Author Interviews, Health Care Systems, JAMA, Outcomes & Safety / 29.02.2016 Interview with: Dr. Alisa Khan, MD MPH Division of General Pediatrics Boston Children’s Hospital Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Khan: Medical errors, or mistakes in the process of caring for patients, occur frequently. While methods of detecting errors have improved, parents and families are not typically included in routine hospital safety monitoring systems. We found that nearly 1 in 11 parents reported their child had experienced a safety incident during hospitalization. Most of these reports were confirmed to be medical errors when reviewed by physicians, and many were not otherwise documented in the patient’s medical record. (more…)
Author Interviews, Emergency Care, Infections, JAMA, Pediatrics, Pulmonary Disease, Respiratory / 29.02.2016 Interview with: Suzanne Schuh, MD, FRCP(C), ABPEM The Hospital for Sick Children affiliated with the University of Toronto Medical Research: What is the background for this study? Dr. Schuh: Routine measurement of oxygen saturation in bronchiolitis is sometimes used as a proxy for illness severity, despite poor correlation between these parameters. This focus on oximetry may in part relate to lack of evidence on the natural history of desaturations in bronchiolitis which are often transient, and frequently not accompanied by increased respiratory distress. Desaturations occurring in infants with mild bronchiolitis in an ED often result in hospitalizations or prolonged hospital stay. They occur in healthy infants and may also occur in infants with mild bronchiolitis at home. The main objective of this study of infants with acute bronchiolitis was to determine if there is a difference in the proportion of unscheduled medical visits within 72 hours of ED discharge in infants who desaturate during home oximetry monitoring versus those without desaturations. Our study shows that the majority of infants with mild bronchiolitis experience desaturations after discharge home. (more…)
Accidents & Violence, Author Interviews, JAMA / 29.02.2016 Interview with: Anna-Karin Numé MD, PhD student Copenhagen University Gentofte Hospital Department of Cardiology Cardiovascular Research Hellerup Denmark  Medical Research: What is the background for this study? Dr. Numé: While it is obvious that a loss of consciousness while driving a car is very dangerous, what is not known is whether individuals who have had an episode of fainting (syncope) have a significantly higher risk of having car crashes in the future. Because about one third of patients with syncope are likely to have a recurrence, physicians face a difficult judgment about whether patients with syncope are fit to drive. Medical Research: What are the main findings? Dr. Numé: In this nationwide study of patients with syncope, having a history of syncope were associated with a 2-fold-higher risk of later motor vehicle crashes requiring medical attention at an emergency department or hospital compared with the general population – a risk that remained elevated throughout a follow-up of 5 years. This risk was small in absolute terms, yet raises important questions about policies towards driving. (more…)
Author Interviews, JAMA, Sexual Health / 29.02.2016 Interview with: Loes Jaspers MD, PhD scientist Dept. of Epidemiology Erasmus University Medical Center Rotterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Dr. Jaspers: In August 2015, the U.S. Food and Drug Administration approved flibanserin as a medical treatment for women with hypoactive sexual desire disorder (HSDD). The approval was accompanied by considerable attention in the media. Some people were positive about the approval, while others questioned whether benefits outweigh the risks. That is why we systematically reviewed eight clinical trials (five published and three unpublished) that included 5,914 women to examine the efficacy and safety of the medication for treatment of hypoactive sexual desire disorder. We found that women taking flibanserin experienced one-half additional satisfying sexual event per month, and that they experienced 2-4 times more side-effects, such as dizziness, sleepiness, nausea, and tiredness, compared to placebo. The overall improvement that women reported while taking the drug was low. It ranged from ‘minimal improvement’ to ‘no change’. The quality of the evidence was graded using established and transparent guidelines, the Grades of Recommendation, Assessment, Development and Evaluation approach (GRADE), which have been adopted by leading scientific organizations globally. Although the studies reviewed were randomized clinical trials, the quality of the evidence was very low, particularly because of limitations in design, the indirectness of evidence, and more favorable efficacy outcomes in published compared with unpublished studies. (more…)
