, yet it is not fully understood how these structures contribute to disease progression and treatment resistance. In this study, we applied our insight in tumor biology – gained over three decades – to explore and exploit the similarities between vasculature (blood vessel network) in solid cancerous tumors and TB pulmonary granulomas. We demonstrate for the first time that TB granulomas have abnormal vasculature. This abnormality provides a mechanism for the observation that TB granulomas are often hypoxic (have low oxygen conditions) and have differential distribution of anti-TB drugs. We showed that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve small molecule delivery. This study suggests that vasculature normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB.

Tuberculosis (TB) is a global scourge that is responsible for nearly 2 million deaths annually. Due to the inability of currently available treatment regimens to eradicate this devastating disease, it is clear that new treatment strategies are urgently needed. Unlike many researchers in the TB field, we do not seek to discover new therapeutics that target bacterial resistance; instead, we strive to overcome physiological resistance to treatment resulting from abnormalities in the granuloma vasculature that impair drug delivery and create hypoxia that impairs efficacy of drugs and immune system. By using an FDA-approved drug, our study has the potential to be rapidly translated into the clinic.

Medical Research: Has any association previously been made between the vascular structure of TB granulomas and the challenges of treating TB – both the fact that treatment takes so long and the development of multidrug resistance?

Dr. Jain: Our study is the first to implicate a specific facet of the granuloma – the abnormal vasculature – as a potential contributor to disease progression and treatment resistance. Granuloma hypoxia is known to negatively affect the local immune system while conferring resistance to some of the TB drugs. Our collaborators have shown that different anti-TB drugs have differential abilities to penetrate the granuloma structure, especially to the interior granuloma regions where the TB bacteria are found in greatest numbers. Our study is the first to provide evidence that by modulating the granuloma vasculature, hypoxia can be alleviated and drug delivery can be improved.

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Isolated Systolic Hypertension in Young Adults Linked To Increased Risk Of Cardiovascular Death

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Donald M Lloyd-Jones, MD/ScM Senior Associate Dean for Clinical and Translational Research Chair, Department of Preventive Medicine Director, Northwestern University Clinical and Translational Sciences Institute (NUCATS) Eileen M. Foell Professor Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with:
Donald M Lloyd-Jones, MD/ScM
Senior Associate Dean for Clinical and Translational Research
Chair, Department of Preventive Medicine
Director, Northwestern University Clinical and Translational Sciences Institute (NUCATS)
Eileen M. Foell Professor
Northwestern University Feinberg School of Medicine

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

Dr. Lloyd-Jones: We undertook this study in order to understand the long-term implications of isolated systolic hypertension (that is, SBP >=140 mm Hg with DBP <90 mm Hg) in younger adults. As you may know, hypertension becomes increasingly common with age. However, it does occur in younger adults, and we are seeing early onset more often recently as a result of the obesity epidemic. In general, we know that diastolic hypertension (DBP >=90 mm Hg) is more common in younger adults, but after age 50 isolated systolic hypertension is by far the most common type of hypertension seen. Prior small studies have suggested that isolated systolic hypertension might be “benign” in younger adults, or just the result of white coat effect with no implications. However, in the current study, we observed that isolated systolic hypertension in younger adults (mean age 34 y) was in fact associated with higher risk (~25% higher risk) for cardiovascular and coronary death over 30 years’ follow up compared with “normal” levels of blood pressure. Interestingly, the relative risk was higher for young women with isolated systolic hypertension, with a doubling of coronary mortality risk. The implications of the study are that clinicians should not ignore isolated systolic hypertension in younger adults, since it clearly has implications for their future health. The USPSTF recently suggested using 24-hour ambulatory blood pressure monitoring to diagnose hypertension. Our results would support the use of this technology in younger adults suspected of having hypertension, to confirm the office-based diagnosis and define the type of hypertension to understand prognosis and inform treatment decisions.

 

Citation:

Yuichiro Yano, Jeremiah Stamler, Daniel B. Garside, Martha L. Daviglus, Stanley S. Franklin, Mercedes R. Carnethon, Kiang Liu, Philip Greenland, Donald M. Lloyd-Jones. Isolated Systolic Hypertension in Young and Middle-Aged Adults and 31-Year Risk for Cardiovascular Mortality. Journal of the American College of Cardiology, 2015; 65 (4): 327 DOI: 10.1016/j.jacc.2014.10.060

 
MedicalResearch.com Interview with:, Donald M Lloyd-Jones, MD/ScM, Senior Associate Dean for Clinical and Translational Research, Chair, Department of Preventive Medicine, & Northwestern University Feinberg School of Medicine (2015). Isolated Systolic Hypertension in Young Adults Linked To Increased Risk Of Cardiovascular Death MedicalResearch.com

Diverse Herpes Viruses Share Ability To Suppress Immune Response

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Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin anMedicalResearch.com Interview with:
Christopher S. Sullivan, Ph.D.
Associate Professor
Dept. Molecular Biosciences
The University of Texas at Austin and
Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory.
Jennifer Cox
, lead author
Graduate student in Dr. Sullivan’s laboratory.

Jennifer Cox’s Replies:

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

Jennifer Cox: In the last decade, researchers have identified that many viruses encode small regulatory molecules known as microRNAs. Some viral microRNAs are able to manipulate host processes including stress responses, proliferation, and cell death. However, there are many viral microRNAs with unknown functions. Many of the viruses that encode microRNAs are associated with severe pathologies including various cancers so understanding the role of viral microRNAs can shed light on virus biology.

For this study, we focused on identifying viral microRNAs that can regulate innate immune signaling for several reasons. First, all viruses have proteins to combat interferon signaling. Second, we have identified microRNAs from two diverse viruses (retro and annello) that can inhibit interferon signaling so we hypothesized that additional viral microRNAs will perform this same function. We screened ~70 viral microRNAs for the ability to regulate innate immune signaling and identified three herpesviruses, Epstein-Barr Virus, Kaposi’s Sarcoma Associated Virus, and Human Cytomegalovirus, that inhibit the interferon response.

Epstein-Barr Virus, causes an estimated 200,000 cancers every year, including lymphomas, nasopharyngeal cancers and some stomach cancers. Interestingly, most of these cancers harbor latent EBV – a state of limited gene expression that produces no virus. microRNAs are one of the few viral gene product expressed during latency.

Our further work identified that Epstein-Barr Virus, KSHV, and Human Cytomegalovirus have converged to inhibit interferon signaling in the same manner – through decreasing expression of a central hub of innate immune signaling, CREB binding protein (CBP). We show that this regulation conveys partial resistance to the negative effects of interferon treatment on an EBV+ lymphoma cell line. Additionally, removing the microRNA from a similar cell line increases the sensitivity to interferon.

Interferon can be used in combination with other chemotherapies to treat lymphomas but varies in success. Our results may partially explain the variability seen in patients with EBV-associated cancers.

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Retinal Artery Occlusion Linked To Increased Risk Of Acute Coronary Syndrome

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MedicalResearch.com Interview with:
Ren-Long Jan
Department of Pediatrics, Chi Mei Medical Center, Liouying, Tainan, Taiwan Graduate Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.

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

Response: The pathologenic factors underlying retinal artery occlusion (RAO) are also associated with acute coronary syndrome (ACS). Previous studies showed the relation but was limited by sample sizes. We used Taiwan Longitudinal Health Insurance Database and found the increased risk of ACS following Retinal artery occlusion. Continue reading