Cystic fibrosis is a common autosomal recessive disease. It is caused by any one of many discrete genetic abnormalities that affect chloride transport. Identification of specific genetic abnormalities enables clinicians to identify drugs that counteract the effects of the abnormal genes. In this podcast we review how genetic defects that cause cystic fibrosis are identified and how drugs that are likely to successfully treat the disease are matched to those genetic abnormalities.
The best evidence for proving cause-and-effect comes from randomized clinical trials. However, they are expensive and difficult to perform. The natural assortment of gene variants at birth can mimic randomization in some circumstances and yield important clinical information that can help physicians better care for their patients.
Read the article: Mendelian Randomization
Bacteriophages are viruses that infect and kill bacteria. When they were first discovered in the early part of the 20th century, there was great enthusiasm for their potential use to treat all sorts of bacterial infections. They were supplanted by antibiotics and although they remained critically important in research that led to the understanding of DNA and how it works, bacteriophages never really made it in the therapeutic world. Now that multiple-drug-resistant bacteria are becoming increasingly common, there is renewed interest in using bacteriophages to treat bacterial infection.
YouTube video summarizing the career and science of Félix d'Hérelle-one of the discoverers of bacteriophages
Detailed history of the development of bacteriophage research in Georgia
A Stalinist Antibiotic Alternative from New York Times Magazine, February 6, 2000
Reprint of Twort’s initial description of a substance killing bacteria discovered while trying to grow viruses. Although Twort did not identify bacteriophages in his experiment, he believed there was some toxic entity that killed bacteria present in his experiments.
An investigation on the nature of ultra-microscopic viruses1 by Twort FW, L.R.C.P. Lond., M.R.C.S.
Reprint and translation of d’Herelle’s original 1917 description of bacteriophages isolated from soldiers recovering from dysentery.
On an invisible microbe antagonistic to dysentery bacilli. Note by M. F. d’Herelle, presented by M. Roux. Comptes Rendus Academie des Sciences 1917; 165:373–5
Review of the non-English-language literature on bacteriophage therapy of infection
Bacteriophage Therapy Antimicrob Agents Chemother. 2001 Mar; 45(3): 649–659.
Review of the history bacteriophage research and its effect on scientific development and clinical medicine
The Murky Origin of Snow White and Her T-Even Dwarfs Genetics 155: 481–486 (June 2000)
News report from UC San Diego on treatment of the patient described in the podcast
2017 JAMA Medical News article on the use of bacteriophage to treat a patient with multidrug-resistant Acinetobacter infection
Urinary incontinence in women is common but not often discussed. Linda Brubaker, MD, and Emily S. Lukacz, MD, review the evaluation and management of incontinence in women, including how to broach the topic with patients and when to use treatments ranging from behavioral interventions and pelvic floor muscle exercises to vaginal devices, medications, and office-based procedures or surgery.
An increasing number of transgender patients are being seen in all care settings. Their medical needs are not too different from those for any primary care patient. New guidelines issued by the Endocrine Society in September 2017 are summarized in this podcast.
Powerful new genetic technologies enable clinicians to detect and sequence tiny amounts of free DNA circulating in blood. DNA gets into blood when cells fall apart. Abnormal DNA from diseased cells can be detected, enabling clinicians to detect cancer or monitor tumor growth by liquid biopsy. In this JAMA Clinical Reviews podcast, we talked with Victor E. Velculescu, MD, PhD, from the Johns Hopkins School of Medicine, and JAMA medical writer M.J. Friedrich about this new technology.
Delirium goes unrecognized in approximately 60% of cases. When it is recognized, it can be difficult to treat. Recognizing and treating, as well as preventing, delirium is important because delirium is associated with poor health outcomes and significant health care costs.
Esther S. Oh, MD, PhD, Tammy T. Hshieh, MD, MPH, and Sharon K. Inouye, MD, MPH, discuss their review article about advances in diagnosis and treatment of delirium, and Dr Maria Duggan provides additional insights about diagnosis and management from her perspective as a clinician and researcher.
Related article: Delirium in Older Persons: Advances in Diagnosis and Treatment
Every successive major clinical trial of less invasive breast cancer surgery seems to show that less is more--less because less surgery seems to not influence outcomes and more because with less surgery, there are fewer complications, resulting in a net benefit for women with breast cancer.