Author Interviews, JAMA, Ophthalmology / 27.02.2016 Interview with: Jason Hsu, MD Retina Service, Wills Eye Hospital Assistant Professor of Ophthalmology Thomas Jefferson University Mid Atlantic Retina Medical Research: What is the background for this study? What are the main findings? Dr. Hsu: There are some patients with the wet type of age-related macular degeneration (AMD) who have persistent swelling in the retina despite regular, repeated eye injections with the anti-vascular endothelial growth factor (anti-VEGF) medications (e.g., Avastin, Lucentis, and Eylea). I had postulated that if we could decrease the turnover of fluid inside the eye, it might allow the injected medicine to stay in the eye for a longer period of time. I chose dorzolamide-timolol (brand name: Cosopt), a commonly available prescription eye drop used for glaucoma, since it is a very potent aqueous suppressant. By slowing down the production of eye fluid, I theorized it might decrease the outflow of fluid and medicine from the eye. Our study was a small, nonrandomized, exploratory pilot study. We enrolled 10 patients with wet AMD who had persistent retinal swelling despite chronic, fixed interval anti-VEGF injections. We kept patients on the exact same anti-VEGF medication and continued to see them at the exact same interval that they had been on before study enrollment. Once enrolled, the only difference is that we had them start using dorzolamide-timolol eye drops twice a day for the course of the study. The results were fairly striking with the retinal thickness decreasing from around 420 microns to 334 microns at the final visit. This decrease in swelling was significant at the first study visit after starting the drops and remained significant throughout the course of the study. (more…)
Author Interviews, JAMA, Ophthalmology, Surgical Research, Toxin Research / 27.02.2016 Interview with: Yu-Chih Hou, MD Department of Ophthalmology National Taiwan University Hospital Taipei, Taiwan MedicalResearch: What is the background for this study? Dr. Yu-Chih Hou: We have encountered 3 patients with right eye pain and corneal edema after left orofacial surgery under general anesthesia since December 6. 2010. The first patient underwent a left tongue tumor excision by an ENT doctor. Postoperative day one, corneal epithelial defect and edema with mild anterior chamber reaction were noted in the right eye. Because his presentation was different from corneal abrasion which was the most common eye injury after general anesthesia, we suspected this ocular complication could be due to toxic reaction to antiseptic. Although corneal edema decreased, corneal endothelial cell density decreased and cataract developed later in the first patient. Two months later, the second patient had a similar toxic keratopathy but with severe corneal edema in his right eye after wide tumor excision of left lower gingival cancer by dentist surgeons. We found the antiseptic they used contained alcohol. We recommended not to use alcohol-containing antiseptics in oral surgery. Unfortunately, more severe toxic keratopathy occurred in the third patient after a left nasal tumor excision by other ENT doctor one year later. Because these severe ocular complications may occur again, it raised us to do detail study and we found all antiseptics they used contained alcohol. We hope to prevent occurrence of this toxic keratopathy in nonocular surgery by reporting our findings to other clinicians. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 25.02.2016 Interview with: Dr. Shoshana Rosenberg ScD, MPH Department of Medical Oncology Dana-Farber Cancer Institute Boston, Massachusetts Medical Research: Why would BRCA testing rates have increased among younger women with cancer?   Dr. Rosenberg: There has been increasing awareness surrounding genetic testing for breast cancer in more recent years, likely contributing to the trend that we saw over time  in our cohort. This has included more media attention, most notably Angelina Jolie’s sharing her story in 2013. Medical Research: Is this increase in testing a good thing? Dr. Rosenberg: Young women who are diagnosed with breast cancer should be getting tested so the fact that an increasing proportion of women have been undergoing BRCA testing in recent years indicates patients (and the physicians who treat them) are following recommendations. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA / 24.02.2016 Interview with: Dr. Manu Shankar-Hari MB BS MD FRCA EDIC FFICM MSc[Epi] Consultant, Intensive Care Medicine; Guy’s and St Thomas’ NHS Foundation Trust Clinical Research Associate, Intensive Care National Audit and Research Centre Honorary Senior Lecturer in Intensive Care Medicine Division of Asthma Allergy and Lung Biology King’s College London, UK  Medical Research: What is the background for this study? What are the main findings? Dr. Shankar-Hari: Septic shock is a complex illness.  The previous Consensus Definitions (1991 and 2001) place emphasis on the circulatory abnormalities as the core concept and neither definitions provide data driven clinical criteria. In addition, last ten years of basic science research has established the concept that septic shock is associated with plethora of cellular and metabolic abnormalities (often referred to as cellular stress), alongside circulatory dysfunction. In this background, the paper published in JAMA provides an updated illness concept (definitions) and data driven clinical criteria for diagnosing septic shock at the bedside.

The updated illness concept: 'Septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone.’

The clinical criteria: 'Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean arterial blood pressure 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.' (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016 Interview with: Frederic T. Billings IV, MD, MSc Assistant Professor of Anesthesiology and Medicine Additional Specialty: Cardiothoracic Anesthesiology Vanderbilt University Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) affects up to 30% of patients following cardiac surgery and is associated with long-term kidney function decline as well as a 5-fold increase in death during hospitalization following surgery. Statins affect several mechanisms of AKI following cardiac surgery including improvement of endothelial function and attenuation of oxidative stress, so we performed a clinical trial to test the hypothesis that high-dose atorvastatin (brand name Lipitor) use prior to and following surgery reduces AKI following cardiac surgery. In 615 patients who completed the study high-dose atorvastatin treatment, compared to placebo administration, did not reduce the risk of AKI overall, among patients naïve to statins, or patients already using a statin. In fact, among patients naïve to statins with baseline chronic kidney disease we found some evidence that atorvastatin may increase risk for kidney injury, although the number of patients was small in this subgroup. (more…)
Anesthesiology, Author Interviews, Critical Care - Intensive Care - ICUs, JAMA, Pulmonary Disease / 22.02.2016 Interview with: John G. Laffey MD Chief, Department of Anesthesia; Co-Director, Critical illness and Injury Research Centre; Scientist, Keenan Research Centre for Biomedical Science ‑ St. Michael's Hospital Professor, Anesthesia, Critical Care, and Physiology ‑ University of Toronto Medical Research: What is the background for this study? Dr. Laffey: Acute respiratory distress syndrome is the commonest cause of severe acute respiratory failure in the critically ill. ARDS is a major cause of death and disability in the critically ill worldwide. Second, there is no treatment for ARDS, and our present management approaches are limited to supporting organ function while treating the underlying causes We performed the LUNG SAFE study to address several clinically important questions regarding ARDS. First, the current incidence in a large international cohort was not known. Large regional differences had been suggested: for example, the incidence of ARDS in the US was reported to be ten times greater of that in Europe_ENREF_4. Second, we wanted to understand how we manage patients with  Acute respiratory distress syndrome in the ‘real world’ situation. Specifically, it was not clear to what extent newer approaches to artificial ventilation, such as reducing the size of the breaths (lower tidal volumes) and keeping the lung pressure positive at all times to minimize collapse (PEEP) were used. The impact of studies showing promise for other measures to improve gas exchange such as turning patients prone during mechanical ventilation, or using neuromuscular blockade, on routine clinical practice in the broader international context was not known. Third, there were some concerns over the extent of clinician recognition of ARDS. This was an important issue because implementation of the effective therapies may be limited by lack of recognition of ARDS by clinicians. A better understanding the factors associated with ARDS recognition and how this recognition influenced patient management could lead to effective interventions to improve care. Lastly we wanted to determine the outcome from  Acute respiratory distress syndrome in a global cohort of patients. Medical Research: What are the main findings? Dr. Laffey: We found that ARDS continues to represent an important public health problem globally, with 10% of ICU patients meeting clinical criteria for ARDS. While there appeared to be some geographic variation, this did not seem as great as previously thought. An important finding was the under-recognition of  Acute respiratory distress syndrome by clinicians, with 40% of all cases not being recognized. In addition, over one third of patients did not receive protective lung ventilation strategies. The use of other measures to aid gas exchange during artificial ventilation, such as turning the patient into the prone position, or the use of neuromuscular blockade was also quite low. Of most concern, ARDS continues to have a very high mortality of approximately 40% of patients dying in hospital. (more…)
Author Interviews, Autism, JAMA, Pediatrics / 18.02.2016 Interview with: Dr. David Grossman MD MPH Vice chair of the U.S. Preventive Services Task Force Professor at the University of Washington Schools of Public Health and Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Grossman: The Task Force cares deeply about the challenges that children affected by autism and their families face in getting the care and support they need. This was the first time that we assessed the evidence around screening young children for autism, and our recommendation was informed by a review of the most up-to-date science, which included randomized trials, observational studies, and research from a number of Federal health agencies. We concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for autism spectrum disorder in children for whom no concerns of autism have been raised by their parents or a clinician. This is an I statement, which is not a recommendation against screening, but a call for more research on screening and treatment in young children who don’t have obvious symptoms. It is important to note that this recommendation will not affect insurance coverage for autism screening, which is currently covered under the Affordable Care Act as a result of the American Academy of Pediatrics’ Bright Futures Guidelines. (more…)
Author Interviews, Breast Cancer, JAMA, Outcomes & Safety, Surgical Research / 17.02.2016 Interview with: Dr. Art Sedrakyan MD PhD ScD Professor of Healthcare Policy and Research in Cardiothoracic Surgery Department of Public Health Weill Cornell Medical College  Medical Research: What is the background for this study? What are the main findings? Dr. Sedrakyan: In the most recent years available to us for research(2011-2013) one in four women underwent repeat surgery within 90 days after breast conserving approach to cancer removal. Patients operated by higher volume physicians had lower chance of undergoing repeat surgery.Uniform guidelines and increased surgical training are needed to standardize the breast conserving surgery to reduce the high rate of repeat surgery. (more…)