Clinicians can now sample DNA from in vitro blastocysts to identify embryos with genetic abnormalities and avoid implanting them. This genetic screening allows couples who carry dangerous genetic diseases to avoid having children with those diseases.
Interviewees: Siobhan M. Dolan, MD, Tamar H. Goldwaser, MD, and Sangita K. Jindal, PhD
Links discussed in this episode:
Some drugs and devices receive accelerated approval from the FDA in order to provide potentially important treatments for patients when effective therapies may not be available. These drugs or devices are supposed to have postmarketing studies to definitively show their efficacy or safety, but sometimes this doesn't happen.
Rita F. Redberg, MD, MSc, Aaron S. Kesselheim, MD, JD, MPH, and Robert M. Califf, MD, discuss their articles characterizing studies used for the approval of high-risk medical devices and accelerated approval of drugs by the FDA.
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Scott Grundy, MD, PhD, is a professor of medicine at UT Southwestern in Dallas and is one of a small group of investigators who saved statins from being dumped as a potential drug class. Dr Grundy tells the story of how studying patients with familial hypercholesterolemia unraveled the mysteries of high cholesterol levels. This resulted in the development of very effective drugs to treat any patient with high cholesterol. Familial hypercholesterolemia is fairly common and when patients have very high cholesterol levels they and their families should undergo cascade screening.
Interviewees: Scott M. Grundy, MD, PhD, and author Joshua W. Knowles, MD, PhD
Links discussed in this episode:
Asthma often develops in childhood but also affects a significant number of adults. It can present in various ways and with varying degrees of severity. William J. Calhoun, MD, of the University of Texas Medical Branch, Galveston, discusses the approach to diagnosis and provides tips for management of this common condition.
Following placement of cardiac stents, patients receive dual antiplatelet therapy (DAPT) to prevent stent thrombosis. Prevention of thrombosis is offset by a risk of bleeding. The optimal balance between thrombosis prevention and bleeding risk is not always known. How to go about optimizing DAPT therapy is discussed by Glen Levine, MD, professor of medicine at Baylor College of Medicine in Houston, Texas, and chair of the combined American College of Cardiology/American Heart Association Guideline Committees.
Allergy to penicillin is one of the most commonly reported allergies by patients. In reality, true penicillin allergy is uncommon. Dr. Elizabeth Phillips from Vanderbilt University discusses her experience with testing for penicillin allergy in patients who thought they had this problem.
Chromosomal microarray technology (CMA) facilitates the genetic diagnosis of intellectual disabilities, autism spectrum disorder, and congenital abnormalities in children. Previously, G-band karyotyping was the test performed for this purpose but it could only identify very large chromosomal abnormalities and was not very sensitive. Being a molecular rather than microscopic technique, CMA is far more sensitive for identifying genetic abnormalities and is now the test of choice.
We interview David H. Ledbetter, MD, and Christa Lese Martin, PhD, from Geisinger Health System, authors of this JAMA Insights article.
Articles discussed in this episode:
Multiple guidelines have been issued regarding how aggressively cholesterol should be managed. These guidelines do not agree with one another and the most significant area of disagreement is in recommendations for high intensity statin therapy. In this podcast we discuss this issue with a number of experts in the field to help better understand how high-intensity statin therapy might be applied to patient care.
Depression is very common in old age. Because it is associated with many issues related to aging such as having diabetes, hypertension, and other diseases and also the general ability to do less than when a person was younger, it is often assumed that depression is just part of the aging process. Inadequate treatment is often given for depression, frustrating patients and clinicians. However, aggressive depression treatment in elderly individuals can be very successful and greatly improve an older person’s quality of life.
Whole-genome sequencing is now easily done for very little cost. It is not known how to interpret the results of this testing. It is inadvisable for healthy individuals to undergo routine whole-genome sequencing but if someone has a reason to suspect a particular disease known to be associated with a unique gene, then targeted genetic sequencing is reasonable.
Interviewee: James P. Evans, MD, PhD, from the University of North Carolina at Chapel Hill.
Much has changed recently in diabetes management. The treatment goal has shifted from rigorous glucose control with HbA1c as the primary target to cardiovascular risk reduction. Risk reduction can be achieved in a variety of ways and does not necessarily depend on expensive new drugs that were shown to achieve this end point. Older, cheaper drugs may achieve the same goal but were never tested in this context.