Author Interviews, CDC, JAMA / 16.02.2016 Interview with: Philip J. Peters, M.D. HIV Testing and Biomedical Interventions Activity Lead Epidemiology Branch CDC’s Division of HIV/AIDS Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Peters:  Acute HIV infection contributes disproportionately to HIV transmission and identifying individuals with acute HIV infection is critical to prevent further HIV transmission, as diagnosis can lead to several effective HIV prevention interventions. Acute HIV infection can be diagnosed with assays that detect either HIV RNA (the reference standard) or the p24 antigen (an HIV core protein), which are both detectable early after HIV infection and before an antibody response develops. HIV immunoassays that detect both the p24 antigen and anti-HIV antibody (fourth generation antigen/antibody [Ag/Ab] combination immunoassays) are currently being implemented as the initial screening test in the 2014 CDC and American Public Health Laboratories (APHL) recommended HIV diagnostic algorithm. In a prospective study we evaluated the performance of an HIV Ag/Ab combination assay to detect acute HIV infection compared with pooled HIV RNA testing in a high-prevalence population. All participants were first screened with a rapid HIV test to detect established HIV infection (antibody detectable).  All participants with a negative rapid HIV test result were then screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled HIV-1 RNA testing.  HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Among 86,836 participants with complete test results (median age, 29 years; 75.0% male; 51.8% men who have sex with men), acute HIV infection was diagnosed in 168 (0.19%). Acute HIV infection was detected in 134 (0.15%) participants with HIV Ag/Ab combination testing (acute HIV infection sensitivity, 79.8%) and in 164 (0.19%) with pooled HIV RNA testing (sensitivity, 97.6%; sensitivity comparison, p<0.001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone (which detected established HIV infection), HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4%. (more…)
Author Interviews, Hospital Readmissions, JAMA, Pediatrics / 16.02.2016 Interview with: Marion R. Sills, MD, MPH Associate Professor, Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine Medical Research: What is the background for this study? Dr. Sills: My co-authors and I know that studies show that patients who are poorer or are minorities are readmitted at higher rates than other patients, and that readmissions penalties, which are far more commonly applied in relation to readmissions of adult patients, have been shown to punish hospitals for the type of patients that they serve, rather than purely for the quality of care they provide.  Currently, these penalties impact hospitals treating Medicare patients in all 50 states but only impact readmissions of children in 4 states, although other states are considering implementing these penalties.  This was our rationale for exploring the impact of patients’ social determinants of health (factors like race, ethnicity, health insurance and income) on how likely it was that a hospital would be penalized for readmissions under a typical state-level pay-for-performance measure based on hospital readmissions. Readmissions penalties are designed to penalize hospitals that provide lower quality care. However, without adjusting for social determinants of health factors, these pay-for-performance measures may unfairly penalize hospitals based on the type of patient they treat as well as the quality of care they provide. Medical Research: What are the main findings? Dr. Sills: We found that risk adjustment for social determinants of health factors changed hospitals’ penalty status on a readmissions-based pay-for-performance measure. Without adjusting the pay-for-performance measures for social determinants of health, hospitals may receive penalties partially related to patient factors beyond the quality of hospital care. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Pharmacology / 15.02.2016 Interview with: Dr. Britta Haenisch PhD German Center for Neurodegenerative Diseases (DZNE)  Medical Research: What is the background for this study? Dr. Haenisch: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases, but have also been shown to be potentially involved in cognitive decline: There were hints from recent other studies that PPIs might affect cognition, e.g. Lam et al. (2013) report a significant association of PPI use with vitamin B12 deficiency in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance amyloid beta peptide (Aβ) levels in mouse brain by affecting the enzymes β- and γ-secretase which leads to increased Aβ levels in mice. Medical Research: What are the main findings? Dr. Haenisch: The current study provides a statistical association (applying a time-dependent analysis) between proton pump inhibitors prescription and occurrence of dementia with a focus on long-term regular PPI prescription in patients aged 75 years and older. In our analysis we focused on long-term regular PPI prescription for at least 18 months. It does not prove that proton pump inhibitors cause dementia. References -Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. -Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837 (more…)
Author Interviews, End of Life Care, JAMA / 11.02.2016 Interview with: Joan M Teno, MD, MS Professor of Medicine Division of Gerontology and Geriatrics Cambia Palliative Care Center of Excellence University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Teno: Hospices in the US are paid a daily rate, regardless of the service delivered. Key to hospice patients dying comfortably is that the caregiver and dying person received the needed visits by hospice professional staff, such as a nurse or social worker. These staff are trained to assess the patient and make appropriate changes to care plan to ensure the comfort and safety of the hospice patient. Multiple studies attest to the finding that pain and other symptoms exacerbate in the last days of life - key is the primary caregiver, usually a close family member receives the need training in administering of medicine to ensure the dying person is comfortable in the last hours of life. We studied visits pattern by professional staff in the last 2 days of life finding that one in eight hospice patients were not visited. While we would not expect every patient to have visits, there was several key finding that raised concern.
  • First, blacks were 30% less likely to receive visits compared to whites
  • Second, 16% persons dying in a nursing home were not visited - historically, bereaved family members identify concerns with the quality of end of life care in NH, even when the person is on hospice services.
  • Third, one in five persons who died on Sunday were not visited in the last 2 days of life - which raises a concern with how hospices are staffing weekend coverage. There is nothing that would suggest biologically that persons don’t experience pain while dying on sturdy.