Interview with JoAnn E. Manson, MD, PhD, from Brigham and Women's Hospital in Boston and Jane Reusch, MD, from University of Colorado, Denver.
Article: Reusch JEB, Manson JE. Management of type 2 diabetes in 2017: getting to goal. JAMA. 2017;317(10):1015-1016. doi:10.1001/jama.2017.0241
A resident is asked to remove a drain that was placed in the lumbar space during an operation. Having never seen this sort of drain before not having removed one, the resident proceeded to remove the catheter. Several days later, the patient complained of persistent drainage. An 11-cm segment of retained catheter was removed. This JAMA Performance Improvement article discusses how to avoid this sort of problem as well as how to ensure that resident physicians have sufficient skills to perform procedures on their own. We talk with Drs Cynthia Barnhard, John DeLancey, authors of Retained Lumbar Catheter Tip, and Dr Aaron Reynolds and Dr David Baker.
Related article: Retained Lumbar Catheter Tip
Alzheimer disease causes progressive neurologic deterioration and is reasonably common in elderly patients. It is characterized by specific patterns of memory loss, which progressively worsens and for which there is no treatment. Recent drug trials have been disappointing in that promising medications have failed to affect the disease. Interesting new hypotheses have emerged from basic science research suggesting that the neurofibrillary tangles characteristic of Alzheimer brain lesions form in response to infection of the brain. Interview with Rudolph Tanzi, PhD, of Harvard University; Berislav Zlokovic, MD, PhD, of the University of Southern California; and Andy Josephson, MD, of the University of California San Francisco, and editor of JAMA Neurology.
Related article: Alzheimer Outlook Far From Bleak
Recent guidelines for how to best manage septic shock have changed. Gone are recommendations for central venous oxygen saturation monitoring and goal-directed therapy. In is the concept that septic shock be treated as an emergency with rapid administration of antibiotics and large amounts of fluids. Our discussants Derek C. Angus, MD, MPH, and Michael D. Howell, MD, MPH, discuss why these recommendations have changed. This is the second podcast in the Surviving Sepsis guideline series. The first podcast reviewed what recommendations are in the guideline itself.
Article discussed in this episode: Management of Sepsis and Septic Shock
Speakers: JAMA Associate Editor Derek C. Angus, MD, MPH, University of Pittsburgh, and Michael D. Howell, MD, MPH, University of Chicago.
In 2017 the Society for Critical Care Medicine updated its guidelines for sepsis management. These new guidelines differ significantly from ones in the past in that they no longer recommend protocolized resuscitation and emphasize early and aggressive fluid resuscitation when patients present with septic shock. This is the first podcast in the Surviving Sepsis guideline series. The next episode discusses why the new sepsis guideline changed.
Article discussed in this episode: Management of Sepsis and Septic Shock
Laura Evans, MD, MSc, of Bellevue Hospital and NYU Medical Center
Andrew Rhodes, MBBS, MD, of St George’s University Hospitals NHS Trust and co-chair of the Surviving Sepsis guideline panel
Mitchell M. Levy, MD, of the Alpert Medical School of Brown University and Rhode Island Hospital
Approximately one-third of all medical school graduates report having been abused as students. Medical student and resident abuse has long been considered unacceptable behavior but still persists in the teaching environment. In this podcast we discuss how students and residents might respond to these events. We interview Geoffrey Young, MD, from the Association of American Medical Colleges and Thomas J. Nasca, MD, from the Accreditation Council for Graduate Medical Education, who discuss how they expect medical schools to respond to abusive behaviors and what resources are available to students and residents who have been abused to report those experiences without fearing retribution.
Article discussed in this episode:
As people age, loss of muscle mass is inevitable, resulting in sarcopenia. Muscle loss contributes to overall weakness, which causes frailty. Frailty, in turn, is the generalized susceptibility to disease and injury, all of which causes loss of autonomy. Because of the potential for progressive decline in physical function in very elderly patients, accurate tools are needed to predict mortality risk to individualize treatments intended to improve longevity such as chemotherapy, management of chronic diseases, and surgery. In this podcast, sarcopenia, frailty, and risk prediction are discussed in the context of major trials studying them being conducted in Europe.