Additionally, the provision of these visits varied by geographic region in the country and by hospice program which suggest this is the practice of organization and not patient preferences. (more…)
Author Interviews, End of Life Care, JAMA, Mental Health Research, NIH / 11.02.2016 Interview with: Scott Y. H. Kim, MD, PhD Department of Bioethics, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? Dr. Kim: Euthanasia and/or physician assisted suicide (EAS) of persons suffering from psychiatric disorders is increasingly practiced in some jurisdictions such as Belgium and the Netherlands but very little is known about the practice.  There is an active debate over whether to legalize such a practice in Canada, after a Supreme Court ruling last year that struck down laws banning physician assisted death.  Medical Research: What are the main findings? Dr. Kim: The main findings are that:
  1. Most patients who receive psychiatric euthanasia and/or physician assisted suicide are women, of diverse ages, with a variety of chronic psychiatric conditions accompanied by personality disorders, significant physical problems, and social isolation/loneliness, often in the context of refusals of treatment.  A minority who are initially refused EAS ultimately receive euthanasia and/or physician assisted suicide through a mobile euthanasia clinic.
  2. Given that the patients have chronic, complicated histories requiring considerable physician judgment, extensive consultations are common. But independent psychiatric input does not always occur; disagreement among physicians occurred in one in four cases; and the euthanasia review committees generally defer to the judgments of the physicians performing euthanasia and/or physician assisted suicide.
Accidents & Violence, Author Interviews, JAMA / 11.02.2016 Interview with: Dr. Andrew Fenelon PhD NIH Postdoctoral Fellow Brown University Medical Research: What is the background for this study? What are the main findings? Dr. Fenelon: The life expectancy of the US population is about 2 years less than that of other high-income nations, which is an important problem in public health. Although much previous work looks at differences in death rates among older adults, some recent work has shown that deaths at younger ages (below age 50) account for a significant fraction of the life expectancy gap. Our study examines the contribution of major injuries, Motor Vehicle Crashes, Firearm-related deaths, and drug poisonings, which often occur at younger ages and account for many years of lost life. Our findings indicate that US men and women experience significantly higher death rates from these three causes of injury death than each of the 12 comparison high-income countries. Overall, these three causes of death explained 48% of the 2.2 year life expectancy gap between the United States and other high-income countries among men, with firearm injuries alone explaining 21%. Among women, these causes explained 19%. (more…)
Author Interviews, JAMA, Surgical Research, Weight Research / 11.02.2016 Interview with: Lance Davidson, PhD Assistant Professor Department of Exercise Sciences Brigham Young University Provo, UT  84602  Medical Research: What is the background for this study? What are the main findings? Dr. Davidson: A growing body of literature indicates that bariatric surgery imparts a mortality benefit in severely obese individuals.  Whether age at surgery affects this relationship is not well established.  One might suppose that a person who has been severely obese for several decades may already have sustained enough metabolic damage that weight loss surgery would have less influence on subsequent mortality.  We conducted an age-specific analysis of a previously-published mortality cohort in gastric bypass patients and severely obese controls, following them for up to 18 years (mean 7.2 years), and examined mortality rates in four age categories: under 35, 35-44, 45-54, and 55-74. The primary finding of this retrospective cohort study was that gastric bypass surgery attenuated the age-related increase in mortality, demonstrating a widening gap in mortality risk when compared to age-matched severely obese controls as age-at-surgery increased, with a 66% reduction in mortality in the oldest group.  Another interesting result, highlighted in our previous publication on this cohort (Adams et al. NEJM 2007), was a higher mortality rate from external causes (accidents, poisonings, suicides, homicides) in surgery patients.  We explored this phenomenon further by age at surgery and found that externally-caused deaths were only increased in women (not men) who had surgery before age 35. (more…)
Allergies, Asthma, Author Interviews, JAMA, Pediatrics, Pulmonary Disease / 09.02.2016 Interview with: Dr. Meghan B. Azad PhD Assistant Professor Department of Pediatrics & Child Health and Community Health Sciences University of Manitoba and Children’s Hospital Research Institute of Manitoba Associate Investigator, Canadian Healthy Infant Longitudinal Development (CHILD) Study Medical Research: What is the background for this study? Dr. Azad: Asthma is the most common reason for children to miss school or be admitted to hospital, and accounts for over 30% of Canadian healthcare billings for children. Although many treatments exist to manage asthma symptoms, it is a lifelong disease and there is no cure.  Prevention is the best approach to reduce the global burden of asthma, and our study provides important new information to inform asthma prevention strategies.   Medical Research: What are the main findings? Dr. Azad: Wheezing is common in babies and young children.  Our study looked at the long-term implications of wheezing in early life, using data from the Canadian Asthma Primary Prevention Study (CAPPS). We followed 320 children from Winnipeg and Vancouver from before birth until adolescence, and found that specific patterns of early wheezing (from age 0 to 7) were associated with decreased lung function and increased risk for asthma by age 15. By age 15, children who wheezed consistently through infancy and early childhood had the worst lung function (9% lower compared to non-wheezers) and the highest asthma risk (11 times higher). Even children with “transient early wheeze” (those who wheezed as babies but not as young children) had reduced lung function (5% lower) and increased asthma risk (4 times higher) as teenagers. (more…)
Author Interviews, Biomarkers, JAMA, Prostate Cancer / 09.02.2016 Interview with: Dr. Quoc-Dien Trinh MD Assistant Professor, Harvard Medical School Brigham and Williams Hospital  Medical Research:  Please briefly explain the potential benefits and harms of PSA testing, the rationale for screening all men, and the reason U.S. guidelines now recommend against routine screening.  Response: The goal of cancer screening is to detect the disease early, and consequently treat it before it becomes more aggressive and spread to other parts of the body (which ultimately leads to death). However, cancer screening may lead to overdiagnosis (detecting cancers that would not have been a problem for a while) and overtreatment. The latter is a problem for prostate cancer, because surgery and radiation therapy (the currently accepted first-line treatments for localized prostate cancer) have significant long-term adverse effects on sexual and urinary function. I wouldn't say that 'US' guidelines are against screening. Many professional societies continue to recommend some form of joint decision-making with regard to PSA screening. the USPSTF recommends against screening for all - they argue that the harms mentioned above outweigh the benefits. (more…)
Author Interviews, Diabetes, Exercise - Fitness, JAMA, Lifestyle & Health, Pediatrics / 08.02.2016 Interview with: Mélanie Henderson, MD, FRCPC, PhD Pediatric Endocrinologist and Assistant Clinical Professor Division of Endocrinology and Diabetes University of Montreal/Centre Hospitalier Universitaire Ste-Justine Montréal, Québec Medical Research: What is the background for this study? What are the main findings? Dr. Henderson: Dysregulation in insulin sensitivity and insulin secretion are the basic elements in the pathophysiology of type 2 diabetes. There is extensive data suggesting that better lifestyle habits are associated with the prevention or the delay in onset of type 2 diabetes in adults, with improved lifestyle habits having been more effective than pharmacologic agents at diabetes prevention in one study. Little work however has been done to determine whether this holds true in children. Cross-sectional studies in youth have found conflicting results and no study has considered the combined effect of physical activity, fitness and sedentary behavior on insulin dynamics in children. Understanding the impact of lifestyle habits on insulin dynamics in childhood has become paramount, given that less than 7% of Canadian children are currently meeting physical activity guidelines and that 1/3 of school-aged Canadian children and 2/3 of Canadian teenagers are exceeding the current guidelines in terms of screen time, which advocate for a maximum of 2 hours daily. Our study shows that adiposity is the central predictor of insulin dynamics in children, and that physical activity and screen time play an important role, in part through their effect on adiposity. Thus, establishing and maintaining a highly physically active lifestyle early on in life, while minimizing sedentary behaviour (specifically screen time) appear to be important strategies to consider to prevent type 2 diabetes in youth. (more…)
Author Interviews, Cancer Research, Heart Disease, JAMA, Pharmacology / 06.02.2016 Interview with: Jonathan Douxfils Pharm.D. - Ph.D. Research assistant Faculty of Medicine - Department of Pharmacy NAmur Research Institute for LIfe Sciences (NARILIS) Namur Thrombosis and Hemostasis Center (NTHC) Medical Research: What is the background for this study? What are the main findings? Dr. Douxfils: We decided to perform this study based on the release of the FDA regarding the risk of arterial occlusive events associated with ponatinib. We then hypothesize that the risk was not only restricted to ponatinib but also to other TKIs. This study shows that dasatinib, nilotinib and ponatinib increase the risk of vascular occlusive events compared to imatinib. Medical Research: What should clinicians and patients take away from your report? Dr. Douxfils: We suggest that patients treated with these molecules should be more frequently monitored, i.e. by an intensive support of associated comorbidities. In addition, even if they appear to have a better efficacy in terms of molecular response, new generation TKIs does not improve the overall survival at one year. As we have not access to individual data, it was impossible to clearly identify categories of patients for whom the risk of cardiovascular occlusive events is predominant. Therefore, the intensive monitoring proposed should be applied to all patients treated with these molecules. Regarding the choice of the therapy, the physician should certainly consider the goals of the treatment. For elderly patients, improving survival is the main objective and in this context, imatinib remains an excellent choice. For patients with a life expectancy greater than 10 years in whom we aim to achieve a deep molecular response to potentially reach a point of treatment cessation, dasatinib and nilotinib could be preferred. However, the choice of dasatinib or nilotinib as first-line treatments should involve a screening for potential risk factors such as diabetes, prior vascular occlusive events or any risk that could increase these adverse events. For second- and third-line treatments, the choice of the treatment has to be based on mutational analysis, previous adverse events, and the medical condition of the patient. Thus, in case of intolerance or resistance, the switch to one of the other TKIs approved for first-line therapy is an option. If treatment failure still occurs, a more potent TKI, i.e. bosutinib, is preferred. Importantly, ponatinib is reserved to patients with the T315I mutation and must be avoided in patients with good prognosis. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 04.02.2016 Interview with: Hannah J. Jones, PhD Centre for Academic Mental Health, School of Social and Community Medicine, Medical Research Council (MRC) Integrative Epidemiology Unit University of Bristol, Bristol, England MedicalResearch: What is the background for this study? What are the main findings? Dr. Jones: Schizophrenia is a highly heritable condition characterised by relatively diverse symptoms and frequent comorbid disorders. However, at present we don’t know how genetic risk for schizophrenia is expressed in children/adolescents in the general population. To investigate this, we studied data from individuals within the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort which consists of approximately 14,000 children born to women living in the former Avon Health Authority area in England with an expected delivery date from April 1, 1991, to December 31, 1992. We used genetic data from approximately 5,000 ALSPAC children and measures from adolescence relating to psychopathology to determine whether genetic risk for schizophrenia is associated with variation in psychotic experiences (e.g. delusions, hallucinations), negative symptoms (e.g. apathy, withdrawal), depressive disorder and anxiety disorder during this developmental period. We derived a score of genetic risk for schizophrenia in each individual within our study. This score is normally distributed such that most people have some genetic risk and a few people have very high or very low genetic risk. We found very weak evidence of an association between genetic risk for schizophrenia and psychotic experiences in adolescence and no evidence of an association with depressive disorder. However, we found strong evidence of association between genetic risk for schizophrenia and negative symptoms and anxiety disorder.  (more…)
Allergies, Asthma, Author Interviews, JAMA / 04.02.2016 Interview with: Prof Dr. Dr. h.c. Claus Bachert Head Upper Airways Research Laboratory (URL) Chief of Clinics ENT-Department University Hospital Ghent Ghent, Belgium Medical Research: What is the background for this study? What are the main findings? Prof. Bachert: Chronic sinusitis with nasal polyposis represents mucosal inflammation, and polyps in the nasal cavity and sinuses, which result in long-term symptoms of nasal obstruction and congestion, reduction in or loss of sense of smell, and loss of quality of life. Patients with nasal obstruction or congestion have a two-fold higher risk of sleep dysfunction, increased fatigue, and decreased work productivity. About 40 percent of chronic sinusitis with nasal polyps patients develop asthma, which often is non-allergic late-onset disease. Treatment options consist of nasal and systemic glucocorticosteroids; long-term or repeated treatment with oral GCS carries a great risk of side effects in these patients. Surgery of the sinuses is another option, but recurrence of polyps is frequent. Further treatment options are highly needed. About 85% of nasal polyps represent a type 2 inflammation, with increased eosinophils and IgE formation. Dupilumab is an investigational therapy that inhibits signaling of IL-4 and IL-13, two key cytokines required for type 2 (Th2) immune responses. Dupilumab has been successfully administered in patients with asthma and atopic dermatitis. The current randomized, double-blind, placebo-controlled group study enrolled 60 adult patients with chronic sinusitis with nasal polyposis refractory to intranasal corticosteroids at 13 sites in the United States and Europe. Following four weeks of mometasone furoate nasal spray (MFNS) run-in, patients in the study received 300 milligrams (mg) of dupilumab or placebo once per week subcutaneously for 16 weeks, after an initial loading dose of 600 mg. All patients in the study continued to receive daily MFNS. Eligible patients had bilateral nasal polyposis and showed chronic symptoms of sinusitis, despite treatment with an intranasal corticosteroid for at least two months. Fifty-eight percent of patients in the study had received prior nasal surgery for their condition.  ​ We found that dupilumab treatment was associated with significant improvements in endoscopic, clinical, radiographic, and pharmacodynamic end points after 16 weeks. Significant improvements in quality of life and in major symptoms, such as sense of smell, nasal congestion, and nocturnal awakenings,were reported. In those patients with asthma, also lung function and asthma control were significantly better with Dupilumab compared to placebo. Dupilumab was generally well tolerated, and no serious adverse events were considered to be related to dupilumab.​ (more…)
Author Interviews, Genetic Research, JAMA, Pediatrics, Surgical Research / 03.02.2016 Interview with: Silje Steinsbekk PhD Associate Professor Dept. of Pschology Norwegian University of Science and Technology  Medical Research: What is the background for this study? Dr. Steinsbekk:  More than every third American child is overweight or obese. Childhood obesity is associated with multiple negative health outcomes such as metabolic syndrome and hypertension, as well as mental health problems, reduced self-esteem and impaired quality of life. Further, overweight and obesity tend to persist from childhood into adulthood, and the risk of adult overweight increases the longer a child has been overweight. Identifying modifiable factors contributing to the development and continuity of unhealthy weight is therefore needed. Genome-wide association studies (GWAS) have identified genetic risks for obesity and these genetic risks have shown to influence development of obesity partly by accelerating weight gain in childhood. Identification of mechanisms through which genetic risks for obesity accelerate weight gain in childhood can therefore provide insight into the developmental pathogenesis of obesity and thus inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Appetite traits may therefore be targets of intervention to protect children against the effect of genetic predispositions to develop obesity. However, such a preventive approach presupposes that appetite traits indeed transmit the genetic effect upon later development of obesity. Notably, cross-sectional studies cannot establish whether appetite traits precede the development of obesity or are caused by it—a critical piece of information for clinicians seeking treatment targets to prevent childhood obesity. We therefore aimed to test whether genetic risk for obesity was associated with rapid childhood BMI growth and if this genetic effect was mediated by appetite traits, following a representative sample of Norwegian children from age 4 to 8. (more…)
Author Interviews, Genetic Research, JAMA, Pediatrics, Weight Research / 02.02.2016 Interview with: Profa. Patrícia Pelufo Silveira, MD, PhD Universidade Federal do Rio Grande do Sul Brazil Medical Research: What is the background for this study? What are the main findings? Response: Previous studies have shown that women who carry a certain gene variant (namely the 7-repeat allele of the dopamine type 4 receptor) have increased risk for obesity, especially if they also suffer from eating disorders. We have also demonstrated that girls who have this gene variant prefer to eat more fat when allowed to choose. However, for some neuropsychiatric conditions, this gene was shown to function as a “plasticity gene”. That is to say that being a carrier makes the individual more or less vulnerable to the disease, depending if the environment in which the person lives is bad (more risk) or good (less risk for the disease). This is called the “differential susceptibility” model. Therefore, in this paper, we wondered if the above described higher fat intake already reported in 7-repeat girls could be modified by the social environment in which they are raised. We saw that if a girl has the gene variant and is raised in a poorer environment, she is more likely to prefer to eat fat in her diet as we knew. However, if she has the gene variant but is raised in a better socioeconomic environment, she actually eats less fat in her regular diet compared to her counterparts who do not carry the gene variant. This is important because we change the focus from the gene (previously "blamed" for increasing fat preference and obesity as the years pass by) to the environment, as the genetic association will increase or decrease the risk according to the conditions in which the child is raised. (more…)
Author Interviews, Depression, JAMA, NYU, Pediatrics / 01.02.2016 Interview with: Briannon O'Connor PhD New York University Child Study Center Department of Child and Adolescent Psychiatry New York University School of Medicine New York Medical Research: What is the background for this study? What are the main findings? Dr. O'Connor: a.      As the health care system continues to emphasize accountability for providing high quality care, the development of meaningful quality standards is critical.  This study came from NCQA’s work to develop these quality measures for adolescent depression care.  Prior to this study, little was known about what routine care looked like for adolescents who showed up at their primary care visits with significant symptoms of depression. This study looked at follow up care documented in an electronic health record in the three months after an adolescent was first identified with significant symptoms of depression. Medical Research: What is the background for this study? What are the main findings? Dr. O'Connor:    Key findings from this study include:
  1. Most adolescents (nearly two-thirds) with newly prescribed depression symptoms received some treatment, usually including psychotherapy, within the first 3 months after depression symptoms were first identified.
  2. Among those adolescents who were prescribed antidepressant medications, 40% had no other follow up care in three months, which is quite concerning since current black box warnings highlight the risk for increased suicidality for youth prescribed antidepressants and clearly recommend close monitoring in the few months following initial prescription.
  3. There were low rates of other follow up care events in the three month follow up period:  19% of adolescents  did not receive any follow up care at all, 36% did not receive any treatment, and the majority (68%) lacked documentation that symptoms were monitored or re-assessed using a valid questionnaire
  4. The sites that participated in the study are highly regarded health care institutions, often looked to as leaders in cutting-edge care. Thus, results from this study, discouraging as they are, may overstate the quality of care in other settings.
Aging, Author Interviews, Cognitive Issues, JAMA, Mayo Clinic, Weight Research / 01.02.2016 Interview with: Rosebud O. Roberts, M.B., Ch.B. Mayo Clinic Rochester, Minn.  Medical Research: What is the background for this study? Dr. Roberts: Decline in weight has been observed 10-20 years prior to onset of dementia. We wanted to study whether this decline also occurs for mild cognitive impairment (an intermediate stage in the progression from normal cognition to dementia). Medical Research: What are the main findings? Dr. Roberts: The main finding was that there was indeed a decline in weight (from the maximum weight in midlife to weight assessed in late life) was associated with a increased risk of mild cognitive impairment. (more…)